The potential impact of partially effective HIV prevention strategies: Insights from mathematical modeling analyses

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Click to edit Master title style Click to edit Master title style The potential impact of partially effective HIV prevention strategies: Insights from mathematical modeling analyses Ruanne V. Barnabas, MBChB, D.Phil Global Health and Medicine University of Washington

Outline Background: Combination prevention to reduce HIV incidence Mathematical modeling methods Results: Incremental impact of prevention Conclusions Next steps

Progress towards UNAIDS 90-90-90 targets UNAIDS, 2017

Substantial declines in new HIV infections 1.8 million

Reductions in new infections are off target 2020 Goal: 500 000 Models assume combination prevention: ART, condoms, VMMC, PrEP, protection of human rights and improved service delivery UNAIDS, 2017

High HIV incidence among young women age 20-24 years in eastern and southern Africa

Gaps in achieving reductions in HIV incidence ART coverage gaps by gender and age Unmet need for primary prevention VMMC PrEP New platforms for prevention To reduce HIV incidence: Maximize the synergy between treatment and prevention When 90-90-90 goals for ART are met, 50% of new infections are estimated to occur from acute HIV infection Acute infections are challenging to identify as ART is scaled up, primary prevention will be critical to decrease incident HIV infections

PHIA: viral suppression lower among men and young persons Population-Based HIV Impact Assessment (PHIA) Zimbabwe Zambia Jessica Justman et. al., ICAP, Columbia, 2017

Low uptake of VMMC

Aim To estimate the incremental impact of partially effective HIV prevention interventions in addition to ART scale up, specifically: - Scale-up VMMC - Provision of oral PrEP (25% of 15-39 year old women) - Modest coverage for the dapivirine ring (10% and 20%)

Methods Adapted a mathematical model of HIV infection in KwaZulu-Natal, South Africa, a high HIV incidence setting Compartmental, deterministic Stratified for gender, age, sexual behavior, CD4, and viral load Continuous for time and age Viral load determines transmission probability Parameterized using local data Validated using independent data source Tracks engagement in treatment and prevention Ying, R., et. al. CEA of home-based HTC, Lancet IHV, 2016

Mathematical modeling estimate of effectiveness Susceptible Acute Stage CD4 >500 CD4 500-350 CD4 350-200 CD4 200 ART *Force of infection per susceptible risk of acquiring HIV (function of sexual mixing, HIV prevalence, transmission probability, viral load) captures indirect effects Ying, R., et. al. CEA of home-based HTC, Lancet IHV, 2016

Model assumptions HIV progression by CD4 and viral load count ART coverage 60% of PLWH are virally suppressed VMMC: 10% then scaled up to 50% Efficacy assumptions: PrEP: 70% (assuming high adherence) Dapivirine ring* Females aged 15-19: 27% Females aged 20+: 50% Circumcision: 60% *Baeten and colleague, ASPIRE and HOPE Studies; Nel and colleagues, The Ring and DREAM Studies

Model validation

Model validation 20 Female Age group 15-19 HIV Prevalence 40 Female Age group 20-24 HIV Prevalence % HIV 10 0 1975 1980 1985 1990 1995 2000 2005 2010 2015 2020 Year 100 Female Age group 25-29 HIV Prevalence % HIV 20 0 1975 1980 1985 1990 1995 2000 2005 2010 2015 2020 Year 100 Female Age group 30-34 HIV Prevalence % HIV 50 % HIV 50 0 1975 1980 1985 1990 1995 2000 2005 2010 2015 2020 Year 50 Female Age group 35-39 HIV Prevalence 0 1975 1980 1985 1990 1995 2000 2005 2010 2015 2020 Year 40 Female Age group 40-44 HIV Prevalence % HIV % HIV 20 % HIV 0 1975 1980 1985 1990 1995 2000 2005 2010 2015 2020 Year 40 Female Age group 45-49 HIV Prevalence 20 0 1975 1980 1985 1990 1995 2000 2005 2010 2015 2020 Year Model Africa Center Data 0 1975 1980 1985 1990 1995 2000 2005 2010 2015 2020 Year

Results HIV Incidence Incidence per 100 4.5 4 3.5 3 2.5 2 1.5 1 0.5 0 2019 2024 2029 2034 2039 2044 2049 Base Year 50% VMMC coverage 50% VMMC, 25% PrEP coverage 50% VMMC, 25% PrEP, 10% Dapivirine coverage 50% VMMC, 25% PrEP, 20% Dapivirine coverage

Results HIV Incidence Reduction 0-10 Percent Reduction -20-30 -40-50 -60-70 2019 2024 2029 2034 2039 2044 2049 Year 50% VMMC coverage 50% VMMC, 25% PrEP coverage 50% VMMC, 25% PrEP, 10% Dapivirine coverage 50% VMMC, 25% PrEP, 20% Dapivirine coverage

Conclusions HIV incidence continues to be high, specifically among young women and priority populations Synergy between treatment and prevention has the potential to reduce HIV incidence compared to treatment alone Modest coverage of partially effective prevention interventions, such as the dapivirine ring, could result in real decreases in HIV incidence at a population level while we await more efficacious long-acting interventions Next step - look at interventions stratified by age and gender

Click to edit Master title style Click to edit Master title style Thank you Nicholas Tan Roger Ying Kathryn Peebles Allen Roberts Jared Baeten Connie Celum