1. The potential and challenges of ARV-based HIV prevention: An overview
Salim S Abdool Karim
Director: CAPRISA
Pro Vice-Chancellor (Research): University of KwaZulu-Natal
Professor in Clinical Epidemiology, Columbia University
Associate Member, Ragon Institute of MGH, MIT and Harvard
Adjunct Professor of Medicine, Cornell University

2. Outline Clinical trial evidence for ARV-based prevention
Challenges in implementing PrEP & TasP
The need for PrEP & TasP to prevent HIV in vulnerable Key Populations
Conclusion

3. Clinical trial evidence for ARV prophylaxis
Effect size (CI)
Prevention
in IDUs
Bangkok Tenofovir Study– daily oral Tenofovir
(IDUs– Thailand)
49% (10; 72)
ART for prevention
HPTN052 Africa, Asia, Americas
96% (73; 99)
Partners PrEP – daily Truvada
(Discordant couples – Kenya, Uganda)
75% (55; 87)
Partners PrEP – daily oral Tenofovir
(Discordant couples – Kenya, Uganda)
67% (44; 81)
TDF2 – daily Truvada
(Heterosexuals men and women- Botswana)
62% (22; 84)
iPrEx – daily Truvada
(MSM - America’s, Thailand, South Africa)
44% (15; 63)
Sexual transmission prevention
CAPRISA 004 – coital Tenofovir gel
(Women – South Africa)
39% (6; 60)
MTN003/VOICE – daily Tenofovir gel
(Women – South Africa, Uganda, Zimbabwe)
15% (-21; 40)
FEMPrEP – daily Truvada
(Women – Kenya, South Africa, Tanzania)
6% (-52; 41)
MTN003/VOICE – daily Truvada
(Women – South Africa, Uganda, Zimbabwe)
-4% (-49; 27)
MTN003/VOICE – daily Viread
(Women - South Africa, Uganda, Zimbabwe)
-49% (-129; 3)
-130
-60
-40
-20 20 40 60 80
100
Effectiveness (%)
Source: Adapted from Abdool Karim SS. Lancet 2013

4. In May 2011, HPTN 052 shows that ART prevents HIV transmission from infected partners in discordant couples
1763 discordant couples in Africa & America
Effect on ART (HIV +ve) on HIV: 96% (CI: 73% - 99%)

5. ARV prophylaxis HIV PREVENTION Male circumcision Treatment of STIs
Auvert B, PloS Med 2005
Gray R, Lancet 2007
Bailey R, Lancet 2007
Treatment of STIs
Grosskurth H, Lancet 2000
Microbicides
for women
Abdool Karim Q, Science 2010
Female Condoms
Male Condoms
HIV
PREVENTION
Grant R, NEJM 2010 (MSM)
Baeten J , 2011 (Couples)
Thigpen M, 2011 (Heterosexuals)
Choopanya K, 2013 (IDU)
Oral pre-exposure prophylaxis
HIV Counselling and Testing
Coates T, Lancet 2000
Sweat M, Lancet 2011
Post Exposure
prophylaxis (PEP)
Scheckter M, 2002
Behavioural Intervention
Abstinence
Be Faithful
Treatment for prevention
Cohen M, NEJM 2011
Donnell D, Lancet 2010
Tanser F, Science 2013
Note: PMTCT, Screening transfusions, Harm reduction, Universal precautions, etc. have not been included – this is focused on reducing sexual transmission

6. July 2012: First antiretroviral approved for HIV prevention - Tenofovir + FTC

7. Interim Guidance for Clinicians Considering the Use of Preexposure
Weekly / Vol. 61/No August 10, 2012
Interim Guidance for Clinicians Considering the Use of Preexposure
Prophylaxis for the Prevention of HIV Infection in Heterosexually Active Adults
Source: CDC. MMWR Morb Mortal Wkly Rep and 2012

8. Tardiness in rolling out PrEP

9. The 7 falsehoods of ARV prophylaxis to prevent HIV
PrEP should only be used for prevention after all eligible AIDS patients are on treatment
It is not safe to give ARVs to healthy people
Asymptomatic people will not adhere to ARVs for prevention or treatment, especially when it is not provided by doctors
Data on effectiveness of PrEP, especially in women, are inconsistent & doubtful efficacy
Treatment in discordant couples ≠ community-level prevention
Drug resistance from PrEP will undermine future AIDS treatment
PrEP will increase HIV risk by ↓condom use
We do not know how to provide PrEP and so need demonstration projects before PrEP roll-out

10. PrEP adherence varies by study & strongly correlates with effectiveness
Pearson correlation = 0.86, p=0.003

11. ART by nurses is effective, sustainable and improved over time in rural SA

12. The 7 falsehoods of ARV prophylaxis to prevent HIV
PrEP should only be used for prevention after all eligible AIDS patients are on treatment
It is not safe to give ARVs to healthy people
Asymptomatic people will not adhere to ARVs for prevention or treatment, especially when it is not provided by doctors
Data on effectiveness of PrEP, especially in women, are inconsistent & doubtful efficacy
Treatment in discordant couples ≠ community-level prevention
Drug resistance from PrEP will undermine future AIDS treatment
PrEP will increase HIV risk by ↓condom use
We do not know how to provide PrEP and so need demonstration projects before PrEP roll-out

