Domestic HIV Prevention Research Agenda: Women At Risk

1. Domestic HIV Prevention Research Agenda:Women At Risk June 7, 2007

2. DWPG-Women at Risk Members Andrew Forsyth Ada Adimora Ann O'Leary Cathie Fogel Danielle Haley David Burns David Metzger David Purcell Dawn Smith Dianne Rausch Eunice Ramirez-Dilone Gina Wingood Jessica Justman Jim Hughes Katherine Davenny Kendall Bryant Nicolette Borek Nirupama Sista Peter Kilmarx Quarraisha Abdool Karim Richard Jenkins Richard Wolitski Sally Hodder Sandra Lerhman Scott Rose Sheryl Zwerski Sten H. Vermund Sue Gibson Tim Mastro Victoria Cargill Vanessa Johnson Wafaa El-Sadr Waheedah Shabbaz-El

3. Outline • Epidemiology of HIV in US women • Defining populations at risk • HIV incidence in US women • Gap analysis • Review biomedical and behavioral interventions in women • Gap delineation • Proposed concepts

7. New Jersey HIV Prevalence (per 100,000 women) • State of New Jersey 263 • Newark EMA 618 • Essex County 927 • Newark 1417 • Black women in Newark 2673

8. Persons living with AIDS in Philadelphia, June 2006

12. North Carolina HIV/STI Rates, 2006

13. HIV Incidence in US women makes RCT feasible • 3.14/100 PY Baltimore IDU • 2.32/100 PY Philadelphia, Black Women • 4.1/100PY Atlanta, GA VCT Clinic (81% African-American and 40% female recruited in 02-04 using BED EIA) • 1.33/100 PY Control Arm, Rakai Circumcision Trial Strathdee SA et al Arch Int Med 161:1281, 2001; Metzger D, Unpublished Data; Gray et al, Lancet Feb 2007; Priddy, F et al., JAIDS, 2007

14. Risk Factors for HIV incidence among STI clinic attendees • Dates: 1993-2002 • Location: Baltimore • Size: 10,535 (13,693 py) • Incidence: 0 .91 / 100 PY (overall) 4.86 / 100 PY (HIV+ partner) 3.06 / 100 PY (IDU) 2.40 / 100 PY (genital ulcers) Metha SD et al, JAIDS, 2006

15. Young Blacks with Low Risk Behavior Have More HIV Than Young Whites Behavior Pattern Adjusted* Odds Ratio Blacks to Whites Low Risk Behavior 24.9 *Adjusted for gender, marital status, school dropout, poverty Hallfors et al. Am J Pub Health 97:125, 2007

16. Target Population • African - American Women • Location, location, location • Partner characteristics • Individual characteristics Black High risk male partner Recent STI: HSV2GC HIV Prevalent Home Neighborhood HIV + male partner Drug use: IDU Cocaine Geography Partner Characteristics Women’s Characteristics

17. HIV and Incarceration: Parallel Epidemics • 1 in 3 black men will be incarcerated (lifetime) compared with 1 in 17 white men • Black women are 7 times more likely to be incarcerated during their lifetime than White women • In NC state prison system, estimated HIV prevalence rate is 1.9% for men and 3.1% for women • Approximately 10-20% of 14,000 inmates in NYC jails are HIV+ • In 1999, 18% of new female entrants in NYC jails were HIV+ compared to 7.6% of men Freundenberg, 2002; Hammett et al, 2002; BJS, 2006; NYC Department of Health, 1999 and 2006

18. AIDS in Prison

19. Interventions in Women • Biomedical • Behavioral

20. Biomedical Interventions in Women Exclusive of Vaccine & Microbicide Studies • PREP: West Africa Study complete but lacking power to demonstrate efficacy • Ongoing studies in women (non-US): • HSV suppression • Diaphragm • PREP • STI treatment as an intervention to lower HIV demonstrated conflicting data (non US)

21. STI Treatment to Prevent HIV • “STI treatment may decrease HIV incidence in emerging HIV epidemic (low & slowly rising prevalence)” Grosskurth H, 1995; Kamali A, 2003, Wawer, 1999; Sangani, 2004

22. Evidence-Based Behavioral Interventions Targeting Women (Lyles, et al, 2007)

24. Existing Gaps in Domestic HIV Prevention in Women • Few biomedical intervention trials have been completed • Conflicting data on STI treatment • No PEP studies • No PREP efficacy • Small number of evidence-based behavioral interventions available for population • No studies with HIV seroconversion as an endpoint • Durability of intervention is unknown as follow-up limited to < 1 year • Few studies specifically address social networks • Few studies target intervention to women’s partners

