A Pocket Guide to Adult HIV/AIDS TREATMENT
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- Title
-
A Pocket
Guide to Adult
HIV/AIDS TREATMENT - extracted text
-
February 2006 Edition
A Pocket
Guide to Adult
HIV/AIDS
Treatment:
p Companion to A Guide
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Primary Care of
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1 John G. Bartlett, MD
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U.S. Department of Health and Human Services
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Health Resources and Services Administration
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To order copies of the guide, contact:
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The Pocket Guide can ah
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February 2006 Edition
A Pocket Guide to
Adult HIV/AIPS Treatment:
Companion to
A Guide fo Primary Care of
People with HIIV/AIPS
John G. Bartlett, MD
Professor of Medicine
Chief Division of Infectious Diseases
Director, AIDS Service
The Johns Hopkins University School of Medicine
Baltimore, Maryland
U.S. Department of Health and Human Services
i
Acknowledgements
Richard W. Dunning, MS, MHS, edited the August 2004 edition.
Helen Schietinger, MA, ACRN, edited subsequent updates.
Paul Pham, Pharm D, reviewed the manuscript. Cover artwork was
created by Laura Spofford. Design and layout was done by
Patrice Lincoln and Jim Concannon.
ZrCT® - SOCHA
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}
Konunangala
jj
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Department of Health and Human Services
Health Resources and Services Administration
HIV/AIDS Bureau
Parklawn Building, Room 7-05
5600 Fishers Lane
Rockville MD 20857
http://www.hab.hrsa.gov
Publication date February, 2006
ii
A Pocket Guide to Adult HIV/AIDS Treatment
February, 2006
u
Table of Contents
References
v
Important Information for Users of This Pocket Guide
vi
List of Abbreviations Used in This Pocket Guide
1
Drug Information
Drug Table 1. Antiretroviral Agent Characteristics
Drug Table 2. Antiretroviral Agents, Class Adverse Reactions
Drug Table 3. Antiretroviral Agents, Adverse Reactions: “Black Box” Warnings
.2
Drug Table 4. Combination Antiretroviral Therapy, Dose Adjustments
Drug Table 5. Drug Interactions: Contraindicated Combinations
Drug Table 6. Drug Interactions: Nucleosides
Drug Table 7. Drug Interactions: Combinations with Pls or NNRTIs
Requiring Dose Modifications
12
.8
11
13
14
15
Antiretroviral Therapy
Adult ART Table 1. When to Start Therapy
Adult ART Table 2. Suggested Minimum Target Trough Levels
Adult ART Table 3. Starting Regimens for Antiretroviral Naive Patients
Adult ART Table 4. Advantages and Disadvantages of Antiretroviral Regimens
17
17
18
19
Adult ART Table 5. Antiretroviral Regimens or Components
That Are Not Generally Recommended
...................
Adult ART Table 6. Laboratory Monitoring
..Lu....:.-.
Adult ART Table 7. Resistance Mutations
Therapeutic Failure
Adult ART Table 8. Methods to Achieve Readiness to Start HAART &
Maintain Adherence
Adult ART Table 9. National Cholesterol Education Program: Indications
for Dietary or Drug Therapy for Hyperlipidemia
Adult ART Table 10. Drug Therapy for Hyperlipidemia
28
29
U.S. Department of Health and Human Services
in
20
22
23
25
27
u
Pregnancy and HIV
Antiretroviral Therapy in Pregnancy.....................................................
Pregnancy Table 1. Preferred Antiretroviral Agents..................................
Pregnancy Table 2. Antiretroviral Agents: Pharmacokinetic and Toxicity Data
Pregnancy Table 3. Antiretroviral Drugs for Delivery.................................
Pregnancy Table 4. Pregnancy Issues....................................................
Pregnancy Table 5. Clinical Scenarios and Management of Untreated
Pregnant Patients Including C-Section......................................
Pregnancy Table 6. Clinical Scenarios and Management of Treated
Pregnant Patients Including C-Section......................................
Pregnancy Table 7. Delivery Procedures and Therapy...............................
30
30
31
32
33
33
34
34
Prevention of HIV for Providers in Three Steps
Step 1: Screen Patients for Risk Behaviors............
Step 2: Behavioral Interventions.........................
Step 3: Partner Counseling and Notification..........
35
36
37
Opportunistic Infections
Adult 01 Table 1.2001 USPHS/IDSA Guidelines for Prevention of
Opportunistic Infections..............................
38
Tuberculosis and HIV...................................................................
42
Adult 01 Table 2. Recommended Drug Regimens for Treatment of
Latent TB in HIV Co-infected Adults...............
Adult 01 Table 3. Monitoring of Patients on Latent TB Prophylaxis...
Special Considerations for TB Treatment with HIV Co-infection.....
Adult 01 Table 4. Treatment of Drug-Susceptible TB.....................
Adult 01 Table 5. Doses of Antituberculosis Drugs - First-line Drugs
Adult 01 Table 6. Management of Opportunistic Infections .........
43
44
45
46
47
48
Occupational HIV Postexposure Prophylaxis (PEP)
Considerations in Occupational Exposure to HIV..................................
Occupational Postexposure Table 1. Exposure Contingencies..................
Occupational Postexposure Table 2. Indications for HIV PEP...................
Management of Health Care Workers (HCWs) With Potential HIV Exposure
Occupational Postexposure Table 3. Recommended Regimens................
Resources for Consultation...............................................................
IV
A Pocket Guide to Adult HIV/AIDS Treatment
52
53
54
55
57
57
February, 2006
References: A Pocket Guide to Adult HIV/AIDS Treatment:
• The (DHHS) Guidelines for the Use of Antiretroviral Agents in
HIV-Infected Adults and Adolescents. (The Living Document:
October, 6 2005). Available at http://www.aidsinfo.nih.gov/guidelines.
• 2001 USPHS/IDSA Guidelines for the Prevention of Opportunistic
Infections in Persons Infected with Human Immunodeficiency Virus.
November 28, 2001. Available at http://www.aidsinfo.nih.gov.
• USPHS/IDSA. Treating Opportunistic Infections Among HIV-Infected
Adults and Adolescents. MMWR Recommendations and Reports 53
(RR1 5): 1 -112, December 1 7, 2004. Available at http://www.aidsinfo.
nih.gov.
• Public Health Service Task Force Recommendations for the Use
of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for
Maternal Health and Interventions to Reduce Perinatal HIV-1
Transmission in the United States. June 23, 2005. Available at
http://www.aidsinfo.nih.gov.
• ATS/CDC Statement on Targeted Tuberculin Testing and Treatment
of Latent Tuberculosis Infection. The MMWR Recommendations
and Reports Vol. 49, No. RR-6, June 9, 2000. Available at
http://www.cdc.gov/nchstp/tb.
• Incorporating HIV Prevention into the Medical Care of Persons
Living with HIV: Recommendations of CDC, the Health Resources
and Services Administration, the National Institutes of Health, and
the HIV Medicine Association of the Infectious Diseases Society of
America. MMWR Recommendations and Reports Vol. 52, No. RR-12,
July 18, 2003. Available at http://www.aidsinfo.nih.gov.
• Integrating Nutrition Therapy into Medical Management of Human
Immunodeficiency Virus. Clin Infect Dis 2003; 36; Suppl 2:551-109.
•American Thoracic Society/Centers for Disease Control and
Prevention/lnfectious Diseases Society of America: Treatment of
Tuberculosis, Am J Respir Crit Care Med 2003; 167(4):603. Available at
http://www.aidsinfo.nih.gov.
• Updated US Public Health Service Guidelines for the Management
of Occupational Exposures to HIV and recommendations for
Postexposure Prophylaxis. MMWR 2005;54:RR-9. Available at http://
www.aidsinfo.nih.gov.
• Antiretroviral Postexposure Prophylaxis After Sexual, Injection-Drug
Use, or Other Nonoccupational Exposure to HIV in the United States:
Recommendations from the U.S. Department of Health and Human
Services. MMWR 2005;54:RR-2. Available at http://www.aidsinfo.nih.gov.
U.S. Department of Health and Human Services
v
u
Important Information for Users of This Pocket Guide
This document is provided as an information resource for
physicians and other health care professionals to guide them
in the appropriate treatment of patients with HIV/AIDS.
Recommendations for care and treatment change rapidly, and
opinions can be controversial; therefore, physicians and other
health care professionals are encouraged to consult other sources,
especially manufacturers’ package inserts, and confirm the
information contained in these tables. The individual physician
or other health care professional should use his/her best medical
judgment in determining appropriate patient care or treatment
because no single reference or service can take the place of
medical training, education, and experience. Although these tables
have been carefully prepared and reviewed, the author makes no
warranty as to the reliability, accuracy, timeliness, usefulness, or
completeness of the information. The data presented herein are
for informational purposes only. Determination of appropriate
treatment is the responsibility of the treating physician.
vi
A Pocket Guide to Adult HIV/AIDS Treatment
February, 2006
Abbreviations Used in This Pocket Guide
Drug Abbreviations
ABC: abacavir (Ziagen)
IVIG: intravenous immune globulin
APV: amprenavir (Agenerase)
LPV/r: lopinavir/ritonavir (Kaletra)
ATV: atazanavir (Reyataz)
NFV: neltinavir (Viracept)
AZT: zidovudine (Retrovir)
NNRTI: non-nucleoside reverse transcriptase inhibitor
CBV: Combivir (AZT+3TC)
NRTI: nucleoside reverse transcriptase inhibitor
ddl: didanosine (V/dex)
NVP: nevirapine (Viramune)
d4T: stavudine (Zerit)
PI: protease inhibitor
ddC: zalcitabine (Hivid)
RBT: rifabutin (Mycobutin)
DLV: delavirdine (Rescriptor)
RTV: ritonavir (Norvir)
EFV: etavirenz (Sustiva)
r: ritonavir in dose <400 mg/day
ENF: enfuvirtide (Fuzeon, T-20)
SQV: saquinavir (Invirase, Fortovase)
FTC: emtricitabine (Emtriva)
TPV: tipranavir (Artivus)
FTV: Fortovase (saquinavir, soft gel cap)
3TC: lamivudine (Epivir)
FPV: fosamprenavir (Lexiva)
T-20: enfuvirtide (Fuzeon)
HU: hydroxyurea
TDF: tenofovir (Viread)
IDV: indinavir (Crixivan)
TMP-SMX: trimethoprim sulfamethoxazole
INH: isoniazid
TZV: Trizivir (ABC+AZT+3TC)
INV: Invirase (saquinavir, hard gel cap)
VZIG: varicella zoster immune globulin
ZDV: zidovudine (Retrovir)
Miscellaneous Abbreviations
ART: antiretroviral therapy
q: every
EC: enteric coated
qd: daily
HAART: highly active antiretroviral therapy
qid: four times per day
IV: intravenous
qm: monthly
IM: intramuscular
qod: every other day
VL: viral load
qw: every week
bid: twice per day
soln: solution
biw: twice per week
tid: three times per day
CNS: central nervous system
tiw: three times per week
hs: bedtime (hour of sleep)
TAMS: thymidine analogue assoc, mutations
mo: month
ULN: upper limit of normal
po: by mouth
U.S. Department of Health and Human Services
1
Drug Table 1. Antiretroviral Agent Characteristics - continued
on"U
Most common and/or important toxicities are in italics.)
