1. Behavior Change Interventions to Prevent HIV among Women Living in Low and Middle Income Countries Sandra I. McCoy, MPH PhD 1 R. Abigail Kangwende, MPH MD 2 Nancy S. Padian, MPH PhD 1,3 1 RTI International, San Francisco, California, USA 2 Africa University, Mutare, Zimbabwe 3 Center of Evaluation for Global Action, University of California, Berkeley, California, USA Perspectives on Impact Evaluation Conference ● April 2, 2009 ● Cairo, Egypt

2. Women and HIV Infection Globally, women and girls are especially vulnerable to HIV infection Globally, women and girls are especially vulnerable to HIV infection Women represent ~50% of all people with HIV infection, but 59% in Sub-Saharan Africa Women represent ~50% of all people with HIV infection, but 59% in Sub-Saharan Africa Structural and social factors drive transmission in women and decrease women’s ability to avoid HIV infection Structural and social factors drive transmission in women and decrease women’s ability to avoid HIV infection Gender inequities■ Violence Gender inequities■ Violence Harmful gender norms■ Poverty Harmful gender norms■ Poverty Lack of education Lack of education

3. HIV Prevalence by Age and Sex among 15-24 year olds, Zimbabwe, 2001 Source: Ministry of Health and Child Welfare (Zimbabwe), Zimbabwe National Family Planning Council, National AIDS Council (Zimbabwe), and U.S. Centers for Disease Control and Prevention. 2004. The Zimbabwe Young Adult Survey 2001-2002.

4. HIV Prevention Approaches HIV prevention for women has been discouraging Not (yet) effective: female barrier methods, microbicides, and vaccines Not (yet) effective: female barrier methods, microbicides, and vaccines Male circumcision may not directly lower women’s risk Male circumcision may not directly lower women’s risk Male and female condoms require male partner knowledge and consent Male and female condoms require male partner knowledge and consent Sexually transmitted disease (STD) services may not be available to all women, esp. those in the developing world Sexually transmitted disease (STD) services may not be available to all women, esp. those in the developing world

5. HIV Prevention Approaches HIV prevention for women has been discouraging Not (yet) effective: female barrier methods, microbicides, and vaccines Not (yet) effective: female barrier methods, microbicides, and vaccines Male circumcision may not directly lower women’s risk Male circumcision may not directly lower women’s risk Male and female condoms require male partner knowledge and consent Male and female condoms require male partner knowledge and consent Sexually transmitted disease (STD) services may not be available to all women, esp. those in the developing world Sexually transmitted disease (STD) services may not be available to all women, esp. those in the developing world HIV prevention efforts in women (and men) must continue to focus on behavior change

6. Behavior Change for HIV Prevention Behavior change interventions aim to: Delay age of sexual debut Delay age of sexual debut Decrease the number of sexual partners or timing of partnerships (e.g., concurrency) Decrease the number of sexual partners or timing of partnerships (e.g., concurrency) Increase protected sex acts Increase protected sex acts Increase voluntary counseling and testing (VCT) Increase voluntary counseling and testing (VCT) Improve adherence to other successful strategies (e.g., condoms) Improve adherence to other successful strategies (e.g., condoms) Source: Coates, T. Lancet 2008; 372:669-84

7. Behavior Change for HIV Prevention Focus on individuals, peers, couples, groups, families, institutions, or communities Focus on individuals, peers, couples, groups, families, institutions, or communities Need to incite change in enough people for enough time to impact population transmission dynamics Need to incite change in enough people for enough time to impact population transmission dynamics Behavioral change interventions are effective at reducing reported HIV-related risk behaviors in : Behavioral change interventions are effective at reducing reported HIV-related risk behaviors in : MSM (Herbst 2005) MSM (Herbst 2005) STD clinic patients (Crepaz 2007) STD clinic patients (Crepaz 2007) U.S. adolescents (Mullen 2002) U.S. adolescents (Mullen 2002) Heterosexual African Americans (Darbes 2008) Heterosexual African Americans (Darbes 2008) People living with HIV (Crepaz 2006) People living with HIV (Crepaz 2006)

8. Impact on HIV, Behavior, and STIs Untangling this (population-level) relationship is critical: Untangling this (population-level) relationship is critical: Intervention Behavior change (how much?) ↓ HIV ↓ Other STIs ? ? ?

