Tenofovir disoproxil fumarate and emtricitabine maintenance strategy in virologically controlled adults with low HIV-1 DNA: 48 week results from a randomized, open-label, non-inferiority trial.

OBJECTIVES: Low HIV reservoirs may be associated with viral suppression under a lower number of antiretroviral drugs. We investigated tenofovir disoproxil fumarate/emtricitabine as a maintenance strategy in people living with HIV (PLHIV) with low HIV-DNA. METHODS: TRULIGHT (NCT02302547) was a multicentre, open-label, randomized trial comparing a simplification to tenofovir disoproxil fumarate/emtricitabine versus a triple regimen continuation (tenofovir disoproxil fumarate/emtricitabine with a third agent, control arm) in virologically suppressed adults with HIV-DNA <2.7 log10 copies/106 PBMCs and no prior virological failure (VF). The primary endpoint (non-inferiority margin 12%) was the percentage of participants with a plasma viral load (pVL) <50 copies/mL in ITT (Snapshot approach) and PP analyses at Week 48 (W48). RESULTS: Of the 326 participants screened, 223 (68%) were randomized to the tenofovir disoproxil fumarate/emtricitabine arm (n = 113) or control arm (n = 110). At W48, the tenofovir disoproxil fumarate/emtricitabine and control arms maintained a pVL < 50 copies/mL in 100/113 (88.5%) and 100/110 (90.9%) participants, respectively (ITT difference 2.4%, 95% CI -5.9 to 10.7; PP difference 3.4%, 95% CI -4.2 to 11.0). Six VFs occurred in the tenofovir disoproxil fumarate/emtricitabine arm (two with emerging mutations M184V and K65R) versus two in the control arm (ITT difference 3.5%, 95% CI -1.9 to 9.4). All VFs were resuppressed after treatment modification. CONCLUSIONS: Although non-inferiority was shown, simplification to tenofovir disoproxil fumarate/emtricitabine should not be used for most PLHIV because of a low risk of VF with resistance.

Prevalence of low bone mineral density in men and women infected with human immunodeficiency virus 1 and a proposal for screening strategy.

We analyzed data collected during screening for eligibility in the ANRS-120 FOSIVIR clinical trial to estimate the prevalence of osteoporosis in patients infected with human immunodeficiency virus 1 (HIV-1), to study its risk factors, and to develop a screening strategy. McNemar test was used to compare the estimated prevalence of osteoporosis, using 3 different definitions. We then derived a screening strategy for HIV-infected men. We analyzed data for 700 men and 192 women. The prevalence of osteoporosis differed markedly according to the definition used. Based on the "T-score ≤ -2.5" definition, 14.9% of men and 1.0% of women had osteoporosis. Factors associated with low bone mineral density comprised not only classical risk factors for osteoporosis such as low body mass index (BMI) or older age but also factors associated with HIV infection such as lower CD4 T-cell nadir in men and AIDS in women, and with antiretroviral treatment such as recent tenofovir therapy. In addition to postmenopausal women, we recommend osteoporosis screening for HIV-infected men older than 60 yr, men younger than 60 yr with BMI < 20 kg/m(2), and men younger than 60 yr with both BMI 20-23 kg/m(2) and a CD4 T-cell nadir ≤ 200/mm(3).

Effect of alendronate on HIV-associated osteoporosis: a randomized, double-blind, placebo-controlled, 96-week trial (ANRS 120).

Low bone mineral density (BMD) is common in HIV-infected patients. Bisphosphonates such as alendronate potently inhibit bone resorption and are effective against osteoporosis. The aim of the ANRS 120 Fosivir trial was to evaluate the effect of alendronate on low BMD in HIV-infected patients. HIV-1-infected adults with a t-score≤-2.5 at the lumbar spine and/or total hip, as assessed by dual x-ray absorptiometry, and no other known risk factors for low BMD, were randomized to receive either extended-release alendronate 70 mg weekly or placebo for 96 weeks, with stratification for gender. All the patients also received daily calcium carbonate (500 mg) and vitamin D (400 U). The primary endpoint for efficacy was the percentage change in BMD at the site with a t-score≤-2.5. Forty-four antiretroviral-treated patients (42 men, 2 women) were enrolled. The median age was 45 years, the median CD4 cell count was 422/mm(3), and viral load was <400 copies/ml in 84% of patients. Baseline characteristics were well balanced between the alendronate (n=20) and placebo (n=24) groups. At baseline, 15 patients (75%) in the alendronate group and 17 patients (71%) in the placebo group had a t-score≤-2.5 at the lumbar spine. In the main analysis, BMD at the site with a t-score≤-2.5 increased by 7.1% and 1.0%, respectively, in the alendronate (n=14) and placebo (n=20) groups at week 96 [mean difference, 6.1% (95% CI 2.8 to 9.3); p=0.0003]. Alendronate 70 mg weekly for 96 weeks improves BMD in HIV-1-infected patients on antiretroviral therapy.