Transcript Barbaro2006[1]

Two Decades of HAART
Past, Present, and Future
Overview
 The Past
– Brief History of HAART
 The Present
– Considerations for Current Regimens
– Role of the CD4 and health
– Issues surrounding transmitted resistance
 The Future
– Prevention is key
Approved Antiretrovirals
Between ’87 and ’95, 5 antiretrovials were launched.
Hivid
Retrovir
Videx
Epivir
Zerit
’87 ’88 ’89 ’90 ’91 ’92 ’93 ’94 ’95 ’96 ’97 ’98 ’99 ‘00 ’01 ‘02 ‘03 ‘04‘05
RTI
NNRTI
PI
Approved Antiretrovirals
Between ’87 and ’95, 4 antiretrovials were launched.
Since ’95, 20 new products have been introduced.
Combivir
Hivid
Retrovir
Videx
Epivir
Zerit
Rescriptor
Truvada
Viread
Ziagen
Viramune
Sustiva Trizivir
Epzicom
Emtriva
Aptivus
’87 ’88 ’89 ’90 ’91 ’92 ’93 ’94 ’95 ’96 ’97 ’98 ’99 ‘00 ’01 ‘02 ‘03 ‘04‘05
RTI
NNRTI
PI
Invirase
Viracept Kaletra
Fortovase Agenerase
Reyataz
Fuzeon
Norvir
Lexiva
Crixivan
FDA-Approved Drugs for HIV Therapy:
2006
PIs
NRTIs
Abacavir (ABC)
Didanosine (ddI)
Emtricitabine (FTC)
Lamivudine (3TC)
Stavudine (d4T)
Tenofovir (TDF)
Zalcitabine (ddC)
Zidovudine (ZDV)
3TC/ABC
3TC/ABC/ZDV
3TC/ZDV
FTC/TDF
Amprenavir (APV)
Atazanavir (ATV)
Darunavir (DRV)
Fosamprenavir (FPV)
Indinavir (IDV)
Lopinavir/ritonavir (LPV/RTV)
Nelfinavir (NFV)
Ritonavir (RTV)
Saquinavir (SQV hgc)
Tipranavir (TPV)
Fusion Inhibitors (FIs)
Enfuvirtide (ENF)
NNRTIs
Delavirdine (DLV)
Efavirenz (EFV)
Nevirapine (NVP)
Atripla (ATP)
Multiple Class
EFV/FTC/TDF
Improving Outcomes With Evolving
Antiretroviral Regimens
CD4+
CD4+ RNA
RNA
Monotherapy
Monotherapy
Dual-NRTI combinations
HAART
300
200
100
0
0
–1
–2
–3
85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 00 01 02 03 04 05 06
Acknowledgement: Cohen C. J.
Years
Change in HIV-1 RNA From Baseline
(log10 copies/mL)
Change in CD4+ Cell Count From Baseline
(cells/mm3)
400
Improving Outcomes With Evolving
Antiretroviral Regimens
CD4+
CD4+ RNA
RNA
Monotherapy
Monotherapy
Dual-NRTI
Dual-NRTIcombinations
combinations
HAART
300
200
100
0
0
–1
–2
–3
85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 00 01 02 03 04 05 06
Acknowledgement: Cohen C. J.
Years
Change in HIV-1 RNA From Baseline
(log10 copies/mL)
Change in CD4+ Cell Count From Baseline
(cells/mm3)
400
Improving Outcomes With Evolving
Antiretroviral Regimens
CD4+
CD4+ RNA
RNA
Monotherapy
Monotherapy
Dual-NRTI
Dual-NRTIcombinations
combinations
HAART
HAART
300
200
100
0
0
–1
–2
–3
85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 00 01 02 03 04 05 06
Acknowledgement: Cohen C. J.
Years
Change in HIV-1 RNA From Baseline
(log10 copies/mL)
Change in CD4+ Cell Count From Baseline
(cells/mm3)
400
The Art of HAART
 Pioneering AIDS
researcher Dr. David D.
