Transcript ARV-based prevention

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
www.aids2014.org
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
www.aids2014.org
Prevention
in IDUs
Clinical trial evidence for ARV
prophylaxis
Effect size (CI)
Bangkok Tenofovir Study– daily oral Tenofovir
49% (10; 72)
(IDUs– Thailand)
ART for prevention
96% (73; 99)
HPTN052 Africa, Asia, Americas
Sexual transmission prevention
Partners PrEP – daily Truvada
75% (55; 87)
(Discordant couples – Kenya, Uganda)
Partners PrEP – daily oral Tenofovir
67% (44; 81)
(Discordant couples – Kenya, Uganda)
TDF2 – daily Truvada
62% (22; 84)
(Heterosexuals men and women- Botswana)
iPrEx – daily Truvada
44% (15; 63)
(MSM - America’s, Thailand, South Africa)
CAPRISA 004 – coital Tenofovir gel
39% (6; 60)
(Women – South Africa)
MTN003/VOICE – daily Tenofovir gel
15% (-21; 40)
(Women – South Africa, Uganda, Zimbabwe)
FEMPrEP – daily Truvada
6% (-52; 41)
(Women – Kenya, South Africa, Tanzania)
MTN003/VOICE – daily Truvada
-4% (-49; 27)
(Women – South Africa, Uganda, Zimbabwe)
MTN003/VOICE – daily Viread
-49% (-129; 3)
(Women - South Africa, Uganda, Zimbabwe)
-130
-60
-40
-20
0
20
40
Effectiveness (%)
www.aids2014.org
Source: Adapted from Abdool Karim SS. Lancet 2013
60
80
100
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%)
ARV
prophylaxis
Male
circumcision
Auvert B, PloS Med 2005
Gray R, Lancet 2007
Bailey R, Lancet 2007
Treatment of
STIs
Grosskurth H, Lancet 2000
Microbicides
for women
Female Condoms
Abdool Karim Q, Science 2010
Oral pre-exposure
prophylaxis
HIV
PREVENTION
HIV Counselling
and Testing
Grant R, NEJM 2010 (MSM)
Baeten J , 2011 (Couples)
Thigpen M, 2011 (Heterosexuals)
Choopanya K, 2013 (IDU)
Post Exposure
prophylaxis (PEP)
Scheckter M, 2002
Male Condoms
Coates T, Lancet 2000
Sweat M, Lancet 2011
Treatment for
prevention
Behavioural
Intervention
- Abstinence
- Be Faithful
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
July 2012: First antiretroviral approved
for HIV prevention - Tenofovir + FTC
Weekly / Vol. 61/No.31
August 10, 2012
Interim Guidance for Clinicians Considering the Use of Preexposure
Prophylaxis for the Prevention of HIV Infection in Heterosexually Active Adults
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Source: CDC. MMWR Morb Mortal Wkly Rep. 2011 and 2012
Tardiness in rolling out PrEP
www.aids2014.org
The 7 falsehoods of ARV
prophylaxis to prevent HIV
1. PrEP should only be used for prevention after all eligible AIDS
patients are on treatment
2. It is not safe to give ARVs to healthy people
3. Asymptomatic people will not adhere to ARVs for prevention
or treatment, especially when it is not provided by doctors
4. Data on effectiveness of PrEP, especially in women, are
inconsistent & doubtful efficacy
5. Treatment in discordant couples ≠ community-level prevention
6. Drug resistance from PrEP will undermine future AIDS
treatment
7. PrEP will increase HIV risk by ↓condom use
8. We do not know how to provide PrEP and so need
demonstration projects before PrEP roll-out
www.aids2014.org
PrEP adherence varies by study &
strongly correlates with effectiveness
80
PartnersPreP
(Truvada)
Effectiveness (%)
60
TDF2
PartnersPrep (TDF)
iPrEX
40
CAPRISA 004
20
VOICE (TFV gel)
FemPrEP
0
VOICE (Truvada)
-20
-40
VOICE (TDF)
Pearson correlation = 0.86, p=0.003
-60
0
20
40
60
Adherence by drug levels
www.aids2014.org
80
100
ART by nurses is effective, sustainable
and improved over time in rural SA
www.aids2014.org
The 7 falsehoods of ARV
prophylaxis to prevent HIV
1. PrEP should only be used for prevention after all eligible AIDS
patients are on treatment
2. It is not safe to give ARVs to healthy people
3. Asymptomatic people will not adhere to ARVs for prevention
or treatment, especially when it is not provided by doctors
4. Data on effectiveness of PrEP, especially in women, are
inconsistent & doubtful efficacy
5. Treatment in discordant couples ≠ community-level prevention
6. Drug resistance from PrEP will undermine future AIDS
treatment
7. PrEP will increase HIV risk by ↓condom use
8. We do not know how to provide PrEP and so need
demonstration projects before PrEP roll-out
www.aids2014.org
PrEP effectiveness is high in men &
women with detectable tenofovir
Overall effectiveness
Effectivess based on detectable drug
HIV effectiveness (%)
100
90
80