Usual
Drug
Form
Adult Dose
Name
CD
—t-
Q
c
CD
Zidovudine
(^Retrovir, AZT)
O
100 cap, 300
mg tab (see
also: Combivir &
Trizivir)
10 mg/mL IV
soln
300 mg bid
200 mg bid
Food
Effects
CrCI 30-59 CrCI 10-29 CrCI < 10
or dialysis
mL/min
mL/min
Toxicity
Liver
Failure (main toxicity
Dosing
- italics)
No effect
300 mg bid 300 mg qd 100 mg tid
Usual
Renal Failure Dosing
Peripheral
neuropathy,
stomatitis§
10 mg/mL po
soln
c”
Protease Inhibitors (Pls)
Take with
food
O
cz>
CD
Q
—H
Atazanavir
(Reyataz, AZT)
3
400 mg qd; ATV 300 mg/RTV 100 mg
qd. Boosting is often preferred and
100, 150, and
200 mg capsules is required it ATV is combined with
TDF or EFV
Avoid
concurrent
buffered
S
CPS* 7-9:
300 mg qd
Standard
CPS* >9:
Avoid
ddl,
CD
Z5
cd
Benign increase
in indirect
antacids
No effect
700 mg/RTV 100 mg bid or
Q
intolerance,
transaminitis,
prolongation
of QTc (caution
with conduction
detects or drugs
that do this) ||
Rash, Gl
CPS* 5-8:
700 mg bid intolerance,
1400 mg bid or
Fosamprenavir ff
700 mg tabs
(FPVZ Lexiva)
bilirubin, Gl
Standard
Avoid
transaminitis,
headache,
hepatitis
C.j o
<
CPS* >9:
1400 mg/RTV 200 mg qd
NO
O
o
CN
i
/
I
/
r
i
I
I
4
<
♦
»
♦
♦
Indinavir (IDV,
Crixivan)
G2
200, 333, 400
mg caps
800 mg q 8h; separate buffered ddl £ 1 hr
IDV 400 mg/RTV 400 mg bid or #
IDV 800 mg/RTV 100-200 mg bid #
1 hr before
or 2 hr after
Standard
meal unless
with RTV
GO
O
o
"O
Q
-->
—43
CD
Z5
—t-
ZD
o
200/50 mg tabs;
Lopinavir/
400 mg LPV 4- 100 mg RTV (2 tabs) bid
LPV 80 mg +
Ritonavir
RTV 20 mg/mL
Soln: 5 mL bid
(LPV/r) (Kaletra)
po solnff
No effect
Standard
250, 625 mg
1250 mg bid or
Nelfinavir (NFVZ tabs
Viracept)
750 mg tid
50 mg/g powder
Take with
high fat
meal
Standard
Gl intolerance,
nephrolithiasis,
transaminitis,
600 mg q8h
benign increase
in indirect
bilirubin ||
§§
Transaminitis,
Gl intolerance
(esp diarrhea),
asthenia
§§
Gl intolerance,
diarrhea,
transaminitis^j:
Q
Q
D
□L
c
3
Q
D
Ritonavir (RTV,
Norvir)
Saquinavir ff
(SQV, Invirase)
100 mg caps
600 mg/ 7.5 mL 600 mg q!2h #; separate ddl > 2 h
po soln
200 mg caps
500 mg tabs
SQV 1000 mg bid + RTV 100 bid ft
SQV 2000 mg qd + RTV 100 mg qa ff
§§
Take within
2 hours of
meal
Standard
§§
Standard
Hepatotoxicity
- monitor ALT,
CPSBorC: skin rash, Gl
Avoid
intolerance,
multiple drug
interactions
CZ)
Q
n'
o
cn
Cn
Tipranavir
(TRY Apitivus)
250 mg caps
500 mg bid with RTV 200 mg bid
Gl intolerance,
paresthesia,
transaminitis,
taste perversion
Food
improves Gl Standard
tolerance
Take TPV
and RTV
with food
Gl intolerance,
transaminitis
Drug Table 1. Antiretroviral Agent Characteristics - continued
o
Most common and/or important toxicities are in italics.)
Non*Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
n
CD
Delavirdine (DLV,
Rescriptor)
100, 200 mg
tabs
400 mg tid
No effect
600 mg hs
Avoid high
fat meal
Standard
§§
Rash
§§
CNSx 2-3
wks, rash,
hepatitis, false +
cannibinoid test
—i-
oc
CD
Efavirenz f++
(EFV, Sustiva)
50, 100, 200
mg caps
600 mg tabs
Standard
—4-
o
Ql
c
ZE
200 mg tabs
Nevirapine
(NVF; Viramune) 50 mg/5 mL po
susp
200 mg qd xl 4 days, then 200 mg bid
No effect
Standard
90 mg (1 mb) SQ q 12h into upper arm,
anterior or abdomen (rotate sites)
N/A
Standard
Standard;
give post Avoid
dialysis
Rash, hepatitis,
hepatic necrosis
esp women with
CD4 >250 in
first 6 wks
Fusion Inhibitors
U
CO
zH
CD
Q
—H
2
CD
D
co
c
Q
NO
O
O
o
90 mg single
Enfuvirtide (ENF, use vials to be
Fuzeon, T-20)
reconstituted
with 1.1 mb H20
Usual Dose
Site reactions
c:
on
t
The combination of ddl & d4T "should be used in pregnant women only
when the potential benefit clearly outweighs the potential risk." Efavirenz
should be avoided in first trimester of pregnancy and used with caution
in women with reproductive potential. Avoid APV liquid in pregnancy.
ft mg cap, amprenavir, or Fortovase.
f
Drug change or dose change could be considered on a case-by-case
basis noting the risk of resistance with underdosing.
**
Class adverse reaction: lactic acidosis with steatosis (see Drug Table 2).
Most common with d4T, ddl, and AZT
#
See Drug Table 4 for dosing recommendations when using dual PI, PI
plus NRTI, or dual PI plus NNRTI.
Give post dialysis
*
CPS=Child Pugh Score
§§
More frequent monitoring required. Drug change or dose change could
be considered on a case-by-case basis noting the risk of resistance with
underdosing.
O
CD
“U
Q
—t-
3
§
l!
The following are no longer available: buffered ddl, lopinovir/r 133/33
CD
Z5
—i-
Registry for hypersensitivity 1 -800-270-0425
o’
Efavirenz should be avoided in first trimester of pregnancy and used
with caution in women with reproductive potential. Avoid APV liquid in
pregnancy.
Q
Q
□
»
ZL
c
3
Q
Z5
on
(D
n
o
co
3TC, FTC, and TDF: Risk of flare of chronic HBV it discontinued.
ft
Capsule is the preferred formulation due to high propylene glycol in the
po solution; po soln contraindicated in pregnancy.
Class adverse effects include lipodystrophy with hyperglycemia, fat
redistribution, hyperlipidemia, and possible increased bleeding with
hemophilia. ATV does not cause hyperlipidemia. All Pls may cause
elevated transaminases (see Drug Table 2).
00
Drug Table 2.
Antiretroviral Agents, Class Adverse Reactions
o
n
CD
—♦-
Reaction
Lactic acidosis
Hepatotoxicity
Definition
Lactic acid >2
mmol/mL usually >5
mmol/mL
Grill = AST/ALT 5-1 OX ULN
o
c
CD
O
Fat
redistribution
Hyper
lipidemia
Rash
DRESS* (NVR ABC)
Fasting glucose
GR IV = AST/ALT > 10 x ULN >126 mg/dL
Fat accumulation
Lipoatrophy
See Adult ART
Table 5
SJS, TEN (NVR EFVZ DLV)
ABC hypersensitivity
NRTIs: d4T, ddl, AZT (lactic
acidosis)
c
X
Frequency
O
GO
—
1
■“s
CD
Q
1.3% NRTI recipients
with median onset at
4 mo
Pls: (15-30%)
NVP: 11% in first 6 wks in
women with baseline CD4
>250; possible hepatic
necrosis and death
3-17% with Pls
4-50%
ABC hypersensitivity: 5-8%, 90% in
1 st 6 wks
EFV, NVP: 8-16% most in 1st 6 wks
NNRTI: (8-15%)_______
—H
3
CD
D
Hyper
glycemia
Agents
NRTI: Lactic acidosis with
NRTIs: d4T+ddl>d4T> steatosis
ddl>AZT; rare with
NVP: Hepatic necrosis
3TC, ABC, FTC orTDF
Pls, NNRTIs: transaminitis
Pls
Fat accumulation: Pls
NNRTI: NVP > EFV & DLV
PI: esp RTV; not
Lipoatrophy: NRTIs
noted with ATV
Pls: FPV, increased risk with sulfa
esp d4T
and reduced
allergy
Also occurs without
frequency with FPV
NRTI: ABC*
antiretrovirals
CD
c
Q
ND
O
O
CN
V
Prolonged use NRTI
(esp d4T)
Risk Factors
Q
GO
Gl (abd pain, anorexia,
nausea, vomiting),
wasting, dyspnea,
cardiac arrhythmias
O
CD
~U
Q
—i-
3
CD
D
Female, pregnancy,
obesity, ribavirin,
metformin
Sx
ZE
CD
Q
Lactate >2 mmol/mL;
life-threatening if >10
mmol/mL
Q
D
ZE
c
3
Q
Z5
CO
CD
n
CD
cn
O
Lab
HCV or HBV infection, ETON,
male sex
NVP: baseline CD4 >250 in
female, > 400 in male
Most common: asymptomatic
♦ ALT/AST due to all Pls and
NNRTIs
NVP: may cause lethal
hepatonecrosis
Note: 1 indirect bilirubin
with IDVor ATVis clinically
inconsequential but may
cause jaundice___________
LFTs; liver biopsy is usually
not helpful.
Pre-existing glucose
intolerance
Risk for CVD:
HBR smoking,
No clear risks defined obesity, genes,
prior Ml/stroke,
diabetes, age
Polyuria, polydipsia, Fat accumulation:
Cardiovascular
polyphagia, weight abd (visceral), buffalo disease with stroke
loss
hump, breasts,
or Ml/angina
lipomas
Triglycerides
Fat atrophy: face,
>2000 mg/dL
extremities, buttocks - pancreatitis
ABC: genetic predisposition
NNRTI: 1st 12 wks
Female
Common: MP rash
Severe: Stevens-Johnson synd, TEN#,
DRESS*
NVP : hepatonecrosis with fever, rash,
and/or Gl sx 1st 16 wks
ABC hypersensitivity: > 2 systems
involved 1 st 6 wks
Fasting glucose
>126 mg/dL
Appearance is best
♦ triglycerides
'lab test", CT scan,
♦ cholesterol,
MRI, waist and
LDL
cholesterol
hip measurement,
Bioelectric Impedence
Analysis, DEXA,
ultrasound
Eosinophilia: variable
Drug Table 2. - continued
Antiretroviral Agents, Class Adverse Reactions
o
Reaction
Lactic acidosis
Hepatotoxicity
Q
Lactate 2-5 mmol/mL
+ Sx -D/C NRTI ifsx
severe
CD
Lactate level is 5-10
mmol/mL: D/C NRTIs.
Hypersensitivity reactions
to ABC or NVP (fever,
eosinophilia, rash, systemic
response usually in first 6-18
wks): D/C drug immediately
and do not rechallenge
O
Lactate >10 mmol/mL
o3
CD
—t-
c
c
ZE
Treatment
of
(medical emergency): Asymptomatic
. _• ■ _ Illklelevations
.
D/C NRTIs + supportive LFJ
ULN): rePeat LFTs
care (ventilator, dialysis, q 1-2 wks
IV HCO3)
Symptomatic or elevations
IV thiamine or riboflavin of LET (>5-10x ULN)
or hyperlactatemia or
(?)
hypersensitivity (ABC or NVP):
Post recovery: use low
D/C ART or change regimen.
risk NRTIs (3TC, FTC,
Some "treat through"
TDF) or avoid class
asymptomatic ALT > 1 Ox ULN.
ALT may return to baseline
or persist; liver biopsy usually
not helpful
O
cn
Zd
CD
Q
—»-
3
CD
Z5
Monitor
During
Therapy
None
CD
LFTs at baseline and q
3-6 mo
NVP: LFTs at wks
0,2,4,8,12,16 then q 3 mo
Hyper
glycemia
Use standard
diabetes treatment
with diet and
exercise
Preferred
hypoglycemics
are metformin or
thiazolidinediones
D/C PI only if
Fat
Hyper
redistribution
lipidemia
D/C d4T, ddl, AZT for NECP guidelines
fat atrophy
(pg 29):
Cosmetic surgery
• General f
Exercise?
• LDL cholesterol
4 Statins
Change PI to ATV or
NNRTI
Lipoatrophy: D/C
d4T
• Triglycerides 4
fib rate
uncontrolled
hyperglycemia
Fasting glucose
baseline, at 3-6
mo, then yearly
c
Q
Rash
Most rashes do not require drug
discontinuation
D/C drug if blisters, bullae, mucous
membranes involved, fever,
elevated ALT/AST
Withdraw NNRTI if severe: mucous
membrane involvement (SJS);
blisters or bullae, epidermal
necrosis (TEN), systemic reaction
(fever, arthralgia, myalgias)
Treatment: IV fluids, antipyretics, pain
management, care in burn unit.
Role of steroids not clear. Do not
rechallenge
Appearance
Fasting lipid
profile at
baseline, at 3-6
mo post HAART
initiation, then
yearly.
NVP and ABC: rash as component
of DRESS* or ABC hypersensitivity
or NVP hepatonecrosis reaction:
D/C drug and supportive care
Appearance
*DRESS: (Drug Rash, Eosinophilia, & Systemic Symptoms) Life threatening complication that is seen with NVP and ABC - usually in the first 6 weeks of therapy
bO
o
o
ex
fLifestyle changes: d/c smoking, diet, weight reduction, exercise, tx HBP and diabetes
# TEN: Toxic epidermal necrolysis
Drug Table 3. Antiretroviral Agents,
Adverse Reactions: "Black Box" Warnings
Agent
Reaction
Abacavir
• Fatal hypersensitivity reactions: do not restart
• Lactic acidosis and steatosis
Amprenavir
Oral soln contains large amounts of propylene glycol: avoid with renal failure,
hepatic failure, pregnancy, & metronidazole
Atazanavir
None
Delavirdine
None
Didanosine
Fatal and nonfatal pancreatitis: do not restart
Lactic acidosis with steatosis
Fatal lactic acidosis when combined with stavudine in pregnancy
Efavirenz
None
Emtricitabine
Lactic acidosis with steatosis
Enfuvirtide
None
Indinavir
None
Lamivudine
Lactic acidosis with steatosis
Patients with HBV infection should receive only dosage and formulations
appropriate tor treatment of HIV
Lopinavir
None
Nelfinavir
None
Nevirapine
Hepatotoxicity including fulminant and cholestatic hepatitis & hepatic necrosis:
monitor intensively in first 18 wks of therapy
Severe, life-threatening skin reaction including toxic epidermal necrolysis
(TEN), Stevens-Johnsson syndrome, etc
Do not restart it there is serious liver injury or serious drug reaction
Ritonavir
Potentially serious drug interactions with nonsedating antihistamines, sedative
hypnotics, antiarrhythmics, or ergot alkaloids
Stavudine
Lactic acidosis with steatosis
Fatal and non-fatal pancreatitis
Fatal lactic acidosis when combined with didanosine in pregnancy
Tenofovir
Lactic acidosis and steatosis; discontinuation in pts with HBV co-infection may
cause exacerbation of acute HBV
Tipranavir
Hepatotoxicity including clinical hepatitis and hepatic decompensation
Severe peripheral neuropathy
Zalcitabine
Zidovudine
Pancreatitis (rare)
Hepatic failure in patients with HBV infection (rare)
Lactic acidosis and steatosis
Hematologic toxicity: anemia & leucopenia
Lactic acidosis and steatosis
U.S. Department of Health and Human Services
11
Drug Table 4.
