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Background: Optimal kidney safety monitoring is a key knowledge gap for wide-scale implementation of tenofovir-based pre-exposure prophylaxis (PrEP) for HIV prevention. We compared 6-monthly to 3-monthly kidney monitoring for the occurrence of clinically relevant decline in creatinine clearance (CrCl; < 60 mL/minute).
Methods: Data were from two prospective PrEP studies in Kenya and Uganda: the Partners Demonstration Project (n=955), a recently completed open-label study that used 6-monthly serum creatinine monitoring to estimate creatinine clearance, and the Partners PrEP Study, a placebo-controlled trial that used 3-monthly monitoring (n=4404 receiving PrEP, n=1573 receiving placebo). CrCl ≥60 mL/minute was required for enrollment in both studies.
Results: With 6-monthly monitoring, the cumulative proportion of participants with unconfirmed CrCl < 60 mL/minute was 0.7% at Month 6 and 1.1% at Month 12, affecting 10 (1%) participants; 2 of these (0.2% overall) had CrCl < 60 mL/minute confirmed on repeat testing, both at Month 6. With quarterly monitoring, the cumulative proportion of participants with unconfirmed CrCl < 60 mL/minute was 1.4% at Month 3, 2.0% at Month 6, and 2.7% at Month 12, affecting 120 (2.7%) participants; 29 of these (0.7%, overall) had CrCl < 60 mL/minute confirmed on repeat testing [cumulative proportion: 16 (0.4%), 21 (0.5%), and (0.7%) at Months 3, 6, and 12, respectively]. The corresponding cumulative frequency of confirmed CrCl < 60 mL/minute in the placebo group was 0.3% at Month 3 and 0.3% at Month 6. Of the 29 participants experiencing confirmed declines in the Partners PrEP Study, 28 (97%) had baseline CrCl 60-90 mL/minute, 19 (66%) were aged ≥45-years, and 16(55%) had baseline weight ≤55 kg (adjusted p< 0.05).
Conclusions: In these two large cohorts of HIV-uninfected persons using PrEP, the occurrence and pattern of clinically relevant decline in CrCl were not qualitatively different based on quarterly or 6-monthly CrCl monitoring. Most measurements of CrCl < 60 mL/minute did not confirm on repeat testing. These data suggest that 6-monthly CrCl monitoring could be equally safe and require fewer resources for a majority of persons receiving PrEP, with more frequent monitoring potentially indicated for those with specific risk factors (older age, lower baseline CrCl, lower weight).