9. Behavioral Intervention Trials Few studies of behavioral interventions for HIV prevention are evaluated with rigorous designs and with HIV infection as an outcome Few studies of behavioral interventions for HIV prevention are evaluated with rigorous designs and with HIV infection as an outcome Evaluation of HIV incidence is critical: Evaluation of HIV incidence is critical: Reported behavior can be biased Reported behavior can be biased Behavior is inconsistently related to STIs, including HIV Behavior is inconsistently related to STIs, including HIV The ultimate objective is to prevent HIV infection The ultimate objective is to prevent HIV infection

10. Goal Systematically review and summarize the effect of behavioral change interventions for HIV prevention in women and girls living in low and middle income countries Systematically review and summarize the effect of behavioral change interventions for HIV prevention in women and girls living in low and middle income countries

11. Study Inclusion Criteria Dates:1990 - February 28, 2009 Designs:Randomized controlled trials, quasi-experimental, or prospective designs with a control group Settings:Low- and middle-income countries Outcome:Incident HIV infection Language:No restrictions Grey Literature: Yes (meeting abstracts) Population:Stratified, female-only estimate OR combined estimate where women were at least 50% of population

12. Study Inclusion Criteria Eligible interventions included, but not limited to: Individual or group counseling Individual or group counseling Conditional and unconditional cash transfers Conditional and unconditional cash transfers Targeted messages and social marketing campaigns Targeted messages and social marketing campaigns School-based HIV prevention education School-based HIV prevention education Voluntary counseling and testing Voluntary counseling and testing Vocational training Vocational training Empowerment training Empowerment training Non-cash incentives (like school uniforms) Non-cash incentives (like school uniforms) Social support programs Social support programs Condom promotion Condom promotion Control interventions could be inactive (e.g., no treatment, waiting list control, or standard of care) or active (e.g., a diluted or different variant of the intervention being investigated) Per-protocol analyses acceptable if community RCT

13. Systematic Review Methods Systematic search of: PubMed/MEDLINE PubMed/MEDLINE Cochrane Library, including: Cochrane Library, including: Cochrane Central Register of Controlled Trials (CENTRAL) Cochrane Central Register of Controlled Trials (CENTRAL) Database of Abstracts of Reviews of Effects (DARE) Database of Abstracts of Reviews of Effects (DARE) PsycInfo PsycInfo Sociological Abstracts Sociological Abstracts Web of Science Web of Science African Index Medicus African Index Medicus Regional Index for Latin America and the Caribbean: Virtual Health Library Regional Index for Latin America and the Caribbean: Virtual Health Library IndMed IndMed NLM Gateway NLM Gateway

14. Systematic Review Methods Communication with investigators for other studies and unpublished trials Communication with investigators for other studies and unpublished trials Current Controlled Trials Register Current Controlled Trials Register International Clinical Trials Registry Platform Search Portal International Clinical Trials Registry Platform Search Portal clinical trials.gov clinical trials.gov Computer Retrieval of Information on Scientific Projects (CRISP) Computer Retrieval of Information on Scientific Projects (CRISP) Cited Reference Search (Web of Science) of key articles Cited Reference Search (Web of Science) of key articles Reviewed reference lists of included papers and other reviews Reviewed reference lists of included papers and other reviews Searched recent conference websites Searched recent conference websites Conference on Retroviruses and Opportunistic Infections (CROI) Conference on Retroviruses and Opportunistic Infections (CROI) International AIDS Society (IAS) International AIDS Society (IAS) International Society for STD Research (ISSTDR) International Society for STD Research (ISSTDR)

15. 3,864 potentially relevant articles retrieved from electronic databases 599 articles eligible for abstract-level review 3,265 articles excluded after title-level review (e.g., excluding studies in men, those in the USA, other types of interventions) 48 articles for detailed review 551 articles excluded after abstract level review (e.g., studies without biological outcomes or uncontrolled designs) 195 studies of behavioral interventions in women and girls without HIV infection as an outcome 8 met inclusion criteria 3 new eligible articles identified via reference lists 11 articles included in review (8 unique study populations) Literature Search

