Researchers have found a small but statistically significant decrease in bone mineral density in the hip and spine for HIV-seronegative patients taking Truvada daily for pre-exposure prophylaxis, Healio reports that recent data has found. Further, changes in bone mineral density (BMD) at 24 weeks for patients taking Truvada (emtricitabine/tenofovir disoproxil fumarate, Gilead Sciences; FTC/TDF) was inversely correlated with intracellular tenofovir diphosphate (TFV-DP), which researchers identified in 53% of study patients.
“We report for the first time a quantitative relationship between bone loss and intracellular TFV-DP after 24 weeks of treatment,” Dr Kathleen Mulligan, professor at the University of California, San Francisco’s division of endocrinology and metabolism, and colleagues wrote. “Bone loss in the spine tended to reverse, albeit not completely, after discontinuation of treatment. These results demonstrate an effect of FTC/TDF that is independent of HIV infection or other ART.”
Mulligan and colleagues performed dual-energy X-ray absorptiometry in 498 patients who were currently enrolled in the Pre-exposure Prophylaxis Initiative Study. The examination was implemented at baseline and 24-week intervals, with plasma and intracellular concentrations of tenofovir measured in those randomly assigned FTC/TDF.
The researchers reported a net difference of 0.91% (95% CI, 1.44% to 0.38%) and 0.61% (95% CI, 0.96% to 0.27%) in spine and hip BMD, respectively, over 24 weeks. There were no statistically significant changes in BMD for the hip and spine after week 24. TFV-DP levels in the spine averaged 1.42% and averaged 0.85% (± 19%) in the hip compared with the placebo group. Mulligan and colleagues noted that the number of fractures in each group did not differ significantly, and all fractures were related to trauma.
“The results … provide no reason to modify the CDC’s recommendation that routine DXA monitoring during FTC/TDF for PrEP is not warranted unless there are additional risk factors for fracture,” the investigators are quoted in the report as saying. “Nonetheless … those beginning PrEP should be counselled on factors important for bone health.”
Background. Daily pre-exposure prophylaxis (PrEP) with oral emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) decreases the risk of HIV acquisition. Initiation of TDF decreases bone mineral density (BMD) in HIV-infected people. We report the effect of FTC/TDF on BMD in HIV-seronegative men who have sex with men and transgender women.
Methods. Dual-energy X-ray absorptiometry was performed at baseline and 24-week intervals in a substudy of iPrEx, a randomized, double-blind, placebo-controlled trial of FTC/TDF PrEP. Plasma and intracellular tenofovir concentrations were measured in participants randomized to FTC/TDF.
Results. In 498 participants (247 FTC/TDF, 251 placebo), BMD in those randomized to FTC/TDF decreased modestly but statistically significantly by 24 weeks in the spine (net difference -0.91 [-1.44 to -0.38]%, P=0.001) and hip (-0.61 [-0.96 to -0.27]%, P=0.001). Changes within each subsequent 24-week interval were not statistically significant. Changes in BMD by week 24 correlated inversely with intracellular tenofovir diphosphate (TFV-DP), which was detected in 53% of those randomized to FTC/TDF. Net BMD loss by week 24 in participants with TFV-DP levels indicative of consistent dosing averaged -1.42±29% and -0.85±19% in the spine and hip, respectively (P Conclusions. In HIV-uninfected persons, FTC/TDF PrEP was associated with small but statistically significant decreases in BMD by week 24 that inversely correlated with TFV-DP, with more stable BMD thereafter.