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HIV Science Update: From Rome to Addis –
Biomedical PreventionElly T Katabira, FRCPDepartment of Medicine Makerere University College of Health Sciences
16th ICASA, Addis Ababa, Ethiopia, December 6, 2011
Treatment as prevention
Population level observational data: British Columbia
All receiving HIV prevention services
Montaner Lancet 2010
HPTN 052: Impact of (earlier) ART on HIV transmission and disease progression
1763 HIV discordant couples (HIV+ partner CD4 350-550)
HAART delayed until CD 250
1° endpoint: HIV infection in HIV-negative partnerCo- 1° endpoint: HIV disease progression in HIV+
partner
Immediate HAART
All receiving HIV prevention services
13 sites in 9 countries: Botswana, Brazil, India, Kenya, Malawi, South
Africa, Thailand, United States, Zimbabwe
Cohen et al NEJM 2011 and IAS 2011
Total HIV-1 Transmission Events: 39
HPTN 052: HIV transmissions
Linked Transmissions: 28
Unlinked or TBD Transmissions: 11
p < 0.001
Immediate Arm: 1
Delayed Arm: 27 96% reduction in risk of HIV
transmission within the partnership (95% CI 73-99%)
Prevention of HIV acquisition in those who are HIV negative
CAPRISA 004: proof of principle for microbicides
Phase 2B trial in 889 women, ages ≥18 years in South Africa
Coitally dependent: gel within 12 hours before & 12 hours after sex, max. 2 applications in 24 hours
Study population: Young women (mean age 23), unmarried
CAPRISA 004: Pericoital 1% tenofovir
gel
Abdool Karim et al, Science July 2010
Q Abdool Karim et al. Science 2010
HIV protection in CAPRISA 004
No HIV resistance mutations among seroconverters
iPrEx: PrEP works for MSM
2499 MSM, randomized 1:1 daily oral FTC/TDF vs placebo
11 sites (Brazil, Ecuador, Peru, South Africa, Thailand, US)• 70% from Andean sites
Young high risk MSM: • 50% <25 yrs• Median 18 partners in 12 wks prior to
enrollment
iPrEx: Daily oral FTC/TDF
PrEP
iPrEx HIV protection100 infections after
randomization
64 on placebo
Efficacy estimate (mITT): 44% reduction in HIV acquisition
(95% CI 15%-63%)
36 on FTC/TDF
Weeks on Study
2 cases of M184V resistance in participants in “window period” at time of PrEP initiation = avoid PrEP initiation in those who have acute HIV infection
Partners PrEP Study 4758 HIV serodiscordant couples
(HIV+ partner not yet medically eligible for ART)
TDF once daily Placebo once daily
Randomize HIV- partners (normal liver, renal, hematologic function)
1° endpoint: HIV infection in HIV- partnerCo- 1° endpoint: Safety
Follow couples for up to 36 months
FTC/TDF once daily
All receiving comprehensive HIV prevention services
Primary efficacy results
TDF FTC/TDF Placebo
Number of HIV infections 18 13 47
HIV incidence, per 100 person-years 0.74 0.53 1.92
HIV protection efficacy, vs placebo 62% 73%
95% CI (34-78%) (49-85%) p-value 0.0003 <0.0001
Z-score, vs. H0=0.7 -2.17 -2.99
• Primary analysis: modified intention-to-treat (mITT)• excluding infections present at randomization (3 TDF, 3 FTC/TDF, 6 placebo)
ITT analysis results similar
Effect of TDF and FTC/TDF statistically similar (p=0.18)
Slides presented IAS 2011
Subgroup analysis - gender
Efficacy 95% CI P-value Interaction p-value
TDF Women
Men
68%
55%
29-85%
4-79%
p=0.01
p=0.04p=0.54
FTC/TDF Women
Men
62%
83%
19-82%
49-94%
p=0.01
p=0.001p=0.24
• Both TDF and FTC/TDF significantly reduced HIV risk in both men and women
Women: 42 total infections: 8 TDF, 9 FTC/TDF, 25 placeboMen: 36 infections: 10 TDF, 4 FTC/TDF, 22 placebo
Slides presented IAS 2011
Safety• No statistically significant difference in deaths, SAEs, key
laboratory AEs
Number of participants with each safety event
Total TDF FTC/TDF Placebo
Death 24(<1%)
8 7 9
SAE 320(7%)
108 107 105
Confirmed creatinine AE 49(1%)
17 20 12
Confirmed phosphorus AE 403(9%)
138 133 132
Slides presented IAS 2011
Some disappointments though…….
• Ongoing safety and effectiveness study of tenofovir gel, oral TDF, and oral FTC/TDF for prevention of HIV
TOTAL SAMPLE
(5000)
Oral Pill (3000)
Vaginal Gel(2000)
Truvada(1000)
Tenofovir(1000)
Oral Placebo(1000)
Tenofovir Gel(1000)
Placebo Gel(1000)
• Ongoing safety and effectiveness study of tenofovir gel, oral TDF, and oral FTC/TDF for prevention of HIV
• Ongoing safety and effectiveness study of tenofovir gel, oral TDF, and oral FTC/TDF for prevention of HIV
A word of caution………..
CAPRISA 004 & iPrEx: PrEP is all about adherence
CAPRISA 004• High (>80% gel adherence) n=336 (38%)
54% effective• Low (<50% gel adherence) n=367 (42%)
28% effective
iPrEx• 8% of seroconverters had detectable drug at first
HIV+ visit (and only 54% of nonseroconverters) 92% estimated efficacy if drug was present
Combination HIV prevention: a package
• What works for HIV prevention:– Male circumcision (FM risk)– Male condoms, female condoms (probably)
– Counseling and testing, particularly as a couple (probably)
– ↓ partner #, delayed sexual debut, abstinence– Treatment of STIs (probably best to decrease infectiousness in HIV+s)
– Conditional cash transfer– ART – Oral/topical PrEP– ? Vaccine
• Multiple, integrated, biomedical and behavioral interventions
Combination prevention.Coates, et al. Lancet 2009
ACKNOWLEDGEMENT• Adaora A. Adimora• Audrey Pettifor• Dannielle Haley• Jessica Justman• Mara Nakagawa-Harwood• Jaread Baeten• Connie Celum• Pedro Cahn• Julio Montaner• And many others behind the scene