Combination Antiretroviral Therapy, Dose Adjustments*
RTV
IDV
RTV
SQV
NFV
FPV
LPV
SQV
IDV
400+
RTV400
bid or
ND
IDV/r
800/
100-200
bid
NFV
FPV
IDV
1200
+ NFV IDV-SD
1250 ARV-SD
LPV/r
ND
ATV
NR
bid
EFV
NVP
NVP-SD
IDV 1000
q8h
EFV-SD
IDV- 1000
q8h or EFV
SD/IDV
800 bid/
RTV 200
bid
FPV/r
SQV/r
1000/100
or
400/400
bid
1400/
ATV/r
NVP-SD
co-form200 qd or
300/100
RTV-SD
ulated
700/100
qd
bid
NFVSD +
SQV
1200
bid or
SQV
800
tid
ND
ND
NVP-SD +
SQV
SQV/RTV
SQV1200
1000 bid
400/400
+ A7V
+ LPV/rbid or
400 qd
SD
1000/100
bid
ND
NR
ND
ND
ND
EFV-SD +
SQV/RTV
400/400
bid
NVP-SD
NFV-SD
EFV-SD
NFV-SD
ND
EFV-SD
FPV/r
1400/300
qd or
700/100
bid
NVP-SD
LPV/r
533/133
bid
ND
ATV
EFV-SD
RTV-SD
EFV-SD
LPV/r
533/133
bid
EFV-SD
+ ATV/r
300/100
qd
TPV*
* Doses are in mg; ND = Inadequate data; NR = Not recommended; SD = Standard dose;
**TPV must be combined with RTV and should not be combined with any other PI
12
A Pocket Guide to Adult HIV/AIDS Treatment
February, 2006
Drug Table 5.
Drug Interactions: Contraindicated Combinations
Class
Contraindicated
Agent
Ca + + channel blocker Bepridil
Antiarrythmics
Flecainide,
Propafenone
ART Agents
Alternatives
RTV, ATV, FPV, TPV
RTV, LPV/r, TPV
Amiodarone, quinidine RTV, IDV, TPV
Lipid lowering
Simvastatin, Lovastatin All Pls, DLV
Pravastatin or
Fluvastatin, possibly
Atorvastatin,
Rosuvastatin
Rifampin
All Pls; all NNRTIs
except EFV
Rifabutin
DLV, SQV (unless used
with RTV)
Rifapentine
All Pls, NVR DLV, EFV
Rifampin or rifabutin
Antihistamine
Astemizole,
Terfenadine
All Pls, DLV, EFV
Loratadine,
Fexofenadine,
Cetirizine, or
Desloratidine
Antineoplastics
Irinoteacan
ATV
Cisapride
All Pls, DLV, EFV
H2 blockers, proton
pump inhibitors
DLV, ATV
Clozapine
RTV
Pimozide
All Pls
Midazolamf
Triazolam
All Pls, DLV, EFV
Alprazolam
DLV
Ergot alkaloids
Ergotamine
All Pls, DLV, EFV
Consider Sumatriptan
Herbs
St. John's wort
All Pls & EFV, DLV, NVP
Alternative
antidepressants
Miscellaneous
Fluticasone
RTV and all RTV/PI
combinations
Antimycobacterials
Gl
Use Rifabutin*
Neuroleptic
Psychotropic
Temazepam,
Lorazepam
* See Drug Table 7, pg 14 for Rifabutin and antiretroviral dose adjustments
•f Midazolam may be used with caution as a single dose given for a procedure
U.S. Department of Health and Human Services
13
Drug Table 6.
Drug Interactions: Nucleosides
Drug
Methadone
d4T
AZT AUC443%;
no dose change;
monitor for AZT
toxicity
d4T427%;
no dose change
No change in
methadone or
TDF levels
Magnifies toxicity
Use with caution
ddl 444%
Pt >60 kg: 250
mg/d (ddl)
Pt <60 kg: 200
mg/d (ddl)
ddl
Ribavirin
ddl
AZT
Inhibits AZT
activation; avoid
if possible
No data
ATV
TDF
Magnifies ddl
toxicity; avoid
No data
ddl EC: separate
dosing due to
food restrictions
Avoid concomitant
use unless ATV
combined with
RTV
Ganciclovir +
AZT4 marrow
toxicity
Monitor CBC
Combinations
may decrease
CrCI
LPV/r
No data
TDFAUC434%
Standard doses
and monitor for
TDF toxicity
TPV
AZT AUCf
31-42%
Right dose?
Cidofovir
Ganciclovir
Valgancyclovir
14
No data
No data
TPV Cminf44%
with ddl EC
Separate by 2 hrs
A Pocket Guide to Adult HIV/AIDS Treatment
-
February, 2006
Drug Table 7.
Drug Interactions: Combinations with
Pls or NNRTIs Requiring Dose Modifications
Class
Agent
ART
IDV: IDV 600 mg tid
Ketoconazole
RTV, LPV/r: Ketoconazole < 200 mg/d, FPV < 400 mg/d
NVP: Not recommended
Voriconazole
Current use with RTV (> 400 mg/d) or EFV is
contraindicated; no data tor NNRTIs, NFV, ATV, TPV, FPV,
LPV/r but bidirectional interaction anticipated; Monitor tor
toxicity; IDV is OK
Itraconazole
IDV and TPV: itraconazole dose < 200 mg or monitor
levels
Antifungal
Additional method of contraception recommended with:
RTV, NFV, EFV, LPV/r, NVF? FPV (IDV & ATV are OK)
Oral
contraceptives
No data for SQV
Anticonvulsants
Phenobarbital,
Phenytoin,
Carbamazepine
Avoid carbamazepine + IDV and phenytoin + LPV;
all other combinations of NNRTIs or Pls & designated
anticonvulsants should be given with caution and
monitoring of anticonvulsant levels or consider
valproic acid
NVP and EFV may decrease methadone substantially;
monitor for withdrawal
IDV has no interaction; other Pls may cause modest
decrease in methadone levels and require monitoring for
withdrawal
Methadone
Methadone decreases buffered ddl levels - consider ddl
EC (no interaction).
Antibiotics
Clarithromycin
RTV, LPV/r, TPV, DLV: Decrease clarithromycin dose in
renal failure.
EFV, ATV: Consider alternative (e.g. azithromycin)
Erectile
dysfunction
Sildenafil
Pls + DLV: < 25 mg q48 h
Vardenafil
Pls + DLV: < 2.5 mg/d
Tadalafil
Pls + DLV: < 10 mg q/2 h
U.S. Department of Health and Human Services
15
Drug Table 7. - continued
Drug Interactions: Combinations with
Pls or NNRTIs Requiring Dose Modifications
Class
Agent
ART
FPV 1400 mg bid + RBT 150 mg/d or 300 mg 3x/wk
ATV 400 mg/d + RBT 150 mg qod or 150 mg 3x/wk
EFV 600 mg/d + RBT 450-600 mg/d or 600 mg 3x/wk
IDV 1000 mg q 8h + RBT 150 mg/d or 300 mg 3x/wk
Rifabutin
LPV/r 400/100 mg + RBT 150 mg qod or 3x/wk
NFV 1000 mg tid + RBT 150 mg/d or 300 mg 3x/wk
Antimycobacterials
NVP standard + RBT standard
RTV 600 mg bid + RBT 150 mg qod or 150mg 3x/wk
RTV (maintain usual dose) + PI (standard dose) +
RBT 150 mg qod or 3x/wk
Rifampin
All Pls & NNRTIs contraindicated except EFV using
standard doses of rifampin; consider EFV daily dose of
800 mg qd
Lipid Lowering
Lovastatin,
Simvastatin
Avoid Pls and DLV; no data for EFV and NVP
Atorvastatin
Atorvastatin levels♦480%-SQV/RTV, 70%-NFV, 9x-TPV,
150%-FPV, 590%-LPV/r; f43% EFV;
No data-IDV, ATV, NVP
Pravastatin
Levels pravastatin 4 33%-LPV/r, f 50% SQV/RTV;
No data for other Pls or NNRTIs
Theophylline
RTV: Monitor theophylline levels
Warfarin
RTV, DLV, EFV: Monitor INR closely it given with any PI or
NNRTI
Trazedone
RTV: lowest dose + monitor CNS signs
Desipramine
RTV: Consider desipramine dose reduction
Grapefruit juice
IDVi, SQV+
Ca channel
blockers
ATV, FPV, RTV: contraindicated
Others: dose titration of
Ca channel blockers + EKG monitoring
Diltiazem
All Pls: Reduce diltiazem dose 50% + monitor EKG
ABC
Antacids
TPVi ABC levels 35-45%; ABC dose?
ATV and TPV levelsf; give PI 2 hrs before or 1 hr after
PPI
ATV: Avoid PPI
Miscellaneous
16
A Pocket Guide to Adult HIV/AIDS Treatment
February, 2006
1/
Anf iretroviral Therapy
Adult ART Table 1.
When to Start Therapy*
Clinical Category
CD4+ Count
Viral Load
Recommendation
Symptomatic (AIDS or
severe symptoms)
Any value
Any value
Treat
Asymptomatic, AIDS
CD4+ < 200/mm3
Any value
Treat
Any value
Offer treatment,
but consider patient
readiness, probability
of adherence, potential
side effects, and
prognosis based on
CD4 count, CD4 slope,
and HIV viral load
Asymptomatic
CD4+ > 200/mm3
but < 350/mm3
Asymptomatic
CD4+ > 350/mm3
> 100,000 c/mL
Consider therapy
or observe (Data
inconclusive for either
alternative)
Asymptomatic
CD4+ > 350/mm3
< 100,000 c/mL
Defer therapy and
observe
* There are special considerations for pregnant women; consult Pregnancy Tables 1 -3
Adult ART Table 2.
Suggested Minimum Target Trough Levels
Drug
Concentration
ARV
400 mg/mL
IDV
100 mg/mL
LPV
1000 mg/mL
NFV
800 mg/mL
RTV
2100 mg/mL
SQV
100-250 mg/mL
EFV
1000 mg/mL
NVP
3400 mg/mL
U.S. Department of Health and Human Services
Adult ART Table 3.
Starting Regimens for Antiretroviral Naive Patients
NRTI-Based Regimens
# of pills per day
efavirenz + (lamivudine or emtricitabine) +
Preferred Regimens (zidovudine or tenofovir DF) - except for pregnant 2-3
women or women with pregnancy potential
• efavirenz + (lamivudine or emtricitabine) +
(didanosine or stavudine or abacavir) - except
for pregnant women or women with pregnancy
potential
2-4
Alternative Regimens • nevirapine + (lamivudine or emtracitabine)
+ (zidovudine or abacavir or tenofovir or
stavudine* or didanosine) (Avoid in women
with baseline CD4>250 and men with baseline
CD4 > 400)
3-6
Pl-Based Regimens
Preferred Regimens
# of pills per day
lopinavir/ritonavir + (lamivudine or emtricitabine)
6-7
+ zidovudine
• atazanavir 4- (lamivudine or emtricitabine)
+ (zidovudine or stavudine* or abacavir or
didanosine) or (tenofovir + ritonavir)
3-6
• fosamprenavir + (lamivudine or emtricitabine) +
(zidovudine or stavudine* or abacavir or tenofovir 5-8
or didanosine)
• fosamprenavir/ritonavir 4- (lamivudine or
emtricitabine) + (zidovudine or tenofovir or
didanosine or stavudine* or abacavir)
5-8
• indinavir 4- ritonavirf 4- (lamivudine or
Alternative Regimens
emtricitabine) + (zidovudine or tenofovir or
didanosine or stavudine* or abacavir)
7-12
• nelfinavir + (lamivudine or emtricitabine)
4- (zidovudine or stavudine* or tenofovir or
didanosine or abacavir)
5-8
• saquinavir (Invirase) 4- ritonavir 4- (lamivudine
or emtricitabine) 4- (zidovudine or stavudine* or
tenofovir or didanosine or abacavir)
7-15
• lopinavir/ritonavir 4- (lamivudine or emtricitabine)
4- (stavudine* or abacavir or tenofovir or
5-7
didanosine)
Triple NRTI Regimen As Alternative to PI- or NNRTI-based regimens
Alternative Regimens • abacavir + lamivudine + zidovudine
# of pills per day
2
* Stavudine is associated with higher rates of lipoatrophy and mitochondrial toxicity than other NRTIs
f Low-dose (100-400 mg) ritonavir
18
A Pocket Guide to Adult HIV/AIDS Treatment
February, 2006
Adult ART Table 4.
