Evaluating long-term programmatic outcomes of patients with advanced HIV disease: Insights from 12 years of antiretroviral therapy scale-up in rural KwaZulu-Natal

BACKGROUND: Advanced HIV disease (AHD) remains a significant public health challenge, despite the widespread scale-up of antiretroviral therapy (ART) in South Africa. Understanding long-term treatment outcomes among patients with AHD under routine programmatic conditions is critical. However, there is a paucity of longitudinal data on clinical outcomes in this population, particularly within high-HIV prevalence rural settings. This study evaluated retention in care and virological outcomes among patients initiating ART with AHD in rural KwaZulu-Natal between 2008 and 2020. METHODS: We conducted a retrospective cohort study using routine data from 10 public health facilities. Adults (≥18 years) with CD4 < 200 cells/μL or WHO stage 3/4 who initiated ART between January 1, 2008, and December 31, 2020, were included. Primary outcomes were retention in care at 6, 12, 24, 36, and 48 months. Secondary outcomes included viral load (VL) completion and suppression (<1000 copies/μL). Competing risk regression and Poisson regression models were used to identify factors associated with loss to follow-up (LTFU) and virological suppression. RESULTS: Of 40,432 individuals who initiated ART between 2008 and 2020, 9,608 met the criteria for AHD. Retention in care was 98%, 94%, 89%, and 85% at 12, 24, 36, and 48 months, respectively. Men (adjusted subdistribution hazard ratio [aSHR]: 1.35; 95% confidence interval [CI]: 1.23-1.47) and individuals with CD4 counts <100 cells/µL (aSHR: 1.13; 95% CI: 1.08-1.26) had a higher risk of loss to follow-up. Although viral load (VL) completion declined over time (49.3% at 6 months to 31.5% at 48 months), suppression remained above 83% among those with available VL data. Undetectable VL increased from 25.5% to 33.0% between 12 and 48 months. Patients initiating ART during the Universal Test and Treat (UTT) era (2016-2020) had higher retention (78.8%) than those treated between 2012-2015 (62.8%) and higher viral load (VL) suppression (risk ratio [RR]: 1.13; 95% CI: 1.01-1.28) compared with the 2008-2011 cohort. Women (RR 1.18; 95% CI: 1.11-1.25) and those initiating ART within 7 days (RR 1.30; 95% CI: 1.04-1.38) were more likely to achieve virological suppression at any time point. CONCLUSION: This study demonstrates high retention and virological suppression rates among patients with AHD in rural South Africa, particularly under the UTT strategy. Despite these successes, VL testing uptake remains suboptimal, and a considerable gap persists in achieving undetectable VL levels. Integrating the WHO AHD care package and prioritizing early ART initiation and male-focused interventions may further improve outcomes and support efforts to end the HIV epidemic.