16. Results: 11 Included Studies Author (year) TypePopulationFollow-upLocation Bhave (1995) Quasi- experimental Female sex workers and madams1 yearMumbai, India Kamali (2003)C-RCTResidents of study communities3-4 yearsMasaka District, Uganda Quigley (2004)C-RCT (PP)Sexually active adults3-4 yearsMasaka District, Uganda Matovu (2005)CohortResidents of study communities1 yearRakai District, Uganda Pronyk (2006)C-RCTResidents of study communities3 yearsLimpopo Province, South Africa Gregson (2007a)C-RCTResidents of study communities3 yearsManicaland Province, Zimbabwe Gregson (2007b)C-RCT (PP)Residents of study communities3 yearsManicaland Province, Zimbabwe Ross (2007)C-RCTAdolescents (years 4-6 of school)3 yearsMwanza Region, Tanzania Jewkes (2008)C-RCTResidents of study communities2 yearsEastern Cape Province, South Africa Patterson (2008)I-RCTFemale sex workers6 monthsTijuana & Ciudad Juarez, Mexico Doyle (2009)C-RCT (LT)Adolescents (years 4-6 of school)6-8 yearsMwanza Region, Tanzania C-RCT=Community randomized controlled trial, I-RCT=individual randomized controlled trial, PP=per protocol, LT=Long term

17. Intervention Characteristics InterventionTargetDeliveryDuration Group educational and motivational sessions Sex workersG 6 months; 3-4 groups discussions and 3-4 video viewing groups Information, education, and communication Adult men and womenI, GActivities throughout 3-4 year study HIV VCTAdult men and womenI, COne post-test counseling session IMAGE – microfinance + SFL behavior program Community residentsI, G, CM 15-21 months; loan center mtgs. & 12-15 month curriculum meetings every 2 weeks Peer education, condoms, and STI services Sex workers, adult residents I, G, CM Activities throughout 3 year study MEMA kwa VijanaAdolescents I, G, CM Activities throughout the 3 year period; annually, 12 40-min school sessions, youth health weeks & days, video shows Stepping StonesMen and women 15-26G, CM 6-8 weeks; 13 3-hr single sex groups, 3 peer groups, and a community meeting Mujer SeguraSex workersI35-min counseling session G=Group, I=individual, C=couple, CM=community

18. Impact on HIV incidence * Note: Quigley (2004) and Gregson (2007b) are per-protocol analyses of C-RCTs described in Kamali (2003) and Gregson (2007a). Doyle (2009) is the 6-8 year follow-up of the MKV study described in Ross (2007).

19. Impact on Behavior and STIs Author (year) Reduced HIV Incidence? Reduced Risk Behavior? Reduced Other STIs? Bhave (1995) Yes Yes: ↑ Condom use with clients Yes: ↓ Syphilis, HBV Kamali (2003) NoNo Yes: ↓ HSV-2* Quigley (2004) YesNoNR Matovu (2005) NoNoNR Pronyk (2006) NoNoNR Gregson (2007a) NoNoNR Gregson (2007b) NoNRNR Ross (2007) NoNoNo Jewkes (2008) NoNo Possibly ↓ HSV-2** Patterson (2008) No Yes: ↑ Condom use, total protected sex Yes: ↓ “Any STI” Doyle (2009) No Yes: ↑ Condom use with non-regular partner No NR=not reported, HBV=Hepatitis B Virus, HSV=Herpes Simplex Virus * No effect found for active syphilis, Chlamydia, or gonorrhea ** Incidence rate ratio for women: 0.69, 95% CI (0.47, 1.03)

20. Conclusions Only two of 11 studies in women and girls showed an effect on HIV incidence Only two of 11 studies in women and girls showed an effect on HIV incidence 3 of 10 studies reduced any risk behavior 3 of 10 studies reduced any risk behavior 4 of 6 studies reduced STI incidence (non-HIV) 4 of 6 studies reduced STI incidence (non-HIV) Important research and prevention gaps remain Important research and prevention gaps remain How and whether to incorporate behavioral change programs into existing prevention packages in the absence of clear data on effectiveness How and whether to incorporate behavioral change programs into existing prevention packages in the absence of clear data on effectiveness

21. Limitations One study not peer-reviewed (meeting abstract) One study not peer-reviewed (meeting abstract) Per-protocol analyses included & 1 follow-up Per-protocol analyses included & 1 follow-up Potential to miss studies if biological outcomes not reported in abstract Potential to miss studies if biological outcomes not reported in abstract Potential to miss studies from other databases Potential to miss studies from other databases Variable statistical power to detect effects Variable statistical power to detect effects

