Evidence of renal tubular impairment and increased bone turnover in HIV-infected adolescents and young adults on tenofovircontaining combination antiretroviral therapy (cART): Baseline results of Adolescent Trials Network (ATN) study 063

Objective: Tenofovir (TDF) is a popular component in cART regimens in adolescents and young adults, despite concerns about its use in an age group that is approaching or achieving peak bone mass. We describe the nature and extent of alterations in renal function and bone metabolism in HIV-infected adolescents on TDF-containing cART, compared to those being treated with other antiretrovirals. Methods: We compared biochemical indices of glomerular and renal tubular function and factors related to bone metabolism in HIV-infected individuals, ages 18-24, on TDF and non TDF-containing cART regimens. Subjects with viral load <5,000 copies/ml on stable cART for ≥90 days were recruited at 15 ATN and 19 International Maternal and Pediatric Adolescent AIDS Clinical Trials Group sites in the US and Puerto Rico. Data are medians. P-values are by Wilcoxon rank sum test. Results: The groups were similar in age, racial/ethnic distribution, BMI, and vitamin D and calcium intake. Serum 25-OH vitamin D concentration was insufficient/deficient Table Presented (<30 ng/ml) in 84% of participants overall but did not differ between groups. Participants not on TDF had significantly longer duration of HIV infection and exposure to ART, higher viral load, and more advanced HIV disease (CDC stage), but higher CD4 counts, compared to those on TDF. A greater proportion of participants on TDF were on regimens containing an NNRTI, while more participants not on TDF were on regimens containing a PI. Creatinine clearance (CrCl; ml/min/1.73 m2) and tubular reabsorption of phosphate (TRP; %) were lower in those on TDF, while urinary β2 microglobulin (uβ2; ng/ml), a nonspecific marker of renal tubular dysfunction, was higher. Participants on TDF had lower urinary calcium excretion (uCa/Cr; mg/mg). Serum calcium and phosphate levels did not differ between groups. The TDF group had higher levels of parathyroid hormone (PTH; pg/ml) and carboxyl terminal collagen crosslinks (CTX; pM), a marker of bone resorption. Bone-specific alkaline phosphatase (BAP; U/L), a marker of bone formation, was not significantly higher in participants on TDF (Table 1). Discussion: Despite shorter duration of HIV infection and less advanced HIV disease, HIV-infected adolescents and young adults on TDF-containing cART regimens displayed evidence of glomerular and renal tubular impairment and increased bone turnover, compared with those not on TDF. These results suggest the observed differences may be associated with TDF administration, rather than HIV disease. Further study is needed to determine if the observed renal tubular changes in calcium and phosphate handling are causally related to the changes in markers of bone turnover, and whether they impact bone mass in this population.