Effect of anti-retroviral regimen on proximal tubular function in Zambian adolescents and young adults living with HIV

We conducted a cross-sectional study involving 180 adolescents and young adults receiving antiretroviral theray for at least 12 months at the University Teaching Hospitals (UTHs) in Lusaka, Zambia. These were either on Tenofovir or Abacavir-based antiretroviral regimen . SmartCare, a national HIV electronic medical database, was used to select eligible participants between May 2018 and March 2019 using a checklist to verify eligibility. All participants were aged between 10 and 24 years who had received ART for a minimum of 12 months and had a documented normal estimated glomerular filtration rate (eGFR) at initiation of the current antiretroviral regimen. Written informed consent and/or assent for participation in this study were obtained from each participant and/or parent or guardian. The study adhered to the declaration of Helsinki <strong>Data collection</strong> Individual participant data were collected from Smart Care, interviews, and physical examination including current age, sex, current weight, body mass index (BMI), current ART regimen and duration, baseline CD4+ cell count, self-reported 85% ART adherence, previous or current tuberculosis, and baseline creatinine or estimated Glomerular Filtration Rate (eGFR). Participants were requested to provide two first-morning spot urine specimens for urinary protein and creatinine levels to calculate a mean (2-sample) urine protein to creatinine ratio (UPCR). The second first-morning urine was obtained within 7-14 days of the first specimen. Each spot urine sample was analyzed for markers of tubular function, urinary b2-microglobulin, a1-microglobulin, creatinine, and urine phosphate. Urine β2-microglobulin and α1-microglobulin were determined by Enzyme-linked immunosorbent assays (ELISA) with detection range of 31.25—2000 ng/mL and 4.69-300 ng/mL. All reagents, samples and standards were prepared according to the instructions in the manufacturer’s manual (Wuhan Elabscience Biotechnology Co. Ltd, Donghu Hi-Tech Development Area, Wuhan, Hubei, China). The urinary proteins were expressed as the ratio-to-creatinine (a1-MCR, b2-MCR, and UPCR) to adjust for variations in urine concentration. Serum or plasma samples were analyzed for CD4+ cell count, HIV viral load, hemoglobin, calcium, potassium, uric acid, urea, phosphate, serum creatinine, and albumin.