HIV Science Update: From Rome to Addis –

Biomedical Prevention

Elly 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 placebo

Men: 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