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Orientation program for Doctors.
Management of Opportunistic Infections
and Anti retroviral therapy.
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Date:
June 17th& 18th; 2005
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Venue:
Frontier Management center,
Hoysala Nagar, Ramurthy Nagar,
Bangalore.
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Conducted by:
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SAMRAKSHA
NO. 17/1,Harris Road,
Benson Town,
Bangalore-560046.
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Schedule for the doctors training programme from June 17th & 18th; 2005.
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DAY-1
Topic details
Registration
Resource person
Introduction to HIV/AJDS
Dr.B.Satish
HIV consultant & doctor in-charge
_____ Seva clinic; Samraksha
PPTCT, universal precautions & PEP
Dr. B. Satish
HIV consultant & doctor In-charge
Seva clinic; Samraksha
Work experience in people living with
HIV/AIDS
Dr.Lal; Delhi
Common OFs in HIV and treatment.
Introduction to Anti-retroviral
therapy
Dr.B.Satish
HIV consultant & doctor In-charge
Seva clinic; Samraksha
*
*
Day-2
ARV’s, challenges, difficulties with
anti-retroviral therapy. Interactions
and side effects of ARV’s and secrets
of successful ART adherence
Dr.K.Satish,
Chest physician, Workhardt hospital
&honorary consultant Samraksha
Management of ART in govt, set
up, challenges, difficulities, with anti
retroviral therapy
Dr. Mahesh
Sr.Research officer, ART Unit, Bowring &
lady curzon hospital
Common OFs in HIV/AIDS
Syndromic case management of STI’s
Management of PLHAs in private
clinics
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Dr.Rao,
Consultant-chest & maternity clinic. Bangalore
Dr. Anna rao.
In-charge doctor, Samraksha, Asha Jyothi,
Kushtagi.
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FOR FREE ARV TREATMENT
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1. ART UNIT,
OPD BLOCK,
KIMS HOSPITAL
HUBLI
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2. BOWRING HOSPITAL
ART UNIT, SHIVAJINAGAR,
BANGALORE.
*
3. ART UNIT,
K.R NAGAR, MYSORE.
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CARE CENTRES FOR IN-PATIENT SERVICES
1.
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SAMRAKSHA
ASHA KIRAN RESPITE HOME
# 37,ST JOHNS ROAD,
NEAR LAXMI THEATRE,
BANGALORE.
SERVICES OFFERED
■ Admissions
■ Medical consultation for opportunistic infections
■ Nursing care
■ Palliative care
• Counseling
■ Monitoring of anti retroviral therapy
■ Out -patient service.
-SAMRAKSHA, ASHA lYOTHI
NH-13, TENGUNTA ROAD,
KUSTAGI, KOPPAL DISTRICT
SERVICES OFFERED
(SAME AS ABOVE)
2 SNEHADAAN
AMBEDKAR NAGAR, SARJAPUR ROAD, BANGALORE-35
SHEHADAAN,
MANGALORE.
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3. FREEDOM FOUNDATION,
#180,HENNUR CROSS,
ST.THOMAS TOWN, MANGALORE.
*
PH.# 25440135.
- FREEDOM FOUNDATION,
BELLARY.
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REFERRALS
HIV TESTING:
*
1. All districts & talukas VCTC/PPTCT
Centers from Monday to Saturday
2. Samraksha-Asha jyothi, Kustagi, NH-13, Koppal district on all
Saturdays.
3. Samraksha-seva clinic, # 37, st. Johns road, near old Laxmi theatre,
Bangalore.ph. # 25512375 on all weekdays.
CD4 COUNT
NIMHANS, DEPT. OF VIROLOGY, ADMINISTRATIVE BLOCK,
BANGALORE.
(Blood to be collected before 11 am.
Testing is done only on Tuesdays / Fridays.
If you’re sending the sample, Rs.500 will be charged.)
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ANAND DIAGNOSTICS LAB
#1 l,blue cross-chambers, infantry road. Bangalore.
(On all days-Monday to Saturday, Rs. 1000/- will be charged.)
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CHAPTER - 2
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Natural History and Clinical Manifestations of HIV/AIDS
Eighteen years ago, the terms HIV/AIDS were not known to the medical fra tern i tv.
But now it is th4^second leading cause of death among young adults in United States
and has had a profound impact on the health of people worldwide. A family physician
has got a very important role in continuum of care of an HIV/AIDS patient while a
specialist is involved only in critical care. So the basic objectives of this chapter revolve
around the following:
i.
To familarise the physician with the course HIV will follow once it enters the
human body.
2.
The various clinical sign and symptoms that indicate clinical diagnosis of AIDS.
3.
When to subject the patient to various laboratory tests.
4.
When to refer the patient to a specialist.
But one must be very clear that as per government policy, there are no special AIDS
clinics, or AIDS hospitals or AIDS specialists. All doctors are expected to treat AIDS
patients without any bias and discrimination.
With a high case fatality rate, significant impact on health and society, lack of definite
curative treatment or vaccine, HIV/AIDS pandemic is one of the most serious health
problems of this century. The current AIDS cases reveal the transmission dynamics of
past years and burden of illness in near future. Similarly, the prevelance and incidence
of HIV infection today may be fully revealed only in future years. The mean time from
initial infection to diagnosis of AIDS is around 9 years but now various epidemiological
studies have been shown that the rate of disease progression varies substantially
depending on various viral, host and environmental co-factors, mode of transmission,
age ^t infection, treatment interventions and prophylaxis strategies. Hence it is very
pertinent to look into natural historv of HIV infection.
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NATURAL HISTORY OF HIV
A.
HIV Transmission
The primary modes of HIX' transmission are sexual contact, receipt of infected blood
and its products, organs and tissue donations and pregnancy and breast feeding,
percutaneous exposures (accidental or I/V drug users). A clear understanding of HIX'
4
Guidelines for Clinical Management of f$l\'/AIL)S
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transmission is integral to providing effective counselling about the risk and prevention
of HIV transmission.
B.
Clinical Stages of HIV Disease
Infection with HIV leads to a progressive impairment of cellular immune function,
characterized by a gradual decline in peripheral blood CD4+T - lymphocyte levels
which results in an increasing susceptibility to wide variety of opportunistic viral,
bacterial, protozoal and fungal infections and to certain malignancies also. The course
of the disease is marked by increasing levels of viral replication, emergence of more
virulent viral strains and progressive destruction of immune system. However, the
natural history of HIV infection is changing with better diagnosis, anti-retro-viral (ARV)
therapy, and early treatment and prophylaxis of various opportunistic infections.
Early, patients with HIV infection were categorized as having either, AIDS-Related
Complex (ARC) or asymptomatic disease. As more information has been gathered on
HIV, these terms have been outdated. Various classifications have been proposed over
years based on various clinical and laboratory parameters but the one proposed by
Centre for Disease Control and prevention (CDC), Atlanta, USA using CD4 count as
marker for relative risk of developing HIV related opportunistic infection is given
below.
9 _
Stage I: Acute (Primary) Infection (SERO
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Initial primary' infection with HIV is usually asymptomatic. However, after an
incubation period of 2-6 weeks, (longest upto 36 weeks), there is a phase of viraemia
and upto 50% of individuals experience an acute infections mononucleosis like illness
or a viral syndrome. There may be high fever, lymphadenopathy, pharyngitis,
arthralagia, amorbillifom rash and myalgia. The illness usually lasts 2 weeks or less and
may even go uninvestigated as possibility of HIV infection is frequently not explored
at this stage. Around 10-20% patients may present with headache, meningo-encephalitis,
peripheral neuropathies, myelopathy, Bell's Palsy or G.B. Syndrome. One may
occasionally also get oropharyngeal candidiasis.
There is severe CD4 lymphepaenia and this may drop to levels indicative of advanced
HIV disease but typically it rebounds to near normal in 2-3 weeks in most of cases. In
some case CD4 count may remain suppressed and this may be harbinger of a more
accelerated course of disease.
HIV antibody tests are often negative in early stages of HIV seroconversion
illness: The diagnosis depends on tests to detect viral antigen (e.g. p24 antigen and
PCR tests).
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Tuberculosis: disseminated, miliary, extra-pulmo:Tiary and extensive pulmonary
tuberculosis.
3.
Neurological impairment preventing independent daily activities, not known
to be due to the conditions unrelated to HIV infection (e.g. trauma).
4.
Candidiasis of the oesophagus (dagnosable by odynophagia with oral
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candidiasis).
5.
Clinically diagnosed life threatening or recurrent episodes of pneumonia, with
or without etiological confirmation.
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Other conditions:
•
•
•
•
•
•
7.
Crytococcal meningitis
Neuro-toxoplasmosis
Cytomegalovirus retinitis
Penicillium marneffei infection
Recurrent Herpes zoster and multi-dermatomal, and
Disseminated molluscum
♦
V
Kaposis sarcoma
For children (upto 12 years of age)
A.
B.
Two positive tests for HIV infection (by ERS test) among children 18 months or
older, or confirmed maternal HIV infection for children less than 18 months; and
Presence of at least two major and one minor signs in the absence of known
causes of immuno-suppression
i
Major Signs
t
2.
Loss of body weight or failure to thrive that is known to be due to medical
causes other than HIV infection.
Chronic diarrhoea (intermittent or
• continuous)
3.
Prolonged fever (intermittent or• continuous)
1.
Minor Signs
II
1.
Repeated common infections (e.g. pneumonitis, ottitis, phayngitis)
2.
Generalised lymphadenopathy
ii
3.
Oropharyngeal candidiasis
ii
4.
Persistent cough for more than one month
5.
Disseminated maculo-papular dematitis
©
Guidelines for Clinical Management of HIV/AIDS
A, A-*
SYMPTOMATIC HIV INFECTION
Various systemic manifestations in patients with HIV include weight loss (more than
10% of body weight), fever (more than one month duration) aeslhen.a diarrhoea
cough, pruritis, dysphagia, headache, dyspnoea, amenorrhoea (females). The various
common manifestations in different organ systems are listed below:
Cutaneous and Oral Manifestation of AIDS
Herpes Zoster and simplex
Infections:
Fungal infection (Candidiasis)
Cryptococcosis
Histoplasmosis
Molluscum Contagiosum
Folliculitis
Polymyositis
Hairy leukoplakia
Pencillium marneffei infections
Neoplastic
Kaposi's Sarcoma
Lymphoma
Basal cell carcinoma
Others
Pruritic papular dermatitis
Seborrhoeic dermatitis
Drug eruptions
Vasculitis/Gingivitis
Pencillium marneffei infections
Gastrointestinal Manifestation
Persistent Diarrhoea
Crytosporidiosis
Isopora
Shigella
Salmonella
E. Histolytica
Giardia, Microspora
Colitis
Cytomegalovirus
Kaposi's sarcoma
Dysphagia
Oral & Oesophageal Candidiasis
CMV Oesophagitis
Oral hairy leukoplakia
Gingivitis/Ulcer
Guidelines for Clinical Management ofHIV/AIDS
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Stage 11: Early (Asymptomatic) Disease (CD4 Counl>5()0lmm3)
This is th(Mc>4gest period in course of HIV disease in which patient is asymptomatic
and remains apparently healthy for a few years or more. This period may be, on an
average,^10 years in Westen^countries but in India it has been found to
years.
But there are still no large epidemiological studies to confirm this. The relatively
symptom free period may be punctuated by variou^ermatological conditions like
seborrhoeic dermatitis, pruritis, cellulitis, reactivation of latent Herpes Zoster infection,
worsening of psoriasis. Sometimes oral hairy leukoplakia may be identified at this
stage of disease. There may be symptoms and signs suggestive (^polyclonal activation
of immune system manifesting as idiopathic thrombocytopenic purpura (ITP), G-B
Syndrome, auto-immune demyelination of peripheral nerves, polymyositis and
mononeuritis multiplex. The manifestation of HIV infection during this period correlates
poorly with risk of disease progression.
Another feature^seen frequently is symptomless Persistent Generalised
Lymphadenopathy v’GL). This is seen 3-5 years after HIV infection and usually involves
one or more extra inguinal lymph nodes (cervical or axillary) with nodes being more
;han pzm in diameter, not matted and persisting,for more than three months duration,
laboratory data shows leukopenia, thrombocytopenia, polyclonal activation of immune
~ell and altered serum transaminase levels. Even without ARV therapy chances of
patients in this stage progressing to AIDS within 2 years is less than 5%. The CD4
count continues to decline progressively and though difficult to predict, on an average
'here is decrease of 40-80 cells/mm3/year without ARV therapy.
David Ho, in his studies, has shown a definite benefit in sense of delay in progression
when ARV therapy is started in this phase. But if antiretroviral therapy is not
jconomincally feasible, one must always be on look out for various opportunistic
nfections which can be effectively cured with locally available drugs.
Stage III: Intermediate HIV infection (CD4 count 200-500/mm3)
As CD4 count falls, the complications of HIV infection begin to occur more frequently
jr worsen in severity. The person gets other disorders (earlier referred to as ARC) like
ecurrent HSV & HZV infection (shingles), mild oropharyngeal or vaginal candidiasis,
^ral hairy leukoplakia indicates a higher risk of progression to AIDS. Mycobacterium
uberculosis is seen commonly with a CD4 count around 250/mm3. Atypical and
xtrapulmonary tuberculosis (affecting lymph nodes or causing tubercular meningitis)
ire also common.
