Transcript Powerpoint

NEW DEVELOPMENTS IN HIV
PREVENTION RESEARCH: WHAT
DO THEY MEAN FOR BLACK
WOMEN IN THE US?
ADAORA A. ADIMORA, MD, MPH
PROFESSOR, SCHOOL OF MEDICINE
UNIVERSITY OF NORTH CAROLINA- CHAPEL HILL
WHAT DO YOU RECOMMEND?
• In addition to condoms, what preventive measures
would you recommend for the following sexually
active HIV- Black women?
• 19 yo living in KwaZulu Natal, S Africa has a boyfriend who
has other female partners
• 33 yo is married to an HIV+ man who takes ART only
intermittently; his viral load typically exceeds 2,000
copies/ml.
• 18 yo college student in Wash, DC
• 27 yo uses crack regularly and exchanges sex to support
herself.
OUTLINE
•
•
•
•
HIV incidence among U.S. Black women
PrEP data
Treatment as prevention: how are we doing
Cash transfer for prevention of HIV infection
MARKED RACIAL DISPARITIES IN HIV INFECTION
AMONG US WOMEN
• CDC estimates
HIV incidence
among US Black
women of
0.0397% – 0.0508%
between 2006
and 2009
Prejean J. PLosOne
2011;e17502
What is incidence among Black women
at very high risk?
HPTN 064 (ISIS): OBJECTIVES
• Accurately estimate new HIV incidence in a group
of women at risk for HIV in the US
• Evaluate new lab methods for identification of new
HIV infections
• Describe factors in participants lives that impacted
HIV risks
• For example, partner risks, alcohol/drug use,
financial factors, condom use
ISIS INCLUSION CRITERIA
• Self identifies as a woman ages 18-44 years
• Residence in area with relatively high rates of HIV
prevalence and poverty
• Unprotected sex with a man during the previous 6
months
• AND at least one additional risk factor
ISIS INCLUSION CRITERIA
CONT.
At least ONE of the following:
INDVIDUAL RISKS
• Illicit drug use (injecting and non-injecting)
• ETOH dependence and/or binge drinking
• Incarceration – within past 5 years
• STI (GC, Chlamydia, Trichomonis, Syphilis)
• Exchange of sex for commodities
PARTNER RISKS
• Illicit drug use (injecting and non-injecting)
• ETOH and/or dependence or binge drinking
• Incarceration – within past 5 years
• STIs
• HIV diagnosis
STUDY SITES
Bronx and Harlem, NY
North and South Newark,
NJ
Baltimore, MD
Washington, DC
Durham and Raleigh, NC
Decatur and Atlanta, GA
10 distinct communities within 6 geographic locations
Qualitative data collected in four communities
HIGH HIV INCIDENCE AND HIGH
MORTALITY RATE OBSERVED
• Age-adjusted annual mortality rate for
ISIS cohort 0.61%/year
• Expected mortality rate for similar aged
cohort is 0.11%/year1
• Incidence of 0.24% (95%CI 0.09 to 0.65) is
more than 5 times the age-adjusted
CDC national estimates for Black women
1. Murphy S, et al. Deaths: Preliminary Data for 2010 National Vital
Statistics Reports. Hyattsville, MD: National Center for Health
Statistics; 2012.
FDA APPROVES TRUVADA FOR PrEP
FDA approved Truvada for
preventing HIV infection
among individuals at high
risk of HIV infection and
who may engage in
sexual activity with HIVinfected partners.(July 16,
2012)
During approval process
some panel members
expressed concern that
not enough safety or
efficacy data was
available for African
American women. (May
10, 2012)
STUDY
POPULATION
AGENT
EFFICACY
ADHERENCE
CAPRISA
004
889 high-risk
South African
women
BAT24 TDF gel
BAT 24 placebo
39% (54% in those > ~38%
80% adherent)
reported
>80%
adherence
Partners
in PrEP
4747
serodiscordant
couples
(~1788 HIV neg
women) –
Kenya, Uganda
Daily oral TDF
Daily oral Truvada
Daily oral
placebo
67% TDF, 75%
Truvada
(Women: 71% TDF;
66% Truvada)
Estimated ~
97%
dispensed
doses taken
TDF2
1200
Heterosexual
men (n =656 )
and women (n
=544 ) Botswana
Daily oral Truvada
62% overall
Reported
80%
Adapted from Caroline Mitchell, MD
Study
Population
Agent
Efficacy
Adherence
FemPrEP
1951 young
Kenya, S
Africa,
Tanzania
women
Daily oral
Truvada
Stopped for
futility
Reported >
90%;
< 50% by drug
levels
VOICE
5000 women
(1000 each
arm) –
Uganda, S
Africa,
Zimbabwe
Daily oral
Truvada,
Tenofovir or
placebo
Daily vaginal TDF
gel or placebo
TDF gel and
Not yet
oral Tenofovir reported
arms stopped
for futility
Adapted from Caroline Mitchell, MD
SIGNIFICANT CHANGES IN BONE MINERAL DENSITY
HAVE BEEN NOTED AMONG TENOFOVIR RECIPIENTS
• Decline in bone mineral density (BMD)
• TDF2: No fx – but  t scores and z scores for BMD at
forearm, hip, lumbar spine among TDF-FTC recipients
(p=0.004).(Thigpen MC. NEJM 2012)
• HIV- men enrolled in PrEP trial, 1.1% (95% CI: 0.4% 1.9%) net  in BMD at femoral neck among TDF vs
placebo (Liu AY. PLoS ONE 6(8): e23688. doi:10.1371)
• A5224s: Among HIV+ (85% men), BMD changes from
baseline after 96 wks. ABC-3TC vs TDF-3TC: Spine = 1.3% vs -3.3% (p=.004); hip = -2.6% vs -4.0% (p=.024).