Advantages and Disadvantages of Antiretroviral Regimens
Advantages
Disadvantages
NNRTIs
Class- less lipodystrophy
Save PI option
Extensive experience
Low genetic barrier to resistance
Class resistance / Drug interactions
High rate of rash reactions
EFV
Potent
Low pill burden qd
Once daily dosing
CNS toxicity
Teratogenic in first trimester
NVP
Extensive experience in pregnancy
No food effect
ADR: hepatotoxicity + rash
Contraindicated in women with baseline CD4
count >250
PI
Class- extensive experience
Save NNRTI option
ADR- lipodystrophy
Multiple drug interactions
Gl intolerance
ATV
Once daily dosing
Low pill burden
No hyperlipidemia
ADR: Jaundice 4- PR interval prolongation
Drug interaction with TDF and EFV
LPV/r
Potency
Coformulated with RTV
ADR: Gl intolerance
Reduced levels in pregnancy
FPV/r
Low pill burden
No food effect
Once daily dosing
ADR: skin rash
IDV/r
No food requirement
bid dosing with RTV boosting
ADR: Nephrolithisis
Requirement for po fluid
NFV
Substantial experience in pregnancy
ADR: diarrhea
High rate virologic failure
Food requirement
SQV/r
Improved Gl tolerance with Invirase
ADR: Gl intolerance
NRTIs
Coformulated
AZT/ 3TC/ ABC No food effect
Preserves PI and NNRTI options
Higher rate of virologic failure if used alone
ADR: ABC hypersensitivity
NRTI pairs
AZT/ 3TC*
Extensive experience
Coformulated
No food effect
ADR: Gl intolerance + narrow suppression
(AZT)
HBV flare when 3TC stopped
d4T/ 3TC*
No food effect
Once daily
ADR of d4T **
HBV flare when 3TC stopped
TDF/ 3TC* or
FTC
Well tolerated
Once daily
TDF + FTC coformulated
HBV flare when TDF, 3TC, or FTC stopped
ddl/ 3TC*
Once daily
ABC/ 3TC*
Once daily
No food effect
Coformulated
ADR: ddl**
Food effect
HBV flare when 3TC stopped
ADR: ABC hypersensitivity
HBV flare when 3TC stopped
* FTC is similar to 3TC; has longer intracellular halt life and has less extensive experience
** ADRs- d4T lipoatrophy, lactic acidosis, peripheral neuropathy; ddl- peripheral neuropathy, pancreatitis
and lactic acidosis
U.S. Department of Health and Human Services
19
Adult ART Table 5.
Antiretroviral Regimens or Components That Are
Not Generally Recommended
Rationale
Exception
Antiretroviral Regimens Not Recommended
• Rapid development of resistance
Monotherapy
• Interior antiretroviral activity when
compared to combination with three or
more antiretrovirals
Pregnant women with
HIV-RNA <1,000
copies/mL using
zidovudine monotherapy
for prevention
of perinatal HIV
transmission
• Interior antiretroviral activity when
compared to combination with three or
more antiretrovirals
For patients currently on
this treatment, it may be
reasonable to continue
it virologic goals are
achieved
ABC + TDF + BTC as a
triple NRTI regimen
High rate of virologic failure and resistance
No exception
TDF + ddl + BTC
High rate of virologic failure and resistance
No exception
TDF + ddl + NNRTI
High rate of virologic failure
Possible reduced CD4 response
No exception
• Rapid development of resistance
Two-agent drug
combinations
Antiretroviral Components Not Recommended As Part of
Antiretroviral Regimen
Saquinavir hard gel
capsule (Invirase) as
single PI
• Poor oral bioavailability (4%)
• Interior antiretroviral activity when
compared to other protease inhibitors
No exception
d4T + ddl
When no other
antiretroviral options
Reports of serious, even fatal, cases of lactic
are available and
acidosis with hepatic steatosis
potential benefits
outweigh the risks*
ATV + IDV
Potential for additive hyperbilirubinemia
No exception
FTC + 3TC
No potential benefit
No exception
Teratogenic in nonhuman primate
When no other
antiretroviral options
are available and
potential benefits
outweigh the risks*
Efavirenz in pregnancy
20
A Pocket Guide to Adult HIV/AIDS Treatment
February, 2006
Adult ART Table 5. - continued
Antiretroviral Regimens or Components That Are
Not Generally Recommended
Exception
Rationale
Antiretroviral Components Not Recommended As Part of
Antiretroviral Regimen (continued)
Amprenavir oral
solution in:
• pregnant women
• children <4 yr old
Oral liquid contains large amount of the
excipient propylene glycol, which may be
toxic in the patients at risk
No exception
d4T + ZDV
Antagonistic
No exception
ddC 4- d4T or
ddC + ddl
Additive peripheral neuropathy
No exception
ATV + IDV
Additive hyperbilirubinemia
No exception
FTC + 3TC
Similar agents; no potential benefit
No exception
• patients with renal or
hepatic failure
• patients treated with
metronidazole or
disultiram
• Decreases CD4 count
Hydroxyurea
• Augments d4T- and ddl-associated side
effects, such as pancreatitis & peripheral
neuropathy
• Inconsistent evidence of improved viral
suppression
No exception
• Contraindicated in pregnancy (Pregnancy
Category D)
Not Recommended As Part of Initial Antiretroviral Regimen
DLV
Modest antiretroviral effect
*
RTV as single PI
Gl intolerance
*
d4T + ddl
Increased peripheral neuropathy, lactic
acidosis, and pancreatitis
*
NFV + SQV
High pill burden of 16-22 caps/day
*
TPV
Tested and approved only for salvage
*
* Reasonable to use in unusual circumstances
- SOCHA
Koramangala
U.S. Department of Health and Human Services
) S’)) \ y
'
21
Adult ART Table 6.
Laboratory Monitoring
• Baseline tests, CBC, chemistry profile including liver and renal
function tests, PAP smear for female patients, Toxoplasma gondii IgG,
VDRL (or RPR), anti-HCV, anti-HBc, and PPD (if no prior positive, see
TB tables)
• Confirm HIV Ab + if not documented
• Viral load at baseline (x2) and 2-8 wks after initiating therapy or
new regimen, then every 3-4 months, clinical event, or significant
(3x or > 0.5 loglO c/mL) change in VL
• CD4 count at baseline and then every 3-6 months
• Antiretroviral agent toxicity (see Drug Table 2, pg 8)
• Resistance tests
Recommended
- Virologic failure within 4 weeks of stopping ART
- Suboptimal suppression
- Acute HIV infection
Consider
- Chronic HIV infection, before therapy
Not Usually Recommended
- After discontinuation of drugs for more than 4 weeks
- Viral load < 1,000 c/mL
22
A Pocket Guide to Adult HIV/AIDS Treatment
February, 2006
Adult ART Table 7.
Resistance Mutations*
Major f
Drug
Minor f
Protease Inhibitors
10 IRV, 20 MR, 24 I, 32 I, 36 I, 54 V,
71 VI, 73 SA, 771, 90 M
10 Fl, 36 I, 46 IL, 71 VL, 77 I, 82
AFTS, 84 V, 88 DS
10FIRV, 20 MR, 32 1, 33 F, 36 I, 46 IL,
50 V, 54 VL, 71 VT, 77 T, 90 M
10 IRV, 54 VL, 71 VT, 73 S, 77 I, 82
A, 84 V
IDV
46 IL, 82 AFT, 84 V
NFV
30 N, 90 M
RTV
82 AFTS, 84 V
SQV
48 V, 90 M
FPV
50 V, 84 V
10 FIRV, 32 I, 46 IL, 47 V, 54 LVM, 73
S, 82 AFST,90 M
LPV/r
32 I, 47 VA, 82 AFTS
10FIVR, 20 MR, 24 1,31 I, 33 F, 46
IL, 50 V, 53 L, 54 VLAMTS, 63 R 71
VT, 73 S, 90 M
AW
50 L, 84 V, 88 S
10IFV, 16 E, 20RMI, 24 1,321, 33
IFV, 36 ILV, 46 I, 48 V, 54 LVMT, 60
E, 62 V, 71 VITL, 73 CSTA, 82 A, 90
M, 93 L
TPV
33 I, 82 LT, 84 V
10 IV, 13 V, 20 MR, 35 G, 36 I, 43 T,
46 L, 47 V, 54 AMV, 58 E, 69 K, 74 R
83 D, 90 M, 46 I, 54 V
* Adapted from IAS-USA Topics HIV Med 2005; 13:125. See http://www.iasusa.org
f Major: usually develop first; associated with decreased drug binding; Minor: also contribute
to drug resistance; may affect drug binding in vitro less than primary mutations. Use of Major
and Minor designations tor NRTIs and NNRTIs has been suspended.
U.S. Department of Health and Human Services
23
Adult ART Table 7. - continued
Resistance Mutations*
Drug
Codon Mutations
Nucleosides and Nucleotides
AZT
41 L, 44D, 67N, 70 R, 118 I, 210 W, 215 YF, 219 Q
d4T
41 L, 44D, 65 R, 67 N, 70 R, 118 I, 210 W, 215 YF, 219 QE
3TC
65 R, 184 VI
FTC
65 R, 184 VI
65 R, 74 V
ddl
ABC
65 R, 74 V, 115 F, 184 V
TDF
65 R
Multinucleoside A- Q 151 M
62 V, 75 I, 77 L, 116 Y, 151 M
Multinucleoside B 69 insertion
41 L, 67 N, 69 insert, 70 R, 210 W, 215 YF, 219 QE
Multinucleoside TAMS
41 L, 67 N, 70 R, 210W, 215YF, 219QE
NNRTIs
NVP
DLV
EFV
Multi-NNRTI resistance
Multi-NNRTI resistance
accumulation
1001, 103 N, 106 AM, 108 I, 181 Cl, 188 CLH, 190 A
103 N, 106 M, 181 C, 188 L, 236 L
100 I, 103 N, 106 M, 108 I, 181 Cl, 188 L, 190 SA, 225 H
103 N, 106 M, 188 L
100 I, 106 A, 181 Cl, 190 SA, 230 L
* Adapted from IAS-USA Topics HIV Med 2005; 13:125. See http://www.iasusa.org
24
A Pocket Guide to Adult HIV/AIDS Treatment
February, 2006
Therapeutic Failure
Definitions
Virologic Failure:
• Failure to achieve VL < 400 c/mL by 24 wks or < 50 c/mL by 48
wks. Note: Most patients will have a decrease in VL of >1 log|0 c/mL
at 1 -4 weeks
• Viral suppression followed by repeated positive viral load
Immunologic Failure:
Failure to increase CD4 count 25-50 cells/mm3 during first year
Note: Mean increase is about 150 cells/mm3 in a year with HAART in
treatment naive patients
Clinical Failure:
Occurrence or recurrence of HIV-related event > 3 months after start
of HAART
Note: Must exclude immune reconstitution syndromes
Management of Regimen Failure
Assessment
• Adherence: Address cause and/or simplify regimen
• Tolerability
- Change one drug within class
- Change classes; e.g. Pl-based HAART vs NNRTI-based HAART
• Pharmacokinetic Issues
U.S. Department of Health and Human Services
25
i
Therapeutic Failure - continued
I
Virologic Failure
Definition:
1) HIV RNA > 400 c/mL (VL) after 24 weeks of treatment
2) VL > 50 c/mL after 48 weeks of treatment
3) Viral load detectable after achieving undetectable (viral rebound) VL
indicating failure should be confirmed; “Blips” (isolated VL values of
50-1,000 c/mL) do not constitute failure if unconfirmed
Assessment:
• Review treatment history and prior resistance tests
• Access adherence, intolerance and pharmacokinetic issues (food/
fasting requirements, drug interactions, malabsorption)
• Distinguish between limited, intermediate, and extensive prior
treatment and drug resistance
• The viral load that defines an indication for therapeutic intervention
is in the range of 400-5000 c/mL; The threshold of 400 may result
in multiple drug exposures and limited access to resistance tests
(since a threshold of 1000 c/mL is often required to do the test); a
delay to a threshold of 5000 c/mL risks accumulation of multiple
resistance mutations including class resistance
• Perform resistance tests while the patient is receiving the failed
regimen or within 4 weeks of stopping it
• Identify 2-3 active drugs for the next regimen; two active drugs are
essential for viral supression
• If no resistance is demonstrated: consider continuation with
emphasis on adherence, possibly with therapeutic drug monitoring
• With low level viremia (< 5000 c/mL) and limited drug exposure
consider boosting a PI, or intensification by adding a nucleoside or
change therapy
• With intermediate or extensive prior drug exposure, consider
an agent with a new mechanism of action (enfuvertide) usually
combined with a Pl including TPV or an experimental drug such
asTMC 114
• With extensive treatment failures, multiple resistance mutations and
no available regimens likely to achieve virologic goals: the goal of
therapy is to preserve immune function and avoid HIV-associated
complications; HIV therapy should be continued
26
A Pocket Guide to Adult HIV/AIDS Treatment
February, 2006
Adult ART Table 8.
Methods to Achieve Readiness to Start HAART
& Maintain Adherence
Patient-related
• Negotiate a plan or regimen that the patient understands and to
which she or he commits
• Take time needed, > 2 visits, to ensure readiness before 1 st prescription
• Recruit family, friends, peer and community support
• Use memory aids: timers, pagers, written schedule, pill boxes/
medication organizers
• Plan ahead: keep extra meds in key locations, obtain refills
• Use missed doses as opportunities to prevent future misses
• Active drug and alcohol use and mental illness predict poor adherence;
race, sex, age, educational level, income, and past drug use do not
Provider/Health Team-related
• Educate patient re: goals of therapy, pills, food effects, and
side effects
• Assess adherence potential before HAART; monitor at each visit
• Ensure access at off-hours and weekends for answering questions
or addressing problems
• Utilize full health care team; ensure med refills at pharmacy
• Consider impact of new diagnoses and events on adherence
• Provide training updates on adherence for all team members
and utilize team to reinforce adherence
• Monitor adherence and intensify management in periods of
low adherence
• Educate volunteers, patient-community representatives
Regimen-related
• Avoid adverse drug interactions
• Simplify regimen re: dose frequency, pill burden,
and food requirements
• Inform patient about side effects
• Anticipate and treat side effects
U.S. Department of Health and Human Services
27
Adult ART Table 9.
National Cholesterol Education Program:
Indications for Dietary or Drug Therapy for Hyperlipidemia
Coronary Heart
Disease Risk
Status
No CHD & 0-1 Risks*
Goal
LDL <160 mg/dL
Threshold for
Diet Rx
LDL >160 mg/dL
Threshold for
Drug Rx
LDL >190 mg/dL (LDL
160-190 Drug therapy
optional)
10 Yr CHD Risk
<10% J
LDL > 160 mg/dL
No CHD &> 2 Risks*
LDL <100 mg/dL
LDL >130 mg/dL
10 Yr CHD Risk 1020% {
LDL >130 mg/dL
CHD or CHD
equivalent:
• Clinical ASCVD f
• Diabetes mellitus
LDL < 70 mg/dL
LDL >100 mg/dL
• Multiple Risk Factors
conferring 10 Yr risk
LDL >130 mg/dL
(100-129 mg/dL: drug
optional)
of CHD of >20% t
Triglycerides are an independent consideration
• For patients with serum triglycerides >500 mg/dL the primary goal is reduction of triglycerides
to prevent pancreatitis and reduce risk of CHD
• For patients with serum triglycerides 200 - 499 mg/dL reduction of non-HDL cholesterol
becomes a secondary goal after reaching LDL goal
Adapted from: JAMA 2001; 285:2486-2497; updated NCEP - Circulation 2004; 110:227.
Editors Note: This table is a basic condensation of complex guidelines. Readers are encouraged
to consult and use the tools available on the NHLBI web site: http://www.nhlbi.nih.gov/
guidelines/cholesterol/
* CHD Risk Factors: Age (men >45 years; women >55 yrs or premature menopause without
estrogen replacement); hypertension, current smoking, history of cardiovascular disease in first
degree relative (<55 years for male relative and <65 years for female relative), or serum HDL
cholesterol <40 mg/dL. It high HDL (>60 mg/dL) subtract one risk factor.
f Atherosclerotic cardiovascular disease (ASCVD) includes peripheral artery disease, symptomatic
carotid artery disease, and abdominal aortic aneurysm.
Calculation of 10 year risk of CHD requires tables which may be found in the JAMA
2001 ;285:2486 or the NHLBI website: http://www.nhlbi.nih.gov/guidelines/cholesterol/index.htm
28
A Pocket Guide to Adult HIV/AIDS Treatment
February, 2006
e
Adult ART Table 10.
Drug Therapy for Hyperlipidemia
(Recommendations of the ACTG [Dube MP et al, CID 2000; 31:1216])
Lipid Problem
Preferred
Alternative
Comment
Isolated high LDL
Statin*
Fibratef
Start low doses and
titrate up; with Pls
watch for myopathy
High cholesterol and
triglycerides
Statin* or fibratef
Start one and
add other
Combination may
increase risk of
myopathy
Isolated high
triglycerides
Fibratef
Statin*
Combination may
increase risk of
myopathy
NOTE:
Optimal management of hyperlipidemia should begin with specific risk factor reduction
interventions such as: low-fat diet; regular exercise; moderation of alcohol intake; smoking
cessation, blood pressure control, and diabetes control (where applicable). The likelihood of
success with drug therapy for hyperlipidemia is substantially reduced in the absence of such
interventions.
* Statin: Pravastatin 20 mg/day (max. 40 mg/day), fluvastatin 20-40 mg/day, or atorvastatin
10 mg/day. Use particular caution when giving LPV/r or NFV with Atorvastatin; also
see Table 5. Drug Interactions: Contraindicated Combinations.
f Fibrate: Gemfibrozil 600 mg bid > 30 minutes before meal or Fenofibrate tablets (e.g. Tricor)
160 mg qd Micronized fenofibrate (capsules) 67mg qd to start, max. dose 201 mg qd
U.S. Department of Health and Human Services
29
a
Pregnancy and HIV
Antiretroviral Therapy in Pregnancy
Continually updated recommendations:
US Department of Health and Human Services. Public Health
Service Task Force Recommendations for Use of Antiretroviral
Drugs in Pregnant HIV-1-Infected Women for Maternal Health and
Interventions to Reduce Perinatal HIV Transmission in the U.S.
November 17, 2005. Available at: http://aidsinfo.nih.gov.
Recommendation for antiretroviral drugs in pregnancy:
All pregnant women with HIV infection should be treated.
Goal of therapy:
VL < 1000 c/mL
Regimen:
See Pregnancy Table 1
Pregnancy Table 1.
Preferred Antiretroviral Agents
NRTI Class
• Preferred: AZT/3TC
• Alternates: ddl, FTC, d4T, ABC
• Insufficient data: TDF
• Not recommended: ddC
NNRTI Class
• Preferred: NVP (if baseline CD4 is < 250/mm3)
• Not recommended: EFV and DLV
PI Class
• Recommended: NFV (1250 mg bid), SQV/r (1000/100 mg bid)
• Alternatives: IDV, LPV/r, RTV
• Insufficient data: APV, FPV, ATV, TPV
Entry Inhibitor Class
• Insufficient data: ENF
30
A Pocket Guide to Adult HIV/AIDS Treatment
February, 2006
Pregnancy Table 2.
Antiretroviral Agents: Pharmacokinetic and Toxicity Data*
Agent
FDA cat.**
Experience in Pregnancy
Nucleoside/nucleotide reverse transcriptase inhibitors
ABC
C
ddl
B
FTC
B
No studies
3TC
C
Well tolerated; usual pharmacokinetics
d4T
C
Well tolerated; usual pharmacokinetics; concern for lactic acidosis;
TDF
B
No studies; animal studies show bone abnormalties
ddC
C
No studies; teratogenic in animals
ZDV
C
Well tolerated; preferred agent
No studies; concern for hypersensitivity
Well tolerated; usual pharmacokinetics; concern for lactic acidosis;
avoid ddl + d4T
avoid ddl + d4T
Nonmucleoside reverse transcriptase inhibitor
DLV
c
No studies
EFV
D
Teratogenic; 4/142 birth defects; avoid in 1st trimester
NFV
C
Well tolerated; contraindicated as initial Rx with CD4 > 250; single
dose with labor causes high rates of resistance
Protease inhibitors
APV
C
No studies; oral solution is contraindicated
ATV
B
No studies; theoretical concern for elevated indirect bilirubin
FPV
C
No studies
LPV/r
c
c
NFV
B
Well tolerated; extensive experience; use 1250 mg bid
RTV
B
No studies
SQV
B
Levels ore low: use SQV: RTV 800/100 mg bid or 1000/100 mg bid
TPV
C
No studies
IDV
Low levels and theoretical concern for elevated indirect bilirubin
No studies
* June 23, 2005
** Pregnancy categories: A=Controlled studies show no risk
B=No evidence of risk in humans
C=Risk cannot be excluded
D=Positive evidence of risk
U.S. Department of Health and Human Services
31
♦
Pregnancy Table 3.
Antiretroviral Drugs for Delivery
A. ACTG 076 Protocol (Should be used as part of ART regimen in all
pregnant women, if possible)
Antepartum: AZT 300 bid or 200 tid po, wk 14 until delivery
Intrapartum: AZT IV 2 mg/kg over first hr then 1 mg/kg/hr until delivery
Postpartum: (Infant): AZT syrup 2 mg/kg po q 6h (or 1.5 mg/kg q 6h IV) x 6 wks
B. Regimen for 2nd & 3rd Trimesters
Standard ART, but:
• Include AZT * according to 076 protocol
• Treat based upon maternal clinical/immunologic status but avoid: EFV, HU, AZT & d4T, d4T &
ddl, APV solution
• Previously untreated pregnant women with VL <1000 c/mL and CD4 >350 cells/mm3 may be
treated with AZT monotherapy, AZT + 3TC, or HAART
C. Choices for Untreated Women Presenting In Labor and Their Infants
NVP: 200 mg po onset labor; Infant: single 2 mg/kg po at 48-72 hrs
(
AZT: 600 mg po onset labor and 300 mg po q3h until delivery PLUS 3TC 150 mg po onset labor
and 150 mg po q 12h until delivery; Infant: AZT 4mg/kg po q 12h PLUS 3TC 2mg/kg po q 12h
for 7 days
AZT: 2mg/kg IV bolus then 1 mg/kg/hr IV infusion until delivery; Infant: AZT 2mg/kg po q6h tor
6 wk (ACTG 076 Protocol)
NVP + AZT: NVP:200 mg po onset labor PLUS AZT 2mg/kg IV bolus then 1 mg/kg/hr IV infusion
until delivery; Infant: NVP single 2 mg/kg po at 48-72 hrs PLUS AZT 2mg/kg po q6h tor 6 wk
* Unless unacceptable side effects or toxicity or requires d4T-containing regimen
**AZT & d4T: pharmacologic antagonism; do not use together. APV oral solution (only) is
contraindicated in pregnancy because it contains large quantities of propylene glycol, which
cannot be metabolized in pregnancy. d4T & ddl: concerns about lactic acidosis; use only when
other NRTIs have tailed or caused unacceptable side effects/toxicity (New Engl J Med 1999;
340:1723). EFV, HU: concerns about teratogenicity or birth defects; EFV: avoid in pregnancy.
Drug Information
A listing of antiretroviral drugs with information pertinent to their use in pregnancy may be found
in Public Health Service Task Force Recommendations for Use of Antiretroviral Drugs in
Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal
HIV-1 Transmission in the United States, Table 3.
32
A Pocket Guide to Adult HIV/AIDS Treatment
February, 2006
Pregnancy Table 4.
Pregnancy Issues
Adverse Drug Reactions (ADR)
Generally, pregnant women are at the same risk of ADRs as non-pregnant individuals, but some
ADRs may be more common because of pregnancy-related physiologic changes: anemia (iron &
folate deficiency), nausea & vomiting (esp in 1st trimester), amniotransferase elevation. Pls may
exacerbate pregnancy-related risk of hyperglycemia and NRTIs (especially d4T/ddI) increase risk
of lactic acidosis.
Risk for Perinatal HIV Transmission
Viral load in plasma & genital tract (most significant), primary infection or late stage HIV, low
CD4 count, STDs/other co-infections, pre-term delivery, increasing duration of membrane
rupture, placental disruption, invasive fetal monitoring or assessment, vaginal delivery, and lack
of AZT prophylaxis.
Post-Partum Risk
Breast feeding: not recommended in U.S.
Pregnancy Table 5.
Clinical Scenarios and Management of
Untreated Pregnant Patients Including C-Section
Scenario 1: No prior ART
• Standard lab and clinical care
• HAARTforVL> 1000 c/mL
• Include the 3—part 076 protocol (see Pregnancy Table 3A)
• Consider delay initial therapy until after 1st trimester
Scenario 2: Currently receiving ART
• Continue therapy, but include AZT according to 076 protocol (see Pregnancy Table 3A)
• Option to stop in 1st trimester
Scenario 3: Woman in labor no prior therapy—options are:
• Intrapartum AZT and 6-week course for neonate
• AZT/3TC during labor and 3 weeks for neonate
• Single dose NVP intrapartum and single dose for infant
• Two-dose NVP and intrapartum AZT and 6 weeks AZT for newborn
Scenario 4: Woman has delivered
• Discuss HIV detection and implications
• Offer AZT to infant
• The mother should be evaluated for HIV management
U.S. Department of Health and Human Services
33
Pregnancy Table 6.
