Characteristics and six-month viral load suppression of clients presenting with advanced HIV disease in South Africa

Introduction Despite advances in antiretroviral therapy (ART), notable proportion of individuals still present with advanced HIV disease (AHD) at treatment initiation, defined by CD4 counts <200cells/µL or WHO stage 3/4 conditions. This group faces higher mortality and more opportunistic infections. While clinical guidelines are available, they do not adequately address the unique needs of AHD patients, particularly early in treatment. Addressing these gaps could improve care and outcomes.

From 9/2022-6/2023 we surveyed a sequential sample of clients presenting for ART initiation or ≤6 months post-initiation at 18 primary healthcare facilities across three provinces. We elicited socio-demographic data, HIV care history, and service delivery preferences and expectations and linked survey responses to routine medical record data. We used descriptive statistics to summarise client characteristics and calculated relative risks and risk differences to compare outcomes between AHD and non-AHD clients. The primary outcomes were 6-month retention and viral load suppression, categorized as suppressed (<50 copies/mL), low-level viremia (50–1,000 copies/mL), or unsuppressed (≥1,000 copies/mL) at the 6-month viral load test.

Of 1,098 clients (72% female, median age=33), 938 had CD4 count or WHO staging recorded at ART initiation. Of these 29% (n=275) had advanced HIV disease (AHD), with a median CD4 count of 108 cells/µL. AHD clients were more likely to be male (44% vs.21%), older (38 vs.31 years), and seek care due to illness (63% vs. 33%). They also had higher rates of TB (42% vs.12%) and TB testing (76% vs. 67%). Service preferences and healthcare resource utilization were similar across groups. Retention at six months was similar (80% vs. 75%), but AHD clients had higher mortality (1.0% vs. 0.2%). AHD clients were more likely to experience low-level viremia (24% vs. 11%; RR=2.27, 95%CI=1.67-3.09) and less likely to achieve viral suppression (43% vs. 47%).

AHD remains a barrier to optimal ART outcomes in South Africa. Low-level viremia in the first six months highlights the need for targeted care models with early detection, rapid ART initiation, and tailored support to address specific needs of AHD clients. Updating ART guidelines to specifically provide for AHD will be important in improving outcomes for this group. Study registration Clinicaltrials.gov NCT05454839, Clinicaltrials.gov NCT05454852 Competing Interest Statement The authors have declared no competing interest. Funding Statement Funding for the study was provided by the Gates Foundation through award INV-031690 to Boston University. The funder had no role in study design, data collection, analysis, or preparation of this manuscript. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The PREFER study protocol was approved by the Boston University Institutional Review Board under protocol H-42726 (PREFER-South Africa) and the University of Witwatersrand Human Research Ethics Committee under protocol M220440 (PREFER-South Africa). Additionally, the protocol received approval from the Provincial Health and Research Committees via each study district's National Health Research Database. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes