Advanced HIV disease and engagement in care among patients on antiretroviral therapy in South Africa: results from a multi-state model

Objective: Despite improved access to antiretroviral therapy (ART) for people with HIV (PWH), HIV continues to contribute considerably to morbidity and mortality. Increasingly, advanced HIV disease (AHD) is found among PWH who are ART-experienced. Design: Using a multi-state model we examined associations between engagement with care and AHD on ART in South Africa. Methods: Using data from IeDEA Southern Africa, we included PWH from South Africa, initiating ART from 2004 to 2017 aged more than 5 years with a CD4(+) cell count at ART start and at least one subsequent measure. We defined a gap as no visit for at least 18 months. Five states were defined: 'AHD on ART' (CD4(+) cell count <200 cells/mu l), 'Clinically Stable on ART' (CD4(+) cell count >= 200 or if no CD4(+) cell count, viral load <1000 copies/ml), 'Early Gap' (commencing <= 18 months from ART start), 'Late Gap' (commencing >18 months from ART start) and 'Death'. Results: Among 32452 PWH, men and those aged 15-25 years were more likely to progress to unfavourable states. Later years of ART start were associated with a lower probability of transitioning from AHD to clinically stable, increasing the risk of death following AHD. In stratified analyses, those starting ART with AHD in later years were more likely to re-engage in care with AHD following a gap and to die following AHD on ART. Conclusion: In more recent years, those with AHD on ART were more likely to die, and AHD at re-engagement in care increased. To further reduce HIV-related mortality, efforts to address the challenges facing these more vulnerable patients are needed.