Curbing HIV transmission by HSV-2 treatment

From the Barnabas and Hughes Laboratory, Vaccine and Infectious Disease Division

HIV is a major public health threat affecting people all over the globe. In resource rich areas like the USA, antiretroviral drug therapy (ART) is easily available and common. However, in Africa many HIV-positive patients lack ART (46-72%) due to eligible CD4 counts, ART is only initiated when CD4 count drop below a specified level. This suggests that other tools should be sought in these areas, one such tool could be treating co-infections. Herpes simplex virus type-2 (HSV-2) is often documented as a co-infection in HIV infected individuals. Co-infected patients show faster decline in CD4 count with increased HIV viral load thus leading to increased transmission risk when compared to individuals infected with HIV alone. Two drugs are commonly used to treat HSV-2, acyclovir and valacyclovir and each has been shown to reduce HIV-viral load (.25 log copies/ mL and 1.2 log copies/mL respectively). In a study by authors from Fred Hutch (Vaccine and Infectious Disease Division) and University of Washington published in Epidemics, a three-step model was used to investigate the effects of HSV-2 drugs on HIV viral load, CD4 counts and transmission. Co-first authors, Dr. Jennifer Ross and Roger Ying stated, “This study brings two primary contributions to the field. The first is a model of HIV disease progression and transmission that explicitly models changes in HIV viral load as the disease progresses. Historically, the majority of HIV disease progression models have modeled changes in CD4+ cell count instead of viral load, primarily because CD4+ data have been available more frequently. However, viral load data are becoming more abundant and important as HIV control programs adopt the UNAIDS 90-90-90 targets and expand access to HIV viral load monitoring. Modeling HIV viral load is important because it is a primary determinant of HIV transmission, and it is also the step at which certain interventions modify the disease course. This brings up the second contribution for our study, which is to examine the potential impact of expanding valacyclovir, a drug which suppresses herpes simplex virus, in people living with HIV who are not taking antiretroviral therapy.”

Model output from HIV prevalence and incidence. Prevalence (A) and incidence (B) is similar between model and what was observed in KZN. Model CD4 counts (C) and viral load (D) are comparable to Home HIV Testing and KwaZulu-Natal.
Model output from HIV prevalence and incidence. Prevalence (A) and incidence (B) is similar between model and what was observed in KZN. Model CD4 counts (C) and viral load (D) are comparable to Home HIV Testing and KwaZulu-Natal. figure provided by Dr. Ross and Roger Ying

In this study, the authors used modeling to create an accurate assessment of HIV viral load and CD4 counts over time. Next, they validated their model against data derived from a trial of home based HIV counseling and testing in KwaZulu-Natal, South Africa (KZN). And lastly, they combined their disease progression model with a dynamic transmission model to compare HSV-2 treatment versus ART treatment on viral transmission. After applying their model to the data set, the authors found that their data were similar to that seen in KZN data (see figure), thus validating the system. In regards to viral and cost impact, valacyclovir treatment decreased transmission and prolonged CD4 count drops; however, this also prolonged ART eligibility. Even though valacyclovir reduced transmission, the overall cost was more than starting ART, the most cost-effective strategy. Dr. Ross sums up the study, “Our finding that expansion of antiretroviral therapy (ART) use was the most cost-effective intervention supports the recent changes in global and national HIV policies of increasing access to ART. However, it is unclear how this will be achieved. This study simulated ART provision for 70% of people living with HIV regardless of their HIV stage, which is substantially more than the approximately 55% of people living with HIV globally who are currently accessing ART. Major questions for the next five years are: How will we expand HIV services so that more people can know their HIV status and more people living with HIV can access ART?“

Ross JM, Ying R, Celum CL, Baeten JM, Thomas KK, Murnane PM, van Rooyen H, Hughes JP, Barnabas RV. 2017. Modeling HIV disease progression and transmission at population-level: The potential impact of modifying disease progression in HIV treatment programs. Epidemics.

This work was supported by the National Institutes of Health and the University of Washington Center for AIDS Research.