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Discussion HIV incidence: two snapshots & a case MSM in U.S. Young women in sub-Saharan Africa Understanding the evidence for new prevention options & implementation Pre-exposure prophylaxis with antiretrovirals (PrEP) Multipurpose prevention Unintended consequences? Slide 4 of 34
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Jeanne M. Marrazzo, MD, MPHProfessor of Medicine
University of WashingtonSeattle, Washington
A Shot in the Arm for HIV Prevention? Opportunities and Challenges in 2016
FORMATTED: 11/17/15
New Orleans, Louisiana: December 15-17, 2015
Slide 2 of 34
Learning Objectives
After attending this presentation, participants will be able to: Discuss the approach to transitioning from PrEP to PEPDefine contraindications to initiating antiretroviral PrEPDiscuss accurate counseling messages for men who elect
to use TDF-FTC as PrEP
Discussion HIV incidence: two snapshots & a case
MSM in U.S. Young women in sub-Saharan Africa
Understanding the evidence for new prevention options & implementation Pre-exposure prophylaxis with antiretrovirals
(PrEP) Multipurpose prevention
Unintended consequences?
Slide 4 of 34
One third of new HIV infections globally occur in young African women
• In context of ART scale up with 40% of HIV+ persons on ART & 6 million medical male circumcisions performed by end of 2013
• Need to implement effective primary prevention strategies
Slide 5 of 34
Diagnoses of HIV Infection among Adults and Adolescents, by Transmission Category,
2009–2013 — United States and 6 Dependent Areas
Note. Data include persons with a diagnosis of HIV infection regardless of stage of disease at diagnosis. All displayed data have been statistically adjusted to account for reporting delays and missing transmission category, but not for incomplete reporting.
a Heterosexual contact with a person known to have, or to be at high risk for, HIV infection. b Includes hemophilia, blood transfusion, perinatal exposure, and risk factor not reported or not
identified.
Accounts for 81% of transmissions among men;
increase highest in 25-34 y.o.
Slide 6 of 34
Rene P, 20 yo man, referred by partner “who had syphilis”
Considers himself healthy, no symptoms HIV Ag-Ab test negative last week Last syphilis serology negative 3 months ago Two episodes of rectal gonorrhea last year Moved to U.S. from Mexico last year Sometimes uses meth on weekends 6 partners in last 3 months, some anonymous.
Last unprotected sex 12 h ago
Slide 7 of 34
Rene P, 21 yo man, referred by a partner “who had syphilis”
What do you do?
Slide 9 of 34
Rene P, 21 yo man, referred by partner “who had syphilis”
Send confirmatory syphilis test (EIA, TPPA) before treating for syphilis
Treat him with BZN PCN 2.4 x 10-6 mu IM weekly for three weeks
Check plasma HIV viral load Offer him TDF-FTC as PrEP and see him in 3
months Treat now for sexual PEP (TDF/FTC/raltegravir)
Slide 10 of 34
HIV Prevention in Clinical Care Settings: 2014
Recommendations of the International Antiviral
Society-USA Panel:
Emphasized biobehavioral nature of the interventions
needed
Marrazzo JM, Holtgrave DR, del Rio C et al, JAMA 2014
Free web access to the paper at jama.com
Slide 11 of 34
Antiretroviral Prevention: A Timeline
1995PMPA
effectivein macaque
2005HPTN-050
Phase 1
2006HPTN-059Phase 2
2010CAPRISA 004
Phase 2B
2010iPrEX
2011FEM-PrEP
2011HPTN-052
2011TDF2
2015PROUD
2013MTN-003VOICE
2007TDFPrEPStudy
2015FACTS
001
2015iPerGay
2011Partners
PrEP
Slide 12 of 34
Efficacy of Biomedical Interventions to Prevent HIV Acquisition: Evidence from Selected Randomized Clinical Trials
Modified from Ambitious Treatment Targets: Writing the Final Chapter of the AIDS Epidemic, UNAIDS, 2014
Key Components of These TrialsHPTN 052 Partners
PrEP iPrEX VOICE & FEM-PrEP CAPRISA 004
Standard prevention “package”* ✔ ✔ ✔ ✔ ✔
Intensive adherence counseling ✔ ✔ ✔ ✔ ✔
Enrolled both members of discordant couples ✔ ✔
Study product use timed with likely HIV exposure ✔
Real-time biological marker of product adherence ✔* Condoms, counseling, STI management
Slide 16 of 34
Key Components of These TrialsHPTN 052 Partners
PrEP iPrEX VOICE & FEM-PrEP CAPRISA 004
Standard prevention “package”* ✔ ✔ ✔ ✔ ✔
Intensive adherence counseling ✔ ✔ ✔ ✔ ✔
Enrolled both members of discordant couples ✔ ✔
Study product use timed with likely HIV exposure ✔
Real-time biological marker of product adherence ✔* Condoms, counseling, STI management
Slide 17 of 34
Adherence & PrEP Efficacy
% of blood samples with TFV detected
HIV protection efficacy in randomized comparison
Partners PrEPFTC/TDF arm 81% 75%
TDF2 79% 62%
iPrEx 51% 44%
FEM-PrEP 26% NS
VOICE 28% NS
Clear dose-response relationship between evidence of PrEP use & efficacyBaeten et al N Engl J Med 2012
Grant et al N Engl J Med 2010Van Damme et al N Engl J Med 2012Thigpen et al N Engl J Med 2012 Slide modified from J. Baeten
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Oral PrEP + ART as Prevention in High-Risk Serodiscordant Couples
• Partners Demonstration Project in Africa– Oral daily TDF/FTC PrEP for HIV-uninfected
partner in serodiscordant couple continued 6 mos beyond initiation of ART for infected partner
– High-risk couples defined as younger age, fewer children, uncircumcised HIV-negative male, cohabitating, unprotected sex in past mo, high HIV-1 RNA in HIV-positive partner
• Interim analysis– > 95% of HIV-negative partners using PrEP– 80% of HIV-positive partners have initiated
ART; of these, > 90% with suppression
96% reduction in expected infections‒ IRR, expected vs observed: 0.04 (95% CI: 0.01-0.19; P
< .0001)
In pts with seroconversion, no TFV detectable in plasma at time of seroconversion
– HIV-positive partner in 1 couple not on ART (high CD4+ count)
– Other couple dissolved and HIV-negative partner in new relationship
Baeten J, et al. CROI 2015. Abstract 24. Reproduced with permission.