Ho, whose novel use of a
"cocktail" of protease
inhibitors and other
antiviral drugs in the
earliest stages of infection
has shown remarkable
promise in beating back
the AIDS virus, is TIME
Magazine's 1996 Man of
the Year
Dr. David Ho
Man of the Year, Dec 30, 1996
Antiretroviral Activity:
An Historical Perspective
HIV RNA change (log10 c/mL)
1987: AZT
Monotherapy
1994:
Two-Drug Therapy
1997:
HAART
0
0
0
-0.5
-0.5
-0.5
-1
-1
-1
-1.5
-1.5
-1.5
-2
-2
-2
-2.5
-2.5
-2.5
-3
24-week response
-3
24-week response
Fischl, NEJM, 1987
Katzenstein, NEJM, 1996
Eron, NEJM, 1995;
Hammer, NEJM, 1996
-3
24-week response
Gulick, NEJM, 1997;
Cameron, Lancet, 1998
Limitations of Early PIs
SQV
IDV
RTV
NFV
APV
 Poor bioavailability
 Complex regimens
 High pill burden
 Unpredictable efficacy
 Hard to manage toxicity
 Signature resistance common
Boosting PI Levels With RTV
Plasma Concentration
PI toxicity
threshold
boosted PI
PI level required
to overcome
“resistant” virus
PI
Time
Moyle G, et al. Drugs. 1996;51:701-712.
PI level required to
overcome WT virus
Advantages of Boosted PIs
SQV/RTV
 Bioavailability improved by
RTV boosting
LPV/RTV
 Less complex regimens
ATV/RTV
FPV/RTV
 Lower pill burden
 More predictable efficacy
 Negligible resistance in naive
patients
 Greater activity against
resistant virus
 Less toxicity?
Recommended Regimens for HIV+
Treatment-naïve Patients: DHHS May 2006
Preferred regimens
Lopinavir/ritonavir +
(3TC or FTC) + ZDV
400/100 mg (2 tablets) BID
or 800/200 mg (4 tablets) QD
Efavirenz* +
(3TC or FTC) + (ZDV or TDF)
Alternative regimens
PI-based
NNRTI-based
Atazanavir + (3TC or FTC) + (ZDV or d4T or ABC or ddI)
Efavirenz* + (3TC or FTC) +
(ABC or ddI or d4T)
or (TDF + RTV 100 mg/d)
Nevirapine‡ + (3TC or FTC) +
Fosamprenavir + (3TC or FTC) + (ZDV or d4T or ABC or TDF or ddI)
(ZDV or d4T or ddI or ABC or TDF)
Fosamprenavir/RTV† + (3TC or FTC) + (ZDV or d4T or ABC
or TDF or ddI)
Triple NRTI**
†
Indinavir/RTV + (3TC or FTC) + (ZDV or d4T or ABC or TDF or ddI)
Abacavir + 3TC + ZDV
Lopinavir/ritonavir + (3TC or FTC) + (d4T or ABC or TDF or ddI)
(only when a preferred or an
Nelfinavir + (3TC or FTC) + (ZDV or d4T or ABC or TDF or ddI)
alternative NNRTI-or PI-based regimen
§
†
cannot or should not be used)
Saquinavir /RTV + (3TC or FTC) + (ZDV or d4T or ABC or TDF or ddI)
*Not recommended for use in 1st trimester, or in women with high pregnancy potential. †Low-dose: 100 to 400 mg/day as a pharmacologic booster.
‡Ritonavir 100 mg/day recommended when tenofovir DF is used with atazanavir. §Adult females and males with CD4 cell counts <250 and <400
cells/mm3, respectively.¶Soft-gel or hard-gel capsules, or tablets.
Available at: http://aidsinfo.nih.gov/guidelines
May 2006
An Issue of the Immune
System
The Role of CD4
Immunosuppression increases risk of
non-HIV related death (D:A:D Study)

Cohort study of >23,000 patients
in Europe, Australia, and the USA
RR of death according to
immunofunction and specific cause
100
Overall
HIV

1,248 (5.3%) deaths 2000–2004
(1.6/100 person-years)
Malignancy
Heart
Liver
– Of these, 82% on ART
RR
10

Both HIV and non-HIV related
mortality were associated with
CD4+ cell count depletion,
suggesting role for
immunosuppression in causes of
death typically considered not
HIV-related*
*Liver-related: Chronic viral hepatitis, liver failure
(other); Malignancy-related: Malignancy, non-AIDS
hepatitis; Heart-related: MI, other CVD, other heart
disease
Weber R, et al. 12th CROI, Boston 2005, #595
1.0
<50
0.1
50–99
100–
199
200–
349
CD4 Cells/mm3
350–
499
>500
Opportunistic Infections
Oral Thrush – CD4 <200
Mycobacterium avium complex
(MAC) spleen - CD4 <50
Kaposi’s Sarcoma – Any CD4
So, it’s important to get that CD4 up!