Clinical Scenarios and Management of
Treated Pregnant Patients Including C-Section
Time of
Presentation
Recommended Management
• Continue ART with standard monitoring, but:
Early In Pregnancy
(<36 Weeks)
o May consider discontinuation during 1st trimester: all drugs
should be stopped and restarted simultaneously to reduce risk of
resistance
o Include AZT if tolerated; see cautions tor antiretrovirals,
Pregnancy Table 3 footnotes
Late In Pregnancy
(> 36 Weeks)
• Continue antiretroviral therapy including AZT without interruption
during labor and delivery
• VL > 1,000 copies/mL: Counsel that C-section is likely to reduce the
risk of transmission to infant, but counsel about risks and benefits of
all choices
• Initiate ACTG 076 Protocol, Intrapartum in Pregnancy Table 3A
C-Section Planned But
• Rapid progression of labor: vaginal delivery
Presents in Labor or With
Ruptured Membranes
• If long labor anticipated: consider C-section after loading dose of
AZT or give pitocin to expedite delivery
Pregnancy Table 7.
Delivery Procedures and Therapy
Procedure
Therapy
• Schedule for 38 wk
Cesarean Section
• If on ART, IV AZT starting 3 hrs before C-section and continue all
other antiretroviral drugs with the exception of d4T
• Infant: Use ACTG 076 Protocol, Postpartum (infant)
In Pregnancy Table 3A
• It on ART give IV AZT with initiation of labor and continue all other
antiretroviral drugs with the exception of d4T
Vaginal Delivery
• Avoid rupture of membranes, fetal scalp electrodes, forceps delivery,
and vacuum extractor
• Infant: If TREATED mother, use ACTG 076 Protocol, Postpartum
(infant) in Pregnancy Table 3A
If UNTREATED mother, use treatment from Pregnancy Table 3C
which matches maternal regimen
Antiretroviral Pregnancy Registry: www.APRegistry.com
1011 Ashes Dr, Wilmington NC 28405
Telephone: 800-258-4263
Fax: 800-800-1052
34
A Pocket Guide to Adult HIV/AIDS Treatment
February, 2006
Prevention of HIV for Providers in Three Steps
Step 1: Screen Patients for Risk Behaviors
• Behaviors and clinical factors associated with HIV, other STDs, and
IV drug use (every visit)
• STD symptoms: most are asymptomatic (every visit)
• Pregnancy
• Screening tests
Test
Patients
Routine
€
• All patients
• Syphilis serology: RPR or VDRL*
• All women
• Trichomonas wet mount or culture
• All women < 25 years
and sexually active
• Cervical specimen for C. trachomatis
Consider
<
• All men and women not
included above
• Screening for GC and C. trachomatis by
urethral (men) or cervical (women) specimen
or first catch urine for NAAT*
• Anal receptive sex
• Anal swab tor GC culture and, if available,
for C. trachomatis
• Oral receptive sex
• Pharyngeal culture for GC
• Possible pregnancy
• Pregnancy test
* Repeat RPR or VDRL annually. Consider repeating screening tests for N. gonorrhea
and C. trachomatis annually or more frequently if sexually active, if screening
previous test positive, or other high risk
U.S. Department of Health and Human Services
35
Step 2: Behavioral Interventions
• Prevention messages should be provided with each visit
• Communicate factors that influence transmission and risk
reduction; i.e. abstinence, sex with condoms, sex exclusively with
HIV-infected person(s). If sex with persons with unknown or
negative serologic status, stress proper condom use.
• IDU
Stop using drugs
Enter substance abuse treatment
If patient continues to use drugs:
- Never reuse or share needles, water, or drug preparation
equipment
- Use only syringes from reliable sources (pharmacies)
4
- Use new syringe; if not possible-boil or disinfect with bleach
(http://www.cdcnpin.org)
- Use sterile water to prepare drugs; otherwise use tap water
- Use new or disinfected cooker and new cotton
- Clean injection site with new alcohol swab
- Safely dispose of needle
• Per act relative risks of HIV transmission
- Condom vs no condom: 1:20
- Compared to insertive vaginal sex: receptive vaginal sex 2:1,
receptive anal sex 10:1, insertive fellatio 1:10, insertive anal
sex 1.3:1, receptive fellatio 1:5 (STD 2002;29:38)
Note: Risks for condom use and acts are multiplicative;
e.g, for the ratio for anal sex without a condom vs vaginal
insertive sex with a condom is 100:1
• Viral load: each log reduction in viral load reduces probability of
transmission 2.5 fold.
• Non-occupational postexposure prophylaxis: not endorsed by
CDC due to “uncertain effectiveness.”
• HAART recipients: decreases in VL probably reduces but risk
transgression in behavior eliminates this benefit; with structured
treatment interruption, warn patient that viral load increases as
does risk of transmission
36
A Pocket Guide to Adult HIV/AIDS Treatment
February, 2006
►
Step 3: Partner Counseling and Notification
• Laws: Follow local and state laws for reporting sex and
needlesharing partners
• Initial Visit: Ask if all sex and needlesharing partners have been
notified
• Follow-ups: Ask about new sex or needlesharing partners who
have not been notified
• Referrals: All contacts should be referred to the Health
Department; arrange for notification and testing without
identifying source; patients who elect not to notify partners should
be referred to the Health Department to conduct these activities
9
U.S. Department of Health and Human Services
37
GO
00
Opportunistic Infections
o’
o
Adult 01 Table 1.
2001 USPHS/IDSA Guidelines for Prevention of Opportunistic Infections
CD
—H
Q
c
o
Episode
Strongly Recommended
Pathogen
Indication*
First Choice
—h-
o
Primary
c
R carinii
zd
Hx POP unless
immune
reconstitution: see
comment
CD
Q
—+-
3
CD
Z5
CN
+ leucovorin 25 mg/wk or
TMP-SMX 1 DS/d f or
TMP-SMX 1 SS/d f
Dapsone 200 mg +
pyrimethamine 75 mg +
leukovorin 25 mg/wk or
Aerosol pentamidine 300 mg/mo
or
Atovaquone 1500 mg/d or
TMP-SMX 1 DSj 3x /wk
Tuberculosis
ND
O
l0&2°
CD4 % <14, thrush,
hx AIDS defining
illness or FUO
Secondary
GO
Q
Dapsone 50 mg/d +
pyrimethamine 50 mg/wk
CD4 < 200 or
zr
d
Comment
Dapsone 100 mg/d or
Q_
O
Alternatives
See Adult 01 Tables
2 and 3
Immune reconstitution
recommendations:
Discontinue primary & secondary
prophylaxis if CD4 >200 cells/mm3
for > 3 mos
Restart Prophylaxis:
Restart prophylaxis it CD4 decreases
to <200 cells/mm3
TMP- SMX 1 SSf qd or
C
co
1°
O
+ anti-Toxoplasma
IgG and CD4 <100
cells/mm3
Dapsone 50 mg/d +
pyrimethamine 50 mg/wk +
Leucovorin 25 mg/wk or
TMP- SMX 1 DS f qd
CD
Immune reconstitution
recommendations:
Dapsone 200 mg/wk +
pyrimethamine 75 mg/wk +
Leucovorin 25 mg/wk or
Discontinue if CD4 >200 cells/mm3
for > 3 mos
Atovaquone 1500 mg/d ±
pyrimethamine 25 mg/d +
Leucovorin 10 mg/d
CD4 falls to <100-200 cells/mm3
Restart Prophylaxis:
“O
Q
-H-
Toxoplasmosis
3
CD
—t-
ZE
2°
CD
Q
Toxo tx unless
immune
reconstitution: see
comment
Mycobacterium
avium complex
1°
CD4 <50 cells/mm3
Q
D
GO
CD
<
n’
CD
(/)
Pyrimethamine 25-50
mg/d +
Leucovorin 10-25 mg/d
Q
D
ZE
c
3
Sulfadiazine 500-1000
mg qid +
Hx MAC disease
Rifabutin|300 mg/d or
Clarithromycin 500mg
Azithromycin 1200 mg / wk +
Rifabutin^ 300 mg/d
Ethambutol 15 mg/kg/d ±
Rifabutin^ § 300 mg/d
CO
O
+ Pyrimethamine 25 mg/d +
Leucovorin 10 mg/d
Azithromycin 1200
mg/wk
Clarithromycin 500 mg
2°
Clindamycin 300-450 mg q 6-8 hr Immune reconstitution
recommendations:
+ Pyrimethamine 25-50 mg/d +
Leucovorin 10-25 mg/d or
Discontinue it HAART 6-12 mos, CD4
>200 cells/mm3, and asymptomatic
Atovaquone 750 mg q 6-12 hr
Azithromycin 500 mg/d +
Ethambutol 15 mg/kg/d ±
Rifabutin^: 300 mg/d
Restart Prophylaxis:
CD4 falls to <200 cells/mm3
Immune reconstitution
recommendations:
Discontinue if CD4 > 100 cells/mm3
for > 3 mo
Immune reconstitution
recommendations:
Discontinue if CD4 > 100 cells/
mm3 x >6 mo and Rx 12 mo and
asymptomatic
Adult 01 Table 1. - continued
2001 USPHS/IDSA Guidelines for Prevention of Opportunistic Infections
O
Pathogen
Episode
o
n
CD
—H
Q
c
Varicella
1°
CD
Indication*
First Choice
Chickenpox
/shingles exposure
+ susceptible (no
history of disease
and varicella
seronegative)
VZIG 5 vials (6.25 ml)
IM <96 h post exposure
o
c
Cryptococcosis
2°
Hx Cryptococcal
meningitis
Fluconazole 200 mg
po qd
ZE
o
CZ)
zH
CD
Q
—H
3
CD
Z5
CD
Q
Q
NO
O
o
CN
Cytomegalovirus
2°
Prior end-organ
disease
Extra ocular: ganciclovir
5 mg/kg/day IV 5-7
days/wk, valganciclovir
900 mg/d, or foscarnet
90mg/kg IV qd or
cidofovir 5 mg/kg q
2 weeks
Alternatives
Comment
Acyclovir has been removed from 01
prophylaxis guidelines due to lack of
documented efficacy
Amphotericin B 0.6-1.0 mg/kg iv
qw-tiw or
Immune reconstitution
recommendations:
itraconazole 200 mg capsule
po qd
Discontinue it CD4 > 100 X 6 mo and
completed initial Rx and asymptomatic
Cidofovir 5 mg/kg IV qow with
probenecid 2 grams po 3 hours
before the dose followed by 1
gram po 2 hours after the dose,
and 1 gram po 8 hours after the
dose (total of 4 grams) or
For retinitis: ganciclovir
Fomivirsen 1 vial (330/jg) injected
sustained release implant into the vitreous, then repeated
q 6-9 months plus
every 2-4 wks H or
valganciclovir 900mg/d
Valganciclovir 900 mg po qd
or ganciclovir or
foscarnet (above doses)
Immune reconstitution
recommendations:
Discontinue it CD4 > 100-150 X 6
mo + no active disease + negative
ophthal exam
Generally Recommended
Immune reconstitution:
C
co
S. pneumoniae
1°
All Patients with CD4
>200
Pneumovax
None
CD4 <200
O
CD
"O
Q
—5-
Hepatitis B
1°
Susceptible- (anti-HBc
HBV vaccine series
negative)
3
CD
ZJ
—t-
Q
Z5
ZE
c
3
Q
D
co
CD
—
Influenza
1°
All patients
Influenza vaccine
Amantadine 100 mg bid
Oseltamivir 75 mg qd
Hepatitis A
1°
Susceptible- (antiHAV neg) and antiHCV positive
Hepatitis A vaccine series None
* Indication is separately defined for:
1° = Primary: No prior infection with this pathogen
2° = Secondary: Prior infection with this pathogen
j- SS= Single strength tablet, DS=double strength tablet
Dose adjusted for concurrent PI/NNRTI
§ Rifabutin reduces levels of clarithromycin by 50% (consider azithromycin if RBT is used)
n’
CD
cn
None
Rimantidine 100 mg bid
zc
CD
Q
Consider reimmunization if CD4
increases to >200 and initial
immunization was given when
H Added Rx needed to protect the contralateral eye and other organ systems
Tuberculosis and HIV
Latent TB and HIV Co-infection Candidates For Testing
• All HIV-infected patients without prior positive PPD test upon entry
into HIV care
• Repeat testing annually for HIV-infected patients at risk of acquiring
TB who have no prior positive tests
• All HIV-infected patients with prior negative skin test who are
discovered to be contacts of pulmonary cases
Indications For Treatment of Latent Tuberculosis Infection
(MMWR 2000;49 RR-6)
• Positive PPD (> 5 mm induration) plus no prior completed
prophylaxis or treatment for TB disease
• Recent contact with TB case (Recent contacts who are initially TST
negative should have TST repeated 12 weeks after last exposure to
TB case; those placed on prophylaxis should be discontinued if PPD
negative at 12 weeks)
• History of inadequately treated TB that healed
Patients meeting skin test positivity criteria should be
evaluated to rule out active TB disease before initiating
treatment
42
A Pocket Guide to Adult HIV/AIDS Treatment
February, 2006
e
Adult 01 Table 2.