Vhen left untreated, patients with intermediate HIV disease have 30-50% chance o£
developing an AIDS defining conditions or dying within next 18-28 months; With ARV
lerapy, however, the risk is reduced two to three folds.
luidelittes for Clinical Management of HIV/AIDS
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Stage IV: Late Stage HIV Disease (CD4 count 50-2001ntnr])
According to revised CDC definition of AIDS, all patients in this group are now
defined as having AIDS. The most commonly noted opportunistic infections during
this stage include cerebral toxoplasmosis, PCP, cryptococcal meningitis, cytomegato
virus retinitis etc.
Combination ARV therapy does halt the rapid progress to some extent and aggressive
nutritional counselling is warranted to maintain immune system function as well as
delay development of AIDS wasting syndrome.
I
Stage V: Advanced HIV Disease (CD4 count <50hnm^)
Even with therapy, the patients with advanced HIV disease have a likelihood of dying
within a 2 year period due to any of opportunistic infections.
As the CD4+ count gets depleted further, the spectrum of infections widens and frequent
relapses are seen despite treatment and secondary prophylaxis.
The common infections seen in this stage are those with M. Avium Complex (MAC),
systemic histoplasmosis, cryptococcal meningitis, progressive multifocal
leukoencephalopathy, CMV retinitis, CMV colitis and CMV encephalitis.
I
Many patients with CD4 count < 50/mm3 present with’direct neurological effects of
HIV known as AIDS Dementia Complex (ADC). It is a subcortical dementing process
which causes motor abnormalities, cognitive impairment and behavioural changes.
The incidence of ADC is decreasing over years with use of ARV therapy. Many patients
in this stage develop significant weight loss, wasting of muscles, various types of
malabsorptions, various features of addison's disease etc. (HIV wasting syndrome).
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Clinical Case Definition of AIDS in India
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For persons (above 12 years of age)
A.
Two positive tests for HIV infection by ERS test); and
B.
Any of the following:
1.
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(a) Significant weight loss (10 per cent or more of body weight) within last
one month) and/or cachexia (not known to 6e due to condition other
than HIV infection) and
(b) chronic diarrhoea (intermittent or continuous) or
(c)
prolonged fever (intermittent or continuous)
Giiiiicliiii’s for Clinical Management of HIV/AIDS
1
Perianal Di scorn fori
Herpes \ iral proctitis
Herpes viral Ulceration
Respiratory Manifestations of AIDS
Persistent cough, dyspnoea,
cyanosis, tachypnoea, fever
haemoptysis, pleural
effusions
Mycobacterium tuberculosis
Bacterial Pneumonia
Streptococcus, H. Influenzae
atypical mycobacterium
Cytomegalo virus
Pneumocystitis carinii
Legionella, Candida
Histoplasma
Lymphoid interstitial pneumonitis
Herpes simplex virus
Kaposi's sarcoma
Neurological Manifestations of AIDS
Headache, lethargy
HIV Encephalopathy
Dementia, ataxia, altered
oersonality, convulsions.
Incontinence
Cryptococcal meningitis
Lymphoma
Herpesvirus
AIDS dementici complex
vleningism
Cryptococcal meningitis
Tubercular meningitis
Bacterial meningitis
Visual impairment
Bye changes)
CMV retinitis
Toxoplasmosis
Keratoconjuctivitis
Microsporidia
I'ocal seizures, hemiplegia &
Hher focal
Neurological deficits
Abscess due to
toxoplasma, cryptococcus,
mycobacteria, Lymphoma
Peripheral neuropathy
HIV vasculitis
Lymphoma
various haematological, renal, cardiac, endocranial, reproductive and other
anifestations have also been reported and must be kept in mind.
Guidelines for Clinical Management of HIV/AIDS
J
INITIAL ASSESSMENT
j
Patients with HIV may present during the seroconversion phase or at any time latei,
perhaps not until they get an AIDS defining illness (or a major opportunistic infection).
A thorough evaluation of patient is called for with a number of investigations and this
may take more than one visit. Each visit of the patient must be utilised adequately for
his counselling on various issues right from testing, antiretroviral therapy, various
opportunistic infections, long term complications morbidity, psychological support,
legal and ethical issues including his rights.
dl
HISTORY
'1
Psychological
Evaluate the patient for anxiety, depression, reduced self esteem, denial. Seek carefully
details of his behaviour that put him at risk, including promiscuity, drug or alcohol
dependence, I/V drug abuse. Assess him for his ability to adjust to the diagnosis and
level of cooperation in medical management.
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Social
‘I
Assess his relationships and supports, and understanding level of family members.
Develop trust with patient and have him faith in you with regard to confidentially.
Never rebuke him for his earlier high risk behaviour.
Risk Factors and Likely Contacts
III
Other Medical Conditions: (e.g. Herpes, STD, liver disorder, bronchiectasis) and
medications (c.g. steroids) that may lead to complications.
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Physical Examination
■
Skin
Weight
Lymphadenopathy
Oral cavity
Systemic examination
Eyes
Check for STDs etc.
Investigations
HIV: Atleast 2 different Antigen based ELISA tests (Western blot no longer required as
a must in our country)
Guidelines for Clinical Management of HIV/AIDS
11
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Immune functions: CD4+, CD8+ Cell counts, CD4/CD8 ratio
6
Plasma viral loads (where-ever possible)
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Full blood counts, Liver & renal functions tests
Mantoux test
X-ray chest
Co-infections: tests for syphilis, gonorrhoea, hepatitis A, B & C, Toxoplasma, E-B
virus, papsmear for women.
e
SPECTRUM OF OPPORTUNISTIC INFECTIONS IN INDIA
Analysis of AIDS cases reported by various States to NACO, the spectrum of various
opportunistic infections (OIs) is shown below:
OIs
Tuberculosis
Candidiasis
Cryptosporidiasis
Herpes zoster
Toxoplasmosis
Bacterial pneumonia
Cryptococcal meningitis
PCP
Kaposi's sarcoma
Others
Percentage
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CHAPTER 14
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Post Exposure Prophylaxis Guidelines
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Introduction
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Health Care Workers (HCW) are normally at a very low risk of acquiring HIV infection
unng management of the infected patient. However, inspite of a low statistical risk
o acquisition of HIV, the absence of a vaccine or effective-curative treatment, makes
the health care worker apprehensive. So, it is very necessary to have a comprehensive
programme in place to deal with anticipated accidental exposure.
Most exposures do not result in infection. The risk of infection varies with type of
exposure and other factors such as:
•
The amount of blood/body' fluid involved in the exposure
The amount of virus in patient's blood/other body fluids at the time of exposure
•
Whether post exposure prophylaxis (PEP) was taken within the recommended
time.
^7
Prevention is the mainstay of strategy to avoid occupational exposure to blood/body
fluids. All the biosafety precautions emphasized in Universal Work Precautions must
be practiced at all times for all patients, blood and body fluids while providing medical
services.
Definition of an Occupational Exposure
An occupational exposure that may place a worker at risk of HIV infection is a
percutaneous injury, contact of mucous membrane or contact of skin (when the skin is
chapped, abraded or afflicted with dermatitis or the contact is prolonged or involving
an extensive area) with blood, tissue or other body fluids to which universal precautions
apply.
Steps to be taken on exposure to HIV infected blood/body fluids and contaminated
sharps etc.
Immediately following an exposure:
Needle sticks and cuts should be washed with soap and water;
•
&
Splashes to the nose, mouth or skin, should be flushed with water;
*
Guidelines for Clinical Management of HIV/AIDS
•
Eyes should be irrigated with clean water; saline, or sterile irrigants;
.
Pricked finger should not be put into mouth, reflexly.
No scientific evidence exists as to the fact that the use of antiseptics for wound care
or squeezing the wound will reduce the risk of transmission of HIV, However, this
must always be done. The use of a caustic agent such as bleach is not recommende .
Report the exposure to the appropriate authority such as Infection Control Officer and
condition must be treated as an emergency. Prompt reporting is eesentional because in
same cases, HIV postexposure prophylaxis (PEP) may be recommended and it should
be standard as soon as possible, preferably within two hours.
Based on animal models, the success of PEP therapy is reported to be maximal when
started within matter of hours after the exposure. Althogh, any cutoff time i arbitrary
initiating treatment more than 72 hours after the exposure is not recommeded. Although
perhaps not as effective as prophylaxis, late PEP (after 72 hours) may still be useful
as early treatment of HIV infection, in case infection has occurred.
Types of Occupational Exposure to HIV for which PEP is recommended
Most occuptional exposures do not lead to HIV infection. The change of possible
serous side effects (toxicity) of the drugs used to prevent infection may be muc
greater then the chance of HIV infection from some kind of exposures. Both risk of
infection and possible side effects of drugs should be carefully considered when deciding
whether to take postexposure prophylaxis. Exposures with a lower infection risk may
not be worth the risk of the side effects associated with these drugs. The decision to
start PEP is made on the following basis:
1.
2.
3.
Degree of exposure to HIV (determined by the Exposure Code - figure 1);
HIV status of the source from whom esposure/infection has occurred (figure 2);
PEP recommendations (figure 3).
Guidelines for Clinical Management o/HlV/AlDS
73
1-
Fig- 1: Determination of the Exposure Code (EC)
IS tl7op0rwen?atCria\bl0°d' bl°Ody fluid' other Potent>aUy infectious
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instrument
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Yes
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No
Blood or bloody fluid
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No PEP needed
________
What type of exposure has occurred ?
Mucous membrane or
j skin, integrity compromised
Intact skin
only
Volume
No PEP Needed
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1
______
Small
(e.g.z few
drops,
short
duration)
ECI
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Large
(e.g., several
drops, major
blood splash
and/or longer
duration (i.e.,
several minutes
or more)
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EC2
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Less Severe
(e.g., solid
needle,
superficial
scratch)
Percutaneous
exposure
Severity
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More Severe
(e.g., large-bore
hollow ’needle,
deep puncture,
visible blood
. on device; or
needle used in source
patient's artery or vein
r~ EC3 7 s
EC2
Fig. 2: Determination of the HIV Status Code (HIV SC)
What is the HIV status of the exposure source?
_____ I.
HIV negative
HIV positive
_______
No PEP needed
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Status
unknown
Source
unknown
\/_____________________
Lower titer exposure
(e.g.z asymptomatic
and high CD4 count)
HIV SC 1
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Higher titer exposure
(e.g.', advanced AIDS,
primary HIV infection, high
or increasing viral load or
low CD4 count)
r HIV1SC2'
HIV SC
Unknoyyn
Guidelines for Clinical Management of HIV/AIDS
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Fig. 3. Determine the PEP recommendation
EC
HIV SC
1
1
PEP may not be warranted. Exposure type does not pose a known
risk for HIV transmission. Whether the risk for drug toxicity
outweighs the benefit of PEP should be decided by the exposed HCW
and treating clinician.^
1
2
Consider basic regimen. Exposure type poses a negligible risk for
HIV transmission. A high HIV titre in the source may justify
consideration of PEP should be decided by the exposed HCW and
treating clinician.
2
1
Recommend basic regimen. Most HIV exposures are in this category;
no increased risk for HIV transmission has been observed but use of
PEP is appropriate.
■
2
2
Recommend expanded regimen. Exposure type represents an
increased HIV transmission risk. ,
2/3
UNKNOWN
If the source, (in the case of an unknown source), the setting where
the exposhre occurred suggests a possible risk-fdr HIV exposure and
the EC is 2 or 3, consider PEP basic regimen.
PEP recommendation
Pre and Post test counselling and testing
The person should be provided with pre test counselling and AZT be started as
discussed above. Before starting AZT, 33-5 ml. of person's reference blood sample is
taken and tested for anti-HIV antibodies immediately after the exposure. In case the
sample tests are positive as per the strategy on the HIV testing the individual is
referred to the clinician for management, as a case of HIV infection. In case the sample
tests are non-reactive, a 2nd sample is collected at 6 weeks and 3rd at 12 weeks after
the exposure and tested for HIV antibodies. The facilities for RT-PCR are available
presently at NARI, Pune and AIIMS, New Delhi and this can give us results even at
2nd week after exposure. Post-test counselling is done in all cases.
I
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During the follow-up period, especially the first 6-12 weeks when most infected persons
are expected to show signs of infection, the recommendations for preventing
transmission of HIV are to be followed by the HCW. This includes refraining from
blood, semen and organ donation and abstaining from sexual intercourse it is
undertaken, a latex condom must be used correctly and consistently. This reduces the
risk of HIV transmission. In addition, women should not breast-feed their infants
during the follow-up period after exposure to prevent exposing their infants to HIV
>
I
in breast milk.
