Download Interventions in Women - HIV Prevention Trials Network

Domestic HIV Prevention
Research Agenda:
Women At Risk
June 7, 2007
DWPG-Women at Risk Members
Andrew Forsyth
Ann O'Leary
Danielle Haley
David Metzger
Dawn Smith
Eunice Ramirez-Dilone
Jessica Justman
Katherine Davenny
Nicolette Borek
Peter Kilmarx
Richard Jenkins
Sally Hodder
Scott Rose
Sten H. Vermund
Tim Mastro
Vanessa Johnson
Waheedah Shabbaz-El
Ada Adimora
Cathie Fogel
David Burns
David Purcell
Dianne Rausch
Gina Wingood
Jim Hughes
Kendall Bryant
Nirupama Sista
Quarraisha Abdool Karim
Richard Wolitski
Sandra Lerhman
Sheryl Zwerski
Sue Gibson
Victoria Cargill
Wafaa El-Sadr
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
New Jersey HIV Prevalence
(per 100,000 women)
State of New Jersey
Newark EMA
Essex County
Newark
Black women in Newark
263
618
927
1417
2673
Persons living with AIDS in Philadelphia, June 2006
North Carolina HIV/STI Rates, 2006
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% AfricanAmerican 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Strathdee SA et al Arch Int Med 161:1281, 2001; Metzger D, Unpublished Data;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
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
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
Target Population
African - American Women
• Location, location, location
• Partner characteristics
• Individual characteristics
Black
HIV Prevalent
Home
Neighborhood
Geography
High
risk
male
partner
HIV +
male
partner
Partner Characteristics
Recent
STI:
HSV2
GC
Drug
use:
IDU
Cocaine
Women’s Characteristics
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
AIDS in Prison
Interventions in Women
Biomedical
Behavioral
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)
STI Treatment to Prevent HIV
“STI treatment may
decrease HIV
incidence in emerging
HIV epidemic (low &
slowly rising
prevalence)”
Trial
Intervention
Rakai
3 rounds
Comm. Rx
OR
(95%CI)
0.97
(.81-1.16)
Mwanza Syndromic
Rx
0.58
(.42-.70)
Masaka
1.00
(.63-1.58)
Behavioral +
STI Rx
Grosskurth H, 1995; Kamali A, 2003, Wawer, 1999; Sangani, 2004
Evidence-Based Behavioral Interventions
Targeting Women (Lyles, et al, 2007)
RCT Trial
Population
Endpoints
SiHLE (DiClemente,
2004)
AA Girls 14-18
Decreased STIs,
Increased condom use
Choices (Baker, 2003)
Low income
heterosexual
women
Decreased STIs
Project FIO (Ehrhardt,
2002)
Heterosexual
women in family
planning clinics
Decreased
unprotected VI/AI,
Decreased VI/AI
Project ConnectAA and Latino
couple or woman
heterosexual
alone (El-Bassel, 2003) couples
Increased condom
use, Decreased
unprotected VI
RCT Trial
Population
Endpoints
Project S.A.F.E (Shain, Mexican American and Decreased STIs,
2004)
AA women dx’d with
Decreased unprotected
STIs in public clinics
sex, decreased N of
sexual partners
Female and Culturally
Specific Negotiation
(Sterk, 2003)
Inner-city, HIV-,
sexually active, out-oftreatment crack or IDU
using women
decreased sex with
paying customers,
decreased trading of
sex for money,
decreased IDU
Women’s Co-op
(Wechsberg, 2004)
Inner-city(south), HIV-, Decreased unprotected
sexually active, out-of- sex
treatment crack using
AA women
WiLLOW (Wingood,
2004)
Sexually active HIV+
female clinic patients
Increased condom use
FOK+ImPACT (Wu,
Stanton, 2003)
Low income AA youth
Decreased STIs,
decreased unprotected
VI
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
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
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
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
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
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.
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);
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?
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
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
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
Intensive STI Treatment
Discussion Points
Exclusion of HSV-2 seropositive persons
Partner treatment vouchers
Frequency of follow-up
Sample size requirements
Behavioral Intervention Targeting AfricanAmericans 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.
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?)
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
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
HIV Reduction for HIV- Female
Inmates (cont.)
Assessments (pre- and post-release)
Pre-release.
(1) ACASI survey
(2) Chart reviews to assess medical history (STIs upon
intake, mental health, general health).
Post release assessments (2 weeks, 1-month, 2-, 46-, 9-,12-,15-, 18-,21, 24 months post-release)
(1) ACASI (per above)
(2) STIs and drug screening
(3) HIV testing (standard and PCR).
HIV- Female Inmates
Endpoints
Primary Outcome: To reduce the HIV
incidence in the treatment condition compared
to the control condition over a 24-month followup 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 24month follow-up period.
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
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
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
Community Men
Intervention
Community
Women
Intervention
Control
Control
MI
WI
M0
WI
MI
W0
M0
W0
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
Back Up
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