Socio-Behavioral Research Experiences and Acceptability of Serial Lymph Node and Gut Biopsies Among Young Women Enrolled in an HIV Cure–Related Trial in Durban, South Africa

Human immunodeficiency virus (HIV) persists in diverse body tissues, including the gut, lymph nodes (LNs), and lungs, requiring direct sampling to characterize heterogeneous reservoirs. HIV cure–related trials may include tissue sampling to evaluate intervention efficacy and mechanisms to eliminate viral reservoirs. Repeated invasive sampling carries risks that must be balanced against safety, acceptability, and scientific value. We assessed the experiences of young women undergoing serial excisional LN and gut biopsies during an HIV cure–related trial in South Africa. We conducted a qualitative secondary analysis of in-depth interviews (IDIs) with women enrolled in a Phase 2A HIV cure–related trial (NCT05281510) that included an analytical treatment interruption (ATI). We conducted IDIs at enrollment and pre-ATI at the Females Rising through Education, Support and Health research site in Durban, South Africa, in isiZulu . We audio-recorded, transcribed, translated, and deidentified the interviews and analyzed them using inductive conventional content analysis. We interviewed 19 participants. Each underwent LN excision 1–3 times (mean 2.6) and gut biopsy 0–3 times (mean 2.5). Motivations included scientific curiosity and contributing to future generations. LN excision was generally painless, although some reported itching and slow healing. Gut biopsies caused abdominal pressure and transient bloating. One adverse event occurred among 48 LN excisions. Initial apprehension was common, but clear communication, supportive staff, and recognition of contributions fostered trust and willingness to undergo repeat procedures. Serial tissue sampling was acceptable among young South African women despite some discomfort. Altruism was a primary motivator, while clear communication and participant-centered care were critical to supporting informed participation and repeat sampling.