I
Guiiielhiea for Clinical Management of HIV/AIDS
75
'L
n
Drugs recommended for postexposure prophylaxis/treatment
It is recommened that in India zidovudine (ZDV - 300 mg BD) and lamivudine (3TC
- 150 mg BD) be used as basic regimen. Both these drugs should be cosidered for
treatment of all exposuers involving HIV infected blood, fluid containing visible blood,
or other potentially infectious fluids or tissue. Used in combination, ZDV and 3TC are
very effective in treating HIV infection after exposure and considerable information
shows, that they are safe when used for a short time.
0
0
e
&
&
In selected cases (HIV Status Code 2 and Exposure Code 2 and 3), and ZDV - 800 mg /
TDS indinavir (or one of the other protease inhibitors) is also being used as per PEP
guideline (in advanced regimen).
&
Duration for which drugs need to be taken
The optimal course of treatment is unknown if tolerated, treatment should be taken for
4 weeks.
Pregnancy and PEP
Based on limited information, ZDV taken during 2nd and 3rd trimesters of pregnancy
has not caused serious side effects in mothers or infants. There is very little information
of the safety of ZDV when taken during the 1st trimester or on the safety of other
antriviral, drugs taken during pregnancy. If the HCW is pregnant at the time of
occupational exposure to HIV, the designated authority/physician must be consulted
about the use of antiviral drugs for PEP.
Facts known about the safety and side effects of these drugs
Most of the information known about the safety and side effects of these drugs is
based on studies of their uses in HIV-infected individuals. For these individuals, ZDV
and 3TC have usually been tolerated well except for nausea, vomiting, diarrhoea,
tiredness or headache for people taking ZDV.
Steps to be undertaken by the Infection Control Officer on receiving information
about occupational exposure
76
•
All the needle stick injuries should be reported to the State AIDS Control Society
giving the exposure code and the HIV status.
•
The State AIDS Control Socities should in turn inform NACO about the cases
periodically.
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**
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Guidelines for Clinical Management of HIV/AIDS
*
()
1
A registry is planned to be opened in NACO soon, for follow-up of all such cases.
5
NACO has decided in principle to supply antiretroviral drugs to all cases for PEP
in Govt. Hospital setting for HCW.
5
♦
Infection Control Officers in all hospitals have been directed to ensure that
entireretroviral drugs for PEP are available in casualty at all the time.
♦
3
5
5
5
5
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5
$
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7
Guidelines for Clinical Management of HIV/AIDS
L
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CHAPTER 18
Management of Opportunistic Infections in AIDS
Acquired Immunodeficiency Syndrome (AIDS) has been defined as the occurrence of
life threatening opportunistic infections, malignancies, neurological diseases and other
specific illnesses in patients with human immunodeficiency virus (HIV) infection and/
or with CD4 count less than 200/cmm.
The timing and development of opportunistic infections in people with HIV are product
of the immune defect of the host and the microbial environment within which we all
live. Although virtually all aspects of the immune system are altered by HIV, defects
in cellular immunity are prominent (involving T-cells and macrophages).
In the west there has been significant decline in the opportunistic infections because
of highly active antiretroviral therapy (HAART).
s
■
However, opportunistic infections still significantly contribute to morbidity and
mortality in HIV disease.
Till the time highly active antiretroviral therapy (HAART) becomes more widely
available to the developing countries, managing opportunistic infections would
constitute the mainstay of managing HIV disease.
Opportunistic infections in these patients are as a rule disseminated, recurrent and
persistent and are seen to be influenced by economy and race e.g. PCP, MAC,
Cryptococcus, cytomegalovirus and toxoplasma gondii are common in developing
countries like Africa, Asia and Southeast Asia.
HIV AND RESPIRATORY DISEASES
Upto 2/3rd of people with HIV will have a respiratory illness associated with their
infection. Many of these illnesses are treatable and preventable.
ill
Table 1. Pulmonary diseases in HIV infection
Condition
Infect ion
Mycobacterium tuberculosis
Bacterial pneumonia
Suppurative lung and sinus disease
Pneumocystis carini pneumonia
Mycobacterium avium complex
Cytomegalovirus
CD 4 cell count/mm3
< 400
< 350
< 100
< 200
< 100
< 100
Guidelines for Clinical Management of HIV/AIIJS
-
103.
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MYCOBACTERIUM INFECTIONS
Tuberculosis is the most common opportunistic infection in AIDS cases in our country
and can present at any stage of HIV infection. In immunosuppressed, tuberculai
infection can be rapid taking months rather than years.
HIV infection represents the greatest risk factor for the development of active
tuberculosis. Instead of a lifetime risk of developing TB of 10%, those with HIV infection
1^8
have a risk of 8% to 10% per yeeir.
Extrapulmonary tuberculosis is much more common in HIV and can present as
•
lymphadenitis
•
miliary disease
gai
CNS TB
bonemarrow TB
genitourinary tract TB
DIAGNOSIS
•
clinical history in form of low grade fever, weight loss, anorecia, fatigue
•
X-ray chest may show;
hilar adenopathy
-
pleural effusion
-
upper zone infiltrates
cavitation or miliary pattern
•
sputum for AFB (positive in 80% of patients)
(3 samples should be tested)
TB lymphadenopathy FNAC - AFB positive in 65%
Treatment standard regimen to be followed.
•
4 drug regime for 2 months
Followed by 2 drugs for 4 months
INH
Rifampicin
PZA
Ethambutol or streptomycin
INH
Rifampicin
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Guidelines for Clinicnl Miiiiii^eiiient of IHV/AIDS
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Do not give thiacetazone to HIV-positive patients (increased risk of severe and
sometimes fatal skin reaction).
Regimens which are adequate for treatment of pulmonary tuberculosis are generally
effective in treating extra-pulmonary tuberculosis also.
Around 6 to 9 months of treatment appears to be sufficient to many sites of extrapulmonary disease, a longer duration of therapy (12 months) is recommended for
some sites including:
(
miliary TB
bone or joint disease
•
tubercular meningitis
Persistently positive sputum culture after 2-3 months of therapy suggests the possibility
of drug resistant tuberculosis or non-compliance with therapy.
t
PNEUMOCYSTIS CARINII PNEUMONIA (PCP)
PCP occurs in advanced HIV disease, when CD4 count falls below 250 cells/cmm.
It has an indolent onset with fever, non-productive cough and progressive dyspnoea,
Physical signs such as crackles and radiological changes such as bilateral pulmonary
infiltrates tend to be late manifestations.
fi
Table 2. Manifestations of pneumocystis carinii pneumonia
Symptoms
Blood gas analysis
Mild_______
Moderate
Severe
Cough,
sweats
exertional
dyspnoea
Dyspnoea
on minimal
exertion, fever
sweats, cough
Dyspnoea at
rest, tachypnoea,
persistent fever
PaO2 normal
PaO2 60-80 mmHg
SaO2 falls on
exertion
PaO2< 60 mmHg
Diffuse bilateral
interstitial
shadowing
Extensive
bilateral
interstitial and
alveolar markings
Normal or
minor perihilar
markings
Chest x-ray
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(=
s
PaO2 = Partial pressure of arterial oxygen and SaO2 - arterial oxygen saturation.
Guiiielincs for Clinical Management of HIV/A1DS
■
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71
105.
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M-
DIAGNOSIS
Diagnosis is often made on (clinical
"
' 'but should be confirmed by sputum
grounds
examination. However, treatment should not be withheld for want of confirmed
diagnosis.
DEFINITIVE DIAGNOSIS
a)
Sputum Induction with hypertonic saline (50-80% sensitive).
b)
Broncho-alveolar lavage (BAL) (86-97% sensitive).
c)
Broncho-alveolar lavage + transbronchial biopsy (99% sensitive).
Clinical worsening during the first 3-5 days of starting treatment is common, but
generally there is improvement by 7-10 days, so avoid early change in treatment.
Trimethoprim 15-20 mg/kg daily + sulfamethoxazole 75-100 mg/kg/day in divided
doses.
(Co-trimoxazole - Double strength tablets, 2 x TDS)
I If allergic to sulfamethoxazole, alternative regimens are
IV pentamidine 4 mg/kg/day
Dapsone 100 mg daily + trimethoprim 300 mg daily
Start steroids within 48-72 hours of specific treatment. Prednisolone 40 mg twice daily
for days and then reduce gradually. This helps in reducing alveolar oedema and
improving oxygen perfusion across alveoli.
PRIMARY PROPHYLAXIS IS RECOMMENDED
1.
When CD+4 count less than 200 cells/cmm.
2.
In patients with higher CD 4 count and persistent fever with
a)
Oral candidiasis.
b)
Along with other AIDS defining conditions.
SECONDARY PROPHYLAXIS
All patients after an episode of PCP.
Oral tnmethoprim-sulfamethoxazole 1 double strength tablet (160/800 mg) daily
0
Guidelines for Cliiiiciil Muiia^eiiieiil of HIV/AIDS
Alternative
Pentamidine 300 mg IV or Inhaled monthly.
BACTERIAL INFECTIONS
Pyogenic bacterial infections occur more frequently in HIV infected patients than in
general population.
Common infecting organisms are similar and include
Streptococcus pneumoniae
Haemophilus influenzae
Staphylococcus aureus
Bacterial chest infections tends to have a very different clinical course as compated to
PCP, with an abrupt onset of fever, productive cough, purulent sputum, dyspnoea and
typical signs of consolidation signs and X-ray findings.
TREATMENT WITH STANDARD AGENTS IS EFFECTIVE AND INCLUDES
i
Penicillin
I
Ampicillin
Erythromycin
■
Cefotaxime
Adequate oxygenation and chest physiotherapy
I
DIARRHOEAL DISEASES
Diarrhoea is the most common gastrointestinal symptom in HIV infection affecting
90% of patients and becoming more frequent as immune deficiency progresses.
i
Diarrhoea and weight loss are independent predictors of mortality.
Gastrointestinal infections are predominant cause of diarrhoea.
Guidelines for Clinical Management of HIV/Al US
!
Table 3. Common pathogens in HIV related diarrhoea
Small bowel
(duodenum / j ej unum)__________
Large bowel
(colon/terminal ileum)
Bacteria
Mycobacterium avium complex
Salmonella species
Campylobacter species
Yersinia species
Aeromonas species
Clostridium difficile
Protozoa
Cryptosporidium species
Microsporidia
Cyclospora species
Giardia lamblia
Entamoeba histolytica
Rotavirus
Astrovirus
Calicivirus
Picornavirus
HIV
Adenovirus
Herpesvirus
Viruses
J
*
Cytomegalovirus
MANAGEMENT OF DIARRHOEA
'ir
Management has three basic aims
1.
Detection of treatable cause.
2.
Relief of symptoms.
3.
Prevention of malnutrition
Table 5. Principles of managing HIV related gut infection
*
Remember pathogens may be involved concurrently
*
Dissemination from the gut can occur in some bacterial infections (MAC,
Salmonella, Shigella, Campylobacter)
Relapse following successful treatment is frequent (CMV Salmonella,
Shigella, Campylobacter, MAC, cryptosporidia, microsporidia, Cyclospora)
Progressive weight loss and reduced performance status are frequent if
there is no resolution of diarrhoea pathogen is not identified. The
*
symptomatic therapy is indicated.
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Table 4. Managing HIV related diarrhoea
1. Take history :
Nutritional status, medication, previous opportunistic infections
* Diarrhoeal symptoms: Small bowel disease (enteritis) usually causes watery, large volume
diarrhoea associated with bloating and often profound weight loss. Large bowel disease
(colitis) usually causes cramping lower abdominal pain, urgent, frequent small volume
stool which often contains blood, mucus and pus, and the presence of fever. In many
clinical situations, the distinction is not possible and indeed , some pathogens cause
significant disease throughout the gut (panenteritis).
2. Withdraw drugs associated with diarrhoea
3. Examine faecal specimen:
Microscopy: blood/pus cells; parasites (special stains for microsporidia if initial specimen
is not diagnostic)
* Culture: Salmonella/Shigella/Campylobacter/Yersinia
* Toxin assay: Clostridium difficile
4. Blood cultures (2):
* Standard broth and, if CD 4 cell count
100 pL, mycobacterium-supporting media
5. Manage according to the findings:
I
Pathogen identified
————————
pathogen identified
i
1
Clinically small bowel disease Clinically large bowel disease
Trea t
Resolution
* maintenance
therapy
MAC
infection
Persistent
diarrhoea
* repeat
faecal
studies
Upper gastrointestinal
endoscopy (duodenal
aspirate and biopsy)
* culture; viral, myco
bacterial and fungal
* microscopy; protozoa,
viruses, acid-fast
bacilli and fungi
* electron microscopy
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No pathogen
identified
Pathogen
Identified
No pathogen
Identified
Colonic
Investigation
Treat
X
Persistent
pathogen
* treat again
* consider long
term therapy
New
pathogen
* treat
Flexible sigmoidoscopy
(and/or colonoscopy) for
biopsy
* culture; viral, myco
bacterial, protozoa,
* microscopy, protozoa,
viruses, acid-fast bacilli
and fungi
* electron microscopy
J,
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Upper
gastrointestinal
investigation
X
No pathogen
identified
Symptomatic
treatment
No pathogen
identified
Guidelines for Clinical Management of HIV/AIDS
i
Table 6. Specific treatment for diarrhoea
CMV colitis: Ganciclovir 5 mg/kg intravenously every 12 hours for 14 days,
or, if unresponsive or intolerant foscarnet 90 mg/kg per day intravenously for
14 days
Salmonella Shingella enterocolitis: (May cause bacteraemia. or focal
extrainte: final infection). Ciprofloxacin 500 mg orally every 12 hours for 14
days
Campylobacter colitis: (May cause bacteraemia). Erythromycin 500 mg orally
every 6 hours
Cryptosporidiosis: Paromomycin 500 mg orally every 8 hours for two weeks.
