Peer Review Report For: Effect of anti-retroviral regimen on proximal tubular function in Zambian adolescents and young adults living with HIV: A cross sectional study [version 1; peer review: 2 approved with reservations]

Background : Tenofovir regimens remain the preferred formulations in the HIV guidelines for adolescents and young adults in Zambia and globally. However, some adolescents and young adults are maintained on abacavir by clinicians because of anxiety about possible proximal tubular dysfunction from tenofovir. We assessed the effect of two regimens on proximal tubular function in adolescents and young adults living with HIV. Methods : This was a cross-sectional study involving 180 participants with HIV receiving either tenofovir or abacavir for ≥12 months at the largest tertiary teaching hospital. Two first-morning urine and blood specimens were collected and analyzed for proximal tubular markers, glomerular function, electrolytes, and routine monitoring tests. Proximal tubular function was determined by measuring the fractional excretion of phosphate (FePO4). Proximal tubular dysfunction was defined by FePO4 ≥20% regardless of serum phosphate and FePO4 ≥10-20% when serum phosphate was below 0.81mmol/L. Results : The prevalence of proximal tubular dysfunction was 6% and was higher in the tenofovir group than the abacavir (10% vs. 2%, p<0.058). However, after adjusting for potential confounders, tenofovir was not associated with worse proximal tubular function. Age, urine b 2- microglobulin: creatinine ratio, C-reactive protein, and urine protein: creatinine ratio was all associated with worsening proximal tubular dysfunction. Reduced estimated glomelurar filtration rate (eGFR) was found in four (2.2%) participants; three of which were on tenofovir. Conclusions : Proximal tubular dysfunction defined by FePO4 was more prevalent in the tenofovir group than the abacavir group, but not after adjusting for age. Our findings should be interpreted with caution as age differences between the two groups confounded the results.