Tenofovir Disoproxil Fumarate in Maternal ART Linked to Modest Creatinine Decline in HIV-Positive Women

This randomized trial, published as a brief report, compared tenofovir disoproxil fumarate (TDF)-containing maternal antiretroviral therapy (ART) with infant nevirapine prophylaxis (iNVP) in 2431 women living with HIV and CD4 counts ≥350 cells per cubic millimeter. The study was conducted at 14 sites in India and Africa. Women were randomized to receive either TDF-containing ART or iNVP, with follow-up at weeks 1, 6, 26, and 74. The primary outcome was change in creatinine clearance (CrCl) from entry through week 74. Secondary outcomes included changes in calcium and phosphate levels.

For the primary outcome, the mean change in CrCl from entry was larger for TDF-ART compared with iNVP. At week 6, the difference was -11.4 mL/min (95% CI: -14.5 to -8.3). At week 26, the difference was -6.9 mL/min (95% CI: -10.0 to -3.9). At week 74, the difference was -5.1 mL/min (95% CI: -9.4 to -0.9; P = 0.019). These results indicate a statistically significant but modest decline in CrCl associated with TDF-ART.

For secondary outcomes, differences in mean change from entry for calcium and phosphate were close to 0, with narrow confidence intervals that excluded clinically relevant differences. This suggests no significant impact on these electrolytes.

Regarding safety, the study reported that TDF-containing ART had no observed safety concerns for maternal renal function during the postpartum period. However, specific adverse events, serious adverse events, and discontinuation rates were not reported in the available summary.

Compared to prior studies, this trial adds data on renal effects of TDF in a large cohort of postpartum women with HIV. Previous research has shown TDF can cause renal tubular dysfunction, but the clinical significance of modest CrCl declines remains debated. The study's strengths include its randomized design and large sample size.

Key limitations include the lack of reporting on adverse events, discontinuations, and funding sources. The brief report format may omit important details. Additionally, the study population was limited to women with CD4 counts ≥350 cells/mm³, which may not generalize to those with lower counts. The clinical relevance of a 5.1 mL/min difference at 74 weeks is uncertain, as it may not translate to increased risk of renal failure.

Clinically, these findings suggest that TDF-containing ART in postpartum women with HIV is associated with a small but statistically significant decline in renal function. However, the absence of observed safety concerns indicates that the benefit of preventing HIV transmission likely outweighs the renal risk. Practitioners should monitor renal function in women on TDF, but the modest effect size does not warrant avoiding TDF in this population.

Unanswered questions include the long-term renal outcomes beyond 74 weeks, the impact in women with lower CD4 counts, and whether the decline in CrCl is reversible after TDF discontinuation. Further research is needed to clarify the clinical significance of these findings.