No proven effective therapy; other possible treatment includes azithromycin
and leetrazuril. The response rate is poor with all available therapies.
Microsporidiosis: Albendazole 400 mg orally every 12 hours for 14 days. No
proven effective therapy; the response rate is poor and relapse is common.
Isospora belli infection: Trimethoprim-sulfamethoxazole 160/800 mg orally
every 6 hours for 10 days, then twice daily for 21 days. Relapse is common.
r
CHRONIC DIARRHOEA LEADS TO MALNUTRITION
Adequate nutritional supplements and specific vitamins and minerals replacement is
ir
essential.
HIV AND OPPORTUNISTIC NEUROLOGICAL INFECTIONS
Opportunistic infection of the centra! nervous system particularly toxoplasmosis and
cryptococcosis are common. There are usually complications of advanced
immunodeficiency when CD count has fallen below 150/cmm or even lower.
Table 7. Neurological syndromes and opportunistic infections in AIDS
1 10,
Syndrome
Clinical features
Aetiology
Meningitis
Headache
Fever
Nausea/vomiting
Altered consciousness
Cryptococcosis
Syphilis
Listeria
Tuberculosis
Focal cerebral
lesions
Headache
Focal signs
Toxoplasmosis
Progressive multifocal
•*
9-
Guidelines for Clinical Management of HIV/AIDS
I
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leukoencephalopathy
Syphilis
Cytomegalovirus
Convulsions
Encephalitis
Myelitis
Cognitive impairment
Psychiatric features
Altered consciousness
Cytomegalovirus
Herpes simplex
Toxoplasmosis
Sensory
Paraparesis
Sphincter disturbance
Cytomegalovirus
Herpes simplex
Varicella zoster
Syphilis
Toxoplasmosis
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CRYPTOCOCCAL MENINGITIS
Cryptococcosis is the most common cause of meningitis in AIDS affecting around
4
10% patients.
I
Common presentation includes
headache
fever
h
nausea and vomiting
If
confusion and impaired consciousness, but
signs of meningism are seen in less than 40% of patients, so diagnosis is missed
quite often.
IDIAGNOSIS
Cryptococcal meningitis is confirmed by CSF examination
>1
positive India ink staining
CSF cryptococcal antigen titre will provide rapid diagnosis
i1
Increase CSF white cell count
decreased CSF glucose
Guidelines for Clinical Management of HIV/AIDS
►
I
•7
Table 8. Treatment of cryptococcosis
i
Primary therapy
Severe case (/.e. nllcrcii consciousness, CSF white blood cell count
> 20/inl, CSF antigen titre > 1:1024 and a positive blood culture)
Amphotericin p 0.7 mg/kg daily by intravenous injection
± 5-flucytosine 100 mg/kg daily by mouth or intravenously for
2 weeks, followed by fluconozole for 10 weeks
€
Mild case
Fluconazole 800 mg loading dose by mouth, then 400 mg daily by mouth
± 5-flucytosine 100 mg/kg daily by mouth
Most patients respond clinically within 1-2 weeks, with an early mortality of
5%-10%. Continue therapy for four to six weeks or until the CSF is sterile.
Without maintenance therapy, relapses will occur in 50%-60% of patients within
six months. With maintenance therapy, relapses are uncommon and usually
related to non-compliance with treatment, but may also occur because of
development of drug resistance and drug interactions which lower fluconazole
levels. Monitoring serum cryptococcal antigen titres is not useful in predicting
relapse
Maintenance therapy (Life long)
Fluconazole 200-400 mg daily by mouth
&
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*
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TOXOPLASMOSIS
Commonest cause of focal cerebral lesions in HIV/AIDS is toxoplasmic encephalitis
and in most cases, it is almost always due to reactivation of past infection.
It usually manifests with subacute development of focal neurological deficit but may
present with seizures, intracranial haemorrhage, disorientation, altered mental state
and coma, CT brain scan shows multiple bilateral ring enhancing cerebral lesions.
Table 9. Treatment of toxoplasmosis.
Primary therapy
Sulfadiazine 100 mg/kg per day, in 4 divided doses up to 8 g daily by mouth
or intravenously
t
c
+ Pyrimethamine 200 mg loading dose, then 75 mg daily by mouth
c
1 12,
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Guidelines for Clinical Muni^emenl of IIIV/AIDS
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+ Folinic acid 7.5 mg daily by mouth
Or
Clindamycin 600 mg 4 times a day by mouth or intravenous injection
+ Pyrimethamine and folinic acid
Maintenance therapy (Life long)
t
Sulfadiazine 500 mg 4 times a day by mouth
+ Pyrimethamine 25 mg daily by mouth
+ Folinic acid 7.5 mg daily by mouth
Or
Clindamycin 600 mg 4 times a day by mouth
+ Pyrimethamine and folinic acid
The dose of clindamycin is not reduced during the maintenance phase as
lower doses are less effective.
j
Guidelines for Clinical Mnna^ement of HIV/AIDS
113.
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COMMON OPPER I I MS I i( INI I ( I IONS DR.R \O
(C Hl SI <NMA I I RN'I I Y ( I Nil R.
ii
Candidacies is an oppoi (imislic endogenous inI< <■(ion caused In yeast like fungus
C andida albicans and <»J11cr ( undid:i species
nSeen in C 1)4<25O,( ommonest ()l in immuno-compromisctl.
nWhite painless plaques seen on the buccal, phanngeal mucosa and tongue surface.
(Pseudomembranous form)
nSome times can present as smooth red patches on the hard or soil palate, buccal mucosa
and dorsal surface of the tongue ( Erythematous form)
nOesophagitis can present as heartburn. od\nophagia- dysphagia.
nVaginilis can present as foulsmelling discharge, pruritus, and l .rythcma of inleroilus.
DIAGNOSIS
KOI I smear shows yeasl and chlamydiospores.
nCulture is used for antiliingal sensitivity
( not for diagnosis)
TRATMENT
^Oral Candida
■Mild ones are belter off with Clotrimazole oral paints. Nystatin paint.
^Flucanozole PO lOOmg od/ Itraconazole 200mg /day X 10 to 14 days.
^In Severe Ressistant Cases Higher dose of flucanozole and IV Amphotorecin B.
^Oesophageal/ Trachco Bronchial Candidiosis.
■Flucanozole 200 to 800mg/day X 14 to 21 weeks.
■Amphotericin B, Caspfungin, Voriconazole.
■85% relapse rate with in One year, which requires maintenance Anti
fungal therapy usually Flucanozole 100-200mg/da}-.
^Candida Vaginitis
0 Treatment is identical for women with and without HIV.
■Clotrimazole lOOmg per vaginal tablets X7 - 14 days.
■Miconozole vaginal suppositories lOOg/day X /days.
■FlucanozolelSOmg od single dose / Itraconazole 200g od X 3 days.
HERPES SIMPLEX (DNA VIRUS)
EaOral (HSV 1), Perirectal and Genital (HSV 2)
^Presents with multiple, recurrent vesicles, some times non
healing ulcers.
I
■I )x- Chai ac ic i isi it M ticoc utancons lesions, Swab lor tzank
smear, PCR.taln immunocompromised it’s recurrant.
TREATMENT'
■Acyclovir 400mg PO rid X 7-10 day s.
■Valcyclovir 1g bid X 7- 10 days.
■Severe Mucocutaneous lesions, Disseminated infection Acyclovir IV 5- lOmg/kg q 8l1' hrly till the lesions or symptoms
subside.
■Herpes encephalitis- Acyclovir lOmg/kg q8th hrly X 14 to 21
days.
■For recurrant cases needs Chronic Acyclovir 400mv bid ,
Valacyclovir 500mg /day.
HERPfES ZOSTER
■Its reactivation of latent varicella virus infection.
■Usually presents as multiple, grouped vesicles along the
dermatomal distribution.
■In immunocompromised patients Herpes Zoaster is Recurrant,
Multidermatomal, and more severe.
■Dx- Characterstic Dermatoal distribution of the vesicles.
Tzank smear and PCR arc suportivc.
TREATMEN 1’
■Vai acyclovir 1g tid X 7-14 days.
■Acyclovir 800mg 5 limes/ day X 7-14 days.
■In Severe Cases Acyclovir IV 30mg/kg/day X 7 days.
■Supportive care.
■Antibiotics for Sec. infections if JIIW
■ Analgesics lor Neuralgia.
■Antihistamines for pruritus.
■Gabapentin /Carbamazepine / fricj clics lor severe post herpetic neuralgia.
CRYPTOCOCCOSIS
■Its siibaciite/Clironic systemic inleciion caused by yeast-Cryptococcus
neoformans.
I
sit can present as Meningitis / Meningoencephalitis / Cutaneous
Cryptococcosis / Pneumonia and Disseminated Cryptococcosis.
^Commonest and most fatal of all these is cryptococcal meningitis and
meningo-encephalitis , usually seen in patients with CD4< 100.
■Cutaneous Cryptococcosis can present as flesh coloured, umbellicated,
papules ressembling Molluscum contagiosum.
Cryptococcal meningitis
■Presents as subacute lever, headache and altered sensorium.
■LP is diagnostic- CSI? showing pleocytosis, low glucose, high protein,
Indian ink smear showing budding yeast, CSF Cryptococcal Ag +ve,
confirmed by CSF fungal culture.
■Sometimes Cryptococcoma seen in CT/MRI Brain.
■Elevated CSF opening pressure, \\7BC<20, Positive Indian Ink Smear,
Cryptococci isolated Irom extra neural sites.
Cryptococcal Meningitis Treatment■ Amphotericin B al
0.7mg/kg/day +5FC PO lOOmg/kg/day x 14days followed by Flucanozole
400mg/day x 8 weeks followed by maintenance therapv of flucanozole 200mg/day.
■Mild cases Flucanozole SOOmg od lollowed b\ -lOOmg/dav x 10 weeks followed by
chronic therapy with flucanozole 200mg od.
■ Repeated LP to control elevated ICT. Ami ( kdema initiallv may be helpful. Steroids
are containdicatcd.
■Regular monitoring of renal lunciions. I I\ di ali<>n.
■Ambisome 4mg/kg/day IV X 14 days (lipid amphotericin reduces the side effects of
Amphotericin B.
•t
Pneumocystis Pneumonia
■Caused by Pneuocystis Jerovicii, a fungus, Usually seen in patients with CD4 < 150
■Sub acute course, presents with low grade lex er, progressive cough and dyspnoea.
■■Dx- CLINICAL SUSPECION Confirmation by Induced sputum smear either
giemsa stain or immunofloroscence. CXl\ can be normal, sometimes prominent
interstitial shadows - nodular. CX1\ rarely can show consolidation or perihilar cysts
or pneumothorax. Desaturation after exercise. Increased 1.1)1 I.
■ Rx. TM17SMX at 15mg/kgof TMP lid IV or 1’0 ( iu 2 DS TM17SMX lid). With
good hydration.
■Severe Cases my require Steroids, Oxvgen, and somelmes Invasive or non invasive
ventillation.
... J .
. j ‘
Toxoplasmosis
■Toxoplasma gondii is an ohligate mira cellular protozoan
parasite which causes latent infection oi brain, skeletal muscle
and heart. Reactivation inlection can be seen with CD4 < 100.
■Encephalitis is the commonest ancI iatal manifestation of the
Toxoplasmosis.
■Presents with subacute onset ol local neurological abnormalities
with headache, altered menial status, and lever.
Toxoplasmosis
■Diagnosis :
■CT/MRI showing multiple ring enhancing lesions in the basal ganglia
and hemispheric conticomedullary junction.
■Positive Anti Toxoplasma IgG Ab.
■D/D : Cryptococcoma, Tuberculoma, CNS lymphoma,
Neurocysticercosis, Brain abscess.
ToXOplsSlTlOSlSa Pyrimethamine 200mg loading dose , then 50 to
75mg/day + 10 -15mg Folinic acid /day + SD 1 to l.SgPO q 6dl hrly X >
6 weeks.
■Pyrimethamine + Leucovorin + Clindamycin 600mg PO/IV 61’1 hrly for 6
weeks.
■Azithromycin, TMP/SMX, Atovaquone also have anti toxo properties.
■Maintenance with Pyrimethamine 25-50ing/day 4-SI) 500-750mg q 6l,‘
hrly (50% ol acme dose.)
■Primary prophylaxis with 4’MP/SMX I)S .
Cytomegalovirus (CMV-DNA Virus) ■Occular
manifestations are commonly presented manifestations of CMV.