13. PrEP effectiveness is high in men & women with detectable tenofovir

14. The 7 falsehoods of ARV prophylaxis to prevent HIV
PrEP should only be used for prevention after all eligible AIDS patients are on treatment
It is not safe to give ARVs to healthy people
Asymptomatic people will not adhere to ARVs for prevention or treatment, especially when it is not provided by doctors
Data on effectiveness of PrEP, especially in women, are inconsistent & doubtful efficacy
Trials in discordant couples ≠ community-level prevention
Drug resistance from PrEP will undermine future AIDS treatment
PrEP will increase HIV risk by ↓condom use
We do not know how to provide PrEP and so need demonstration projects before PrEP roll-out

15. High ART coverage reduces HIV transmission & increases survival in a rural African community

16. The 7 falsehoods of ARV prophylaxis to prevent HIV
PrEP should only be used for prevention after all eligible AIDS patients are on treatment
It is not safe to give ARVs to healthy people
Asymptomatic people will not adhere to ARVs for prevention or treatment, especially when it is not provided by doctors
Data on effectiveness of PrEP, especially in women, are inconsistent & doubtful efficacy
Trials in discordant couples ≠ community-level prevention
Drug resistance from PrEP will undermine future AIDS treatment
PrEP will increase HIV risk by ↓condom use
We do not know how to provide PrEP and so need demonstration projects before PrEP roll-out

17. Drug resistance and condom use in PrEP / ART
Estimated prevalence of drug resistance after 10 years (2012–2022)
ART
Overlapping
ART + PrEP 10 8 6 4 2
Prevalence of drug resistance
6.6
4.2
2.4
0.5
0.3
8.2
4.6
3.3
0.2
0.1
PrEP
PrEP transmitted resistance
PrEP acquired resistance
Overall
ART acquired resistance
ART transmitted resistance
Source: Abbas U, 2013
Self-reported condom use in the CAPRISA 004 trial
Source: Adapted from Abdool Karim Q. Science 2010

18. The 8 falsehoods of ARV prophylaxis to prevent HIV
PrEP should only be used for prevention after all eligible AIDS patients are on treatment
It is not safe to give ARVs to healthy people
Asymptomatic healthy people will not adhere to ARVs for prevention or treatment
Data on effectiveness of PrEP, especially in women, are inconsistent & doubtful efficacy
Trials in discordant couples ≠ community-level prevention
Drug resistance from PrEP will undermine future AIDS treatment
PrEP will increase HIV risk by ↓condom use
We do not know how to provide PrEP and so need demonstration projects before PrEP roll-out

19. Early experiences with implementing PrEP in San Francisco
49% (261/531) of eligible individuals offered PrEP in a STD clinic setting did initiate PrEP
59% (70/118) of those referred for PrEP in a Reproductive Health program did initiate PrEP
64% (7/11) of women with HIV+ve male partners initiated PrEP in prenatal or preconception care

20. Key Population 1: PrEP & TasP for young women in Africa Women acquire HIV ±8 years earlier than men
<9
10-14
Prevalence (%)
15-19
20-24
25-29
30-39
40-49 2 4 6 8 10
Female
Male
>49
1990
Source: Abdool Karim Q, Abdool Karim SS, Singh B, Short R, Ngxongo S. Seroprevalence of HIV infection in rural South Africa. AIDS 1992, 6:

21. High burden of HIV in young women in Africa:
HIV in 15–24 year men and women
(2008–2011)
Young women have up to 8 times more HIV than men
Zimbabwe
Source: Adapted from UNAIDS 2012

22. Key Population 2: TasP & PrEP for MSM
Country
HIV prevalence among MSM (%, 95%CI)
Population prevalence (>15 years) %
HIV prevalence among MSM vs general population
scenario 1: MSM predominant mode of exposure for HIV infection in the population
Mexico
25.6 ( )
0.26
98.5
Bolivia
21.2 ( )
0.13
163.1
scenario 2: MSM risk occur within established HIV epidemics driven by IDU
Serbia
8.7 ( )
0.08
108.8
Georgia
5.3 ( )
0.07
75.7
Scenario 3: MSM risks in context mature & widespread HIV epidemics among heterosexuals
Nigeria
13.5 ( )
2.88
4.7
Sudan
8.8 ( )
1.26
7.0
Source: Beyrer et al. Epidemiol Rev 2010; 32:

23. Key population 3: PrEP & TasP for IDUs
Country
Country prevalence of IDU (%)
HIV prevalence among IDUs (%)
HIV prevalence among IDU vs general population
Ecuador
0.59
28.8
106.6
Bolivia
221.3
Argentina
0.29
49.7
124.3
Poland
1.50
8.9
148.3
Serbia
27.0
338.0
Armenia
0.10
13.4
134.0
China
0.19
12.3
175.7
Indonesia
0.13
42.5
265.6
Source: Beyrer et al. Epidemiol Rev 2010; 32:

24. What are the potential gains from PrEP in Key Populations?
NNT*
Overall 62
Any cocaine use in the past month 12
Any anal sex with an HIV+ partner* 43
Receptive anal intercourse without a condom
Only negative
Unknown serostatus
HIV positive 15 41 24
Number of partners 1
2-5
>5
100 60 58
Self-reported STI
CAPRISA 004
*number needed to treat

25. Conclusion There is new hope in HIV prevention…
More positive trials since July 2010 than in previous 29 years
Treatment for prevention in particular provides huge hope
Microbicides and oral PrEP: Promising new HIV prevention technologies for women, MSM and IDU
Need to convert hope into actual benefit – Fast-track implementation for Key Populations