Science and Sex:
HPTN 052 and Treatment as Prevention
Monica Gandhi MD, MPH
Associate Professor and Women’s HIV Clinic provider, HIV/AIDS Division
San Francisco General Hospital/ UCSF
Safe Poz Love, U.S. Positive Women’s Network
February 14, 2012
Percent of adults (15+) living with HIV who are
female, 1990–2009
70
60
Sub-Saharan Africa
GLOBAL
Caribbean
Asia
E Europe & C Asia
Latin America
50
Percent
40
female
(%)
30
20
10
0
1990‘91 ‘92 ‘93‘94‘95 ‘96 ‘97 ‘98 ‘99 ‘00 ‘01 ‘02 ‘03 ‘04 ‘05 ‘062009
Year
www.unaids.org
Proportion of all AIDS cases in women: 7% in 1985 to 26% today
We already thought HIV-positive people on antiretrovirals
cannot pass on the virus readily
– The lower your HIV viral load in plasma, the
lower the viral load in semen and vaginal
secretions
– Concentration of HIV in the genital area
correlates with sexual transmission
– Observational studies had shown very low rates
of transmission to sexual partners if HIV-infected
person is on treatment
– But in MEDICINE, “evidence” means a
randomized controlled trial
Cohen MS et al. Prevention of HIV-1 infection
with early antiretroviral therapy. NEJM
August 2011 (HPTN-052)
HPTN 052 Study Design
Stable, healthy, serodiscordant couples, sexually active
CD4 count: 350 to 550 cells/mm3
Randomization
Immediate ART
CD4 350-550
Delayed ART
CD4 <250
Primary Transmission Endpoint
Transmission events that were linked to that primary partnership
Primary Clinical Endpoint
WHO stage 4 clinical events, pulmonary tuberculosis, severe bacterial
infection and/or death
HPTN 052 Enrollment
10,838 Individuals Screened
Major reasons for exclusion:
1763 Couples
(3526 Individuals)
Randomized
Immediate Arm
886 Couples
Delayed Arm
877 Couples
3058
2565
308
155
HIV+ but CD4 count out of range
HIV- but HIV+ partner ineligible
Seroconcordant couples
Ineligible due to sexual history
HPTN 052 Enrollment
(Total Enrollment: 1763 couples)
U.S.
Thailand
Americas
278
India
Kenya
Malawi
Brazil
Zimbabwe
Botswana
South Africa
Africa
954
Asia
531
HPTN 052: Baseline Characteristics
Index
Partner
Immediate
Delayed
Immediate
Delayed
N = 886
N = 877
N = 893
N = 882
Female
49%
50%
49%
47%
Age (median)
33
32
32
32
Married
94%
95%
93%
94%
Any unprotected sex
6%
8%
8%
8%
442
428
[373-522]
[357-522]
---
---
4.4
4.4
[3.8-4.9]
[3.9-4.9]
---
---
CD4 (median [IQR])
HIV RNA log10
(median [IQR])
The Data safety and monitoring board announced
April 28, 2011
“The Board recommends that the results of the
trial be announced as soon as possible” (was
supposed to go until 2014)
HPTN 052 continues to follow couples, but all
HIV-infected participants are being offered ART
HPTN 052: HIV-1 Transmission
Total HIV-1 Transmission Events: 39
Immediate Arm
4
Delayed Arm
35
p < 0.0001
HPTN 052: HIV-1 Transmission
Total HIV-1 Transmission Events: 39
Linked
Transmissions: 28
Unlinked or TBD
Transmissions: 11
People have sex outside of their partnerships. .
Wait, REALLY????!!!
Immediate
Arm: 1
Delayed
Arm: 27
p < 0.001
• 23/28 (82%) transmissions in subSaharan Africa
• 18/28 (64%) transmissions from
female to male partners
• 238 pregnancies
People have unprotected sex . Wait, REALLY????!!!
HPTN 052: HIV-1 Transmission
Study Arm
Follow-up (PY)*
Immediate
1585
Delayed
1567
Incidence/100PY
[95% CI]
Linked
Overall
0.1
0.3
[0.0 – 0.4]
[0.1 – 0.6]
1.7
2.2
[1.1 – 2.5]
[1.6 – 3.1]
*Person-years specific for transmission events
0.1/1.7 = 96% reduction
HPTN 052: Effect of ART
100
Proportion of participants with VL<400 at each visit
0
20
40
60
80
Immediate Arm
Delayed Arm (not on ART)
Delayed Arm (on ART)
0
3
6
9
12
15
18
21
24
Months
27
30
33
36
39
42
45
One Transmission Event on ART
Index begins ART
AZT/3TC/EFV
Index VL<400
Partner HIV+ (WB)
28
85
Enrollment
Screening
Days
-14
0 1
Partner VL < 400
Index CD4 = 482
Index VL = 87,202
Single Genome Analysis: 1-2 viruses transmitted
Analysis of Transmission: >50 days earlier (84 – 190 days)
HPTN 052 Prevention Conclusion
Early ART that suppresses viral replication led to 96%
reduction of sexual transmission of HIV-1 in
serodiscordant couples
Sex and sexuality for HIV-positive women
With such strong evidence for protection and
prevention, let’s think about sexual rights in women
living with HIV infection!