Advanced HIV disease during the first six months on antiretroviral therapy in Zambia: research protocol for a prospective, observational, multi-cohort study.

Background: The proportion of HIV-positive individuals who present for initiation or re-initiation of antiretroviral therapy (ART) with advanced HIV disease (AHD) and are at risk for morbidity and mortality remains high throughout sub-Saharan Africa. In Zambia, where 20% of ART initiators are diagnosed with AHD, little is known about the characteristics of those starting ART with AHD, why treatment initiation is delayed, how AHD clinical management influences clinical and non-clinical outcomes, or implementation of national AHD guidelines at facility level.

Protocol: AHD-Zambia is a mixed-methods observational study to describe AHD clients and care during the first six months after starting or re-starting ART in Zambia. The study will be conducted at 24 public sector primary health facilities in four provinces. It will enroll ART clients screened for AHD during a three-month data collection period (Cohort 1), clients screened for AHD in the 12 months prior to the data collection period (Cohort 2), patients hospitalized for AHD-related conditions (Cohort 3); and clinical providers at the study sites who manage clients with AHD (Cohort 4). Data collection will include quantitative surveys, medical record review during the 12 months before and after enrollment, qualitative interviews, and focus group discussions. Facility-level indicators will also be collected. Outcomes will include detailed profiles of AHD clients and their 6 and 12-month retention in care and viral suppression, provider and client views on barriers to and preferences for AHD care, and assessment of facility fidelity to AHD guidelines.

Discussion: This study will generate a comprehensive profile of clients presenting with AHD in Zambia, including clinical, demographic, social, and behavioral characteristics, treatment outcomes, and barriers to providing guideline-compliant care. Findings will provide insight into the delivery of AHD services, identify gaps in implementation, and support improvements to retention and care during the early treatment period.

Registration: Clinicaltrials.gov NCT06904456.