HIV Science Update:
From Rome to Addis –
Biomedical Prevention
Elly T Katabira, FRCP
Department 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
13 sites in 9 countries:
Botswana, Brazil, India,
Kenya, Malawi, South
Africa, Thailand, United
States, Zimbabwe
(HIV+ partner CD4 350-550)
Immediate
HAART
HAART delayed
until CD 250
All receiving HIV prevention services
1° endpoint: HIV infection in HIV-negative partner
Co- 1° endpoint: HIV disease progression in HIV+
partner
Cohen et al NEJM 2011 and IAS 2011
HPTN 052: HIV transmissions
Total HIV-1 Transmission
Events: 39
Linked
Transmissions: 28
Immediate
Arm: 1
Delayed
Arm: 27
p < 0.001
Unlinked or TBD
Transmissions: 11
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
CAPRISA 004:
Pericoital 1% tenofovir
gel
 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
Abdool Karim et al, Science July 2010
 Study population: Young women
(mean age 23), unmarried
HIV protection in CAPRISA 004
No HIV resistance mutations among seroconverters
Q Abdool Karim et al. Science 2010
iPrEx: PrEP works for MSM
iPrEx:
Daily oral FTC/TDF
PrEP
 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 HIV protection
100 infections after
randomization
36 on
FTC/TDF
64 on
placebo
Efficacy estimate (mITT):
44% reduction in HIV acquisition
(95% CI 15%-63%)
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)
Randomize HIV- partners
(normal liver, renal, hematologic function)
TDF once daily
FTC/TDF once daily
All receiving comprehensive
Placebo once daily
HIV prevention services
Follow couples for up to 36 months
1° endpoint: HIV infection in HIV- partner
Co- 1° endpoint: Safety
Slides presented IAS
2011
•
Primary efficacy results
Primary analysis: modified intention-to-treat (mITT)
• excluding infections present at randomization (3 TDF, 3 FTC/TDF, 6 placebo)
TDF
FTC/TDF
Placebo
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
Number of HIV infections
Effect of TDF and FTC/TDF
statistically similar (p=0.18)
ITT analysis results similar
Slides presented IAS
2011
•
Subgroup analysis - gender
Both TDF and FTC/TDF significantly reduced HIV risk in
both men and women
Women: 42 total infections: 8 TDF, 9 FTC/TDF, 25 placebo
Men: 36 infections: 10 TDF, 4 FTC/TDF, 22 placebo
Efficacy
95% CI
P-value
68%
29-85%
p=0.01
Interaction pvalue
TDF
Women
p=0.54
Men
55%
4-79%
p=0.04
62%
19-82%
p=0.01
FTC/TDF
Women
p=0.24
Men
83%
49-94%
p=0.001
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
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)
Truvada
(1000)
Tenofovir
(1000)
Vaginal Gel
(2000)
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
TOTAL
SAMPLE
(5000)
Oral Pill
(3000)
Truvada
(1000)
Tenofovir
(Discontinued)
Vaginal Gel
(2000)
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
TOTAL
SAMPLE
(5000)
Oral Pill
(3000)
Truvada
(1000)
Tenofovir
(Discontinued)
Vaginal Gel
(2000)
Oral Placebo
(1000)
Tenofovir Gel
(Discontinued)
Placebo Gel
(1000)
A word of caution………..
CAPRISA 004 & iPrEx: PrEP is all about
adherence
CAPRISA 004
• High (>80% gel adherence)
54% effective
• Low (<50% gel adherence)
28% effective
n=336 (38%)
n=367 (42%)
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 (FM 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
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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