Extra Occular manifestations may be CMV colitis, CMV
oesophagitis, CMV encephalitis, CMV Dementia, CMV
polyradiculomyelopathy, (',MV Pneumonitis.
CMV RetillitiSaMay be asymtpmatic or can have floaters,
field defects, scotomata or decreased acquity. Seen in patients
with CD4 < 50.
A
nFundus showing Cottage cheese and ketchup (peri vascular
yellow white retinal infiltrates±Intra retinal haemorrhages)
Retinal thinning and sometimes detachment.
■Diagnosis is by fundoscopy. Vitreous PCR CMV may be
rarely considered.
CMV RetillitS Treatment Blntra-Ocular Gancyclovir
every 6-8 months + Valgancyclovir 900mg Po bd X 14-21 days
■Gancyclovir 5mg/kg IV q 12th hrly x 14-21 days then
valgancyclovir Po 900mg qd.
■Forcarnet, Cidofovir, Intraoccuiai Fomivirensen are alternate
treatments.
■As relapse is common, maintenance therapy with
Valgancyclovir 900mg po qd
CMV Oesophagitis / Colitis-One of the important
cause of odynophagia and AIDS Cholangiopathy. Can present
with Fever, diarrhoea and abdominal pain.
■Rx
■Valgancyclovir 900 mg PO bd with food X 3 to 4 weeks . Maintenance
with Valgancyclovir PO 900mg od .
CMV
Encephalitis-Polyradiculomyelopathy-Dementia.aProgressive leg
paresis, bladder/bowel dysfunction.
■Delerium with Cranial nerve defects, ataxia and nystagmus.
■Dx by CSF showing increased protein and mononuclear pleocytosis.
MRI showing periventricular enhancement. CSF PCR CMV is also
helpful.
■Treatment Gancyclovir 5mg/kg bid X 3 to 6 weeks + Foscaranet 90mg
IV bid x 3 to 6 weeks then maintenance with Gancyclovir or Vai
gancyclovir
CMV Pneumonitis■Fever, cough , dyspnoea and
interstitial infiltrates.
■DX by pulmonary infiltrates, Characteristic inclusions in lung
tissue.
■Treatment by Gamcyclovir 5mg / kg bid X 21 days or
Valgancyclovir 900mg PO bid X 21 days.
Mycobacterium avium Complex
(MAC)■Disseminated disease seen in CD4 < 50.
■Presents with Fever, night sweats, weight loss, diarrhoea and
abdominal pain.
■Diagnosis by culture of MAC from non pulmonary site.
■RX: Clarithromycin 500mg bidPO+ ethambutal 15mg/kg/day
1O + Rifabutin 30Omg/day or Levofloxacin 500mg qd till
immune reconstitution after early HAART.
Diarrhoea-Causes of chronic Diarrhoea in HIV patients.
■Protozoa (70%)
■Isosporabelli, Giardia lamblia, Crvptospondia, Microsora, Cyclospora, E.
Histolytica, Blastomycosis.
■■Bacteria (23%)
■Shigella, Salmonella, Aeromonas.
■Helimenths (6%)
■Strongoloids stercoraiis.
Evaluation of Chronic Diarrhoea■Stool culture for
bacteria
■Stool specimens for parasites using saline, iodine, trichrome and acid fast
preparations.
■Consider eniparic therapy if all tesu are negative.
■Gastodudenoscopic or colonoscopic inspection of tissues and biopsy.
■Biopsy stained with H&E for protozoa, Giemsa or Methanamine silver for fungii,
AFB staining for mycobacteria.
■Duodenal/colonoscopic biopsy culture for Mycobacteria.
■Duodenal fluid examination for parasites.
■Biopsy specimen examined by electron microscopy.
Immune Reconstitution Inflammatory
Syndrome
■Blurring of vision following ART.
■Crypto meningitis, TE following ART.
■Flaring of Tb following ART.
M
■Rised AST/ALT in HBsAG + ve, seropositive individuals
following ART.
■PUO following ART.
oHZ following ART.
Primary Prophylaxis-TMP/SMX ds od CD4 < 200 (
for prevention of PCP, TE, Diarrhoeal diseases, Skin infections)
■Azithromycin 1.2g od once a week CD4 < 50 (MAC)
■INH prophylaxis (not practicised in INDIA)
Secondary Prophylaxis
■Flucanozole 200mg PO od (following Cryptococcal
meningitis).
■Valgancyclovir 900 mg PO od (following CMV infection).
■SD +Pyrimethamine (50% of treatment dose) (following
Toxoplasmosis.
■For any CJUerrieSaEmail: drbsrao@gmail .com,
bsrao@sancharnet.in.
□■Chest and Maternity Centre
878, 5th Block, Rajajinagar, Bangalore-10
Ph: 23408006.
UNAIDS
UNicH-wp-Lttbr-UM-’A-uscor.
world Heal
oraanlzall
!
UNAIDS/WHO Policy Statement on HIV Testing
The Context
As access to antiretroviral treatment is scaled up in low and middle income countries,
there is a critical opportunity to simultaneously expand access to HIV prevention,
which continues to be the mainstay of the response to the HIV epidemic. Without
effective HIV prevention, there will be an ever increasing number of people who will
require HIV treatment. Among the interventions which play a pivotal role both in
treatment and in prevention, HIV testing and counselling stands out as paramount.
The current reach of HIV testing services remains poor: in low and middle income
countries only 10 per cent of those who need voluntary counselling and testing,
because they may have been exposed to IIIV infection, have access to it. Even in
settings In which voluntary counselling and testing is routinely offered, such as
programme^ for prevention of mother-to-child transmission, the number of people
who avail themselves of these services remains low in many countries. The reality is
that stigma and discrimination continue to stop people from having an HIV test.
To address this, the cornerstones of HIV testing scale-up must include improved
protection from stigma and discrimination as well as assured access to integrated
provonllon, treatment and cam services. I he conditions under which people undergo
HIV testing must bo anchored in a human rights approach which protects their
human rights and pays due respect to ethical principles, (cf Appendix 1). Young
people require special attention to their needs through the provision of confidential youth
friendly health services. Public health strategies and human rights promotion are
mutually reinforcing.
The conditions of the ‘3 Cs’, advocated since the HIV test became available in 1985,
continue to be underpinning principles for the conduct of HIV testing of individuals.
Such testing of individuals must be:
•
o
•
confidential
be accompanied by counselling
only be conducted with informed consent, meaning that it s both informed
and voluntary.
In many low and middle income countries, the primary model for HIV testing has
been the provision of client-initiated voluntary counselling and testing services. \
Increasingly, provider-initiated approaches in clinical settings are being promoted,
i.e. health care providers routinely initiating an offer of HIV testing in a context in
which the provision of, or referral to, effective prevention and treatment services is
assured. To reach people in need of treatment, lens ol millions of tests, will have to
be conducted among those who may have been exposed to HIV.
UNAIDS/WHO recommend that the following four types of HIV testing be
clearly distinguished:
June 2004
1
1) Voluntary counselling and testing
I
X
i
Client-initiated HIV testing to learn HIV status provided through voluntary counselling
and testing, remains critical to the effectiveness of HIV prevention. UNAIDS/WHO
promote the effective promotion of knowledge of HIV status among any population
that may have been exposed to HIV through any mode of transmission. Pre-testing
counselling may be provided either on an individual basis or in group settings with
individual follow-up. UNAIDS/WHO encourage the use of rapid tests so that results
are provided in a timely fashion and can be followed up immediately with a first post
test counselling session for both HIV-negative and HIV- positive individuals.
2) Diagnostic HIV testing is indicated whenever a person shows signs or
symptoms that are consistent with HIV-related disease or AIDS to aid clinical
diagnosis and management. This includes HIV testing for all tuberculosis patients
as part of their routine management.
3) A routine offer of HIV testing by health care providers should be made to all
patients being:
•
•
•
assessed in a sexually transmitted infection clinic or elsewhere for a
sexually transmitted infection - to facilitate tailored counselling based on
knowledge of HIV status
seen in the context of pregnancy - to facilitate an offer of antiretroviral
prevention of mother-to-child transmission
seen in clinical and community based health service settings where HIV is
prevalent and antiretroviral treatment is available (injecting drug use
treatment seivices, hospital emergencies, internal medicine hospital
wards, consultations etc.) but who are asymptomatic.
Explicit mechanisms are necessary in provider-initiated HIV testing to promote
referral to post-test counselling services emphasising prevention, for all those
being tested, and to medical and psychosocial support, for those testing positive.
The basic conditions of confidentiality, consent and counselling apply but the
standard pre-test counselling used in VCT services is adapted to simply ensure
informed consent, without a full education and counselling session. The minimum
amount of information that patients require in order to be able to provide informed
consent is the following:
> the clinical benefit and the prevention benefits
benefifts of testing
> the right to refuse
> the follow-up services that will be offered and
> in the event of a positive test result, the importance of anticipating the need
to inform anyone at ongoing risk who would otherwise not suspect they were
being exposed to HIV infection
For provider-initiated testing, whether for purposes of diagnosis, offer of antiretroviral
prevention of mother-to-child transmission or encouragement to learn HIV status,
patients retain the right to refuse testing, i.e. to 'opt out’ of a systematic offer of
testing.1
1 HIV testing without consent may be justified iia the r< ire circumstance in which a
palionl is iincoiiscioiis, hi: , oi hei |). ii ml di <ji i. iiidi. ii i rs ahsonl, and knowledge of IIIV
status is necessary lor purposes ol optimal treatment..
June 2004
2
• i
i
u
4) Mandatory IIIV screoniinj
7;
UNAIDS/WHO support mandatory screening for HIV and other blood borne viruses of
all blood that is destined for transfusion or foi manufacture of blood products.
Mandatory screening of donors is required prior to all procedures involving transfer of
bodily fluids or body parts, such as artificial insemination, corneal grafts and organ
transplant.
UNAIDS/WHO do not support mandatory testing of individuals on public health
grounds. Voluntary testing is more likely to result in behaviour change to avoid
transmitting HIV to other individuals. Recognising that many countries require HIV
testing for immigration purposes on a mandatory basis and that some countries
conduct mandatory testing for pro-recruitment and periodic medical assessment of
military personnel for the purposes of establishing fitness, UNAIDS/WHO
recommend that such testing be conducted only when accompanied by counselling
for both HIV-positive and I IIV negative individuals and referral to medical and
psychosocial services for those who receive a positive test result.
Appendix 1 Ensuring a rights based approach
The global scaling up of the response to AIDS, particularly in relation to HIV testing
as a prerequisite to expanded access to treatment, must be grounded in sound public
health practice and also respect, protection, and fulfilment of human rights norms
and standards.
The voluntariness of testing must remain at the heart of all HIV policies and
programmes, both to comply with human rights principles and to ensure sustained
public health benefits.
The following key factors, which are mutually reinforcing, should be addressed
simultaneously:
1. Ensuring an ethical process for conducting the testing, including defining the
purpose of the test and benefits to the individuals being tested; and assurances
of linkages between the site where the test is conducted and relevant treatment,
care and other services, in an environment that guarantees confidentiality of all
medical information;
2. Addressing the implications of a positive test result, including non-discrimination
and access to sustainable treatment and care for people who test positive
3. Reducing HIVIAIDS-related stigma and discrimination at all levels, notably within
health care settings;
4. Ensuring a supportive legal and policy framework within which the response is
scaled up, including safeguarding the human rights of people seeking services;
5. Ensuring that the healthcare infrastructure is adequate to address the above
issues and that there are sufficient trained staff in the face of increased demand
fortesting, treatment, and related services.
UNAIDS Global Deference Group on HIV1AIDS and Human Hights
June 2004
3
NACO Guidelines
Guidelines on HIV Testing
HIV testmg carried out on a voluntary basis with appropriate pre-test and post-test counselling is
considered to be a better strategy and Is In line with the WHO guidelines on HIV testinq The basis
and objectives of testing are to :
♦ monitor the trend of HIV infection in a population or subgroup for facilitation of intervention usinq
unlinked anonymous testinq.
y
♦test blood or organs or tissue for ensuring safety of the recipients.
identify an individual with HIV infection for diagnosing or voluntary testing purposes.
There is an active debate in the country on the issue as to whether there should be mandatory
es mg of people suspected of carrying HIV infection. Considerable thought has been given to this
issue. Testing for HIV is more than a mere biological test for it involves ethical, human and legal
dimensions. The government feels that there is no public health rationale for mandatory testing of
a person for HIV/AIDS. On the other hand, such an approach could be counter productive as it
may scare a large number of suspected cases from getting detected and counselled to take
mef SUuV/°* imProve hls quality of life and Prevent spread of infection to other persons
2<Jthrn?^TI?|Un • ■ H
!
? tCalri’ed 0Ut on a vo,untary basis With appropriate pre-test and post
test counsell ng Is considered to be a better strategy and is in line with the national policy on HIV
testing and also the WHO guidelines.
y
GENERAL PRINCIPLES OF HIV TESTING
It should be a part of the overall comprehensive preventive and promotive programme.