600
Mean change from
baseline in CD4 count
Cells/mm 3
500
+529
cells/mm3
400
300
All Patients
Baseline <50 (n=17)
Baseline 50-200 (n=19)
Baseline 200-350 (n=19)
Baseline 350-500 (n=19)
Baseline >500 (n=26)
200
100
0
0
24
48
72
96
120 144 168 192 216 240 264 288 312
Week
Gulick RM. et al., HIV7, Glasgow, UK, Nov. 2004; #P28
Study 720
An Issue of Resistance
Prevalence and Risk of
Transmitted ARV Resistance
Evolution of HIV Drug Resistance
 Factors associated with development of resistance:
– Generation of genetic variation in the virus
– Selection of drug resistant variants during therapy
– Extent of viral replication during therapy
– Ease of acquiring a particular mutation
– Effect of mutation on drug susceptibility and viral fitness
 Resistant HIV strain can also be transmitted between
individuals
hivinsite.ucsf.edu
Serosorting of sexual partners
Serosorting implies that partners with
similar HIV infection status seek each
other as sexual partners to decrease
HIV transmission risk
600
500
– Serosorting does not occur when HIV
infection status is unknown, and may
lead to increases in unsafe sex


100
0
1998 1999 2000 2001 2002 2003 2004
Widely reported in diverse populations
(MSM, heterosexuals) and geographic
areas (San Francisco, Atlanta, South
America, Europe, Australia)1-9
May be facilitated by internet
communications in some areas4
San Francisco: Stable to decreasing HIV
incidence rates but increased incidence
of syphilis and rectal gonorrhea among
MSM1
300
200
Early syphilis
Male rectal gonorrhea
6
HIV incidence1
5
Percent

Early syphilis and male rectal
gonorrhea1
400
Cases

4
3
2
1
0
1998 1999 2000 2001 2002 2003 2004
Anon testing site
Sex trans infection site
1. Truong H-H, et al. XVI IAC, Toronto 2006, #MOAC0105; 2. Xia Q, et al. ibid, #MOPE0476; 3. Melo L, et al. ibid,
#MOPE0493; 4. Berry M, et al. ibid, #TUPE0471; 5. Zablotska I, et al. ibid, #TUPE0760; 6. Cowan S, et al. ibid,
#WEPDC03; 7. Elford J, et al. ibid, #WEPDC05; 8. Lama J, et al. ibid, #WEPE0298; 9. Kurtz S, et al. ibid, #THPE0475
CDC survey: Drug-resistant HIV among newly
diagnosed patients
Prevalence of Drug Resistance (%)
1998
(n=257)
1999 (n=239)
2000 (n=299)
2003-2004
(n=787)
5.5
8.8
10.7
14.5
NRTI
5.1
7.1
7.7
7.1
NNRTI
0.4
2.1
1.7
8.4
PI
0
0.8
3.0
2.8
>2 drug class
0
1.3
1.3
3.1
Resistance to:
Any drug
Bennett D, et al. 9th CROI, Seattle, 2002. Abstract 372.
12th CROI. Boston, 2005. Abstract 674.
US surveillance of HIV drug resistance
 Drug resistance in 787 newly diagnosed ART-naïve subjects from 89
sites in 6 states (2003–2004)
16
14.5
14
Prevalence of resistance
by drug class
12
Patients (%)
Prevalence of drug resistance
Men
14.9%
Women
13.8%
MSM
15.9%
Hetero
13.0%
IDUs
14.1%
Black
14.2%
Hispanics
13.6%
White
15.3%
10
8.4
7.1
8
6
4
2.8
3.1
PI
>2
classes
2
0
Any
class
Bennett D, et al. 12th CROI, Boston 2005, #674
NRTI
NNRTI
Primary resistance
in ARV-naïve adolescents
Female
(n=19)
Male
(n=36)
– recently infected adolescents
– 12-24 years old (mean age 19.7)
African
American
58%
42%
Hispanic
21%
25%
White
10.5
28%
Other
 N=55
10.5%
5%
 Sample from 15 US cities
 Overall rate of resistance – (genotype
18%; phenotype 22%)
– NNRTI:
15%; 18%
– PI:
3.6%; 5.5%
– NRTI:
4%; 4%
 81% of male risk was MSM
Viani R, et al, 13th CROI, Denver 2006, #21
Use of ED drugs and crystal meth, and
high-risk sexual behaviors
 Random telephone survey conducted in San Francisco,
June 2002 to January 2003
Phoned
733,787
Responded
15,272
Eligible
2,676
Completed interview
1,976
100
80
Unprotected insertive anal sex
Unprotected receptive anal sex
HIV+
60
%
40
20
0
Median # sexual
partners
Neither
n=1388 (84%)
ED drug only
n=266 (16%)
Meth only
n=100 (5%)
Both
n=139 (7%)
2
6
5
20
Spindler H, et al. XVI IAC, Toronto 2006, #MOPE0342
Methamphetamine use and infection with
resistant HIV
 214 recently infected, treatment-naïve MSM cohort in southern
California
 15% of patients infected with drug-resistant HIV
– ~50% resistance to NNRTIs
– ~25% NNRTI + ≥ 1 other class resistance
 ⅓ of men reported using methamphetamine with at least 1 of their
last 3 sexual partners
 MV regression analysis: pts who had drug-resistant virus were 5
times more likely to have used methamphetamine (odds ratio:
4.86; p=0.005)
Drumright et al, XV IHDRW, Sitges, Spain, 2006, #99
How long does transmitted
resistance last?
