Efficacy and safety of switching to raltegravir plus atazanavir dual therapy in pretreated HIV-1-infected patients over 144 weeks: a cohort study.

BACKGROUND: To decrease drug burden among HIV-1-positive adults, we need a new gold standard for antiretroviral therapy maintenance strategies. METHODS: This retrospective study aimed to assess efficacy in maintenance strategy of atazanavir (ATV) and raltegravir (RAL) dual therapy. The proportion of patients with HIV-1 RNA < 40 copies/ml at specific time points was recorded. Immunological response, safety, and pharmacokinetics were assessed. RESULTS: Overall, 39 patients were switched to a RAL/ATV (n = 32) or RAL/ATV plus ritonavir (n = 7) regimen. Almost all patients (95%) received RAL twice daily. Most patients (70%) received a 400 mg ATV dosing per day, once (26%) or twice daily (44%). The percentages of virological success at weeks 24, 48, 96, and 144 were 92% (95% confidence interval (CI), 83-10), 86% (95% CI, 74-98), 70% (95% CI, 52-88), and 63% (95% CI, 42-84), respectively. Overall, 12 (31%) patients stopped dual therapy: 7 patients because of adverse events, mostly clinical myositis (n = 3). Confirmed virological failure occurred in three patients; two of them developed RAL resistance patterns. A significant increase in the CD4+/CD8 + T-cell ratio was observed at week 48 (p < 0.005). Only grade 1-2 adverse events were observed. Trough plasma levels presented a wide variability. Suggested trough concentrations were achieved in 79% and 94% of patients for ATV and RAL, respectively. An unboosted 400 mg per day ATV dosing seemed to be appropriate, regarding the targeted levels achieved and the lack of grade 3 or 4 hyperbilirubinemia. CONCLUSIONS: We demonstrated, on a 3-year follow-up, the efficacy and safety of RAL plus ATV maintenance dual therapy.

Bone mineral density changes after 2 years of ARV treatment, compared to naive HIV-1-infected patients not on HAART.

BACKGROUND: The prevalence of osteopenia and osteoporosis is increased in human immunodeficiency virus (HIV)-infected patients. The pathogenesis of this low bone mineral density (BMD) is multifactorial. METHODS: We conducted a prospective study over a 2-year period of the BMD in non-treated ARV-naïve HIV-infected-males, in comparison to HIV-infected males commencing a first ARV treatment, and analyzed the evolution of bone turnover markers. RESULTS: A total of 39 caucasian males (median age 38.6 years) were enrolled, including 10 who started ARV treatment (group 1), and 29 without indications for ARV therapy (group 2). In the latter group, 11 subjects commenced ARV during the study; therefore the remainder of their follow-up was within group 1, which finally consisted of 21 patients. At baseline, 9 patients (19.5%) had osteoporosis at least at 1 site, while 28 (61%) showed osteopenia. Lower BMD was correlated with tobacco use. Lumbar spine and total hip BMD significantly decreased in group 1 patients after 6 months of treatment, then stabilized (2.4% and 4% loss, respectively, at 24 months), while no significant change in BMD was observed in group 2 subjects. At baseline, one patient had an increased CTX (C-terminal cross-linking telopeptide of type 1 collagen) and all BSAP (bone-specific alkaline phosphatase) results were normal. During follow-up, both CTX and BSAP increased in group 1 patients, while they did not change in group 2. CONCLUSION: Osteoporosis and osteopenia are frequent in HIV-infected males. After ARV initiation, BMD decreased, and bone turnover markers increased, even though the BMD remained stable in non-treated patients. These results underline the impact of HIV treatment on BMD and bone metabolism.

Predictors of Standard Follow-Up Completion after Sexual Exposure to HIV: Five-Year Retrospective Analysis in a French HIV-Infection Care Center.

