This presentation is intended for educational use only, and does not in any way constitute medical consultation or advice
related to any specific patient.
Frontier AIDS Education and Training Center
CROI 2016
HIV Prevention Updates
Ruanne V Barnabas, MBChB, DPhil
Global Health and Medicine, University of Washington
Outline
• Treatment as Prevention studies
• Focus on partner testing
• New approaches to PrEP
• PrEP failure
Treatment as Prevention
• Avert 28 million HIV infections by 2030
• Encouraging implementation results
• Botswana
- Random sample of 20% of households (N=12,610)
- 29% were HIV+
- 83% known HIV+ - 87% of those eligible on ART - 96% on
ART were virally suppressed
- Decentralized ART provision
Gaolathe, T, CROI 2016
Treatment as Prevention: Clinical Trials
• Evidence that treatment as prevention works
Fidler, S; Chamie, G; Larmarange, J CROI 2016
Study N Testing On ART Viral
suppression
PopART/HPT
N 071
(Zambia &
SA)
101,578
16% HIV+
89% 71% -
SEARCH
(Kenya &
Uganda
73,284
8.5% HIV+
98% - 71%
TasP
(South Africa)
28,000
~30% HIV+
- - 50% (from
20%)
Spotlight on Partner Testing
• Male partner home testing vs. Clinic invitation in pregnancy (HOPE Study) (Kenya)
- Individual randomized trial (N=620)
- HOPE intervention - 87% of men tested
- INVITE strategy – 39% of men tested
- Home testing doubled uptake of testing among men
• Partner services (outreach to partners of HIV+ persons) for HIV in Kenya
- Cluster randomized trial (N=1,119 index cases, 1,872 partners)
- 43% of partners tested in the immediate arm
- 12% of partners tested in the delayed arm
- 4 fold increase in testing and 3 fold increase in linkage to care
- No significant social harms reported
Krakowiak, D; Cherutich, P; Farquhar, C; CROI 2016
Next Generation PrEP
ASPIRE
A Phase III Trial of the
Dapivirine Vaginal Ring
for HIV-1 Prevention in Women
The MTN-020/ASPIRE Study Team
CROI 2016, Boston, USA
Baeten, J; CROI 2016
MTN-020/ASPIRE
• MTN-020/ASPIRE was a multi-center, randomized, double-blind, placebo-controlled phase III trial of a vaginal matrix ring containing the non-nucleoside reverse transcriptase inhibitor dapivirine.
• The primary objectives were to determine the effectiveness andsafety of dapivirine (25 mg) administered in a silicone elastomer vaginal matrix ring, when inserted once every 4 weeks, in preventing HIV-1 infection among healthy sexually active HIV-1 uninfected women.
Trial Design
• At enrollment, women (N=2,629) were
randomized 1:1 to dapivirine:placebo.
• Women were counseled to wear the
ring continuously, and a new ring was
provided at scheduled monthly visits.
• Follow-up was for a minimum of 1 year.
• All received a comprehensive package
of HIV-1 prevention services.
• Conducted in Malawi, South Africa,
Kenya and Zimbabwe
HIV-1 Protection
• Overall, women in the dapivirine vaginal ring arm had a 27%
reduction in the rate of HIV-1 acquisition, compared to placebo.
Primary HIV-1 effectiveness
intention-to-treat analysis (15 sites)
Dapivirine Placebo
# HIV-1
infections71 97
HIV-1 incidence,
per 100 person-
years
3.3 4.5
HIV-1 protection
effectiveness
95% CI, p-value
27%
(1, 46)
p=0.046
No difference in safety between arms
Age and HIV-1 Protection
• HIV-1 protection effectiveness was explored in additional age-
stratified categories, and lack of HIV-1 protection was limited to
those ≤21 years of age:
Age 18-21
-27% (-133,31)
placebo incidence
5.4%/yr
Age 22-26
56% (19,76)
placebo incidence
6.1%/yr
Age 27-45
51% (8,74)
placebo incidence
3.0%/yr
Design
• Women Aged 18-45 years enrolled
• 2:1 randomized dapivirene ring:
placebo ring
• Women self inserted and removed the
ring at 4-weekly visits
• A fixed 2-year follow-up
• All received a comprehensive HIV-1
prevention package
Primary Analysis:
Time to HIV-1 Seroconversion: m-ITT
Conclusions
The Ring Study
• 31% (95% CI 1 to 52, p=0.040)
Relative reduction in HIV-1 incidence
overall
• 37% (95% CI 3.5 to 59, p-value for
treatment by age interaction: 0.43)
Reduction in an as-randomized analysis
among women older than 21 years of
age
Aspire
• 27% (95% CI to 46, p=0.046)
Relative reduction in HIV incidence
overall
• 56% (CI 31 to 71, p=0.0003)
Reduction in an as-randomized
analysis among women older than 21
years of age
No safety concerns or clinically relevant differences in safety
parameters were observed between study arms
New PrEP formulations: CAB
• Cabotegravir long-acting injection protects 21/24 macaques
against IV challenge
• Supports evaluation of CAB as PrEP for PID
Andrews, C; CROI 2016
PrEP: TAF is effective
• TAF – more active against HIV with improved safety
• FTC/TAF prevented rectal SHIV infection in macaques
(equal to FTC/TDF)
Massud, I; CROI 2016
Very rare PrEP Failure
• PrEP has near 100% prevention efficacy with high
adherence
• Case report 43 year old man, excellent PrEP adherence,
seroconverted with multiresistant HIV (including 184V and
INST resistance mutations)
• Exposure to single source with FTC/TDF resistant virus
(failing on c/EVG/TDF/FTC)
Knox, D; CROI 2016
Links to CROI talks
• ASPIRE: http://www.croiwebcasts.org/console/player/29584?mediaType=audio&
• The Ring Study: http://www.croiwebcasts.org/console/player/29585?mediaType=audio&
• Cabotegravir injectable PrEP:
http://www.croiwebcasts.org/console/player/29580?mediaType=audio&
• FTC/TAF as oral PrEP: http://www.croiwebcasts.org/console/player/29582?mediaType=audio&
• Symposium on PrEP implementation (especially talks by Sheena McCormack and James
Pickett): http://www.croiwebcasts.org/console/player/29561?mediaType=audio&
http://www.croiwebcasts.org/console/player/29562?mediaType=audio&
• Oral abstracts and discussion about renal function and STIs within PrEP delivery on
Wednesday at 1:45pm: http://www.croiwebcasts.org/y/2016/24?link=nav&linkc=date
• Oral abstracts about ART delivery and meeting the UNAIDS 90-90-90 targets on Thursday at
10am: http://www.croiwebcasts.org/y/2016/24?link=nav&linkc=date
Thank you! Connie Celum, Jared Baeten, Renee Heffron
Questions: [email protected]