Transcript The 16th Conference on Retroviruses and Opportunistic Infections

Antiretrovirals for HIV Prevention:
Progress and Challenges
Kenneth H. Mayer, M.D.
Brown/Miriam/Fenway
HIV PREVENTION 2010
DECREASE SOURCE OF
INFECTION
•Barrier protection
•Blood screening
•IDU harm reduction
•STI Treatment?
•Antiretroviral Therapy
•PMTCT
•Rx infected partners
DECREASE HOST
SUSCEPTIBILITY
•Barrier protection
•Infection Control
•Circumcision
•Vaccines?
•STI Treatment?
•PEP
•Oral PREP
•Topical Microbicides
ALTER BEHAVIOR
•Condom and HIV testing promotion
•Individual interventions
•Couples interventions
•Community-based interventions
•Structural interventions (e.g., economic)
HOW ANTIRETROVIRALS CAN
AFFECT HIV TRANSMISSION
PLASMA

HIV

GENITAL TRACT
HIV

TRANSMISSION
SURVIVAL
 PLHIV

DURATION OF
INFECTIOUSNESS

TRANSMISSION
• RELEVANT ISSUES: ACCESS, ADHERENCE,
PREVENTION, STI RX.
Treatment as Prevention:
Discordant Couples
2,993 couples were followed for a
median of 512 days
HIV-free Survival of HIV- partners,
by ARV status of HIV+ Partner
1.0
Both ART and change in behavior
independently reduced HIV
transmission Sullivan P. CROI 2009
0.8
Survival Probability
Sexual risk behaviors lower in those
on ART (19% vs 25%, P<0.05)
Censored
Logrank P<.0001
0.6
0.4
On ARV
Off ARV
0.2
0.0
2073
920
1035
475
0
500
598
256
252
69
1000
1500
Days
80
6
0
0
2000
2500
Donnell, D. CROI, 2010: 1 linked transmission in Partners study from one
person who had been on HAART for 18 days in a sample with 236 py f/u,
compared to 2.23% incidence in untreated couples
Over 90% decrease in HIV transmission with HAART
Can Antiretrorivals ↓ HIV Transmission?
HIV in several countries where treatment and
prevention have been integrated, e.g.
Brazil and Taiwan (Porco, AIDS, 2004; Fang, JID, 2004)
Counter: Resistant HIV transmission (Imrie, JID, 1997; Little,
NEJM, 2002; Angarano, AIDS, 2004) but prevalence may be
decreasing because of HAART efficacy(Routy, AIDS, 2004)
MSM: ↓ Community Viral Load, ↓ HIV incidence in SF
(Das-Douglas, CROI, 2010, Session 10, 2/17)
Counter: ↑ HIV incidence in Amsterdam MSM
(Jansen, CROI 2010, Session 10, 2/17)
HPTN 052 will answer whether starting earlier
treatment can decrease HIV incidence
But, Cell-Associated HIV is a major source of
infectious virus (Anderson et al, AIDS, 2010)
HPTN 065 (TLC Plus)
Testing, Linkage to Care, Treatment,
Plus Lots More….
Enroll in Care
Test
Initiation
of ART
Testing
Treat
HIV Positive
Linkage
to care
Positive
Prevention
Adopt safer behaviors
Adherence
to ART
Maintain viral
suppression
Decrease in HIV
Transmission
Why Antiretrovirals for 1° Prevention?
• Non-human primates
– Multiple drugs have been shown to decrease HIV
transmission pre or post exposure
• PMTCT, even single dose NVP to Mother/Infant
was protective
– ? Enough time to lower VL in mother
– ? Direct infant benefit from antiretrovirals
• Occupational Post Exposure Prophylaxis (PEP)
after percutaneous exposures
– Associated with lower risk in HCW
– AZT alone associated with 80% decrease
– Not RCT, retrospective case-control
MMWR 2005
Non-Occupational PEP
Schechter et al, JAIDS, 2004
• N=200 high risk Brazilian MSM
– Followed over 24.2 months
• PEP (AZT/3TC) 4 day starter pack
– 28 day course
• 68 used PEP 109 times
• HIV incidence 2.9/100py
– 10 infected who did not use PEP (N=132)
– Assumed partner was HIV-Uninfected
– 1 infection in a PEP user (N=68)
– Risk Behavior Decreased
Similar to SF experience (Martin et al, AIDS, 2004)
Topical PrEP in Macaques with
TDF or TDF/FTC

Study to assess most effective modality for topical ARV gels

1% TDF or 1% TDF/5% FTC gels in 23 macaques



Gel (matrix + preservatives) clear, viscous, odorless, stable at 37° x 6 months
3 ml gel applied 30 mins before vaginal challenge with R5 virus inoculum (10 TCID50)
Challenges 2x/week for total 20 challenges
% Protected
100
no gel (n=2)
placebo gel (n=9)
FTC/TDF gel (n=6)
TDF gel (n=6)
75
50
25
0
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
Challenges
Dobard C, et al, CROI, 2009; Dobard et al, CROI, 2010, poster 949
What if PrEP “Works”?
• Block other steps in HIV life cycle, e.g. binding and
integration? Develop drugs just for prevention?
• New Co-formulations: Generic PrEP?
• Topical vs. Oral: VOICE and beyond
• What is the optimal drug delivery system: gel, ring,
suppository, diaphragm, injection, or pill?
• How to best dose: Fixed intervals vs. pre/post coital?
• PrEP and the immune system: adjuvant for vaccines?
• Special populations: youth, pregnant women
What if PrEP “Works”?
• Who should prescribe: How best to train providers?
• How will access be ensured in resource-limited
settings?
• Prevention package: What is optimal counseling?
• How to often to monitor: safety labs, and test for new
HIV infection/resistance? Home testing?
• How to facilitate best practices? New roles for ASO’s;
use of new media to educate
• Will need enhanced surveillance for intended
(decreased HIV incidence) and unintended (risk
compensation, resistance) consequences