Transcript Convergence in the scientific agendas across the HPTN, MTN

Does Africa need a rectal
microbicide?
IRMA and AVAC presentation
27 September 2011
Salim S. Abdool Karim
Pro Vice-Chancellor (Research), University of KwaZulu-Natal
Director: CAPRISA
Professor of Clinical Epidemiology, Columbia University
Adjunct Professor of Medicine, Cornell University
Associate Member, The Ragon Institute of MGH, MIT and Harvard University
Outline
 The HIV epidemic in Africa
 Prevalence of HIV in MSM
 Rates of bisexual partnerships
 Prevalence of anal sex
 Risk factors for unprotected anal intercourse
 A new hope…
 Conclusion
HIV prevalence in
pregnant women in
rural Vulindlela,
South Africa (2005-2008)
Age Group
(Years)
HIV Prevalence
(N=1237)
≤16
10.6%
17-18
21.3%
19-20
33.0%
21-22
44.3%
23-24
51.1%
The HIV epidemic in Africa:
HIV prevalence by age and sex in four
African countries
Kenya
Men
Men
Women
Women
20
HIV prevalence (%)
HIV prevalence (%)
Malawi
25
15
10
5
15
10
5
0
0
15-19
20-24
25-29
30-34
35-39
40-44
45-49
50-54
15-19
55-59
50
Cameroon
Men
10
5
25-29
30-34
35-39
40-44
Lesotho
45-49
Men
Women
40
Women
HIV prevalence (%)
HIV prevalence (%)
15
20-24
30
20
10
0
15-19
20-24
25-29
30-34
35-39
40-44
45-49
50-54
55-59
0
15-19
20-24
25-29
30-34
35-39
40-44
45-49
50-54
55-59
The HIV epidemic in Africa:
The hidden side
African Men who have Sex with Men
 Population-level data on MSM are rare
• same-sex relations are criminalized in 37 out of 54 African
countries and are punishable by death in four of these.
 Recent studies on MSM sex workers indicates
widespread existence of MSM groups in Africa
• Mombasa, Kenya:
± 739 MSM sex workers working in the city
• Johannesburg, South Africa:
± 496 MSM sex workers (95% CI 437–555)
working in city on any given Saturday night
The HIV epidemic in Africa:
A mosiac of both heterosexual and
homosexual HIV transmission
Source: UNAIDS. 2006 Report on the global AIDS epidemic. UNAIDS, Geneva
HIV
prevalence
among MSM
in Africa
HIV prevalence
in MSM:
Range:
6.2% in Egypt
to
30.9% in Cape Town
Source: Griensven et al.
Current Opinion in HIV and AIDS
2009, 4:300–307
Estimates of HIV prevalence
among MSM in sub-Saharan Africa
Year
HIV prevalence (95%CI)
n
2002–2005
10.6% (9–13)
780
Tanzania
2007
12.3% (10–15)
509
Nigeria
2006
13.4% (11–15)
1125
2003–2005
14.1% (12–17)
728
Malawi
2008
21.4% (16–28)
201
Senegal
2007
21.8% (18–25)
501
Zambia
2006
33% (29–37)
641
Kenya
South Africa
Adapted from: Smith AD, et al. Men who have sex with men and HIV/AIDS in sub-Saharan Africa. Lancet 2009; 374: 416–22
Factors associated with HIV
infection among MSM
 In South Africa
• Soweto Men's Study (N=378) HIV infection
associated with:
• 6-9 partners (past 6 months) (OR 5.7, CI 4.0-8.2)
• any unprotected anal sex*
(OR 4.4, CI 3.5-5.7)
*past 6 months
 In Kenya
• Prevalent HIV infection in MSM (n=285) was
associated with:
• recent receptive anal sex (OR, 6.1; CI, 2.4-16)
• exclusive sex with men (OR, 6.3; CI, 2.3-17),
Rates of bisexual partnerships in
Africa
 In Malawi, Namibia and Botswana
• cross-sectional study of MSM (n=537) showed:
• 34.1% were married or had a stable female partner,
• 53.7% had both male and female sexual partners
 In Egypt
• Survey among MSM (n=73) showed:
• 73.3% of MSM reported being bisexual
 In Kampala, Uganda
• Survey among MSM (n=224) reported:
• 39% self-identified as "bisexual”
Studies providing estimates of
heterosexual sex among MSM (2003–2007)
Global studies
(range of results)
African studies
(range of results)
Heterosexual sex in MSM, lifetime
20 (25–86)
3 (41–86)
Heterosexual sex in MSM, last year
16 (8–98)
2 (50–69)
Proportion of MSM who are married
16 (3–42)
2 (8–15)
Source: Caceres, C. F., et al. (2008). Sex Transm Infect 84 Suppl 1: i49-i56.