HIV Incidence, Actual vs Expected
Group Infected, n Incidence/100 PY (95% CI)
Expected 39.7 5.2 (3.7-6.9)
Actual 2 0.2 (0-0.9)
Slide 19 of 34
PrEP Safety• Rates of death, serious adverse events, and laboratory abnormalities
(including renal dysfunction) very low• Not significantly different between those on PrEP and placebo
• PrEP well tolerated• Adverse effects occurred in minority of subjects• GI adverse effects (e.g., nausea) more common in those receiving PrEP
than placebo (< 10%, primarily during the first month only)• PrEP safe during pregnancy (Mugo JAMA 2014)• No reduction in contraceptive efficacy (Murnane AIDS 2014)• Rare acquired resistance (about 3%); 12 infections averted for each
case of resistance
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Randomized, open-label trial of daily oral TDF/FTC PrEP in HIV- MSM in 13 clinics in London
– Immediate (n = 267) vs
– Deferred for 12 mos (n = 256)
Primary endpoint: HIV infection in 12 mos
86% reduction in risk seen over 60 wks with immediate PrEP (90% CI: 58% to 96%, P = .0002)
– Number needed to treat to prevent 1 infection: 13 (90% CI: 9-25)
DMSB interrupted trial; recommended that all participants be offered PrEP
HIV Incidence
Group Infected, n Incidence/100 PY (90% CI)
Immediate 3 1.3 (0.4-3.0)
Deferred 19 8.9 (6.0-12.7)
Lancet 2015
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Slide 18 of 34
NEJM 14 Dec 2015
Randomized double-blind trial of event-driven oral TDF/FTC* (n = 199) vs placebo (n = 201) (both with prevention services) in France– 2 tablets taken 2-24 hrs before sex– 1 tablet 24 hrs after sex – 1 tablet 48 hrs after first event-driven dose
Primary endpoint: HIV seroconversion
Patterns of Pill Use on the Basis of Clinic Visits
Molina J-M et al. N Engl J Med 2015;373:2237-2246
Probability of HIV-1 Infection
Molina J-M et al. N Engl J Med 2015;373:2237-2246
86% reduction in risk in PrEP arm (95% CI: 40% to 99%, P = .002)
• Number needed to treat for 1 yr to prevent 1 infection: 18
• Median of 16 pills taken per mo in each arm
Clinical Infect Dis, Sept 2015
Slide 24 of 34
The Good News: No new HIV infections
in over 600 PrEP initiators at Kaiser Permanente San Francisco
Volk et al. CID 2015; Image courtesy J Volk
PrEP in the “Real” WorldSlide 25 of 34
PrEP and STIs in >600 MSMKaiser Permanente San Francisco
Any S
TI
Rectal
STI
Chlamyd
ia
Gonorr
hea
Syph
ilis HIV0%
20%
40%
60% 50%33% 33% 28%
5.5%0%
STI Incidence After 12 Months of PrEP Use
Volk et al. CID 2015 Slide courtesy J. Volk
Expected HIV incidence with this STI
incidence: 8.9%
Slide 26 of 34
HIV incidence = 0.43 cases / 100 py (95% CI 0.05-1.54)STI incidence (90 cases/100 py) stable across quarterly intervals (P> 0.1)50.9% of participants had at least one STI during follow-upAs expected, >75% of GC and >85% of CT infections were asymptomatic
Screening 12 24 36 4805
1015202530
GC, CT or SyphilisRectal GC or CTPharyngeal GC or CT
Visit Week
% P
ositi
vePrEP Demo Project (NIAID), n=557
Cohen 2015, ISSTDR
Slide 27 of 34
Syphilis rates among MSM: timeline
Peterman, 2015, Expert Rev Anti Infect Ther
Syphilis rates among MSM will soon be similar to those in the early 1980s
Slide 28 of 34
A Vicious Cycle: STDs predict future HIV Risk
1 in 15 MSM were diagnosed with HIV within 1 year.*
1 in 53 MSM were diagnosed with HIV within 1 year.*
Rectal GC or CT
1 in 18 MSM were diagnosed with HIV within 1 year.**
Primary orSecondarySyphilisNo rectal STD or syphilis infection
*STD Clinic Patients, New York City. Pathela, CID 2013:57; **Matched STD/HIV Surveillance Data, New York City. Pathela, CID 2015:61
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Goal: reliable, long-lasting, woman-initiated method to protect against HIV acquisition
ASPIRE (MTN-020) studied dapivirine, with complementary studies: IPM 027 (efficacy & safety) >25 completed phase I/II studies Results anticipated early 2016
Vaginal Rings for HIV PreventionSlide 30 of 34
Thoughts & Next Steps PrEP works, when taken consistently, and is the most
effective tool for preventing sexual HIV transmission we have so far Only one ARV (TFV) available; data for women still limited
Critically dependent results coming up: Intravaginal dapivirine ring HPTN studies of long-acting ARV (cabotegravir, rilpivirine) Rectal microbicide development
Combination product development Antiretroviral + hormonal contraceptive
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