Persistence of transmitted resistant
virus
 Reversion of MDR is rare even after 1 year
Primary HIV
Infection
n=101
NNRTI
NRTI
PI
(n=9)
(n=3)
(n=3)
Follow-up (Weeks)
9-145
Reversions
1 of 10
n=1 PI2
156
None
n=4 MDR3
36-260
None
26-156
None
n=24
MDR
NNRTI
(n=1)
(n=1)
Little SJ, et al. XII Resistance Workshop, Los Cabos 2003, #115; 2. Ravaux I, et al. 2nd IAS, Paris
2003, #822; 3. Brenner B, et al. J Virology 2002; 766:1753; 4. Chan K, et al. AIDS 2003; 17:1256
An Ounce of Prevention
Risk Factors for SeroconversionOccupational
Risk Factor
OR*
95% CI
Deep injury
15
6.0 – 41
Visibly bloody device
6.2
2.2 – 21
Device in artery/vein
4.3
1.7 – 12
Terminally ill SP
5.6
2.0 – 16
AZT PEP
0.19
0.06 – 0.52
*p<0.01 for all
Cardo DM et al. NEJM 1997;337:1485-90
Exposure Risks –
Non-Occupational
Percutaneous (blood)1
Mucocutaneous (blood)2
Receptive anal intercourse3
Insertive anal intercourse4
Receptive vaginal intercourse5
Insertive vaginal intercourse6
Receptive oral (male)7
Female-female orogenital8
IDU needle sharing9
Vertical (no prophylaxis)10
0.3%
0.09%
1 - 2%
0.06%
0.1 – 0.2%
0.03 – 0.14%
0.06%
4 case reports
0.67%
24%
average, per episode, involving HIV-infected source patient
Does Offering Non-occupational PEP
Encourage High-Risk Behavior?
– 379 sexual exposures; 336
involved MSM
 Most MSM reported decrease
in risky behaviors on followup
questioning
 By 12 months of follow-up,
17% of MSM had received
PEP for one or more repeat
exposures
Percentage of participants
 N = 401 participants receiving
PEP following unprotected
sexual or IDU exposure to HIV
increase
no change
decrease
100
90
80
74
72
70
60
50
40
30
20
10
16
10
14 14
0
6 months
12 months
Change in Risky Behavior
Martin J et al, 8th CROI, February 2001, Abstract 224.
Tolerability of HIV PEP in Health Care
Workers
Incidence of Common Side Effects
Percent of HCWs
100
90
80
70
60
50
40
30
20
10
0
Nausea
Fatigue Headache Vomiting Diarrhea Myalgias
Wang SA. Infect Control Hosp Epidemiol 2000;231:780-5.
When should PEP be started?
 Efficacy of PEP thought to wane with time
 At what point is PEP “no longer worth it”?
benefits of PEP
risks of PEP
time
exposure
Timing of PEP: what’s the evidence?
 Animal models and animal PEP studies: suggest
substantially less effective beyond 24 - 36 hours1,2
 Case-control study: most subjects in each group received
PEP within 4 hours3
 Analysis of PEP failures does not suggest a clear cut-off4
1. Tsai C-C et al. J Virol 1998;72:4265-73.
2. Shih CC et al. JID 1991.
3. Cardo DM et al. NEJM 1997;337:1485-90.
4. MMWR June 29, 2001:50(RR11);1-42.
Timing of PEP: CDC Guidelines
 “PEP should be initiated as soon as possible, preferably
within hours rather than days of exposure.”
