Switch to Ritonavir-Boosted versus Unboosted Atazanavir plus Raltegravir Dual-Drug Therapy Leads to Similar Efficacy and Safety Outcomes in Clinical Practice.

OBJECTIVES: To assess immunovirological response, safety and pharmacokinetic of NRTI-sparing regimen dual therapy of atazanavir (ATV) and raltegravir (RAL) in maintenance strategy. METHODS: A retrospective analysis was conducted on a cohort of HIV-infected adults followed in French centers (Dat'AIDS cohort), comparing the proportions of virological and therapeutic failures between ATV + RAL and ATV/ritonavir + RAL dual therapy regimens. RESULTS: 283 patients were assessed: 185 switched for ATV + RAL and 98 for ATV/ritonavir + RAL dual therapy. Virological failure rate at week 96 was 13.8% (95% CI, 9.8-17.8), without difference between the two groups (Log-rank Test, p = 0.87). The cumulative percentages of patients remaining free of therapeutic failure at week 24, 48 and 96 of dual therapy were 74.9% (95% CI, 69.9-80.0), 65.4% (95% CI, 59.8-70.9) and 53.4% (95% CI, 47.5-59.2), respectively. Four out of 39 confirmed virological failures developed RAL resistance. By multivariate analysis, virological failure was associated with high HIV-1 RNA zenith (p = 0.02), low CD4+ T-cell count at baseline (p<0.001) and short duration on antiretroviral therapy (p<0.001). Before week 96, dual therapy was discontinued in 44 patients (16%) because of various adverse events, with no difference between the two groups. Minimal plasma levels were targeted in 84% and 87% of patients for ATV and RAL, respectively, and both were significantly higher in ritonavir-boosted regimen. CONCLUSIONS: Emerging RAL-resistance and discontinuations for adverse events resulted in moderate efficacy rates of ATV and RAL dual therapy in heavily pretreated patients.

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.

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.

Fluorescence in situ hybridization sperm analysis of six translocation carriers provides evidence of an interchromosomal effect.

OBJECTIVE: To investigate the existence of an interchromosomal effect in balanced reciprocal translocation carriers and to evaluate their risk of having an affected child or repeated spontaneous abortions. DESIGN: Analysis of chromosomal sperm content by fluorescence in situ hybridization (FISH) using probes for chromosomes 1, 15, 16, 17, 18, X, and Y. SETTING: University hospital. PATIENT(S): Six male carriers of balanced chromosome rearrangements, one with normal sperm parameters and five with oligoasthenoteratozoospermia, and seven fertile controls. INTERVENTION(S): Fluorescence in situ hybridization for chromosomal enumeration on sperm samples. MAIN OUTCOME MEASURE(S): Rate of disomy for the studied chromosomes. RESULT(S): A total of 123,842 spermatozoa were scored (82,181 for controls and 41,661 for patients). For each patient, at least one chromosome studied presented a significantly increased rate of disomy. One patient showed a clear interchromosomal effect for at least three of the six chromosomes studied. Disomy rates were statistically significantly and inversely correlated with the total progressive motility of spermatozoa. CONCLUSION(S): The observed interchromosomal effect seems to be translocation, patient, and chromosome dependent. Variable effects were observed, according to the chromosome studied. When we looked at patients carrying the same translocation, the level of disomy rate was variable and affected different chromosomes.