Anal intercourse in heterosexual
men & women
 In Cape Town, South Africa:
• Anonymous surveys of 2593 men and 1818 women:
• Anal intercourse (past 3 months): Men = 14%; Women = 10%
• Condom use during anal intercourse: Men = 67%; Women = 50%
Kalichman et al (2009)
 In KwaZulu-Natal, South Africa:
• 42% of truck drivers (n=320) reported anal sex with female sex workers
Ramjee et al (2002)
 In Kenya:
• Survey among FSW (n=147):
• 40.8% reported ever practising anal intercourse, 30% reported never or
rarely using condoms during anal intercourse
• consistent condom use lower in anal sex than peno-vaginal intercourse
Schwandt et al (2006)
 In Nigeria:
• anal sex practiced by 12% of public secondary schools students (N= 521)
Bamidele et al (2009)
Factors associated with unprotected
anal intercourse (UAI) in Africa
 Cameroon: UAI risk increased in those not knowing any
HIV-infected person (N=168, OR 1.89)
Henry et al (2010)
 South Africa: UAI risk associated with regular drinking
(N=147; OR 4.1)
Lane et al. (2008)
 Uganda: UAI associated with having had an HIV test in
the past 6 months (N=215, OR 2.81)
Raymond et al (2009)
 Kenya: UAI linked to poor knowledge of increased HIV
risk from UAI (N=425, OR: 1.9)
Geibel et al. (2008)
Risks associated with unprotected
anal intercourse: HIV transmission
Source: Baggaley et al. Int. J. Epidemiol. Advance Access published April 20, 2010
A new hope…
July 2010: Proof of Concept for microbicides
1st class:
Surfactants
2nd class:
Polymers
3rd class:
ARVs
eg. N9, SAVVY
eg. PRO2000,
Carraguard,
Cellulose Sulfate (CS)
eg. Tenofovir gel
Kenya
N-9 sponge
trial
CONRAD
CS trial
FHI CS
Trial
FHI
N-9 film trial
PopCouncil
Carraguard trial
UNAIDS
COL-1492
trial
HPTN
PRO2000 &
BufferGel
trial
FHI SAVVY
trial
CAPRISA 004
Tenofovir gel trial
MTN003 –VOICE
Tenofovir gel & tablet trial
FACTS 001
Tenofovir gel trial
CAPRISA 008
Tenofovir gel
implementation
trial
MDP 0.5%
PRO2000
trial
2%
IPM
dapivarine
ring
PRO2000
‘90
‘92 ’98 ’00
Safe but not effective
‘03
‘04 ‘04 ’05
Increased HIV infection
’05
’07 ’09
‘11
Stopped for futility
Effective
Planned
23
November 2010: Oral PrEP
prevents HIV in MSM – iPrEx trial
131 infections after
randomization
83 in
48 in
FTC/TDF placebo
• Primary HIV analysis (1 May): 44% protection
• At the end of the study: 42% (95% CI 18%-60%)
• No effect on HSV-2 TDF-DP drug levels in blood << EC50 for HSV
25
CAPRISA 004 and iPrEX trials are in Science’s
Top 10 Scientific Breakthroughs in 2010
May 2011: Proof that ART
prevents HIV transmission from
infected partners (HPTN 052)
- 1763 discordant couples
- 13 sites in Africa, America & Asia
- ART at CD4 up to 550 vs only <250
- HIV incidence (placebo) = 2.2 per 100pys
- 28 matched HIV infn: 27 in delayed ART
- 96% effective (excl. non-matched viruses)
- Trial halted early for effectiveness
July 2011: Oral PrEP prevents
HIV transmission in discordant
couples (PartnersPrEP)
-
4,758 HIV serodiscordant couples enrolled
Kenya and Uganda
Daily oral TDF or TDF/FTC or Placebo
HIV incidence (placebo group) = 1.9 per 100pys
78 HIV infections after randomization
- 18 in TDF arm (62% protection)
- 13 in FTC/TDF arm (73% protection)
- 47 Placebo
July 2011: Oral PrEP prevents
HIV in heterosexual men &
women (Botswana TDF2)
-
1219 heterosexual men & women enrolled
Botswana
Daily oral TDF-FTC
HIV incidence rate (placebo) = 3.1 per 100pys
33 HIV infections after randomization
- 9 in FTC/TDF arm (63% protection)
- 24 in Placebo
Clinical trial evidence for preventing