Toting by itself does not result in behavioural changes that restrict transmission of HIV to others
and therefore testing should be a part of the total control programme which is conducive for
behavioural change of the individual by providing social support, means and skills to reduce or
eliminate risk behaviour.
Testing without explicit’ consent of the patients (mandatory testing) has proved to be counter
n thu S09 r?n ,n u,ie contro1 of HIV epidemic. Social support and intervention must be
directed to anybody vulnerable to risk behaviour irrespective of whether an individual or group
participate in testing procedure or not. Otherwise such testing can drive the target people
underground and make it more difficult for launching intervention.
Any health programme which does not maintain the dignity of a patient or deprives him of his
basic right to employment or access to medical care or social support is a harmful on a long term
a
DdSIS.
hp NQodftl0?hW kCh T+UStf be,asked before a testin9 Procedure is undertaken is how this result will
fP?r™s™gSto bean eLf™™“tooQlUESTIONS ARE prerequ's’^
THE TESTING SHOULD BE TECHNICALLY SOUND AND APPROPRIATE
CPHE - SOCHa%a
Tc I
J?IS ^7-
1 <> '- -■'-4
Kom m a ng ala
FC) *
' n Ji
vvp
7 11 1,1 '“
'''nh;i Uiu best laboratory conditions. For example if
reactive o first0EL?SATinTn0'na|t'TH'^
PGrS°n by USing EUSA (2nd EUSA done orl sera
reactive to first ELISA) in a population where the prevalence of infection is 1% the chance tha* a
tes7InddW/ ^|P0TVef 'S actl,ally P°sitive (Positive predictive value) is only 50% after one ELISA
Iven bv Zt f yirafter W°
tS' ™S meanS one result wil1 be false|y Positive in every 100 tests
even by two tests if we use a western blot as supplemental test instead of 2nd ELISA the chance
,o 99
™“s "'•™»«' ■» »• '«>• p°*.
°<
rnuid ahppreciat.® ‘he limitation of any test which could measure the HIV status the cheaper test
v P^esentiv th^a
m9'
ERS lnS‘ead °f ELISA and Westem Blot) to achieveP yield
raton
a
types u es S are a'/allable on Similar principle to ELISA which have been broadlv
categorized, as one which can be completed within half an hour.
y
♦A simn'ip
tes,‘sin?'.ia^ ‘° that done for examination of sugar in urine for diabetic.
car Z HI n rnnh6; whlchdoes( n°‘involve any sophisticated instrument and even could be
carried out in conditions without electricity.
THE TEST PROCEDURE MUST BE APPROPRIATE TO THE FIELD SITUATION
d^nCpenSd^ere eleCtriCKy iS not available for maior part of tbe workin9 hours, use of techniques
rerornmn a a 3 soph'stlcated Procedures will be inappropriate. Rapid or simple testsq are
ecommended where Infrastructure is minimal or where quick screening of sample is needed.
THE TESTING PROCEDURE MUST BE COST EFFECTIVE
mass screening for HIV patient seeking hospital admission can only dZy implementatZof'
dlseasZkeXeJatitis'B'S'C'prOceduras that could have prevented more infective
QUALITYTORY procedure must be monitored for ensuring
NACO POLICY ON HIV TESTING
TRANSFUSION SAFETY
A '2s 1RS( e,S Is sufflclent t0 ensure transfusion safety with the provision of simple tests in
rtnnnr nOhh0USe e.ClrlClty' The objecti'/e of the transfusion safety doesnot require identification of
at lea^nno/1
.bl°°d and in lQW Prevaler>ce settings of HIV single ERS would detect
surety that h°innH^PLaS FALSELY POSITIVE. However the same test gives more than 99 9%
aa
1 b Ld .f°?nu ne9atlve 13 actually free of infection. Therefore, while we can label blood
as safe is risky to label any donor HIV positive on such test result and employees of blood bank
with situ 'f6 T'6 °f 'nterpre(ation of *he test. Often employees of blood bank are confronted
rtnnnr C IH h
a donor m'3ht ask why his blood has been rejected. In such situation the
XX™
",,hM“•>
•«
SURVEILLANCE
The objective of surveillance is best achieved by annual cross sectional survey of same risk orotm
de ®®rne P|ace over few years by unlinked anonymous testing, following test procedures^y 2
ERS. The mam purpose of the survey is to monitor the trend of infection of HIV UnhnL
nonymous tests are only possible if blood is drawn for some other purpose and a portion of that
is tested for HIV without identification data.
P
IDENTIFICATION OF HIV POSITIVE INDIVIDUALS
This testing procedure must offer pre and post test counselling of the client and involve explicit
»
consent. Voluntary HIV testing and counselling when offered to any asymptomatic person must
have any of the following purposes:
Oto permit early institution of an specific drug therapy if found to be effective (however at present
no such therapy has proved to be beneficial including antiretroviral drugs or chemoproohvlaxis).
Oto help infected or non-infected persons be more aware of their health status and prognosis to
take decisions of child bearing, breast feeding and reduce or eliminate risk behaviour.
Increasing number of AIDS cases in the country calls for availability of diagnostic facilities for
clinically suspected cases of AIDS. However, such testing procedure must be of highest
specificity, accuracy and coupled with trained man power for counselling. The result of the test
must be kept confidential and even health care workers who are not directly involved in care of the
patient should not be told about the result. Surveillance of AIDS cases in the country does not
require reporting of the identification data of the patient.
In the case of diagnosis of clinically suspected cases and for voluntary testing, the testinq is done
with 3 ERS using HIV kits with different antigens.
RESEARCH
Testing procedure for research are designed according to specific objectives and could be
decided by the researcher. However, all the studies undertaken must follow ethical standards
which primarily involves full explicit consent of the patient and pre decided mutually agreed terms
for any eventuality of the patient due to research activities.
Govt, of India has earlier issued a comprehensive HIV testing policy and the following issues are
reiterated here:-
ONo individual should be made to undergo a mandatory testing for HIV.
ONo mandatory HIV testing should be imposed as a precondition for employment or for providinq
health care facilities during employment.
♦Adequate voluntary testing facilities with pre tests and post test counselling should be made
available throughout the country in a phased manner. There should be at least one HIV testing
centre in each district in the country for voluntary testing in the Governmental sector.
National Ald-sCnnimLErnQiam 11 ^poodios.oLPM/MQll 11
I
11 About HIV/AIDS 11 Indian Scenarin
Ask.ihe DogIql 11 AnDouncnmanis. 11 Letter from Ihn PmieotniL^ffEeedback 11 Site Alan 11 Related Sites 11 Newsletter
C^d'^S
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1.
INTRODUCTION
Treatment is now perceived as a critical component of a comprehensive program
to combat HIV/AIDS, along with prevention and improvement of health care
infrastructure for the delivery and monitoring qf care and support. This integration has
recently become, more feasible. Political leadership and commitment has shifted
significantly in favor of providing access to anti-retroviral treatment (ART) for people
living with HIV/AIDS. Earlier, high costs, demanding treatment regimens, and the
absence of
basic
health
infrastructure were repeatedly cited
as potentially
insurmountable barriers.
The “Call to Action” at the UN General Assembly Special Session on HIV/AIDS
(June 2001), pushed forward a new global consensus on the need for ART. This led to
a cumulative response from diverse quarters. It put pressure on pharmaceutical
manufacturers, and ever since, we are witnessing dramatic reductions in drug prices.
Brazil’s national ART distribution programme added to the public debate. WHO
released guidelines for anti-retroviral use in resource constrained settings in April 2002,
added 10 ART drugs to its list of “essential medicines” for all countries, and for the first
time qualified a number of generic manufacturers. WHO declared the lack of access to
ARV treatment for HIV/AIDS a “global health emergency” in September, 2003, and
announced that it would release an emergency plan to scale up access to ARV
treatment for at least three million people by the end of 2005. This joint WHO/UNAIDS
announcement popularly can it; to be known as the 3 by 5 initiative. The WHO
guidelines for anti-retroviral use in resource constrained settings have since been
revised in Dec 2003.
Admittedly, antiretroviral therapy is no cure for HIV/AIDS. Effective antiretroviral
regimens inhibit replication of HIV virus, reduce viremia to undetectable levels and
significantly lower the frequency of opportunistic infections, thus reducing the cost of
management of HIV. This helps people lead more productive lives, with perceptibly
reduced stigma and discrimination. Successes achieved in delaying the onset of AIDS
by ART, has now transformed the common perception about HIV from being an
immediately fatal scouigc to somewhat more inanageabie, chronic illness.
6 1
9. t. First line regimens
The overwhelming short term priority is for first-line regimens which will facilitate
the scaling up of treatment. Second-line treatment is not a priority in the short-term. The
characteristics of an ideal first-line ARV combination should:
Be effective and well tolerated, with minimal side effects
Be potent, even in advanced disease, and favourable resistance profile
Have no drug interactions or contra indications
Be safe for use in patients with TB and in pregnant or lactating women
Be available in a fixed dose combination (once or twice a day;
Be stable in tropical conditions
Do not require laboratory monitoring
Be affordable
The first recommended choice for first-line combinations is d4T/3TC/NVP (Stavudine +
Lamivudine + Nevirapine), taken twice daily (BID) as a fixed dose combination (FDC)
Advantages: It is well tolerated in most cases, has few contra-indications and is
appropriate for use in women of child bearing age. It has proven efficacy under actual
i
field conditions, is affordable, and is easy to take.
Limitations: The major side effects with d4T (stavudine) are neuropathy and
1
pancreatitis.
Nevirapine causes hepatotoxicity and severe rash. NVP has drug
3
interaction with rifampicin.
r
It should therefore be avoided with rifampicin for both
reasons of interaction as well as possibility of naepatoxiciticty. It is ineffective on HIV2.
9.2. Alternate to first-line combinations
of
it
1. AZT/3TC and NVP (Zidovudine + Lamividine) and Nevirapine taken twice daily.
Advantages'. Largest experience with Zidovudine use, easy to take, well tolerated.
al
at
Can be used where d4T (Stavudine) use is contraindicated.
Limitations: Major potential tcxicities with AZT are anemia and neutropenia. In
resource poor settings where anaemia is common it may be an issue for concern. The
treatment reouires Hb monitoring. Zidovudine is more expensive than d4T (Stavudine)
and therefore this combination is also more expensive.
21
22
Th ~
\
* ((j
2. d4T/3TC + EFV (Stavudine+Lamivudine) and Efavirenz, taken as EFV (600 mg)
once per day plus d4T/3TC as twice daily fixed dose combination.
Advantages: can be used with rifampicin, and easy to take.
Limitations: EFV has potential for CNS toxicity and teratogenecity
It is therefore
contra-indicated in pregnant women and women of child bearing age who are not on
contraception.
In both regimens d4T + 3TC + NVP and AZT + 3TC + NVP fixed dose
combinations, Nevirapine should be administered in 200 mg dose as a single drug for
15 days as lead-in dosing and if tolerated only then FDC should be started.
9.3. Fixed dose combination.
Fixed dose combinations are considered important tools for scaling up in
resource-poor, high HIV prevalence settings. These medicines are preferable because
they are easy to
use, have distribution advantages (procurement and stock
management), improves adherence ensuring intake of ail medicines and reduces the
chances of development of resistance. Though once-a-day dosing is an ultimate goal,
however it is not essential as field experience clearly has shown that BID regimens with
co-formulations are easy for patients to adhere to. Therefore, WHO must guide both
p
commercial and non-commercial efforts by communicating attributes of the ideal future
first-line ARV therapy.
r
Up to the present the Government provides first line regimen(s), consisting of fixed
does combinations of the following ARV drugs:
Zidovudine/ Lamivudine and Stavudine/ Lamivudine
alongwith Nevirapine and Efavirenz.
(i)
Stavudine(30mg) + Lamivudine(150mg) + Nevirapine(200 mg)
(N)
Stavudine(40 mg) + Lamivudine(150mg) + Nevirapine(200 mg)
(iii)
Stavudine(30 mg) + Lamivudine(150mg)
(iv)
Stavudine(40 mg) + Lamivudine(150mg)
(v)
s
,
•
Zidovudine (300mg) + Lamivudine(150mg) 1
23
(vi)
Nevirapine (200mg) for lead in dosage and combination with (v)
(vii)
Efavirenz (600mg) for single dose
The physician will prescribe one of the regimens of first line ARV drugs indicated
above. The assumption is that 80% of the people seeking treatment for HIV/AIDS
require Stavudine+Lamivudine+Nevirapine combination; 10% require Zidovudine*
3
Lamivudine+Nevirapine fixed dose combination; the remaining 10% of people seeking
*1
treatment may require Efavirenz combinations on account of toxic reaction to
Nevirapine.
a
9.4. Criteria for starting ARV therapy in adolescents and adults:
)f
Confirmed HIV infection and one of the following conditions:
> WHO Stage IV HIV disease irrespective of CD4 cell count
> WHO Stage III disease with consideration of using CD4 cell counts < 350/mm,33 to
assist decision making
in
> WHO stage I or II HIV disease with CD4 cell counts < 200/mm,3
se
ok
If CD4 Testing Available:
le
al.
