Changes in bone mineral density over a 2-year period in HIV-1-infected men under combined antiretroviral therapy with osteopenia.

OBJECTIVE: Although osteopenia is common in HIV-infected patients, there is by now limited data on the evolution of bone mineral density in this population. We aimed to evaluate the course of osteopenia over a 2-year period in HIV-1-infected men, and to identify risk factors for abnormal bone mineral density (BMD) decline. METHODS: HIV-1-infected men on combined antiretroviral therapy (cART) screened in the ANRS 120 Fosivir trial, diagnosed with low BMD (-2.5 ≤T-score <-1), not receiving antiosteoporotic agents, with sequential dual-energy-X ray-absorptiometry (DXA) available at baseline were eligible for this study and had a second DXA performed between months 24 and 36. RESULTS: We enrolled 94 men with a median age of 46 years [interquartile range (IQR), 41-53], BMI 22 kg/m² (21-25) and a CD4 cell nadir of 164/µl (69-261). They were receiving cART for a median of 7.5 years (5.8-9.5). Over a median interval of 2.6 years (2.3-2.9) between the two DXA tests, the mean change in BMD was -0.5 ± 1.7% per year (P = 0.010) at the lumbar spine and -0.4 ± 1.8% per year (P = 0.033) at the hip. BMD fell by more than the smallest detectable difference (SDD) in, respectively, 25.5 and 27.7% of patients at the lumbar spine and hip. Tenofovir (TDF) exposure was independently associated with a larger decline in BMD at both sites [lumbar spine, OR = 2.4 (1.2-4.9); hip, OR = 2.8 (1.3-5.9)]. CONCLUSION: Although osteopenia overall modestly changes over 2 years in long-term cART-treated patients, a quarter of patients experienced a significant loss (>1 SDD) associated with TDF exposure.

Visiting one's native country: the risks of nonadherence in HIV-infected sub-Saharan migrants--ANRS VIHVO study.

The aim of this study was to evaluate to what extent travel-related factors may cause adherence failure to antiretroviral therapy (ART) in otherwise adherent migrants when traveling back to Africa. HIV-infected sub-Saharian migrants living in France with a plasma HIV viral load < 200 copies/mL, with no change in ART for ≥3 months and who were about to visit their native country for between 2 weeks and 6 months were enrolled for the study. Patients completed a self-administered adherence questionnaire both at enrollment and during the week following their return to France. Adherence failure occurred in 23 (11.5%) of 200 patients. Negative perception about ART effectiveness (adjusted odds ratio = 4.3; 95% confidence interval = 1.3-13.7), unexpected traumatic events during their stay in their native country (7.8; 2.3-26.1), and a prolongation of their stay (5.2; 1.4-20.4) were independently associated with a higher likelihood of adherence failure. Owning/renting one's house in France (0.30; 0.10-0.96), singlehood (0.23; 0.05-1.00), and HIV status disclosure (0.19; 0.05-0.76) were correlates of sustained adherence during traveling.

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.

Efficacy and safety of ritonavir-boosted dual protease inhibitor therapy in antiretroviral-naive HIV-1-infected patients: the 2IP ANRS 127 study.

OBJECTIVES: We evaluate the efficacy and tolerability of ritonavir-boosted dual protease inhibitor as a nucleoside reverse transcriptase inhibitor-sparing regimen in a prospective open-label randomized pilot trial in antiretroviral-naive patients. METHODS: Thirty patients received fosamprenavir/atazanavir/ritonavir (Group 1) and 31 patients received saquinavir/atazanavir/ritonavir (Group 2). The primary endpoint for efficacy was the rate of early virological success, defined as plasma viral load <50 copies/mL at week 16. The study is registered with ClinicalTrials.gov (NCT00122603). RESULTS: At baseline, median (range) viral load was 4.8 log(10) copies/mL (4.0-5.7) and the median CD4 cell count was 271/mm(3) (197-740). Viral load was <50 copies/mL in 12/30 patients [40%, 95% confidence interval (CI) 23%-58%] and 13/31 patients (42%, 95% CI 25%-59%) at week 16 in Groups 1 and 2, respectively. Patients with failing regimens (viral load >or=400 copies/mL at week 16 or >or=50 copies/mL at week 24) were switched to a standard antiretroviral regimen. At week 48, by an intention-to-treat analysis, 23/30 patients (77%) and 26/31 patients (84%) had plasma HIV-1 RNA <50 copies/mL in Groups 1 and 2, respectively. Four patients discontinued treatment for adverse events, all before week 4. No major changes in the protease gene were detected at treatment failure relative to baseline. Baseline viral load <50 000 copies/mL was the only predictor of virological success at week 16. CONCLUSIONS: Ritonavir-boosted dual protease inhibitor regimens targeting only one step of viral replication were insufficient to rapidly suppress plasma HIV RNA to <50 copies/mL in antiretroviral-naive patients with high viral load at baseline.

Immunological success is predicted by enfuvirtide but not interleukin-2 therapy in immunodepressed patients.