(McComsey GA. JID 2011;203:1791
RATES OF ADVERSE EFFECTS VARY
AMONG PREP STUDIES FOR WOMEN
• PARTNERS PrEP: No difference in adverse effects (Baeten JM NEJM
2012)
• TDF2: TDF-FTC group had higher rates of:
• Nausea (18.5% vs 7.1%, p = .03
• Vomiting (11.3% vs 7.1%, p = .008)
• Dizziness (15.1% vs 11.0%, p = .03)(Thigpen MD NEJM 2012)
• FEM-PrEP: TDF-FTC group had higher rates of
• Nausea (p=.04), vomiting (0<.001) and ALT (p=.03)
(Van Damme L. NEJM 2012)
• No evidence of increased renal toxicity in Partners PrEP
or TDF2
• BUT FEM-PrEP: Higher rates of drug discontinuation due to
hepatic or renal abnormalities in TDF-FTC group (4.7%)
than placebo (3.0%, p = .051)
(Van Damme L. NEJM 2012)
ANTIRETROVIRAL RESISTANCE MUTATIONS
OCCURRED (IN A FEW PARTICIPANTS) IN ALL 3 ORAL
PrEP STUDIES
• PARTNERS PrEP
• No participants who acquired HIV after randomization
developed resistance mutations
• Of 8 TDF, TDF-FTC participants infected at randomization
who took either TDF or TDF-FTC, resistance noted in 2:
• 1(TDF) with K65R
• 1 (TDF-FTC) with M184V
• TDF2
• 1 TDF-FTC participant with unrecognized wild type acute
infection at enrollment developed K65R, M184V, and A62V
• FEM-PrEP
• TDF-FTC group M184V (3), M184I (1)
STUDY POPULATIONS AND ADHERENCE IN
PREP STUDIES VARY
• CAPRISA
• Median age = 23; 3.6-6.5% married. Urban HIV incidence rate =
15.6%, rural = 11.
• Adherence (based on returned applicators): mean of 72.2%
(median 60.2%) of sex acts in last 30 days were covered by 2
doses of gel.
• PARTNERS PREP
• Serodiscordant couples, aged 18->45, ~97% married, living
together median of 7 yrs
• Estimates (returned study bottles): 97% of tablets taken
• TDF2
• Men and women, 18-39 yrs old (5-6% married), Botswana
• Adherence (pill counts) ~84%
STUDY POPULATIONS AND ADHERENCE IN
PREP STUDIES VARY (2)
• FEM-PrEP
• PLACE used to recruit high risk participants
• 99% had primary partner; 26% had other, non-primary
partner
• 13% exchanged sex for $ or gifts with non-primary partner in
past 4 wks
• Perceived risk as low: 70% baseline, 75% last visit
• Adherence
• Self report: 95% “usually or always” took pills. Pill count
suggested adherence
• Drug-levels low: Plasma TDF levels > 10 ng/ml if drug taken
in preceding 48 h; target level attained in only 15%-26% of
seroconverters
INTERMITTENT AND COITALLY DEPENDENT
ORAL PREP DOSING: LOW ADHERENCE
• MSM (N=67) and FSW (N=5) in Kenya randomized to
• Daily oral TDF-FTC or placebo, or
• Intermittent (Mon, Fri, and within 2 h of sex)
• Adherence assessed via MEMS; sexual activity data
collected
• Acceptability of PrEP high, regardless of dosing
regimen - BUT
• Adherence
• 83% daily dosing
• 55% fixed intermittent doses
• 26% post-coital doses
Mutua G. PLoS ONE 2012;7(4) e33103
EXPOSURE TO TDF, FTC, AND ACTIVE METABOLITES
VARIES WIDELY IN DIFFERENT MUCOSAL TISSUES
• Vaginal and cervical tissue levels of TDF are low after oral
dosing
• 24 hr after oral dose of TDF-FTC, median TDF-DP (active
metabolite) concentration was 2.2 logs lower in vaginal
tissue than in rectum and below detectable in cervical
tissue.
Patterson KB. Sci Transl Med 2011;3:112re4.
ORAL TDF PHARMACOKINETICS AND
VAGINAL SEX: NO FORGIVENESS FOR LOW
ADHERENCE
• Threshold concentration
for protection against HIV
is not yet established, but
likely that > 1000 fmol/mg
TDF-DP needed for gel.