22. Ongoing Behavioral Intervention Trials for HIV Prevention NameTypeLocationInterventionResults Community Popular Opinion Leader (CPOL) C-RCTChina, India, Peru, Russia, Zimbabwe 15% of population trained as CPOLs to diffuse HIV prevention messages 2009 Regai Dzive Shiri C-RCT30 communities in Zimbabwe Youth, community, and clinic- based prevention intervention for adolescents 2009-2010 Project ACCEPT C-RCT34 communities in South Africa, Tanzania, and Zimbabwe and 14 in Thailand Community-based HIV VCT intervention plus standard clinic- based VCT (SVCT), or SVCT alone 2011

23. Acknowledgements International Initiative for Impact Evaluation (3ie) Center of Evaluation for Global Action (CEGA), University of California, Berkeley Women’s Global Health Imperative (RTI International)

24. Questions?

25. HIV Prevalence by Age and Sex among 15-24 year olds, South Africa, 2003 Source: Pettifor, A. AIDS 2005;19:1525-34.

26. Data Abstraction Data were abstracted from each eligible study by one investigator (SM) and reviewed for accuracy Data were abstracted from each eligible study by one investigator (SM) and reviewed for accuracy Most adjusted measure of effect on HIV incidence (e.g. incidence rate ratio or risk ratio) in women Most adjusted measure of effect on HIV incidence (e.g. incidence rate ratio or risk ratio) in women Overall incidence rate ratio if women-only not presented Overall incidence rate ratio if women-only not presented Measure of effect and/or 95% CI calculated if necessary Measure of effect and/or 95% CI calculated if necessary Trial years, location, population, intervention Trial years, location, population, intervention Impact on knowledge, behavior and other sexually transmitted infections, when available, in women Impact on knowledge, behavior and other sexually transmitted infections, when available, in women

27. Why don’t behavioral interventions translate to reductions in HIV incidence? Greater than observed behavioral change required Greater than observed behavioral change required Follow-up times too short Follow-up times too short Behavior changes misreported Behavior changes misreported Traditionally “low-risk” women may be at high-risk independent of their personal behavior Traditionally “low-risk” women may be at high-risk independent of their personal behavior We are measuring the wrong behavioral intermediates We are measuring the wrong behavioral intermediates Sexual networks or concurrency, or Sexual networks or concurrency, or Which behavior is important depends on the STI in question Which behavior is important depends on the STI in question Structural factors (e.g., poverty) further up the causal chain drive transmission and individual behavior Structural factors (e.g., poverty) further up the causal chain drive transmission and individual behavior

28. Impact on HIV, Behavior, and STIs Despite variability in the intensity, delivery, and target populations, only 2 interventions reduced HIV incidence Despite variability in the intensity, delivery, and target populations, only 2 interventions reduced HIV incidence 6-month program for female sex workers in India 6-month program for female sex workers in India ↑ condom use with clients, ↓ syphilis and HBV infection ↑ condom use with clients, ↓ syphilis and HBV infection Per-protocol analysis of sexually active women in Uganda who attended at least one intervention activity Per-protocol analysis of sexually active women in Uganda who attended at least one intervention activity No reduction in risk behavior, STIs not measured No reduction in risk behavior, STIs not measured

29. Intervention Characteristics InterventionStudy(s)TargetDeliveryDuration Group educational and motivational sessions Bhave (1995)Sex workersGroup6 months; 3-4 video viewing groups, 3-4 group discussions Information, education, and communication Kamali (2003) Quigley (2004) Adult men and women Individual and groupActivities implemented throughout the 3-4 year study period Voluntary HIV counseling and testing Matovu (2005)Adult men and women Individual and couplesOne session IMAGE – microfinance + behavior program Pronyk (2006)Community residents Individual, group, and community 15-21 months; loan center mtgs. and 12-15 month curriculum meetings every 2 weeks Peer education, condoms, and STI services Gregson (2007a) Gregson (2007b) Sex workers, adult residents Individual, group, and community Activities implemented throughout the 3 year study period MEMA kwa VijanaRoss (2007) Doyle (2009) AdolescentsIndividual, group, and community Activities implemented throughout the 3 year period; annually, 12 40- min school sessions, youth health weeks & days, and video shows Stepping StonesJewkes (2008)Men and women 15-26 Group and community6-8 weeks; 13 3-hr single sex groups, 3 meetings of peer groups, and a community meeting Mujer SeguraPatterson (2008)Sex workersIndividual35-min counseling session