OBJECTIVES: To evaluate the efficacy of adding interleukin-2 (IL-2) to an optimized background treatment in HIV-1 patients with advanced failure. DESIGN: Randomized, open-label, multicentre controlled trial. METHODS: Patients with CD4 T-cell count of less than 200 cells/microl, plasma HIV-1 RNA of more than 10 000 copies/ml and a genotypic sensitivity score showing two or less active drugs were randomized to either eight IL-2 cycles with optimized background treatment or optimized background treatment alone. Optimization was made according to genotypic sensitivity score. Enfuvirtide was added in enfuvirtide-naive patients. Evaluation was performed at week 52 on the proportions of patients with CD4 cell count of at least 200 cells/microl (primary outcome), of patients with a CD4 cell count increase of at least 50 cells/microl from week 0, on plasma HIV-1 RNA and HIV-related events. RESULTS: Fifty-six patients were analysed. Median age was 43 years, 61% were at Center for Disease Control and Prevention stage C, 43% had a genotypic sensitivity score of 0, median baseline CD4 cell count and plasma HIV-1 RNA values were 64 cells/microl and 4.9 log10 copies/ml, respectively. Treatment could be optimized in 23 patients. At week 52, in the IL-2 and control groups, the proportion of patients with CD4 cell count of at least 200 cells/microl (14 and 18%) or a CD4 cell count increase of at least 50 cells/microl (25 and 32%) and median plasma HIV-1 RNA were not significantly different. In multivariate analysis, optimization with enfuvirtide and baseline CD4 cell count were statistically associated with CD4 cell count of at least 200 cells/microl at week 52 (P = 0.003 and P = 0.01). Optimization with enfuvirtide was the only factor associated with a CD4 cell count gain of at least 50 cells/microl (P < 0.001). There was no difference in the rate of AIDS events between groups. CONCLUSION: IL-2 failed to increase CD4 cell count in immunocompromised patients with multiple therapeutic failures. Enfuvirtide use was highly associated with success.

Efficacy and tolerability of a nucleoside reverse transcriptase inhibitor-sparing combination of lopinavir/ritonavir and efavirenz in HIV-1-infected patients.

BACKGROUND: Recommended antiretroviral regimens include a nucleoside reverse transcriptase inhibitor (NRTI) component. Class cross-resistance and mitochondrial toxicity are recognized as problems with this class of antiretrovirals. METHODS: In a pilot open-label study, 65 antiretroviral-naive and 21 experienced but nonnucleoside reverse transcriptase inhibitor-naive HIV-1-infected adults were given a combination of lopinavir/ritonavir (533.3/133.3 mg twice daily) and efavirenz (600 mg once daily) for 48 weeks. RESULTS: At baseline, the mean viral load was 4.84 log10 copies/mL and the mean CD4 count was 311 cells/mm. At week 24, the proportions of patients with a viral load <400 copies/mL were 78% and 93% using an intent-to-treat and on-treatment analysis, respectively. At week 48, proportions were 73% and 97%, respectively. Treatment discontinuation occurred in 21 patients during the 48-week period, with 33% of those attributable to drug-related adverse effects. A viral load >400 copies/mL at week 24 or 48 was associated with nonadherence in 3 patients and virologic failure in 1 patient. After an increase during the first 8 weeks, fasting lipid levels remained stable up to 48 weeks. CONCLUSION: The lopinavir/ritonavir-efavirenz combination is associated with a high rate of virologic response and should be compared with more classic NRTI-containing regimens in randomized and controlled clinical trials.

[Prophylaxis against adverse effects of chemotherapy for HIV positive patients]. / Mesures préventives des effets secondaires de la chimiothérapie chez les patients infectés par le VIH.

Since the era of HAART cancers in patients infected with HIV are responsible for more than 10% of the residual deaths. One of the more important goal to achieve a better prognosis in these patients, is to prevent the adverse drug events. Unfortunately, these adverse events are frequent because of the chemotherapy-antiretrovirals drug-drug interactions, poor physiologic status, hematologic toxicity enhanced by HIV dysmyelopoiesis and infectious complications. The risk is to be unable to pursue the entire therapeutic program. This paper describes how a narrow collaboration between the oncologist and the specialist of HIV disease could prevent such events.

Phylogenetic analyses confirm the high prevalence of hepatitis C virus (HCV) type 4 in the Seine-Saint-Denis district (France) and indicate seven different HCV-4 subtypes linked to two different epidemiological patterns.

Hepatitis C virus (HCV) has been classified into six clades as a result of high genetic variability. In the Seine-Saint-Denis district of north-east Paris, the prevalence of HCV-4, which usually infects populations from Africa or the Middle East, is twice as high as that recorded for the whole of continental France (10.2 versus 4.5%). Although the pathogenicity of HCV-4 remains unknown, resistance of HCV-4 to therapy appears to be similar to that observed for HCV-1. In order to characterize the epidemiology of HCV-4 in Paris, sequences of the non-structural 5B gene (332 bp) were obtained from 38 HCV-4-infected patients. Extensive phylogenetic analyses indicated seven different HCV-4 subtypes. Moreover, phylogenetic tree topologies clearly distinguished two epidemiological profiles. The first profile (52.6% of patients) reflects the intra-suburban emergence of two distinct HCV-4 subclades occurring mainly among intravenous drug users (65% of patients). The second profile shows six subclades [HCV-4a, -4f, -4h, -4k, -4a(B) and a new sequence] and accounts for patients from Africa (Egypt and sub-Saharan countries) who have unknown risk factors (77.8% of patients) and in whom no recent diffusion of HCV-4 is evident. This study indicates the high diversity of HCV-4 and the extension of HCV-4a and -4d subclades among drug users in FRANCE: