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: rbarnaba@uw.edu