Brief Report: Postpartum Maternal Monitoring for Renal Safety Related to Tenofovir Exposure During Breastfeeding in the PROMISE 1077BF Randomized Trial.

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.