Executive Summary

South Africa has made remarkable progress in expanding access to antiretroviral therapy (ART) for people living with HIV. However, optimal strategies are needed to monitor ART patients to maximize treatment outcomes. Historically, CD4 count testing was used to monitor disease progression and treatment response. However, viral load testing is now recommended by WHO as the preferred monitoring approach to diagnose and confirm ART failure. This report evaluates the cost-effectiveness of implementing routine viral load monitoring compared to CD4 monitoring for HIV patients on ART in South Africa.

This report aims to provide evidence to inform policy decisions on adopting routine viral load monitoring in South Africa. The objectives are to evaluate and compare the two monitoring approaches’ costs, health outcomes, and cost-effectiveness. The target population is HIV-positive adults initiated on first-line ART in South Africa. A Markov model was constructed to simulate HIV disease progression under routine viral load monitoring versus CD4 monitoring. CD4 count, viral load, and ART regimen defined health states. Transition probabilities were derived from published studies. The perspective was that of the South African public healthcare system. Incremental cost-effectiveness ratios were calculated in terms of cost per quality-adjusted life year (QALY) gained.

The report includes an introduction that provides background on the HIV epidemic in South Africa and a rationale for evaluating viral load monitoring. This is followed by a comprehensive evaluation of routine viral load monitoring compared to CD4 monitoring using the Markov model. Key parameters include health states, transition probabilities, lab tests and ART regimens costs, and health state utilities. The model estimates the two monitoring approaches’ lifetime costs, life expectancy, QALYs, and incremental cost-effectiveness.

The results show that routine viral load monitoring generates improved health outcomes compared to CD4 monitoring, with incremental gains in life expectancy and QALYs. Although viral load monitoring increases lifetime costs, the total cost-effectiveness ratio is within accepted thresholds, indicating it is cost-effective given South Africa’s GDP per capita. Extensive sensitivity analyses assess uncertainty in key parameters. The model results recommend adopting routine viral load monitoring in South Africa. Implementation considerations are discussed, including strategies to improve cost-effectiveness through integrated care models and task-shifting.

The report concludes by summarizing the essential findings and health systems implications. The results strongly support the adoption of a national policy for routine viral load monitoring, which has the potential to substantially improve the quality and outcomes of South Africa’s HIV treatment program. However, budget impact analysis shows that considerable investments are required to expand access to routine viral load monitoring. This should be pursued through an equitable approach that strengthens the overall HIV clinical infrastructure. Additional research can inform the optimal design of viral load monitoring programs. Overall, this evaluation provides valuable evidence to guide policies that maximize the long-term health impact of South Africa’s unprecedented public sector ART program.

Introduction and Background

South Africa has the largest HIV epidemic in the world, with an estimated 7.5 million people living with HIV in 2020 (Zuma et al., 2022). The country has made remarkable gains in expanding access to antiretroviral therapy (ART) for people living with HIV. Free ART was introduced in public clinics in 2004; by 2020, over 5 million people were receiving treatment (Dorward, 2023). However, major challenges remain in patient retention and ensuring optimal treatment outcomes. A key priority is developing effective and sustainable approaches to monitor patients on ART.

Historically, clinical and immunological monitoring using CD4 cell counts has been the standard of care to determine ART eligibility and assess response to treatment. CD4 count thresholds guide ART initiation and regimen switching (‌Hoffmann, Gonzalez, and Stein, 2023). However, CD4 monitoring has limitations. CD4 counts can remain low even when the patient is virally suppressed on treatment. CD4 counts provide limited information about adherence and treatment failure. For this reason, viral load testing is now recommended as the preferred monitoring approach by the World Health Organization (Mnzawa et al., 2023).

Viral load testing directly measures the amount of virus in the blood. Higher viral loads are associated with disease progression and transmission risk. Viral load monitoring can accurately diagnose poor adherence and treatment failure. The