> WHO Stage IV disease irrespective of CD4 cell count
I
> WHO stage III disease with consideration of usjng.pyD_4 cell counts < 350/mm3 to
ith
assist decision making
)th
ure
If CD4 Testing Unavailable:
> WHO Stage IV disease irrespective of total lymphocyte count
> WHO Stage III disease irrespective of total lymphocyte count
<ed
> WHO Stage II disease with a total lymphocyte count = 1200/mm3
9.5. Side Effects
Side effects could be caused by the followings:
•
A side effect of the ARV therapy;
•
A new opportunistic infection;
•
An immune reconstitution syndrome (stronger immune system reacting to
infection that had been invisible; usually within 2-3 months after starting
treatment).
23
24
Ciinicai monitoring at the first-level facility requires the ability to consult with the district
clinician on higher level clinical team. This will require support fc-r cell phone or radio
telephone communications. The followings are signs or symptoms T the side effects
and suggested response.
Signs or symptoms
Nausea
Response:
Take the medicines with food (except for ddi or IDV). If on zidovudine, I
reassure the patient that this is common, usually self-limited Treat i
symptomatically.
i
i
Give paracetamol. Assess for meningitis. If on z.'dc"/,jd'r'0 or f-f-v i
reassure that this is common and usually self-limited. If persists more
than 2 weeks, call for advice or refer.
Diarrhea
Hydrate. Follow diarrhea guidelines. Reassure patient that if due to
ARV, will improve in a few weeks. Follow up in 2 weeks. If not
improved, call for advice or refer.
This commonly lasts 4 to 6 weeks especially when starting ZDV. If
severe or longer than this, call for advice or refer.
Fatigue
Anxiety, nightmares,
psychosis,
depression
l___
Blue /black nails
Rash
Fever
This may be due to efavirenz. Give at night; counsel aud support
(usually lasts < 3 weeks). Call for advice or refer if severe depression
or suicidal or psychosis. Initial difficult time can be managed with
amitriptyline at bedtime
_______________
Reassure. It's common with zidovudine
If on nevirapine or abacavir, assess carefully. Is it a dry or wet lesion?
Call for advice. If generalized or peeling, stop drugs and refer to
hospital
Call for advice or irefer.
'
“
(This
could be a drug side effect, an
opportunistic infection a new infection,, or immune reconstitution
syndrome.)
Yeliow eyes
(jaundice) or*
abdominal or flank
pain
Pallor: anemia
Stop drugs. Cail for advice or refer. (Abdominal pain may be
pancreafit18 from ddi or d4T.) If jaundice or uver tenderness, send for j
Al.T test and stop ART (nevirapine is most common cause.) Ca'I for
advice nr refer.______________
If possible, measure hemoglobin. Refer if sever pallor or symptoms of
anemia or very low hemoglobin (<8 grams).
Tingling, numbers
or painful feet/legs
If new or worse on treatment, call for advice or refer. Patient on
d4T/3TC/NVP should have the d4T discontinued - substitute ZDV if no
anemia (check hemoglobin).
Cough or difficult
breathing
This could be immune reconstitution syndrome. Call for advice. If on
abacavir, this cou.'d be iife-mieatening drug reaction. (Stop druq and
. consult/refer.)________ _ ___________________
Discuss carefully with your patient- can he or she accepFit?
I Changes in fat
I distribution
25
I
i
i
The following table indicates the possible side effects caused by the ARV therapy and
the suggested drug substitution:
Regimen
___________ Toxicity
D4T/3TC/NVP
71
Switch d4T to ZDV
d4T -related lipoatrophy
NVP - related severe hepato-toxicity
Switch d4T to TDF or
ABC
Switch NVP to EFV
(except in pregnancy)
NVP - related severe rash (but not life
threatening)
Switch NVP to EFV
NVP - related life threatening rash (Stevens
- Johnson syndrome)
Switch NVP to PI
ZDV relate to persistent gastro-intestinal
intolerance or severe hematological toxicity
Switch ZDV to d4T
NVP - related severe hepato-toxicity
Switch NVP to EFV
(except in pregnancy. In
this situation switch to
NFV, LPV/r or ABC.)
Switch NVP to EFV
i.
I
i
Ii
i
e
o
?t
I ZDV/3TC/NVP
•
If
•rt
>n
th
I
i
•
•
i?
to
D4T/3TC/EFV
an
on
•
•
' •
ZDV/3TC/EFV
oe
i
i *
l
i
for
I*
for
Drug Substitution
d4T - related neuropathy or pancreatitis
NVP - related severe rash (but not life
threatening)
NVP - related life threatening rash (Stevens
- Johnson syndrome)
.
d4T - related neuropathy or pancreatitis
d4T-related lipoatrophy
Switch NVP to PI
Switch d4T to ZDV
Switch d4T to TDF or
ABC
EFV -related persistent CNS toxicity
ZDV -related persistent Gl intolerance or
severe hamate logical toxicity
EFV - related persistent CNS toxicity
Switch EFV to NVP
Switch ZDV to d4T
Switch EFV tn NVP
of
9.6. First line ARV Drug Interaction
on
io
If patient is taking:
Nevirapine (NVP)
on
nd
Do not co-administer with
________ these drugs1:______
• Rifampin
• Ketoconazole
Other cautions:
Do not rely on estrogen-based
oral contraceptives-switch or
use additional protection.
if on methadone, will need to
increase dose. Monitor for
withdrawal signs.
Call for advice for alternative medicines
25
26
--------------------------------- 1
No major drug interactions
Lamivudine (3TC)
i
Stavudine (d4T)
Do not give with ZDV (zidovudine,
AZT)
Zidovudine (ZDV, AZT)
Do not give
ganciclovir
with
d4T
or
_________________________ i
Higher risk of d4T neuropathy
when also taking INH
Higher risk of anaemia when
also taking acyclovir or sulpha
drugs
__________________________
Efavirenz (EFV)
• Diazepam (OK for convulsions
in emergency)
• utner benzodiazepines other
than lorazepam
• Phenobarbital
• Phenytoin
• Protease inhibitor ARV
:___________ i
Do not take with high fat meal |
If on methadone, will need to |
increase dose. Monitor tar I
withdrawal signs
9.7. ART for Women at Reproductive Age
ARV Regimen
d4T/3TC/NVP
Usage in women in child bearing
age or who are pregnant
• Can be used
ZDV/3TC/NVP
• Can be used
d4T/3TC/EFV
• Should be avoided
ZDV/3TC/EF\/
• Should be avoided
Major Potential Toxicities
• d4T related neuropathy, pancreatitis
and lipoatrophy
• NVP related hepato-toxicity and
severe rash
• ZdV related Gl, intolerance, anemia
and neutropenia
• NVP related hepato-toxicity and
severe rash
• d4T related neuropathy,
pancreatites and lipoatrophy
• EFV related CNS toxicity and
potential for teratogenicity
• ZDV related Gl intolerance, anemia
and neutropenia
• EFV related CNS toxicity and
potential for teratogenicity.
S.8. Second line regimens
In the event of treatment failure, a number of second line regimens have been
found to be effective in prolonging the benefits of ART. Here, the programme needs to
guard against cross resistance. Ideally, second line regimens should include at least
27
(
three new drugs. WHO’s recommended second line regimens corresponding to each
—1
failed first line regimen are summarized below.
hy
First-line regimen
en
ha
d4T otZdv”...
3TC
2l
to !
for I
Second-line regimen
TDF or ABC
ddl 1
4-
NVP or EFV
L VP/r or SQV/r2
I
I
dose of ddl should be reduced from 400 mg to 250 mg when administered with TDF
2
i
LVN/r and SQV/r require secure cold chain. NFV can be considered as an alternative
in resource settings without cold chain.
atitis
i
3mia
smia
a
.o
i
st
J7
I
28
10.
TREATMENT OF HIV/AIDS WITH ART IN CHILDREN
Laboratory diagnosis of HIV infection in infants less than .3 months of age Is difficult doe
to the persistence of maternal antibody, for whip-, a virological test is requ
definitive diagnosis. In resource-limited settings, CM cells assay can be use
0'
decision for staging antiretroviral (ARV) treatmem. As CO4 abso.ule ,s ahested by vano^
factors, it is recommended that CD4 percentages should be used. It shou
e no
onmstfeedmg infants are at risk of HIV infection during the entire period of breasheedmg. an a
negative virologfasl or antibody lest does not exclude possibility of the child becoming mfeoU
at a later stage if breastfeeding is continued.
The tota, lymphocyte count signlhcn.y eoceLa.es with the risk Ct modality in the H!Vinfected children. The 12-month risk of modality is more than 20% for children ess tan
months of age haying a feta, Lymphocyte count < 2500/mm>and for ohiidren >18 months of eg
with a total Lymphocyte count of Less than 1500/mm’. In oases where the CD4 ce« count ca
be assessed, the total lymphocyte count may be used as a substitute for an in >
treatment of infants and cn.dren with documented HiV Infection in the presence o^^symptoma
disease - Stage II and Stage III of the WHO Clinical Classification. An abnorma, I
lymphocyte count or CD4 cell count or percentages should be confirmed with a second
prior to taking a therapeutic decision, but this may not always be possible.
10.1. WHO Staging System for HIV Infection and
.n Children
Clinical Stage I:
• Asymptomatic
• Generalized lymphadenopathy
Clinicai oiage 11:
. Chronic diarrhea >30-days, duration in absence of known etolo97^
. Severe persistent or recurrent canoidiasis outside the n
p
. Weioht loss or failure to thrive in the absence of known etiology
. Xistent fever >30-days, duration in the absence of known etiology
. Recurrent severe bacterial infections other^than sept^em.a or memngi i
osteomyelitis, bacterial (non-TB) pneumonia, abscesses)
-9
Clinicai Stage III:
: SSS SXX absence of Known ebo.og,
• Progressive encephalopathy
• Malignancy
• Recurrent septicemia or meningris
2
10.2. HiV pediatric immune category ciassificati on system
<12 months
Immune category
No./mmJ
No suppression
5
2
1-5 yrs
No./rnrrT :
t
Category 1:
i
|
|~
6-12 yrs
(%)
No./mm3
i(%)
(>25%)
>500
(>25%)
200-499
(15%-24%) !
275
20%
<200
(<15%)
I
(>1500)
(>25%)
750-1499
(15%-24%)
(1000)20% f
20%
I
>1000
Category 2:
a
Moderate
hsuppression
d
Category 3:
Severe suppression
<750
i (<io%) J
500-999 I (15%-24%)
(650) j
20%
i
5uu
j
(<15%)
10.3. Criteria for starting ARV therapy in infants and children
8
(i) • or HIV seropositive infants aged below 18 months, WHO recommends initiation of
ARV therapy if:
ot
of
tic
•ta!
est
•
The infant has virologically proven infection (using HIV DNA PGR, HIV RNA or p24
antigen) and b°s:
(a) WHO paediatric Stage III HIV disease (e.o. clinical AIDS) irrespective of CD4
percentage.
or
(b) WHO paediatric Stage II disease with consideration of using CD4<20% to assist
in decision-making.
or
(c) WHO paediatric Stage I (e.g. asymptomatic) and CD4<20% (to be treated only if
CD4 assay available).
if virological tests to confirm the HIV-infection status are not available but CD4 cell
assays are available, WHO recommends that the ARV therapy can be initiated in
HIV-seropositive infants who have WHO Stage II or Hi disease and the C-D4
percentage is less than 20%. In such cases, HIV antibody testing must be repealed
at age 18 months to definitively confirm that the child is HIV-infected. Only infants
with confirmed infection should have ARV therapy.
•g.
(ii) For HIV-seropositive children aged >18 months, WHO recommends the initiation of
ARV therapy if:
(a) WHO paediatric Stage III HIV disease (e.g. clinical AIDS) irrespective of CD4 %.
(bz WHO paediatric Stage II disease with consideration of using CD4< 15% to assist
in decision making.
i
or
(c) WHO paediatric Stage I (e.g. asymptomatic) and CD4<15%.
29
30
The penetration of ARVs into human milk in lactating women has not been
quantified for most of ARV drugs Although some ARVs, such as nevirapine, are
known to be present in breast milk, the concentration and the quantity of the drug
that would be ingested by infants would be less than that needed to achieve
therapeutic levels. Thus, if a breastfeeding infant is ill enough to require ARV
treatment, then ARVs at the standard paediatric doses should be initiated
regardless of whether the mother is receiving ARV therapy or not.
10.4. Recommended First-line ARV Regimens for infants and Children:
Formulations appropriate for use by young children who cannot swallow whole
tablets or capsules are currently widely available. However, National AIDS Control
Organization (NACO) and (SHI) recognize that until such time as appropriate
formulations can be made more widely available, the splitting of adult dose solid
formulations, ARV's should be resorted to. While such dosages may be suboptimal in
their effect, this is the only way a severely j|| child can receive therapy when no other
alternatives are available. The pharmacokinetics of crushed tablets or sprinkled capsule
contents in children has been evaluated.