 Interval after which there is no benefit for humans is not
known
 Obtain expert advice when interval has exceeded 24-36
hours
MMWR 2005;54(No. RR-9).
How Long Should PEP be
Administered?
 N = 24 macaques inoculated
with SIV intravenously
 PEP initiated 24 hours postinoculation
100
90
80
70
60
50
 PEP administered for 3, 10, or
28 days
3 days PEP
10 days PEP
28 days PEP
50
40
30
20
10
0
25
0
seroconversion rate (%)
Tsai C-C et al. J Virol 1998;72:4265-73.
Duration of PEP
 In animal model, 28 days more effective than 10 days or
3 days of PEP1
 4 weeks (28 days) used in case-control study2 and
recommended by CDC guidelines3
1. Tsai C-C et al. J Virol 1998;72:4265-73.
2. Cardo DM et al. NEJM 1997;337:1485-90.
3. MMWR June 29, 2001:50(RR11);1-42.
Which PEP regimen should
be considered?
PEP Regimens: Basic regimens
 Two NRTIs
 Simple dosing, fewer side effects
 Preferred basic regimens:
zidovudine (AZT) OR tenofovir (TDF)
plus
lamivudine (3TC) OR emtricitabine (FTC)
 Alternative basic regimens:
stavudine (d4T) OR didanosine (ddI)
plus
lamivudine (3TC) OR emtricitabine (FTC)
MMWR 2005;54(No. RR-9).
Expanded PEP Regimens
 Basic regimen plus a third agent
 Rationale: 3 drugs may be more effective than 2 drugs,
though direct evidence is lacking
 Consider for more serious exposures or if resistance in the
source patient is suspected
 Adherence more difficult
 More potential for toxicity
Expanded PEP Regimens
 Preferred Expanded Regimen:
– Basic regimen plus lopinavir/ritonavir (Kaletra)
 Alternate Expanded Regimens:
– Basic regimen plus one of the following:
– Atazanavir* +/- ritonavir
– Fosamprenavir +/- ritonavir
– Indinavir +/- ritonavir
– Saquinavir (hgc; Invirase) + ritonavir
– Nelfinavir
– Efavirenz
MMWR 2005;54(RR-9)
*Atazanavir requires ritonavir boosting if used with tenofovir
Adverse Effects:
Basic vs Expanded Regimens
60
2 NRTI
2 NRTI + 1 PI
% of individuals
50
40
30
20
10
0
General
Lower GI Upper GI
elevated
TG
hyperbilirubinemia
Puro V et al. 9th CROI, February 2002, Abstract 478-M
2x ALT
Other Antiretrovirals
 ARVs to be considered only with expert consultation:
– Enfuvirtide (Fuzeon; T-20)
 ARVs not generally recommended for PEP:
– Delavirdine
– Zalcitabine
– Abacavir
– Nevirapine
MMWR 2005;54(No. RR-9).
Post-Exposure Prophylaxis:
Core Principles
 Evidence is limited
 Balancing of risks vs benefits
 Timing: the sooner the better, but
interval beyond which there is no
benefit is unclear
Post-Exposure Prophylaxis:
Core Principles
 Optimal duration unclear, 28 days is recommended
 Decision making can become very complex when
drug resistance in the SP is suspected
 Offering non-occupational PEP is indicated for risky
exposures, and does not appear to increase unsafe
sexual behavior for most recipients
Summary
Two decades of HIV have produced many advances
But a few things haven’t changed
 Current HAART does not eradicate HIV
 Treatment will be life-long
 Patients will never be 100% adherent
 Behavioral changes are difficult to achieve
 Transmitted resistance can occur as a result
 Prevention is key!!
Back Up Slides
Retrovirus life cycle
Entry inhibitors
ENF MRV
VCV TNX355
AMD11070
Reverse
transcriptase
inhibitors
ZDV NVP
ddI DLV
ddC EFV
d4T 3TC
FTC ABC
TDF
Integrase
inhibitors
GS9137
MK0518
others
Protease
inhibitors
SQV IDV
RTV NFV
FPV LPV
ATV TPV
DRV
Maturation
inhibitor
bevirimat
Mutations Selected by NNRTIs
K V
103106
Y
Y
P
181
188
236
N M
C
L
L
L K V V
100 103 106 108
Y
Y
Delavirdine
Efavirenz
I
Nevirapine
N M
I
L K V V
100 103 106 108
I N AM I
181
G
188 190
CI
L
SA
Y
Y
G
181
CI
188 190
CLH A
P
225
H
Mutations Selected by PIs
Atazanavir
+/-ritonavir
Fosamprenavir
ritonavir
Lopinavir/
ritonavir
Nelfinavir
Saquinavir/
ritonavir
Indinavir/
ritonavir
Tipranavir
/ritonavir
Darunavir/
ritonavir
L
G K
10 16 20
20
10
L
V
24
24
32
IFVC E RMI
TV
I
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L E M
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33 34 36
I Q I
F
L
V
V
M
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G
I
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IL
V
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I D I
54 60 62 64
LY LV E V LMV
MTA
A
G
71
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V
82
L
V
M
I
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32
46
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50
I
54
G
73
V
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FIRV
I
IL
V
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LVM
S
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L
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V
L
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M
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MR
I
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IL
VA
V
F
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I
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L
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A
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G
73
P
VT
S
S M LM
84
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AFT
S
V
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V
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82
82 84
L
D
M
M
A
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FI
N
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IL
VT
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AFT
S
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DS
M
MTS
V
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G
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G V V
I
L
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A
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73 77 82
84
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IRV
I
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VL
V
VT
S
V
M
A
G
V
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L
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77
L
10
K
20
L
24
V
M
M
I
32
36
46
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71
IRV
MR
I
I
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IL
V
VT SA
L I
K
L
EM
K M
I
43 46
L
10 13
20
33 3536
V V
MR
F G I
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I Q
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H
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AMV E
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AFT
V
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90
V
M
V
82
N
83
LT D
I
84 85 88 90 93
AFT
S
V
V
L
L VLA
N L
I
ATFI V V
VI CSTA
TL
10
L
10
FIRV
I
54
G L
73 76
84
L
89
ML
S V
V
V
I
Recent data on transmitted resistance in
the U.S.
Author
Region
No of
Patients
NRTI
NNRTI
PI
Any
(%)
(%)
(%)
(%)
Years
Little
USA/AU
1191
3
11
3
13
2000-2006
Ross
USA
1795
4
6
3
10
2000-2004
Eshleman
USA
195
9
7
2
16
1999-2003
Chicago
66
15
12
3
25
2003-2005
Los Angeles
73
14
11
2
20
2003-2005
SF – STD
54
5
5
0
9
2004
SF - PHI
48
4
0
5
10
2004
Bennett
Truong
XV IHDRW, Sitges, Spain, 2006 References at Medscape.com
CDC Post-Exposure
Prophylaxis Guidelines
MMWR 2005;54(No. RR-9).
http://www.aidsinfo.nih.gov
CDC Post-Exposure Prophylaxis Guidelines
MMWR 2005;54(No. RR-9).
CDC Post-Exposure Prophylaxis Guidelines
MMWR 2005;54(No. RR-9).
Situations for which expert consultation* for HIV
postexposure prophylaxis (PEP) is advised
* Either with local experts or by contacting the
National Clinicians’ Post-Exposure Prophylaxis
Hotline (PEPline), 888-448-4911.
MMWR 2005;54(No. RR-9).
Follow-up of health-care personnel (HCP) exposed to known or
suspected HIV-positive sources
 Exposed HCP should be advised to use precautions (e.g., avoid blood
or tissue donations, breastfeeding, or pregnancy) to prevent secondary
transmission, especially during the first 6–12 weeks post-exposure.
 For exposures for which PEP is prescribed, HCP should be informed
regarding:
– need for monitoring
– possible drug interactions
– the need for adherence to PEP regimens.
 Consider re-evaluation of exposed HCP 72 hours post-exposure,
especially after additional information about the exposure or SP
becomes available.
MMWR 2005;54(No. RR-9).
Follow-up HIV Testing
 CDC recommendations: HIV Ab testing for 6 months
post-exposure (e.g., at 6 weeks, 3 months, 6 months)
 Extended HIV Ab testing at 12 months is recommended if
health care worker contracts HCV from a source patient
co-infected with HIV and HCV
 VL testing not recommended unless primary HIV infection
(PHI) suspected
MMWR 2005;54(No. RR-9).