Globally, the majority of people living with HIV are cis-women, who are underrepresented in clinical trials. Tenofovir alafenamide (TAF) has demonstrated an improved renal and bone safety profile relative to tenofovir disoproxil fumarate (TDF) in multiple randomized trials with similar efficacy. We pooled 7 studies to evaluate the efficacy and safety of TAF vs. TDF for ART initiation or switch in women.
Data from 779 cis-women in 7 randomized, double-blind clinical trials (2 in treatment-naïve adults, 5 in virologically suppressed adults) through W96 were analyzed. All participants who initiated or switched to TAF-based regimens (elvitegravir/cobicistat/emtricitabine [FTC]/TAF, rilpivirine/FTC/TAF, FTC/TAF, or bictegravir/FTC/TAF) were compared with those who initiated or continued TDF-based regimens. Virologic suppression (VS; HIV-1 RNA <50 c/mL) rates at W96 were determined by FDA snapshot analysis. Bone mineral density (BMD) and the renal tubular biomarkers urine beta-2-microglobulin (B2m):creatinine (Cr) ratio and retinol binding protein (RBP):Cr ratio are reported at W96. Differences were compared using Wilcoxon rank sum test.
A total of 779 cis-women were enrolled (n=429 TAF, n=350 TDF). Treatment-naïve women (WTN) had a median age of 37, 35.4% were black, 26% were Hispanic/Latina, with median HIV-RNA 4.47 log10 c/mL and CD4 365 cells/mm3. Women with VS (WVS) had a median age 47 years, 50% were black, 25% were Hispanic/Latina, with median CD4 711 cells/mm3. Of WTN, 86% (TAF) and 85% (TDF) achieved VS (p=0.71) at W96. VS was maintained in 86% of WVS switching to TAF and 85% continuing TDF (p=0.99). Overall TAF and TDF were well-tolerated. Discontinuation due to adverse event/death was 0% (TAF) vs. 1.6% (TDF) in WTN and 1.3% (TAF) vs. 2.2% (TDF) in WVS. At W96 there was less impact on renal biomarkers in WTN initiating TAF- vs TDF-based regimens (p<0.001; Table), and decreases in BMD were smaller (p<0.001; Table). Women switching from TDF to TAF experienced decreases in tubular proteinuria (p<0.001; Table) and increases in BMD (p<0.001; Table) at W96.
Similar to the overall results in pivotal naïve and switch trials of FTC/TAF-based regimens, cis-women who initiated or switched to TAF had significantly improved bone and renal safety parameters compared to TDF, with similar rates of virologic suppression through W96. These pooled data from 7 studies demonstrate a safety advantage for initiating therapy with or switching to TAF compared to TDF in women.