sexual HIV transmission – July 2010
Study
Effect size (CI)
Medical male circumcision
54% (38; 66)
STD treatment
42% (21; 58)
HIV Vaccine
31% (1; 51)
(Orange Farm, Rakai, Kisumu)
(Mwanza)
(Thai RV144)
0%
10
20
30
40
50
60
Efficacy
70
80
90 100%
Clinical trial evidence for preventing
sexual HIV transmission – July 2011
Study
Treatment for prevention
Effect size (CI)
96% (73; 99)
PrEP for discordant couples
73% (49; 85)
PrEP for heterosexuals
63% (21; 48)
Medical male circumcision
54% (38; 66)
PrEP for MSMs
44% (15; 63)
STD treatment
42% (21; 58)
Microbicide
39% (6; 60)
HIV Vaccine
31% (1; 51)
(Africa, Asia, America’s)
(Partners PrEP)
(Botswana TDF2)
(Orange Farm, Rakai, Kisumu)
(America’s, Thailand, South Africa)
(Mwanza)
(CAPRISA 004 tenofovir gel)
(Thai RV144)
0%
10
20
30
40
50
60
Efficacy
70
80
90 100%
Microbicides
for women
Abdool Karim Q, Science 2010
Male
circumcision
Auvert B, PloS Med 2005
Gray R, Lancet 2007
Bailey R, Lancet 2007
Treatment of
STIs
Grosskurth H, Lancet 2000
Treatment for
prevention
Female Condoms
Donnell D, Lancet 2010
Cohen M, NEJM 2011
Behavioural positive
prevention
Fisher J, JAIDS 2004
COMBINATION
HIV
PREVENTION
Male Condoms
HIV Counselling
and Testing
Oral pre-exposure
prophylaxis
Coates T, Lancet 2000
Grant R, NEJM 2010 (MSM)
Baeten J , 2011 (Couples)
Paxton L, 2011 (Heterosexuals)
Post Exposure
prophylaxis (PEP)
Scheckter M, 2002
Behavioural
Intervention
Vaccines
Rerks-Ngarm S, NEJM 2009
- Abstinence
- Be Faithful
Note: PMTCT, Screening transfusions, Harm reduction, Universal precautions, etc.
have not been included – this is focused on reducing sexual transmission
Microbicides
for women
Abdool Karim Q, Science 2010
Male
circumcision
Auvert B, PloS Med 2005
Gray R, Lancet 2007
Bailey R, Lancet 2007
Treatment of
STIs
Grosskurth H, Lancet 2000
Treatment for
prevention
Donnell D, Lancet 2010
Cohen M, NEJM 2011
Behavioural positive
prevention
Fisher J, JAIDS 2004
Female Condoms
HIV
PREVENTION
FOR MSM
Male Condoms
HIV Counselling
and Testing
Oral pre-exposure
prophylaxis
Coates T, Lancet 2000
Grant R, NEJM 2010 (MSM)
Baeten J , 2011 (Couples)
Paxton L, 2011 (Heterosexuals)
Post Exposure
prophylaxis (PEP)
Scheckter M, 2002
Behavioural
Intervention
Vaccines
Rerks-Ngarm S, NEJM 2009
- Abstinence
- Be Faithful
Note: PMTCT, Screening transfusions, Harm reduction, Universal precautions, etc.
have not been included – this is focused on reducing sexual transmission
Limitations of current HIV
prevention in Africa
 MSM and their needs are largely ignored in HIV
prevention and treatment efforts in Africa
 Most AIDS prevention messages are targeted at
heterosexual men and women emphasizing the risks
of transmission through peno-vaginal sex and not
through anal intercourse
 The needs of the many women who are unable to get
men to use condoms in anal sex are ignored
 Hence the need for a rectal microbicide in Africa…
WHO is preparing to develop guidelines for
tenofovir gel implementation for women
Conclusion
 HIV spreading in MSM AND heterosexuals in Africa
 Unprotected anal sex is a key HIV risk factor
 Current HIV prevention efforts are unable to contain
or reduce the spread of HIV infection thro anal sex
 Combating HIV is not only about scaling-up proven
prevention – but also new prevention technologies
 A rectal microbicide, as a new HIV prevention
technology is urgently needed in Africa for the large
number of people practicing anal sex, ie:
• Men who have Sex with Men
• Bisexual men
• Women