Abstract
BACKGROUND: Tenofovir disoproxil fumarate (TDF) is frequently used in antiretroviral therapy (ART) for pregnant and breastfeeding women living with HIV. Although TDF-containing ART is known to be effective for prevention of perinatal transmission, there is limited information about renal safety of maternal TDF during the breastfeeding period. SETTING: In the postpartum component of the PROMISE (Promoting Maternal and Infant Survival Everywhere) trial, 2431 women living with HIV and CD4 counts ≥350 cells per cubic millimeter were randomized to either TDF-containing maternal ART (TDF-ART; n = 1220) or infant nevirapine prophylaxis (iNVP; n = 1211) for the prevention of HIV transmission through breastmilk at 14 sites in India and Africa; 400 women had additional renal evaluations in the P1084s substudy. METHODS: Calculated creatinine clearance (CrCl), calcium (P1084s only), and phosphate (P1084s only) were evaluated at postpartum weeks 1 (entry), 6, 26, and 74. Two-sided Student t tests compared change in CrCl from entry with week 74 (primary). RESULTS: Mean change in CrCl from entry was larger for TDF-ART compared with iNVP; differences [95% confidence intervals (CIs): -11.4 mL/min (-14.5 to -8.3) at week 6, -6.9 mL/min (-10.0 to -3.9) at week 26, and -5.1 mL/min (-9.4 to -0.9; P = 0.019) at week 74]. Differences in mean change in calcium and phosphate from entry were close to 0 with narrow CIs that excluded clinically relevant differences. CONCLUSION: Although participants randomized to TDF-ART had larger decreases in CrCl from entry compared with participants randomized to iNVP, differences attenuated overtime and were not clinically significant. TDF-containing ART had no observed safety concerns for maternal renal function during the postpartum period.