Renal function in African women receiving tenofovir disoproxil fumarate as pre-exposure prophylaxis for HIV during pregnancy and postpartum: A postpartum safety analysis in the CAP016 randomized control trial.

BACKGROUND

The effect of tenofovir disoproxil fumarate (TDF) when used as pre-exposure prophylaxis (PrEP) on renal function in pregnant and postpartum women is understudied. An open-label clinical trial (CAP016 study) was designed to examine the safety of TDF-PrEP use during pregnancy and breastfeeding.

METHODS

Women were randomized (1:1) to either initiate PrEP at enrolment in pregnancy (Immediate PrEP-IP) or initiate PrEP (Deferred PrEP-DP) at the time of breastfeeding cessation. We compared changes in creatinine clearance and frequency of adverse renal events in women randomized to initiate TDF-PrEP in pregnancy versus women randomized to defer initiation of TDF-PrEP to the time of breastfeeding cessation. Participants were recruited between 28 September 2017 and 3 December 2019. Serum creatinine was measured at baseline during pregnancy and at 6, 26, 54 and 74 weeks postpartum. Creatinine clearance (CrCl) (mL/min) was calculated using the Cockroft-Gault equation. CrCl ≥90 mL/min was considered normal, CrCl 60-90 mL/min (moderate) and CrCl <60 mL/min (abnormal). We used mixed-effects linear regression models to test for differences in the change in CrCl between the IP and DP arms. The frequency of adverse renal events between the randomization arms was examined using χ2/Fisher's exact tests. The CAP016 parent study was registered on ClinicalTrials.gov under NCT03227731.

RESULTS

Mean difference in CrCl change from 6 to 74 weeks between IP and DP arms was -0.67% (p = 0.809). There was no correlation between randomization arm and change in CrCl over time (β-2.08; p = 0.094). There were 16 (4%) moderate/Grade 2 CrCl abnormalities during the postpartum period, which were comparable between randomization arms. BMI of <18.5 kg/m2 was significantly associated with a moderate renal adverse event (OR 71.8; 95% CI 17.0-302.8) (p < 0.0001).

CONCLUSION

Tenofovir disoproxil fumarate, when given in combination with emtricitabine as pre-exposure prophylaxis during pregnancy and lactation, appears not to have an effect on creatinine clearance and the frequency of adverse renal events in African women without HIV during the 74 week postpartum period. More research is needed to support our findings.