by Loveleen Bansi-Matharu, Daniel T. Citron, Rowan Martin-Hughes, Haroon Moolla, John Stover, Michael Pickles, Tara Mangal, Jenny Smith, Owen Mugurungi, Mmatlou Simeon Kubyana, Isaac Taramusi, Valentina Cambiano, Amon Mpofu, Debra ten Brink, Edinah Mudimu, Tsitsi Apollo, Anna Bershteyn, Linley Chewere, Dobromir Dimitrov, Stephen Macheso, Leigh F. Johnson, Andrew Phillips
Background
Antiretroviral therapy (ART) has greatly reduced HIV-related mortality and improved life expectancy in sub-Saharan Africa since the early 2000s. However, HIV-related mortality remains high. To guide intervention priorities, we used seven established HIV simulation models to identify where in the HIV care cascade deaths occur in Zimbabwe, Malawi, and South Africa. This multi-model approach provided a more comprehensive and robust assessment than could be achieved using any single modelling approach.
Methods and findings
To assess alignment, each model generated key HIV metrics from 2000 to 2045, including total population, HIV prevalence, annual new infections, and proportions of people with HIV (PWH) who were diagnosed, on ART, and virally suppressed. HIV-related deaths were estimated annually and categorised by whether they occurred in individuals who were (1) undiagnosed, (2) diagnosed but had not yet started ART, (3) on ART, or (4) had interrupted ART.The models showed strong consistency with population estimates and HIV prevalence across the different settings. There was, however, variation in the absolute number of HIV-related deaths between models; in Zimbabwe in 2025, this ranged from 3,666 to 17,475; in Malawi from 4,580 to 17,835; and in South Africa from 39,470 to 114,968. In Zimbabwe, all models consistently indicated that PWH receiving ART made up the largest proportion of HIV-related deaths, though this proportion differed across models, ranging from 35% to 64%. This was followed by HIV-related deaths amongst those who had interrupted ART, ranging from 17% to 29%. Similar trends were seen in Malawi. In South Africa, a high proportion of HIV-related deaths occurred amongst people who had interrupted ART (23% to 74% in 2025) as well as those who were currently receiving ART (23% to 56%). Models are reliant on empirical data and limited data availability—in this instance, lack of national death registries—is a key constraint on modelling studies.
Conclusion
Absolute numbers of HIV-related deaths vary substantially between models, highlighting wider issues around ascertainment of death in the region. However, our results do consistently show that most deaths are occurring amongst PWH on ART in Zimbabwe and Malawi, and amongst those who have interrupted treatment in South Africa, suggesting interventions around adherence counselling and retention in care need to be prioritised.
Andrew Phillips
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