90
86
74
75
72
67
60
62
40
39
44
27
20
6
0
CAPRISA 004
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iPrEX
PartnersPrep PartnersPreP
(TDF)
(FTC)
TDF2
FemPrEP
The 7 falsehoods of ARV
prophylaxis to prevent HIV
1. PrEP should only be used for prevention after all eligible AIDS
patients are on treatment
2. It is not safe to give ARVs to healthy people
3. Asymptomatic people will not adhere to ARVs for prevention
or treatment, especially when it is not provided by doctors
4. Data on effectiveness of PrEP, especially in women, are
inconsistent & doubtful efficacy
5. Trials in discordant couples ≠ community-level prevention
6. Drug resistance from PrEP will undermine future AIDS
treatment
7. PrEP will increase HIV risk by ↓condom use
8. We do not know how to provide PrEP and so need
demonstration projects before PrEP roll-out
www.aids2014.org
High ART coverage reduces HIV
transmission & increases survival in
a rural African community
www.aids2014.org
The 7 falsehoods of ARV
prophylaxis to prevent HIV
1. PrEP should only be used for prevention after all eligible AIDS
patients are on treatment
2. It is not safe to give ARVs to healthy people
3. Asymptomatic people will not adhere to ARVs for prevention
or treatment, especially when it is not provided by doctors
4. Data on effectiveness of PrEP, especially in women, are
inconsistent & doubtful efficacy
5. Trials in discordant couples ≠ community-level prevention
6. Drug resistance from PrEP will undermine future AIDS
treatment
7. PrEP will increase HIV risk by ↓condom use
8. We do not know how to provide PrEP and so need
demonstration projects before PrEP roll-out
www.aids2014.org
Prevalence of drug
resistance
Drug resistance and condom use in
PrEP / ART
10
8.2
6.6
6
Condom use (%)
4.6
4.2
4
3.3
2.4
2
0.5
0
Overall
Estimated
prevalence of
drug resistance
after 10 years
(2012–2022)
8
ART
ART acquired resistance
0.2
0.3 0.2
PrEP
ART transmitted resistance
0.1
Source: Abbas U, 2013
Overlapping
ART + PrEP
PrEP acquired resistance PrEP transmitted resistance
90
75
60
45
30
15
0
Self-reported
condom use in
the CAPRISA
004 trial
6
www.aids2014.org
12
18
Months in follow-up
24
Source: Adapted from Abdool Karim Q. Science 2010
30
The 8 falsehoods of ARV
prophylaxis to prevent HIV
1. PrEP should only be used for prevention after all eligible AIDS
patients are on treatment
2. It is not safe to give ARVs to healthy people
3. Asymptomatic healthy people will not adhere to ARVs for
prevention or treatment
4. Data on effectiveness of PrEP, especially in women, are
inconsistent & doubtful efficacy
5. Trials in discordant couples ≠ community-level prevention
6. Drug resistance from PrEP will undermine future AIDS
treatment
7. PrEP will increase HIV risk by ↓condom use
8. We do not know how to provide PrEP and so need
demonstration projects before PrEP roll-out
www.aids2014.org
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
www.aids2014.org
Key Population 1:
PrEP & TasP for young women in Africa
Women acquire HIV ±8 years earlier than men
10
Male
Female
8
Prevalence (%)
1990
6
4
2
0
<9
10-14
15-19
20-24
25-29
30-39
Source: Abdool Karim Q, Abdool Karim SS, Singh B, Short R, Ngxongo S.
Seroprevalence of HIV infection in rural South Africa. AIDS 1992, 6:1535-1539
40-49
>49
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
Source: Adapted from UNAIDS 2012
Zimbabwe
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 (24.8-26.5)
0.26
98.5
Bolivia
21.2 (17.6-24.7)
0.13
163.1
scenario 2: MSM risk occur within established HIV epidemics driven by IDU
Serbia
8.7 (5.4-12.0)
0.08
108.8
Georgia
5.3 (1.2-9.4)
0.07
75.7
Scenario 3: MSM risks in context mature & widespread HIV epidemics among
heterosexuals
Nigeria
13.5 (12.0-15.0)
2.88
4.7
Sudan
8.8 (7.1-10.4)
1.26
7.0
www.aids2014.org
Source: Beyrer et al. Epidemiol Rev 2010; 32: 137-51
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
0.59
28.8
221.3
Argentina
0.29
49.7
124.3
Poland
1.50
8.9
148.3
Serbia
1.50
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
www.aids2014.org
Source: Beyrer et al. Epidemiol Rev 2010; 32: 137-51
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
CAPRISA 004
15
41
24
Number of
partners
• 1
• 2-5
• >5
100
60
58
Self-reported STI
41
www.aids2014.org
*number needed to treat
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
www.aids2014.org