Bone Mineral Density in HIV-Negative Men Participating in a Tenofovir Pre-Exposure Prophylaxis Randomized Clinical Trial in San Francisco

Abstract

BackgroundPre-exposure prophylaxis (PrEP) trials are evaluating regimens containing tenofovir-disoproxil fumarate (TDF) for HIV prevention. We determined the baseline prevalence of low bone mineral density (BMD) and the effect of TDF on BMD in men who have sex with men (MSM) in a PrEP trial in San Francisco.Methods/FindingsWe evaluated 1) the prevalence of low BMD using Dual Energy X-ray Absorptiometry (DEXA) in a baseline cohort of 210 HIV-uninfected MSM who screened for a randomized clinical trial of daily TDF vs. placebo, and 2) the effects of TDF on BMD in a longitudinal cohort of 184 enrolled men. Half began study drug after a 9-month delay to evaluate changes in risk behavior associated with pill-use. At baseline, 20 participants (10%) had low BMD (Z score≤−2.0 at the L2–L4 spine, total hip, or femoral neck). Low BMD was associated with amphetamine (OR = 5.86, 95% CI 1.70–20.20) and inhalant (OR = 4.57, 95% CI 1.32–15.81) use; men taking multivitamins, calcium, or vitamin D were less likely to have low BMD at baseline (OR = 0.26, 95% CI 0.10–0.71). In the longitudinal analysis, there was a 1.1% net decrease in mean BMD in the TDF vs. the pre-treatment/placebo group at the femoral neck (95% CI 0.4–1.9%), 0.8% net decline at the total hip (95% CI 0.3–1.3%), and 0.7% at the L2–L4 spine (95% CI −0.1–1.5%). At 24 months, 13% vs. 6% of participants experienced >5% BMD loss at the femoral neck in the TDF vs. placebo groups (p = 0.13).ConclusionsTen percent of HIV-negative MSM had low BMD at baseline. TDF use resulted in a small but statistically significant decline in BMD at the total hip and femoral neck. Larger studies with longer follow-up are needed to determine the trajectory of BMD changes and any association with clinical fractures.Trial RegistrationClinicalTrials.gov: NCT00131677

High Prevalence of Low Bone Mineral Density and Substantial Bone Loss over 4 Years Among HIV-Infected Persons in the Era of Modern Antiretroviral Therapy

“…The association of tenofovir has been reported not only among HIV-infected treatment-naive persons started on tenofovir but also among HIV-uninfected persons receiving tenofovir for preexposure prophylaxis. 7,22 Longer cumulative exposure to tenofovir has also been independently associated with an increased risk of osteoporotic fracture. 23 We also found novel associations of osteoporosis with being unemployed or retired and with lower serum apolipoprotein E. To our knowledge, the independent association with being unemployed or retired has not previously been reported in the HIV literature, although, a link between the level of education and low BMD has been seen in a cohort of HIV-infected persons in Ireland.…”

2016 United Kingdom national guideline on the sexual health care of men who have sex with men

“…Proximal renal tubular dysfunction and measurable loss in bone mineral density have been reported with therapeutic tenofovir (TDF) use. A 1% reduction in bone mineral density was observed when TDF was used as PrEP but has not been associated with increased fracture rate and no increase in renal complications was reported (366). Viral resistance to either tenofovir DF or emtricitabine was rare and almost all cases were thought to be infected at or immediately after enrolment in the study (360,361).…”

An Overview of Antiretroviral Pre‐Exposure Prophylaxis of HIV Infection

“…38,39 In contrast, less is known about the long-term safety of antiretroviral microbicides. The CAPRISA 004 study demonstrated a significant increase in diarrhea in the women randomized to receive TFV gel.…”