TY - JOUR T1 - Modeling HIV disease progression and transmission at population-level: The potential impact of modifying disease progression in HIV treatment programs JF - bioRxiv DO - 10.1101/097337 SP - 097337 AU - Jennifer M. Ross AU - Roger Ying AU - Connie L. Celum AU - Jared M. Baeten AU - Katherine K. Thomas AU - Pamela M. Murnane AU - Heidi van Rooyen AU - James P Hughes AU - Ruanne Barnabas Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/01/06/097337.abstract N2 - Introduction Mathematical models of HIV transmission that incorporate the dynamics of disease progression can estimate the potential impact of adjunctive strategies to antiretroviral therapy (ART) for HIV treatment and prevention. Suppressive treatment of HIV-positive persons co-infected with herpes simplex virus-2 (HSV-2) with valacyclovir, a medication directed against HSV-2, can lower HIV viral load, but the impact of valacyclovir on population HIV transmission has not been estimated.Methods We applied data on CD4 and viral load progression in ART-naïve persons studied in two HIV clinical trials to a novel, discrete-time Markov model. We validated our disease progression estimates using data from a trial of home-based HIV counseling and testing in KwaZulu-Natal, South Africa. Finally, we applied our disease progression estimates to a dynamic transmission model estimating the impact of providing valacyclovir to ART-naïve individuals to reduce onward transmission of HIV in three scenarios of different ART and valacyclovir population coverage. We assumed that valacyclovir reduced HIV viral load by 1.23 log copies/μL, and that persons treated with valacyclovir initiated ART more rapidly when their CD4 fell below 500 due to improved retention in pre-ART care.Results The average duration of HIV infection following acute infection was 9.5 years. The duration of disease after acute infection and before reaching CD4 200 cells/μL was 2.53 years longer for females than males. Relative to a baseline of community HIV testing and counseling and ART initiation at CD4 <=500 cells/μL, valacyclovir with increased linkage to care resulted in 166,000 fewer HIV infections over ten years, with an incremental cost-effectiveness ratio (ICER) of $4,696 per HIV infection averted. The Test and Treat scenario with 70% ART coverage and no valacyclovir resulted in 202,000 fewer HIV infections at an ICER of $6,579.Conclusion Even when compared with initiation of valacyclovir, a safe drug that reduces HIV viral load, universal treatment for HIV is the optimal strategy for averting new infections and increasing public health benefit. Universal HIV treatment should be pursued by all countries to most effectively and efficiently reduce the HIV burden. ER -