Clinical impact and cost-effectiveness of the WHO-recommended advanced HIV disease package of care

Abstract

Background: In sub-Saharan Africa, 20-40% of people living with HIV present with advanced HIV disease (AHD), which can be diagnosed, treated, and prevented using a package of care recommended by WHO. We aimed to project the cost-effectiveness and budget impact of the WHO-recommended AHD package in Malawi.

Methods: Using the Cost-Effectiveness of Preventing AIDS Complications-International model, we simulated a cohort of non-hospitalised people living with HIV (aged >19 years) initiating antiretroviral therapy (ART), 25% of whom had AHD (CD4 count <200 cells per μL and/or WHO stage 3 or 4 disease). We assessed 13 increasingly comprehensive strategies, ranging from ART only to the WHO-recommended AHD package, including tuberculosis diagnostics (ie, sputum Xpert and urine lipoarabinomannan), tuberculosis preventive therapy, serum cryptococcal antigen (CrAg) screening with pre-emptive fluconazole treatment if CrAg-positive, and co-trimoxazole to prevent bacterial infections. Model outcomes included 1 year survival, life expectancy, costs, and incremental cost-effectiveness ratios (ICERs, US$ per quality-adjusted life-year [QALY]); we considered a strategy cost-effective if the ICER was less than $600 per QALY (based on 2023 Malawi per capita gross domestic product).

Findings: ART only resulted in life expectancy of 17·45 undiscounted QALYs and discounted lifetime costs of $1450. All other strategies would increase both QALYs and costs. The WHO-recommended AHD package would result in the greatest life expectancy (19·30 undiscounted QALYs) and be cost-effective (ICER $580 per QALY). AHD prevalence and intervention efficacy had the greatest influence on ICERs; however, the WHO-recommended AHD package would remain cost-effective over a wide range of estimates.

Interpretation: The WHO-recommended AHD package of care at ART initiation would provide substantial clinical benefits and be cost-effective in Malawi. This package for AHD should be made widely available in Malawi and similar settings.

Funding: WHO, the HIV Modelling Consortium within the Institute for Global Health at University College London, the Bill & Melinda Gates Foundation, the National Institute of Allergy and Infectious Diseases, the Massachusetts General Hospital Jerome and Celia Reich Endowed Scholar in HIV/AIDS Research Award, and the Steve and Deborah Gorlin Massachusetts General Hospital Research Scholars Award.

Translation: For the Chichewa translation of the abstract see Supplementary Materials section.

Figure 1

Scenario assessing how the proportion of the cohort initiating or reinitiating ART with AHD impacts the cost-effectiveness of different strategies for the prevention, diagnosis, and treatment of AHD among people living with HIV in Malawi The preferred strategy depends on the proportion of the cohort with AHD (horizontal axis) and the cost-effectiveness threshold (vertical axis) and is shown in the colour defined in the legend, where the strategy components are shown to the right of the colour box and details explaining the missing components of the WHO-recommended AHD package in the strategy are to the left of the box. The base case (ie, the most likely scenario) is marked with a black X. AHD=advanced HIV disease. ART=antiretroviral therapy. CrAg=cryptococcal antigen. CTX=co-trimoxazole. LAM=urine lipoarabinomannan. QALY=quality-adjusted life year. TPT=tuberculosis preventive therapy.

Figure 2

Selected bivariate sensitivity analyses to assess the cost-effectiveness of different strategies for the prevention, diagnosis, and treatment of AHD among people living with HIV in Malawi at a cost-effectiveness threshold of US$600/QALY Each panel represents a bivariate sensitivity analysis. The horizontal and vertical axes show the range of each parameter varied and the most cost-effective strategy is shown in colour for each combination of parameters. The results are shown for a cost-effectiveness threshold of $600/QALY. The strategy components are shown to the right of the coloured key; details to the left explain the missing components of the WHO-recommended AHD package in the strategy. The base case is marked with a black X. The WHO-recommended AHD package (green) is the most frequently preferred strategy, despite the wide variation in input parameters. AHD=advanced HIV disease. ART=antiretroviral therapy. CrAg=cryptococcal antigen. CTX=co-trimoxazole. LAM=urine lipoarabinomannan. QALY=quality-adjusted life-year. TPT=tuberculosis preventive therapy.

Figure 3

Budget impact analysis for the WHO-recommended AHD package of care for people living with HIV and initiating or reinitiating ART in Malawi Each bar represents all HIV-related costs accrued over the first 5 years of HIV clinical care for 80 000 outpatients living with HIV initiating or reinitiating ART in Malawi, of whom 25% have AHD. The majority of costs are due to ART and HIV clinical care (gray). AHD=advanced HIV disease. ART=antiretroviral therapy. CrAg=cryptococcal antigen. CTX=co-trimoxazole. LAM=urine lipoarabinomannan.