Modeling HIV disease progression and transmission at population-level: The potential impact of modifying disease progression in HIV treatment programs
Jennifer M. Ross,
Roger Ying,
Connie L. Celum,
Jared M. Baeten,
Katherine K. Thomas,
Pamela M. Murnane,
Heidi van Rooyen,
James P. Hughes,
Ruanne V. Barnabas
Affiliations
Jennifer M. Ross
Department of Medicine, University of Washington, Seattle, WA, USA; Division of Allergy and Infectious Disease, University of Washington, 1959 NE Pacific St., Box 356423, Seattle, WA 98195, USA; Corresponding author at: Department of Medicine, Division of Allergy and Infectious Disease, University of Washington, 1959 NE Pacific St., Box 356423, Seattle, WA 98195, USA.
Roger Ying
Weill Cornell Medical College, Cornell University, 420 E 70th St., 12J-3, New York, NY 10021, USA
Connie L. Celum
Department of Medicine, University of Washington, Seattle, WA, USA; Department of Global Health, University of Washington, 325 9th Ave., Box 359927, Seattle, WA 98104-2420, USA; Department of Epidemiology, University of Washington, Seattle, WA, USA; Division of Allergy and Infectious Disease, University of Washington, 1959 NE Pacific St., Box 356423, Seattle, WA 98195, USA
Jared M. Baeten
Department of Medicine, University of Washington, Seattle, WA, USA; Department of Global Health, University of Washington, 325 9th Ave., Box 359927, Seattle, WA 98104-2420, USA; Department of Epidemiology, University of Washington, Seattle, WA, USA; Division of Allergy and Infectious Disease, University of Washington, 1959 NE Pacific St., Box 356423, Seattle, WA 98195, USA
Katherine K. Thomas
Department of Global Health, University of Washington, 325 9th Ave., Box 359927, Seattle, WA 98104-2420, USA
Pamela M. Murnane
Department of Global Health, University of Washington, 325 9th Ave., Box 359927, Seattle, WA 98104-2420, USA; Department of Epidemiology, University of Washington, Seattle, WA, USA; Center for AIDS Prevention Studies, Department of Medicine, University of California San Francisco
Heidi van Rooyen
Human Sciences Research Council, Durban, South Africa
James P. Hughes
Department of Biostatistics, University of Washington, 1959 NE Pacific St., Box 357232, Seattle, WA 98195, USA; Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
Ruanne V. Barnabas
Department of Medicine, University of Washington, Seattle, WA, USA; Department of Global Health, University of Washington, 325 9th Ave., Box 359927, Seattle, WA 98104-2420, USA; Department of Epidemiology, University of Washington, Seattle, WA, USA; Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Division of Allergy and Infectious Disease, University of Washington, 1959 NE Pacific St., Box 356423, Seattle, WA 98195, USA
Introduction: Mathematical models that incorporate HIV disease progression dynamics can estimate the potential impact of strategies that delay HIV disease progression and reduce infectiousness for persons not on antiretroviral therapy (ART). Suppressive treatment of HIV-positive persons co-infected with herpes simplex virus-2 (HSV-2) with valacyclovir, an HSV-2 antiviral, can lower HIV viral load, but the impact of partially-suppressive valacyclovir relative to fully-suppressive ART on population HIV transmission has not been estimated. Methods: We modeled HIV disease progression as a function of changes in viral load and CD4 count over time among ART naïve persons. The disease progression Markov model was nested within a dynamic model of HIV transmission at population level. 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 retention in HIV care. We estimated the potential impact of valacyclovir on onward transmission of HIV in three scenarios of different ART and valacyclovir population coverage. Results: The average duration of HIV infection was 9.5 years. The duration of disease before reaching CD4 200 cells/μL was 2.53 years longer for females than males. Relative to a baseline of ART initiation at CD4 ≤ 500 cells/μL, the valacyclovir scenario resulted in 167,000 fewer HIV infections over ten years, with an incremental cost-effectiveness ratio (ICER) of $5276 per HIV infection averted. A Test and Treat scenario with 70% ART coverage and no valacyclovir resulted in 350,000 fewer HIV infections at an ICER of $2822 and $812 per HIV infection averted and QALY gained, respectively. Conclusion: Even when compared with valacyclovir suppression, a 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 would most effectively and efficiently reduce the HIV burden. Keywords: HIV, valacyclovir, herpes simplex virus, disease progression, mathematical modeling, ART, HIV prevention
