Antiretroviral Preexposure Prophylaxis for HIV Prevention

n engl j med 368;1 nejm.org january 3, 2013 82 To the Editor: Thigpen et al. (Aug. 2 issue)1 report that persons who are seronegative for the human immunodeficiency virus (HIV) and who are receiving tenofovir disoproxil fumarate and emtricitabine (TDF–FTC) for preexposure prophylaxis had decreased bone mineral density at 24 months, as compared with those receiving placebo. In HIV-infected cohorts, TDF causes an initial loss of bone density over a period of 6 to 12 months, but there is stable bone density subsequently.2,3 These findings are consistent with other studies that have shown short-term loss of bone density in patients initiating antiretroviral treatment but stable bone density in those already receiving antiretroviral treatment.4 In contrast, Thigpen et al. found the opposite pattern: participants receiving TDF–FTC had relatively stable bone density for 12 months and then lost bone density between 12 and 24 months. The bone-density substudy had a high withdrawal rate, with only 40% of the participants having a bone-density measurement at 12 months and 26% at 24 months. This pattern could occur if participants with either normal bone density on the initial measurement or stable bone density on early serial measurements were more likely to withdraw. Can the authors report the baseline bone-density results and the changes over time among participants who withdrew, as compared with those who completed the study?