Recommended Drug Regimens for Treatment of Latent TB in HIV Co-infected Adults
C
GO
U
Regimen
Adult Dosage (max)
INH daily for 9 mos
300 mg qd + pyridoxine 50
mg qd
INH may be administered
270 doses within 9 mos (up to concurrently with NRTIs, Pls, or
12 mos with interruptions)
NNRTIs; contact with provider
monthly
INH twice-weekly tor 9 mos
900 mg + pyridoxine 100
mg 2x/wk
76 doses within 9 mos (up to
12 mos with interruptions)
RIF 10 mg/kg (600 mg) RBT
is alternative if patient is
receiving HAART*
120 doses within 6 mos
Criteria for Completion
Comments
Preferred Regimens
CD
“O
Q
—L
3
All patients
CD
Z5
—t-
x
CD
Q
Q
Alternative Regimen
D
X
c
Contacts of isoniazid-resistant,
RIF daily for 4 mosf
rifampin-susceptible TB
3
Q
Z5
CO
O
—s
n’
CD
cn
8 week regimen: PZA + RIF
No longer recommended due
to excessive hepatotoxicity
including 7 deaths (not in
persons known to have
HIV co-infection) MMWR
2003;52:735
Abbreviations: INH = isoniazid, RIF = rifampin, RBT= rifabutin, PZA = pyrazinamide, DOT =
directly observed therapy
4^
GO
* See Drug Table 7 tor RBT & PI/NNRTI dose adjustments
f May not be used with patients taking PI/NNRTI with the exception of RTV/SQV, RTV, or EFV
Acceptable alternative for
HIV-infected adults; DOT
must be used with twice
weekly dosing
9
Adult 01 Table 3.
Monitoring of Patients on Latent TB Prophylaxis
Latent TB Regimen
Monitoring
• Initial clinical evaluation
All patients
• Educate patients about side effects associated with LTBI treatment
• Advise to stop treatment and promptly seek medical evaluation if
these occur
• Contact with patient monthly; LFTs at baseline and 3 mo * and
with hepatitis sx
INH
• Include careful questioning about side effects and a brief physical
examination checking for evidence of hepatitis or other side
effects
Rifampin or
rifabutin + PZA
• Clinic visits at 2,4,6, & 8 wks; CBC & LFTs at baseline, 2,4, & 6
wks or with symptoms^
• Include careful questioning about side effects and a brief physical
examination checking for evidence of hepatitis or other side
effects
* INH: D/C if ALT 5X ULN or symptoms plus ALT > 3X ULN
j- Rifampin/rifabutin + PZA: D/C it ALT > 5X ULN or if symptoms plus any abnormal LFTs
44
A Pocket Guide to Adult HIV/AIDS Treatment
February, 2006
Special Considerations for TB Treatment with HIV Co-infection
Treatment of Tuberculosis Disease
American Thoracic Society/Centers for Disease Control and
Prevention/lnfectious Diseases Society of America: Treatment
of Tuberculosis Am J Respir Crit Care Med 2003; 167(4):603
Special Treatment Notes
PREGNANCY: INH regimens preferred for pregnant women.
Some experts would use RIF plus PZA as alternate regimen in
HIV-infected pregnant women. PZA should be avoided during
first trimester.
MDR-TB Exposure
Expert consultation is recommended for persons who are likely
to be infected with INH and RIF (multidrug) resistant-TB and at
high risk of reactivation.
ART/TB Treatment Interactions
* Rifabutin should not be used with hard-gel saquinavir (as sole PI)
or delavirdine.
Rifampin/Rifabutin
See Drug Table 7
Identical for General Population Except:
• CD4 <100/mm3: Continuation phase should be daily or 3x/week; once weekly
rifapentine regimen should not be used
• Positive cultures at 2 months: "Strongly consider" 7 month continuation phase
(total 9 mo)
• In absence of prior HIV therapy and CD4 < 350/mm3: delay antiretroviral drugs
for 4-8 weeks
• RIF may be used with 2 NRTIs + EFV, RTV + SQV (Invirase or Fortovase) or
AZT/3TC/ABC
• Rifabutin combined with other Pls and NNRTI requires dose adjustment of both;
See: www.cdc.gov/nchstp/tb/orwww.medscape.com/updates/quickguide
• When starting NNRTI or PI in patient receiving RIF, substitute rifabutin 2 weeks prior
to NNRTI or PI to give a 2 week washout period for RIF
• Paradoxical reaction: Frequency is 7-36%; clinical features: high fever, increased
adenopathy, CNS lesions, pulmonary infiltrates and pleural effusions; treatment:
symptomatic; if severe give prednisone 1 mg/kg and reduce dose at 1-2 weeks
U.S. Department of Health and Human Services
45
Adult 01 Table 4.
Treatment of Drug-Susceptible TB
Drugs
INH
RIF
PZA
EMB
Phase 1 (8 weeks)
Phase 2*: regimen, doses,
minimal duration
8 weeks
• INH/RIF 7 d/wk for 18 weeks (126 doses) or
• 7 d/wk for 8 wks (56 doses) or
• INH/RIF 5 d/wk for 18 weeks (90 doses) or
• 5 d/wk for 8 wks (40 doses)
• INH/RIF 2x/wk for 18 weeks ( 36 doses)
INH
RIF
PZA
2 wk/6 week
7 d/wk, for 2 wks (14 doses), then INH/RIF 2x/wk for 18 weeks (36 doses)
2x/week for 6 wks (12 doses)
EMB
INH
RIF
8 weeks
PZA
3 x/week for 8 weeks (24 doses)
INH/RIF 3x/week for 18 weeks (54 doses)
EMB
INH
8 weeks
RIF
♦ 7 d/week for 8 wks (56 doses)
EMB
• 5 d/week for 8 wks (40 doses)
• INH/RIF 7 d/week for 31 weeks (217 doses)
or
• INH/RIF 5 d/wk for 31 weeks (155 doses) or
• INH/RIF 2x/wktor 31 weeks (62 doses)
INH = isoniazide, RIF = rifampin, RPT = rifapentine, PZA = pyrazinamide, EMB = ethambutol
* Patients with cavitation at baseline and positive cultures at 2 months should receive 31 week
continuation phase for total of 9 months
46
A Pocket Guide to Adult HIV/AIDS Treatment
February, 2006
Adult 01 Table 5.
Doses of Antituberculosis Drugs - First-line Drugs
Daily
l/wk
2x/wk
3x/wk
INH
5 mg/kg (300)*
15 mg/kg (900)
15 mg/kg (900)
15 mg/kg (900)
RIF
10 mg/kg (600)
10 mg/kg (600)
10 mg/kg (600)
Drug
RPT
10 mg/kg (600)
PZA (wt)
40-55 kg
1 gm
2.0 gm
1.5 gm
56-75 kg
1.5 gm
3.0 gm
2.5 gm
76-90 kg
2.0 gm
4.0 gm
3.0 gm
40-55 kg
800 mg
2000 mg
1200 mg
56-75 kg
1200 mg
2800 mg
2000 mg
76-90 kg
1600 mg
4000 mg
2400 mg
EMB (wt)
*
Dose in mg/kg and (usual dose in mg)
U.S. Department of Health and Human Services
47
Adult 01 Table 6.
Management of Opportunistic Infections
(MMWR 2004; 53 RR15)
Bartonella*. Treat > 3 mo
• Preferred: erythromycin 500 mg qid po or IV or doxycycline 100 mg bid po or IV x > 3 mo
• Alternative: azithromycin 600 mg/d po or clarithromycin 500 mg bid po x > 3 mo
• Note: If relapse: treat lifelong; CNS: Use IV or po doxycycline
Candida Thrush: Treat 7-14 days
• Preferred: clotrimazole troches 10 mg po 5x/d or Nystatin susp 5 ml qid or
pastilles 4-5 x/d or fluconazole 100 mg po/d; all 7-14 days
• Fluconazole-refractory: Itraconazole oral solution > 200 mg/d po or
amphotericin B 0.3 mg/kg/d IV
• Recurrent disease: Consider chronic fluconazole or itraconazole
Candida Esophagitis: Treat 14-21 days
• Preferred: Fluconazole 100 mg/d (up to 400 mg/d) po or IV x 14-21 days
• Alternative: Itraconazole oral soln 200 mg/d, capsotungin 70 mg IV x 1, then 50 mg/d
x 7 days or amphotericin B 0.3-0.7 mg/kg/d or voricomazole 200 mg/d po or IV or
liposomal amphotericin 3-5 mg/kg/d
Candida Vaginitis: Treat 3-7 days
• Preferred: Topical azole (clotrimazole, butoconazole, miconazole, ticonazole, terconazole)
x 3-7 days or topical nystatin or fluconazole 150 mg x 1 day or itraconazole 200 mg bid
x 1 day or 200 mg/d x 3 days
• Recurrent: Daily topical azole
Cryptococcoisis: Treat lifetime unless immune reconstitution
• Acute phase: Amphotericin B 0.7 mg/kg/d IV 4- flucytosine 25 mg/kg qid po x 14 days
• Consolidation phase: Fluconazole 400 mg/d po x 8 weeks
• Chronic maintenance phase: Fluconazole 200 mg/d po until CD4 >
100-200/mm3 x > 6 mo
• Alternative — Acute phase: Amphotericin B 0.7 mg/kg/d x 14 days (without 5FC) or
fluconazole 400-800 mg po or IV qd ± flucytocine 25 mg/kg/ qid po
• Alternative — Consolidation phase: Itraconazole 200 mg bid po
• Alternative — Chronic maintenance phase: Itraconazole 200 mg/d po until CD4 >
100-200/mm3 x > 6 mo
• Note: Drain CSF if OP > 200 ml H2O
Cryptosporidiosis
• Preferred: Symptomatic treatment + HAART
• Alternatives: Nitazoxanide 500 mg po bid or paromomycin 25-35 mg/kg/d in 2-3 doses
48
A Pocket Guide to Adult HIV/AIDS Treatment
February, 2006
Adult 01 Table 6. - continued
Management of Opportunistic Infections
(MMWR 2004; 53 RR 15)
Cytomegalovirus retinitis
• Immediate sight-threatening lesions: Intraocular implant + valganciclovir 900 mg/d po
• Peripheral lesions: Valganciclovir 900 mg bid po x 14-21 days, then 900 mg/d
• Alternative: Ganciclovir 5 mg/kg q 12h IV x 14—21 days, then 5 mg/kg/d or foscarnet 60
mg/kg IV q 8 h x 14-21 days, then 90-120 mg/kg/d single dose x 14 days or cidofovir
5 mg/kg/d weekly x 2 IV or 1 hr x 2 wks, then 5 mg/kg IV every other wk; patient must be
hydrated with > 1 L saline prior to cidofovir and receive probenecid 2 gm 3 hrs prior to
cidofovir and 1 gm at 2 and 8 hrs after or tomivirsen intravitreal infections (relapses only)
• Maintenance therapy:
- Preferred: Valganciclovir 900 mg po qd or foscarnet 90-120 mg/kg/d IV until: inactive
disease, CD4 > 100-150 mm3 x 6 mo and consultation with ophthalmologist
- Implant: Need replacement q 6-8 mo if CD4 < 100-150/mm3
- Alternative: Maintenance ganciclovir, cidofovir
• Immune reconstitution uveitis (IRU): periocular steroids or short course systemic steroids
CMV esophagitis or colitis
• Preferred: Ganciclovir or foscarnet IV x 21-28 days or until symptoms resolve;
valganciclovir po is appropriate if symptoms are not severe
• Maintenance: Not necessary except it there are relapses
CMV pneumonia
• Indication to treat: Histologic evidence of disease and failure to respond to other pathogens
CMV neurologic disease
• Preferred: Ganciclovir + foscarnet IV (above doses) until improvement
• Maintenance: Lifetime
Hepatitis B
• Indication for treatment: HBV:(HbeAg pos or HBV DNA > 105/mL) + (liver disease by
histopathology or ALT > 2x ULN)
• HBV + HAART:
- Preferred: TDF/FTC or TDF/3TC
- Alternative: (3TC or FTC) + adetovir or entecavir
- Preferred eAg pos: Peginterferon x 48 weeks
• HBV without HAART: Adotovir, entecavir or peginterferon
U.S. Department of Health and Human Services
49
Adult 01 Table 6. - continued
Management of Opportunistic Infections
(MMWR 2004; 53 RR 15)
Hepatitis C
• Indications to treat: HCV RNA > 50 lU/mL, liver biopsy showing fibrosis or inflammation,
no contraindications, stable HIV and (?) CD4 > 200/mm3
• Preferred: Peginterferon alfa2a 180ug or peginterferon alfa 2b 1.5 mg/kg, each SC q 9
weekly + ribavirin 400 mg bid po x 48 weeks
Herpes simplex: Moderate or severe mucocutaneous
• Preferred: Acyclovir 5 mg/kg q 8 h IV, then famciclovir 500 mg bid po or valacyclovir 1 gm
bid po or acyclovir 400 mg tid po until lesions heal
• Acyclovir resistant: Foscarnet 120-200 mg/kg/d IV in 2-3 doses or cidofovir 5 mg/kg
weekly until clinical response
Herpes zoster
• Dermatomal: Famciclovir 500 mg tid po or valciclovir 1 gm tid po x 7-10 days
• Extensive cutaneous or visceral: Acyclovir 10 mg/kg q 8 h IV until response
Microsporidiosis
• Preferred: HAART + symptomatic treatment
• Enterocytozoon bieneusi (80% of diarrheal disease due to microsporidia): Fumagillin 60
mg/d po
• Non-enterocytozoon bieneusi (20% of diarrheal disease): Albendazole 400 mg po bid until
CD4 > 200/mm3
• Disseminated disease: Itraconazole 400 mg/d, albendazole 400 mg bid (Brachiola or
Trachipleistophora)
Mycobacterium avium
