Viral load monitoring of antiretroviral therapy, cohort viral load and HIV transmission in Southern Africa

Abstract

Objectives In low-income settings treatment failure is often identified using CD4 cell count monitoring. Consequently, patients remain on a failing regimen, resulting in a higher risk of transmission. We investigated the benefit of routine viral load monitoring for reducing HIV transmission. Design Mathematical model Methods We developed a stochastic mathematical model representing the course of individual viral load, immunological response and survival in a cohort of 1,000 HIV infected patients receiving antiretroviral therapy (ART) in southern Africa. We calculated cohort viral load (sum of individual viral loads) and used a mathematical relationship between individual viral load values and transmission probability to estimate the number of new HIV infections. Our model was parameterized with data from the IeDEA Southern African collaboration. Sensitivity analyses were performed to assess the validity of the results in a universal ‘test and treat’ scenario where patients start ART earlier after HIV infection. Results If CD4 cell count alone was regularly monitored, the cohort viral load was 2.6*106 copies/mL and the treated patients transmitted on average 6.3 infections each year. With routine viral load monitoring, both cohort viral load and transmissions were reduced by 31% to 1.7*106 copies/mL and 4.3 transmissions, respectively. The relative reduction of 31% between monitoring strategies remained similar for different scenarios. Conclusions While routine viral load monitoring enhances the preventive effect of ART, the provision of ART to everyone in need should remain the highest priority.

The need for second-line antiretroviral therapy in adults in sub-Saharan Africa up to 2030: a mathematical modelling study

“…Our model was applied to each country separately, but we used the same parameters, fixed over time and based mainly on routine ART programmes from southern Africa. 7–11 Baseline characteristics of these programmes are typical for SSA, but there are differences in the standard and practices of care. The standard of care has also changed over time: in the data used for parameterisation, most patients started ART at the late stage of the infection.…”

Delayed switch of antiretroviral therapy after virologic failure associated with elevated mortality among HIV-infected adults in Africa

“…Third, our analyses underestimate the benefits of routine viral monitoring in that they do not account for reduction in unneeded switches due to poor specificity of immunologic failure criteria, improved opportunity for targeted adherence interventions, decreased acquired and transmitted resistance, or reduced infectivity [3,7,41–44]. Although simulation models can investigate these broader health, transmission and costing implications, such models rely on understanding the mortality impact of deferred switch following virologic failure; our analyses contribute to this knowledge base [45–49]. …”

Sustainable HIV treatment in Africa through viral-load-informed differentiated care

“…The HIV Synthesis Transmission model is an individual-based stochastic model of heterosexual transmission, natural history, clinical disease, and treatment of HIV infection incorporating use of specific drugs, resistance mutations, and adherence, which has been described previously (8,32–36). …”