25. Existing Gaps in Domestic HIV Prevention in Women (cont.) • Internet as a social networking tool on HIV transmission in women • Scant data on alcohol and non-IDU interventions • Effectiveness studies lacking • Cost Effectiveness of prevention interventions

26. Unifying Themes • Interventions to focus on identified populations with high HIV prevalence/incidence (by U.S. standards) • Decrease HIV acquisition in at-risk women • Decrease HIV transmission by their male partners • Consideration of biomedical & behavioral interventions (stand alone or in combination) • HIV incidence as the primary endpoint • Duration of follow-up > 1 year

27. Concepts • nPEP in HIV- women: • Vanguard cohort • Definitive study • STI Treatment • Behavioral intervention in HIV+ men • Behavioral intervention in HIV- women being released from prison and jails • Combined Intervention

28. nPEP Concept: Impact of Access to Non-occupational Post-Exposure Prophylaxis • Rationale: • nPEP guidelines exist and nPEP is in use yet no RCT studies of nPEP have been done • Little to no data on use of nPEP in women • Combinations of interventions need to be assesses • Objectives • To assess the impact of access to nPEP using a combined nPEP plus behavioral/informational approach on HIV seroincidence among HIV-negative African-American women with defined high risk factors

29. nPEP Concept: Design • Phase III randomized control trial with 2 arms, and 2 years of follow-up: • Arm 1: Control group: group counseling sessions to include brief risk reduction/safe sex content plus other content such as money management, nutrition, exercise. Participants will receive condoms. • Arm 2: nPEP Plus: group counseling sessions to include brief risk reduction/safe sex content, plus discussion of nPEP, and a supply of condoms and nPEP (such as TDF/ZDV/3TC) to be commenced immediately after unprotected vaginal or anal intercourse. Four weeks of ART would be recommended after an exposure. • Background seroincidence rate: May be estimated by running BED-type detuned assays on all the HIV-positive women screened for the study, plus NAAT for HIV RNA on pooled samples from all HIV-negative women screened and otherwise eligible.

30. nPEP Concept • Endpoints • Primary: HIV seroincidence (monthly vs quarterly testing) • Secondary: combined HIV + STI incidence, condom use frequency, nPEP use frequency and acceptability, # partners with risk characteristics • Inclusion Criteria HIV-negative African American women with at least one defining risk factors: • sexual intercourse with HIV-infected male partner(s) at least once once in 30 days prior to screening [known status vs unknown status] • number of lifetime partners, • history of exchanging sex for drugs or money, • history of > 2 STIs, • substance use history • recent or anticipated release from jail or prison • other sexual network characteristics (to be further defined);

31. nPEP Concept: Discussion Points • control group: low intensity intervention vs. higher intensity behavioral intervention? • Advantage of low intensity: ability to assess impact of a more feasible intervention. • Advantage of higher intensity: ability to assess impact of nPEPControl group: • Inclusion criteria: sexual intercourse with HIV-infected male partner(s) at least once once in 30 days prior to screening [known status vs unknown status] • Will many PEP users repeat PEP frequently, and therefore approximate PREP? • Monthly, every other month or quarterly study visits?

32. nPEP: Vanguard study • Qualitative study of nPEP among women who would be potential participants • Focus groups • Individual interviews • Acceptability, HIV risk perceptions, awareness of nPEP, awareness of other prevention methods

33. Intensive STI Treatment • Rationale: • Conflicting data regarding efficacy of STI treatment to decrease HIV acquisition • At risk women of color reside in communities with high STI rates • Design: Phase III RCT with a 24 month follow-up period. • Study Population: HIV-negative African American women with at least one defining risk factors: • sexual intercourse with HIV-infected male partner(s) at least once once in 30 days prior to screening • history of exchanging sex for drugs or money, • history of > 2 STIs, • substance use history

34. Intensive STI Treatment • Intervention: Arm 1: (Control group) safe sex and condom distribution Arm 2: Intensive (3X yearly) assessment/treatment for gonorrhea, Chlamydia, and syphilis • Endpoints: • Primary: HIV seroincidence (yearly testing) • Secondary: Episodes of unprotected sex # partners

35. Intensive STI TreatmentDiscussion Points • Exclusion of HSV-2 seropositive persons • Partner treatment vouchers • Frequency of follow-up • Sample size requirements

36. Behavioral Intervention Targeting African-Americans HIV+ men & their female partners • Rationale: Few HIV prevention studies target African-American males. Innovative study designed to reduce HIV in female partners. • Design: A phase III RCT with an 18-month follow-up period. • Sample: HIV+ African-American males, 18 and older recruited from various venues (HIV clinics, STI clinics, prisons) and who have had vaginal/anal sex with female sexual partner. And female sexual network partners, 18 years+ who provide consent. • Assess: In males we will consider: (1) ACASI, (2) HIV testing, (3) STI testing, and (4) HIV typing and (5) viral loads. • Assess: In females we will consider: (1) ACASI, (2) HIV testing and HIV typing.