• Preferred: Clarithromycin 500 mg bid po plus ethambutol 15 mg/kg/d po ± rifabutin 300
mg/d po until treatment > 12 mo 4- asymptomatic + CD4 > 100/mm3 > 6 mo
• Alternative: Azithromycin 500-600 mg/d po in place of clarithromycin
• Alternative "3rd drug": ciprofloxacin 500-750 mg bid po or levofloxacin 500 mg/d po or
amikacin 10-15 mg/kg/d IV
• Immune reconstitution: Moderately severe — NSAIDs; severe or persistent
20-40 mg/d x 4-8 weeks
prednisone
Mycobacterium tuberculosis (see Adult Ol Tables on tuberculosis)
50
A Pocket Guide to Adult HIV/AIDS Treatment
February, 2006
Adult 01 Table 6. - continued
Management of Opportunistic Infections
(MMWR 2004; 53 RR15)
Pneumocystis jiroveci (also known as Pneumocystis carinii)
• Preferred: TMP-SMX 15-20 mg TMP/kg/d IV in 3-4 daily doses or 2 DS tid po x 21 days
• Alternative (IV therapy): Pentamidine 3-4 mg/kg IV infused over 1 hr or dapsone 100
mg/d po + TMP 15 mg/kg/d (3 daily doses) or primaquine 15-30 mg (base)/d po +
clindamycin 600-900 mg q 6-8 h IV or 300-450 mg q 6-8 po or atovaquone 750 mg bid
po (with food)
• PaO? < 70 mm/Hg room air or A-a gradient: Day 1-5 40 mg bid; Day 6-10 40 mg/d;
Day 11-21 20 mg/d
• Maintenance
- Preferred: TMP-SMX 1 DS/d or 1 DS bid po
- Alternative: Dapsone 100 mg/d po or dapsone 50 mg/d + pyrimethamine 50 mg/wk
po + leucovorin 25 mg/wk po or aerosolized pentamidine 300 mg q mo or atovaquone
1500 mg/d po; All until CD4 > 200/mm3 x > 3 mo
Toxoplasmosis
• Preferred: Pyrimethamine 200 mg/d po x 1 then 50 mg/d (<60 kg) or 75 mg/d (> 60
kg) plus sulfadiazine 1000 mg q 6 h po (< 60 kg) or 1500 mg q 6 h po (> 60 kg) plus
leucovorin 10-20 mg/d po (up to 50 mg/d) x > 6 weeks
• Alternative: Pyrimethamine and leucovorin (above doses) plus
1) Clindamycin 600 mg q6 h IV or po or
2) Atovaquone 1500 mg bid po or
3) Azithromycin 900-1200 mg/d po
4) TMP-SMX 5 mg/kg TMP bid IV or atovaquone 1.5 gm bid po (with meals)
• Maintenance
- Preferred: Sulfadiazine 500-1000 mg qid po + leucovorin 10-25 mg/d
- Alternative:
1) Clindamycin 300-400 mg q 6-8 h plus pyrimethamine 25-50 mg/d +
leucovorin 10-25 mg/d
- 2) Atovaquone 750 mg q 6-12 h ± pyrimethamine 25 mg/d + leucovorin 10 mg/d
Continue until CD4 > 100/mm3, continue maintenance until CD4 >200/mm3 x > 6 months
^"CPHE - SOCHAiiA^A
Koram-tngala
Bangalore -
V
U.S. Department of Health and Human Services
51
Occupational HIV Posfexposure Prophylaxis (PEP)
Considerations in Occupational Exposure to HIV
PEP Guidelines
Updated US Public Health Service Guidelines for the Management
of Occupational Exposures to HIV and Recommendations for
Postexposure Prophylaxis. MMWR Recommendations and Reports.
September 30, 2005; 54 (RR-9): 1. Available at http://www.cdc.gov/mmwr/
Risk of HIV transmission
The risk of transmission continues to be related to exposure to
infectious material and the source of that material. Exposure is
defined as either percutaneous injury with a contaminated sharp
object or exposure of mucous membranes or nonintact skin (skin
that is abraded, chapped or with dermatitis) to infectious material.
The current understanding of exposure contingencies is summarized
in Occupational Postexposure Table 1.
The risk of HIV transmission (without prophylaxis) is 0.3 % (3/1,000)
from percutaneous injury and 0.09% (9/10,000) from mucocutaneous
exposure. The following are associated with increased risk of
transmission: device (needle) with visible blood, needle placed in
artery or vein, deep injury, large volume, high viral load.
Efficacy of PEP
The efficacy of AZT monotherapy prophylaxis is estimated to be
80% in retrospective case control series. To date there have been
only six recorded prophylaxis failures associated with occupational
exposures in the US.
52
A Pocket Guide to Adult HIV/AIDS Treatment
February, 2006
Occupational Postexposure Table 1.
Exposure Contingencies
Explanation
Exposure Element
Material
Blood or bloody body fluid
Established risk of transmission with
occupational exposure
CSF; pleural pericardial, peritoneal, amniotic
and vaginal fluids; semen
Theoretical risk of transmission
Urine, stool, nasal secretions, sputum, tears,
vomitus (if not bloody)
Not potentially infectious
Type of Exposure
Percutaneous
Not severe
Solid needle or superficial injury, etc.
More severe
Large bore hollow needle, deep injury, or
visible blood on needle/device
Mucocutaneous
Small volume
Few drops
Large volume
Major splash
Source of Infectiousness
HIV positive
Low risk
HIV positive and asymptomatic,
viral load < 1500 c/mL
High risk
HIV positive and symptomatic, AIDS, acute
retroviral syndrome, or known high viral load
Source unknown
For example, deceased source person with
no samples available for HIV testing
U.S. Department of Health and Human Services
53
Occupational Postexposure Table 2.
Indications for HIV PEP
Type of Exposure
Source
Percutaneous
Not Severe*
More Severe*
Muscocutaneous
Small Volume*
Large Volume*
HIV Positive
Low Risk*-)-
2 drugs
> 3 drugs
2 drugs
2 drugs
High Risk*f
3 drugs
> 3 drugs
> 3 drugs
> 3 drugs
None or
2 drugsT
None or
2 drugs^:
Source Unknown
None or
2 drugsT
None or
2 drugs^:
* See Occupational Postexposure Table 1 for explanation
f HIV resistance is a concern get expert consultation
PEP is optional based on discussion of rislcbenefit
54
A Pocket Guide to Adult HIV/AIDS Treatment
February, 2006
Management of Health Care Workers (HCWs)
With Potential HIV Exposure
The importance of rapid action in the event of a potential exposure
cannot be over-emphasized since PEP, if warranted, needs to be
initiated within hours.
Assessment
Documentation of the nature and degree of the exposure and the
HIV status of the source patient need to be identified. Rapid testing
of previously untested source patients is valuable in determining the
need for PEP. The need for PEP and potential number of drugs may
be determined by using Table 2.
Initiation of HIV PEP
Initiate PEP as soon as possible, preferably within hours after
exposure, and continue for 4 weeks. From a practical point of
view, PEP should be initiated if the source person is HIV-infected
or thought to be infected, especially if the results of HIV serology
likely to be delayed. PEP may be discontinued if the source is '
determined to be uninfected. The current recommended PEP
regimens are listed in Table 3.
The following drugs are not recommended because of the
potential for adverse events: abacavir, delavirdine, zalcitabine,
didanosine with stavudine, and nevirapine. During pregnancy
efavirenz should be avoided because of the risk of teratogenic
effects and the combination didanosine with stavudine because
of toxicity concerns. Additionally, indinavir should be avoided
because of side effects in the newborn.
Health care workers taking PEP report adverse reactions at the
rate of 17-47 %. The most frequently reported reactions were
nausea — 27 %, malaise and fatigue — 23 %. Of 503 HCW who
prematurely (<28 days) stopped PEP, 24% did so because of
adverse reactions. Regardless, the HCW should be advised on the
need to complete the 4-week course of PEP.
U.S. Department of Health and Human Services
55
Management of Health Care Workers (HCWs)
With Potential HIV Exposure - continued
Expert Consultation
Consultation with an expert in HIV exposures and PEP is
encouraged especially in the following instances:
• Initiation of PEP is delayed to > 24-36 hrs post-exposure
• The status of the source patient is unknown
• The HCW is currently pregnant or is breastfeeding
• The source patient is known to have a resistant HIV strain
• There are toxicity problems in the initiated regimen
Monitoring
• Re-evaluate HCW at 72 hours, especially if additional
information becomes available about the status of the source
• HIV serology testing should be conducted at baseline, and then
at 6 weeks, 12 weeks, and 6 months after exposure; if the
HCW experiences hepatitis C seroconversion after exposure,
HIV serology should be conducted 12 months after exposure
• Tests for HIV (P24 Ag or HIV PCR) in HCW are not routinely
recommended due to high rates of false positives; these tests
should be done if there are symptoms compatible with the
acute retroviral syndrome
• Toxicity monitoring
Laboratory: CBC, liver and renal function tests at baseline and
at 2 weeks; HCWs given indinavir should also have urinanalysis
monitoring for crystalluria and hematuria
Self Report: HCWs should be advised to report rash, fever, back
or abdominal pain, dysuria, blood in urine, and symptoms of
hyperglycemia; they should also be counseled on the possibility
of drug interactions and advised to report these should they occur
Prevention Warnings
HCW with exposure to HIV should be counseled on measures to
prevent secondary transmission including: avoidance of blood or
tissue donations; pregnancy and breastfeeding, especially in the
first 6—12 weeks; and the use of condoms for sexual transmission.
Seroconversions
Report any Seroconversion to your local Health Department.
56 A Pocket Guide to Adult HIV/AIDS Treatment
February, 2006
Occupational Postexposure Table 3.
Recommended Regimens
2 Drug Regimen
Lamivudine or emtricitabine plus
zidovudine, stavudine or
tenofovir
3 Drug Regimen
Two nucleosides plus
Preferred: lopinavir/ritonavir
Alternates: atazanavir, fosamprenavir, ritonavir boosted
indinavir, ritonavir boosted saquinavir or nelfinavir*
* Consider EFV if PI resistance in source and HCW has no pregnancy risk
Resources for Consultation
The following resources are available for consultation regarding HIV PEP:
• PEPline: http://www.ucsf.edu/hivcntr
Telephone: 1-888-448-4911
• HIV Pregnancy registry: http://www.apregistry.com/index.htm
Telephone: 1-800-258-4263, email —registry@nc.crl.com
• FDA (for reporting unusual or severe toxicity to antiretroviral
agents) at http://www.fda.gov/medwatch
Telephone: 1-800-332-1088
• Report HIV infections in HCP and failures of PEP to local
Health Department.
• HIV/A1DS Treatment Information Service: http://aidsinfo.nih.gov
U.S. Department of Health and Human Services
57
A Pocket Guide to Adult HIV/AIDS Treatment
provides treatment information in table format
for easy reference in clinical settings:
Drug Information
Pages 2-16
Adult ART Tables
Pages 17-29
Pregnancy Tables
Pages 30-34
Prevention for Providers
Pages 35-37
Adult Ol Tables
Pages 38-51
Occupational PEP
Pages 52-58
Recommendations for HIV care and treatment
are complex and change rapidly. In addition
to the Pocket Guide and A Guide to Primary
Care of People with HIV/AIDS, which the Pocket
Guide supports, consult the following resources
provided by the U.S. Department of Health
and Human Services for frequently updated
HIV treatment information:
AIDSInfo: http://www.aidsinfo.nih.gov
National HIV/AIDS Clinical Consultation Center Warmline:
1-800-933-3413
(toll free in the U.S.)
St^VtCBs.
U.S. Department of Health and Human Services
<SH
Health Resources and Services Administration
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