• Vaginal gel yields 1000
fold greater TDF-DP
vaginal tissue levels than
oral dosing.
• TDF-DP concentration
after oral dose: only 206
fmol/mg in rectum and 2
fmol/mg in vaginal tissue.
• Oral dose yields 100-fold
greater concentrations of
TDF-DP in rectum than
vagina
Abdool Karim SS. Lancet
2011;378:279
HPTN 052: EARLY ART REDUCES HIV
TRANSMISSION AND CLINICAL PROGRESSION
•
•
•
•
96% reduction in HIV transmission among discordant couples.
Virologic failure among 5% in early therapy group;
>95% adherence among 79% of participants;
What about “the real world” outside a clinical trial setting?
ONLY A SMALL PROPORTION OF HIV+ PEOPLE IN
THE US HAVE UNDETECTABLE VIRAL LOADS
• Deficiencies in
diagnosis,
linkage to care,
retention in
care, receipt of
ART, adherence.
• Of the 24% of
PLWH who are
on ART, 20%
have
detectable viral
loads
Gardner EM. CID 2011;52:795
RACIAL DISPARITIES IN ART RECEIPT AND
OUTCOMES: CDC MEDICAL MONITORING
PROJECT, US, 2008-2010
RACE/ETHNICITY PRESCRIPTION
AMONG THOSE
OF ART, %
PRESCRIBED ART,
(95% CI)
MOST RECENT VIRAL
LOAD < 200
COPIES/ML, % (95%
CI)
Black
86 (83-88)
70 (66-74)
Hispanic
89 (86-92)
79 (75-82)
White
92 (91-94)
84 (80-87)
Compared to
Whites, Blacks are
less likely to be
prescribed ART
and, when ART is
prescribed, less
likely to have low
HIV viral load.
CDC. MMWR 2011;60:1618.
AND NOW FOR SOMETHING
COMPLETELY DIFFERENT…
CONDITIONAL
CASH
TRANSFER
CURRENT
POVERTY
EDUCATION
FUTURE
POVERTY
CASH TRANSFER PROGRAM REDUCED
HIV/HSV-2 PREVALENCE AMONG
SCHOOLGIRLS IN MALAWI
• Cluster randomized trial of never-married women, aged
13-22 to receive cash payment or nothing
• At follow-up, among girls enrolled in school at baseline,
those who received $ less likely to have:
•
•
•
•
HIV (1.2% vs 3.0%; OR 0.36, 95% CI 0.14-0.91) (18 mos)
HSV-2 (0.7% vs 3.0%; OR 0.24, 0.09-0.65)
Older male partner (0.5% vs 2.5%; OR 0.20, 0.07–0.59)(12 mos)
Sexual intercourse once per wk (3.0% vs 6.5%; OR 0.46, 0.26-0.82)
• No difference between intervention and control groups in
adjusted estimates for pregnancy, sexual debut, condom
use; HIV knowledge or education
• No effect of intervention on girls who had already
dropped out of school at baseline
Baird SJ. Lancet 2012;379:1320
IMPLEMENTATION OF THE AFFORDABLE
CARE ACT IS ESSENTIAL TO IMPROVE HIV
PREVENTION AND CARE IN THE US
• ~15% of the US population lacks health insurance
• Among those with insurance, substantial proportion
is underinsured
• Proper implementation of the ACA could
conceivably increase response in each component
of HIV treatment cascade – and decrease ongoing
transmission
• Individuals with incomes 134%-400% fed poverty eligible to
purchase subsidized private insurance
• Expansion of preventive coverage for women’s health,
including annual counseling and testing for HIV and other
STIs
• Coverage for ART
SUMMARY
• Anti-retroviral PrEP can prevent men and women from
acquiring HIV
• Issues with currently available drugs: TDF-FTC achieves
lower concentrations in vaginal than rectal tissues and
therefore seems less forgiving of low adherence for
vaginal sex than anal sex – hence conflicting results of
studies
• Early ART of infected people can prevent men and
women from acquiring HIV
•
But only a small proportion of HIV+ people in the US
achieve viral suppression
• Adherence varies widely by context
• Economic interventions can reduce risk of HIV infection
WHAT DO WE NEED FOR THE WAY
FORWARD?
• Understand
• Threshold tissue concentration of drug that is required to prevent HIV
infection
• Drug concentration attainable at exposed site
• Extent of adherence needed to achieve threshold concentration
• Adherence, factors that affect it, and how to increase it
• Better biomedical products
•
•
•
•
Safe, effective
Products that don’t require adherence
Dual contraception/HIV/STI prevention
Others that allow fertility while preventing acquisition of HIV/STIs
• Health care coverage that permits implementation of the
recent advances in HIV prevention and care
• Change the context of people’s lives that structures their risk
for acquiring HIV in the first place
ACKNOWLEDGMENTS
• Catalina Ramirez, MPH
• Mike Cohen
• Sally Hodder
THANK YOU