37. HIV+ Males and Female Partners (cont.) • Intervention (male): Arm 1 (Control): Males receive 4 group sessions on fitness and 5 individual sessions on fitness. Arm 2: Males receive 4 adapted group sessions of two EBIs, Healthy Relationships and WiLLOW and, 5 individual sessions adapted from RESPECT. Female partners receive HIV pretest/postest counseling. • 1o Outcome: To reduce the HIV incidence in the treatment condition compared to a control condition over an 18-month follow-up period, as indicated by acquisition of HIV in HIV- female sexual network partners. (Should explore reinfection in males and HIV+ female network partners?)

38. HIV+ Males and Female Partners Discussion points • Sample size requirements • Likelihood of male participant referring female sexual network partners • Identification of female sexual network partners • Retention over extended follow-up

39. Behavioral intervention for HIV- women exiting jails and prisons • Rationale: Nexus of HIV, incarceration, and drug use in U.S. well documented. Female inmates especially vulnerable to HIV infection, not only biologically, but through social forces such as poverty and social networks characterized by drug use and domestic violence. • Design: Phase III RCT with a 24 month follow-up period. • Sample:HIV negative female inmates, between one month and one year of release, who report a history of unprotected heterosexual sex, drug use, are > 18 years of age • Intervention:Arm 1 (Control): NIDA standard intervention Arm 2: Adapted female and culturally enhanced motivation intervention + booster (Sterk et al, 2003). 4 sessions: 1 pre-release, 3 post-release +2 post-release boosters

40. HIV Reduction for HIV- Female Inmates (cont.) Assessments (pre- and post-release) • Pre-release. • ACASI survey • Chart reviews to assess medical history (STIs upon intake, mental health, general health). • Post release assessments (2 weeks, 1-month, 2-, 4-6-, 9-,12-,15-, 18-,21, 24 months post-release) (1) ACASI (per above) (2) STIs and drug screening (3) HIV testing (standard and PCR).

41. HIV- Female Inmates Endpoints • Primary Outcome:To reduce the HIV incidence in the treatment condition compared to the control condition over a 24-month follow-up period. • Secondary Outcomes: To evaluate STI incidence as well as drug use and sexual risk behaviors/mediators in treatment condition compared to the control condition over a 24-month follow-up period.

42. HIV- Female Inmates Discussion points • Sample size requirements • Retention over 2 year period • Unique needs of incarcerated female populations • Established relationships with prison, but little experience with jails

43. Combining “Women at risk” & “Partners of high risk HIV+ men” • Two-level factorial design • Level 1: Male intervention • Community randomized trial (CRT) of a behavioral intervention among HIV+ heterosexual men to reduce HIV transmission • Level 2: Female intervention • Within each community, randomize a cohort of high risk, HIV-negative women to a female risk reduction intervention • Primary outcome is HIV infection in the women enrolled in the cohorts

44. Discussion Points • Design allows addresses multiple questions • What is the direct effect of the female intervention (FI)? • What is the community level effect of the male intervention (MI)? • What is the incremental effect of the MI above and beyond the risk reduction achieved by the FI? • Are the 2 interventions supplemental, independent, or synergistic Need to ensure males reached in the MI represent the pool of potential partners of females enrolled in the cohorts. • Sample size requirements

46. Conclusions • Incidence data support feasibility of a prevention intervention with HIV incidence as endpoint • New insights into women at risk • Research gaps defined in behavioral and biomedical interventions • Innovative approaches identified • Opportunity to stem HIV transmission in the US

47. Back Up

49. Characteristics of heterosexually acquired infections in the US: 1999 - 2004 • Dates: 1999 - 2004 • Location: 29 US states with name-based reporting • Size: 52,569 • Correlates: • 69% women • 73% Black • significant increases among Hispanics Espinoza L et al, AJPH 2007