In order to improve adherence, regimens chosen for children should take into
account those eventually used by the patients to avoid different timings, and, if
possible, to permit the use of same drugs. The drug doses must be adjusted as the
child grows, otherwise there is a risk of under-dosage and development of resistance.
Therefore, dosing in children should be based either on body surface area or weight.
The preferred first-line treatment option for children includes d4T or ZDV + 3TC
plus an NNRTI (NVP or EFV) for the same rationale as discussed for the adult initial
ARV regimen. A caveat is that EFC cannot be used for children under three years of
age due to lack of appropriate formulation and dosing information. Thus, for children
aged <3 years or weighing <10 kg, NVP should be the NNRTI of choice.
31
r^/„f2^f?l.ClJOSeJCornbinatlori (FDC) containing 30 mg of stavudine, the
recommended fractions will be:
2
wt.
Sta 30
Stavudine
Lam
NVP
7.5 - 12.5 kg
os-’
10
50
66
g
’ 12.5-17.5 kg
0.5
15
75
100
V
i 17.5-22.5 kg
0.66
20
100
133
id
: 22.5- 27.5 kg
0.75
22
112
~150
j
^-32.5 kg
i’m’
30
150
”200
I
3u
150
Too
r> 32.5 kg
4e
rol
”1
FDC 30:
Stavudine : 30 mg
Lamivudine : 150 mg
Nevirapine . zuu mg j
i hese doses will be administrated twice a day.
For FDC containing 40 eng of stavudine, the recommended fractions will be:
i Wt.
Sta 30
Stavudine
Lam
NVP
>iid
j 7.5 - 12.5 kg
0.25
W
37.5
50
; in
^2.5-17.5 kg
ner
I 17.5-22.5 kg
0.5
20
75
100
ule
122.5 - 27.5 kg
06
26
W0
133
0.75
30
7l2
1
40
iso"
^27.5-32.5 kg
pTzsk^
_____
150
FDC 40:
Stavudine : 40 mg
Lamivudine : 150 mg
Nevirapine : 200 mg
200
into
as
line of therapy is now considered a secondary
the
ice.
For children <3 years who require ARV therapy while receiving anti-TB therapy,
the use of ADV+3TC=ABC should be- considered, as SQV/r is not available in a
formulation appropriate for children of this age.
3TC
itial
s of
ken
Because of the age-related decline in the CD4 absolute count upto 6 years of age,
when nearly adult levels are reached, it is difficult to use the CD4 cell count to
assess the failure of the therapy in younger children. For children aged 6 years or
more, a similar CD4 count criteria as used in adults is appropriate.
10.5. Assessment of Infants and Children Receiving ARV Therapy
Important clinical signs of. response io the ARV therapy in children include:
improvement in the growth of children who were failing to grow; improvement in the
31
32
\ /
neurological
symptoms
and
general
in
development
of
children
who
were
demonstrating delay in developmental milestone or encephalopathy; and/or decreased
frequency of infections (bacteria! infections, oral thrush, and / or other opportunistic
infections).
Laboratory assessments in children on ARV therapy should be done routinely to
monitor the side-effects of drugs. It should also include monitoring of
•
Nutrition and nutritional status
•
Weight and height growth
•
Developmental milestones
•
Neurological symptoms
10.6. Side Effects and Drug Interaction
Availability as
three-drug
fixed-dose
combination
Yes
Dose
escalation
required
Laboratory
monitoring
requirements
^s, in
rifampicin-free
continuation
phase of TB
treatment. Use
with caution in
rifampicinbased
regimens
Yes
Yes
Yes, but EFV
should not be
given to
pregnant
I No,- EFV not
I available as
i part of FDC.
I However,
No
ARV regimen
Major
potential
toxicities
Usage in TB
co-infection
D4T/3TC/NVP
D4T-related
neuropathy,
pancreatitis
and lipoatrophy
Yes, in
rifampicin-free
continuation
phase of TB
treatment. Use
with caution in
rifampicinbased
regimens
i
NVP-related
hepatotoxicity
and severe
rash
ZDV/3TC/NVP
ZDV-related
neuropathy,
pancreatitis
and lipoatrophy
EFV-related
CNS toxicity
and potential
for
treatogenicity
D4T/3TC/EFV
ZDV-related Gl
intolerance,
anaemia and
I neutropenia
1
No
33
/
EFV-related
CNS toxicity
and potential
for
teratogenicity
I
I ZDV/3TC/EFV
)
I
ZDV-related Gl
intolerance,
anaemia and
neutropenia
EFV-related
CNS toxicity
and potential
for
teratogenicity
women or
women of
childbearing
potential,
unless effective
contraception
can be assured
Yes, but EFV
should not be
given to
pregnant
women or
women of
childbearing
potential,
unless effective
contraception
can be assured
partial FDC
available for
d4T/3TC
No, EFV not
available as
part of FDC.
However,
partial FDC
available for
ZDV/3TC
Yes
10.7. Reason for changing ART in children
ART may need to be changed for cither toxicity or drug failure.
>
l
Toxicity is
related to the inability to tolerate the side-effects of the medication and to significant
organ dysfunction that may result. This can be monitored clinically and bylaboratory
i
I
■
tests.
If a change in regimen is necessary because of treatment failure, a new secondline regimen may be used. When the toxicity is related to a single drug, the offendinq
_ J
*
$
drug can be replaced with the ether drug that does not have the same side-effects.
i
i
Regimen
D4T / 3TC ! NVP
33
Drug substitution
Toxicity
•
D4T-related neuropathy or
pancreatitis
•
Switch d4T ZDV
•
D4T-related lipoatrophy
•
•
NVP-related severe hepatotoxicity
•
Switch d4T TDF
or ABC
Switch NVP EFV
•
NVP-related severe rash (but not
’ife-threatening
•
Switch NVP EFV
•
NVP-related life-threatening rash
(Stevens-Johnson syndrome)
Switch NVP PI
34
<1
Drug Failure. Important clinical signs of drug failure in children include a lack of
growth, loss of neuro developmental milestones, development of enuphalopathy and
recurrence of new opportunistic infections that is refractory to treatment.
Before an
ARV regimen is considered to be failing based on clinical criteria, the child should have
had a reasonable trial on the ARV regimen for at least 24 weeks.
Due to age-related CD4 count changes in children aged less than 6 years, it is difficult
to use the CD4 cell count to assess the failure of ARV therapy in young children.
10.8. Second-line ARV therapy for Infants and Children:
The second-line therapy for children in the event cf the first-line regimen failure
would include: change in nucleoside backbone based on the same principles as for
adults (e.g. from ZDV+3TC to ABC+ddl) plus a protease inhibitor (LPV/r or NFV). TDF
cannot be recommended for paediatric use at the current time due to limited data
available on appropriate dosing in children, particularly children under 8 years of age.
I
First -line regimen
D4T or Zidovudine
+
3TC
+
NNRTI:
Nevirapine or Efavirenz
Second-line regimen
ABC
r
+
Didanosine
+
LPV/r or NFV or
SQV if weight >25 kg
10.9. Adherence to ART
Structured HIV management conducted by trained and committed health care
workers, together with informed patients, can result in improved adherence to ART.
This can lead to-
.
•
delayed onset of viral resistance
•
delayed virological failure
•
delayed treatment failure
•
improved quality and length of life
A large number of ART-related adverse effects have a direct or indirect impact on
the treatment outcomes. Differences in diet, environment and physiology are important
factors. The population-level occurrence of ART-relateo adverse effects should be
35
)f
monitored in new populations taking ART. At any rate, the occurrence of adverse
d
effects in individuals needs to be anticipated and planned for. Patients taking ART
n
should be counselled in advance about these effects so that their occurrence is not
e
totally unexpected.
Compliance can be a special problem in paediatrics, yet rigorous adherence to the
lit
prescribed regimen is essential to achieve an effective antiretroviral effect from therapy.
Unpalatable liquid formulations can cause the child to reject medications; therefore,
innovative techniques may be nfteded to ensure compliance.
re
dr
DF
Paediatric patients depend on their care takers for drug administration and the
I
families of paediatric HIV patients may face many challenges that can affect their ability
to deliver effective care. Close family and medical follow up are essential to ensure
ita
compliance with ARV regimens.
i
10.10. Children with Tuberculosis and HIV Co-infection
If the child’s condition permits, anti-tubercular therapy (ATT) should be
completed before starting the NVP-based ART.
In case a child’s clinical or
immunological status warrants administration^of^ART along with ATT, efavirenz based
regimens are recommended. The dose of efavirenz should be:
:are
KT.
Weight
Dosage
10-15 kg
15-20 kg
20-25 kg
25-35 kg
35-40 kg
> 40 kg
200mg once a day
250mg once a day
300 mg once a day
350mg once a day
400mg once a day
600mg once a day
This should be given with the combination of two NRTI drugs: zidovudine and
lamivudine or stavudine and lamivudine.
ct on
»rtant
d be
35
36
r
13.
MANAGING HIV/TB CO-IN^ECTION
HIV/TB co-infection is one of the most challenging issues in the scale-up efforts
since more than 25% of people living with HIV develop TB. Likewise, in some highprevalence countries like South Africa, 55-60% of people with TB are HIV positive.
Patients with TB merit special consideration because co-management of HIV and
TB is complicated by rifampicin drug inieracuons with NNRTIs and Pls, pill burden,
adherence and drug toxicity. Data to support specific treatment recommendations are
incomplete and research is urgently needed in this area.
I
The management of patients with HIV and TB poses many challenges including
patient acceptance of both diagnoses. Pending ongoing studies, WHO recommends
that ART in patients with CD4 cell counts < 200 / mm3 be started 2 vyeeks tn 2 months
after the start of TB therapy, when the patient has stabilized on TB therapy. This
provisional recommendation is meant to encourage rapid initiation of therapy in patients
who may have a high mortality rate. However, deferral of ARV initiation may be
reasonable in a variety of clinical scenarios. For example, patients with higher CD4
cells may wait to start ART until after the induction of first phase of TB is completed in
order to simplify management of their treatment.
\A/-
l
ART Recommendations fur individuals with Tuberculosis disease and HiV coinrection:
CD4< 200 mm3
Recommended Regimen
Comments
Start TB treatment. Start ART
as soon as TB treatment is
tolerated (between 2 weeks
and 2 months)(1)
Recommended ART. EFV is
contraindicated in pregnant women or
women of childbearing potential
without effective contracepxion
EFV containing regimens (2,3,4)
45
46
CD4 between
200-350 mm 3
CD4> 350 mm 3
CD4 not
| available
Start TB treatment. Start one
of the below regimens after
initiation phase (if severely
compromised start earlier):
EFV containing regimens or
NVP containing regimens in
case of rifampicin-free
continuation phase TB
treatment regimen
Start TB treatment
Start TB treatment
Consider AR I
~ Defer ART (3)~
Tm>7
’Consider ART
I
k
J
I on other signs of immunodeficiency
1 Timing of ART initiation should be up to clinicaljudgement based
re,”ARf should be started as soon as TB treatment .s
as per WHO guidelines. For extra pulmonary
tolerated irrespective of CD4 cell count.
SQV/r (400/400 mg bid or 1600/200 qd in sge),
2 Alternatives to the EFV portion of the regimen include
LPV/RTV (400/400 mg bid) and ABC (300 mg bid).
NVP (200 mg gd for 2 woks flowed by 200
of EFV in abs.nes
3
options
4
NVP containing regimens include d4T/3TC/NVP
EFV containing regimens include d4T/3TC/EFV or ZDV. 3TC/EFV
5 Unless non-TB stage IV conditions are present as per WHO guidelines,
Otherwise start ART upon
completion of TB treatment.
6 If no other signs of immunodeficiency are present and patient is improving on
TB treatment. AR i
should be started upon completion of TB treatment
new innovative
Since TB may be masked in people with advanced HIV disease
needed io support diagnosis, so that iB
tools that are more sensitive and specific are 1-----can be definitively diagnosed before ARVs are considered.
A number of service deilvery strategies can be used tor improving adherence to
ARV treatment and safe behavior. Expenenoe from TB and Leprosy prevention and
control programmes has shown that eady community invo.vement is essential tor good
treatment outcomes.
Much experience has been gained trom the Revised Nato a
Tuberculosis Control Programme (RNTCP) In which the DOTS strategy ,s used for
delivery of anti TB drugs. However, in RNTCP twice weekly regimen is
during first eight weeks patients are administered drugs in the presence 0 a
Provider. But in case of antiretroviral treatment the drugs have to be raxen on
,y
basis and at least twice a day. it may. therefore not be possible to translate the DOTS
47
I
strategy used in RNTCP for application in HIV treatment.
New strategies and tools
have to be developed to support treatment adherence and safe behavior to prevent
■
transmission of HIV.
1
Treatment education is an important component of this strategy. It is important
that the patient on ART knows how drugs work in the body and why it is important to
adhere to treatment regimens. It should be done in a setting where the person is
morai-y supported to integrate this into his or her life.
eucy
’ is
sye).
r
er
Upon
ATT
at
i
ice to
i a. id
g^jd
tk al
*
cr
d
id
d~ily
DOTS
47
48
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