OBJECTIVES: The care of exposed individuals to HIV remains a challenge regarding follow-up completion and HIV-testing of the partner. Identifying patients with risk of not fulfilling HIV-testing follow-up completion (FC), among patients demanding non-occupational post-exposure prophylaxis (nPEP), may improve clinical practice. METHODS: A retrospective chart review was conducted in a single French HIV-infection care center. FC predictors were assessed in a multivariate logistic regression model (Likelihood ratios test). RESULTS: Between 2009 and 2013, 646 sexual exposures to HIV were evaluated for nPEP, of which 507 effectively received nPEP (78%). FC rate was 30% (194/646). In the multivariate analysis, FC rates rose with age of exposed individuals (OR, 1.04 [0.25-4.28]; p<0.001) and decreased with the year of sexual exposure (OR, 0.74 [0.65-0.85]; p<0.001). FC was associated with sexual encounter with a sex worker (OR, 4.07 [0.98-16.82]; p<0.001) and nPEP use (OR, 2.69 [2.37-3.06]; p<0.001). nPEP early discontinuation was associated with decreased FC rates (OR, 0.18 [0.08-0.39]; p<0.001). No documented nPEP failure was identified. However, five Men who have Sex with Men (MSM) nPEP recipients for unprotected anal receptive intercourse subsequently seroconverted to HIV more than 6 months after nPEP. Seroconversion to HIV was associated with the lack of FC (p = 0.04) and multiple presentations for nPEP over the study period (p = 0.002). CONCLUSIONS: We identified significant predictors of not fulfilling sequential HIV-testing. They appear to be linked with a self-perceived HIV risk, especially in young adults recently exposed. Enhanced counseling in targeted individuals with high risk behaviors and using smartphone and internet-based strategies may be interesting retention in care options.

Virologic response of zidovudine, lamivudine, and tenofovir disoproxil fumarate combination in antiretroviral-naive HIV-1-infected patients.

BACKGROUND: High rates of virologic failure have been reported in antiretroviral-naive patients receiving triple-nucleoside reverse transcriptase inhibitor (NRTI) combinations containing tenofovir disoproxil fumarate (TDF) with lamivudine (3TC) and didanosine or 3TC and abacavir (ABC). A regimen of once-daily zidovudine (ZDV), 3TC, ABC, and TDF showed an acceptable virologic success rate, however. METHODS: This was a pilot prospective cohort study. Treatment-naive subjects were offered a fixed-dose combination of ZDV/3TC (300 mg/150 mg) twice daily and 300 mg of TDF once daily. RESULTS: Fifty-one patients were enrolled between April 2002 and March 2005. At baseline, the median CD4 count was 230 cells/microL (range: 23-425 cells/microL), 20 (39%) of 51 subjects had CD4 counts of < 200 cells/microL, the median HIV-1 viral load was 4.89 log (3.14 to >5.87 log), and 24 (47%) of 51 subjects had a viral load >5 log. The median follow-up was 12 months (range: 1 week to 38 months). On-treatment analysis showed a median HIV RNA load decrease of -1.7 log after 1 to 2 weeks of treatment and -2.41 log after 1 month, and 34 (89%) of 38 subjects had a viral load < 50 copies/mL at month 6, 21 (78%) of 27 at month 12, and 13 (81%) of 16 after 18 months (intent-to-treat results were 34 [72%] of 47 subjects, 21 [56%] of 36 subjects, and 13 [50%] of 25 subjects at months 6, 12, and 18, respectively). The median CD4 count increase at month 18 was 142 cells/microL. Nine (17.6%) of 51 treatment interruptions for adverse effects were seen. Six viral failures occurred, including 2 with K65R mutations (alone or associated with Y115F and M184V). CONCLUSION: The combination of ZDV/3TC + TDF in treatment-naive HIV-infected subjects induces a rapid and sustained HIV-1 RNA decrease and is associated with a good immunologic response. No severe adverse events occurred. This triple-NRTI combination needs to be evaluated further.

Tolerance of a short course of nevirapine, associated with 2 nucleoside analogues, in postexposure prophylaxis of HIV.

A combination of 2 nucleoside analogues and 1 protease inhibitor is usually recommended in postexposure prophylaxis. Because of the complex treatment schedule and frequent adverse effects, however, this regimen is often not completed. Therefore, since January 2000, we have used nevirapine (NVP), 200 mg/d, for only 4 days in combination with 2 nucleoside analogues for 1 month to improve adherence and completion rates. We present a 2-year retrospective analysis on 120 individuals who received this prophylaxis. Only 2 subjects stopped NVP because of a clinical event, whereas 10 interrupted the nucleoside analogues. We observed 3 (2.8%) of 104 slight alanine aminotransferase (ALT) increases in the first 2 weeks of treatment (grade 1). Three additional (month 1 or 3) ALT augmentations also occurred (also grade 1). No HIV or hepatitis C virus seroconversion occurred during follow-up. Twenty-nine (38.2%) of 76 individuals and 21 (47.7%) of 44 individuals were seen 3 months after nonoccupational and occupational exposure, respectively. We believe that such a short course (4 days) of 200-mg NVP treatment once a day in combination with 2 nucleoside analogues for 1 month is clinically and biologically safe.