The HIV Pandemic

2.6 MillionNew HIV Infections in 2009

41% in Young People (ages 15-24)

• MSM and Trans Women• Randomized 1:1 Daily Oral PREP• FTC/TDF vs Placebo• Followed on Drug for:

- HIV seroconversion- Adverse Events (especially renal & liver)- Metabolic Effects (Bone, Fat, Lipids)- HBV Flares among HBsAg+- Risk Behavior & STIs- Adherence- If infected

‣Drug Resistance‣Viral load‣Immune responses & CD4 Count

The iPrEx Study

Grant et al, CROI 2010

Fully enrolled as of December 2009

Lima

IquitosGuayaquil

Sao Paulo

Rio de Janeiro

Boston

San Francisco

Cape Town

Chiang Mai

Sites 11Participants 2,499

New England Journal of Medicine, online Nov 23, 2010

Efficacy (MITT) 44% (15-63%) Through May 1, 2010Durable Through 144 Weeks in the Final Analysis

P = 0.002

Grant et al, CROI 2010

New England Journal of Medicine, online Nov 23, 2010

Drug Levels

• Cases matched to controls by site and time on study

• Drug Detection Correlated with Seronegative Status (OR 12.9, P<0.001)• 92% reduction in

HIV risk• 95% reduction if

controlled for URAI

7Anderson et al, CROI 2010

HIV Infections During PrEP TrialsIn The USA

On PrEP Off PrEP• CDC Safety Study (US sites) 0 6

– Daily Oral TDF vs Placebo– 3 in placebo arm, – 3 in differed arm

• NIH iPrEx (US Sites) 0 3– Daily Oral FTC/TDF vs. Placebo– 2 in placebo arm– 1 in active arm 9 weeks

after stopped due to depression

Grohskopf, IAS Vienna 2010; Grant NEJM 2010

Genotypic Resistance

HIV Status at Enrollment

Infected Uninfected

PlaceboN=8

FTC/TDFN=2

PlaceboN=83

FTC/TDFN=48

65R 0 (0%) 0 (0%) 0 (0%) 0 (0%)

70E 0 (0%) 0 (0%) 0 (0%) 0 (0%)

184I 0 (0%) 1 (50%) 0 (0%) 0 (0%)

184V 1 (13%) 1 (50%) 0 (0%) 0 (0%)

TDF Resistance 0 (0%) 0 (0%) 0 (0%) 0 (0%)

FTC Resistance 1 (13%) 2 (100%) 0 (0%) 0 (0%)

Drug Resistance

Grant et al, CROI 2010

Sexual Partners

Condom Use with High Risk Sex

Grant NEJM 2010

Will pill taking increase if people are given FTC/TDF (without placebo) and know it can be effective?

What will happen to sex practices?

Collect more safety data over longer periods of time

Open Label Extension Aims:

The NIH ADAPT Study (HPTN 067)Alternative Dosing to Augment PrEP Pill Taking

• Intermittent PrEP in:–MSM (N = 180, Bangkok, Thailand)–WSM (N = 180, Cape Town, South Africa)

• Oral FTC/TDF in three dosage groups: –Daily dosing–Time-driven dosing group: FTC/TDF twice weekly with a

post-exposure boost. –Event-driven dosing group: FTC/TDF before and after a

potential exposure to HIV infection.

Conclusions

Oral FTC/TDF PrEP provided additional protection against the acquisition of HIV infection among MSM receiving a

comprehensive package of prevention services.

Detectable drug in blood strongly correlated with the prophylactic effect.

Efficacy was durable through 144 weeks.

Collateral BenefitsAll observed during PrEP in iPrEx

• Found the epidemic with surveillance• Increased HIV testing and counseling• Decreased partners• More condom use• HBV vaccination• STI screening and treatment• Treatment of HIV Infections• Community building• 687 people employed

16