Efficacy and safety of hepatitis C direct-acting protease inhibitors (DAA-PI ) in real life in HIV-HCV coinfected patients

International audienc

Dolutegravir and weight gain: an unexpected bothering side effect?

International audienceno abstrac

Toward chronic hepatitis C eradication in HIV-positive patients, including those cirrhotic and infected with genotype 3 viruses

International audienc

Metabarcoding analysis of eukaryotic microbiota in the gut of HIV-infected patients.

Research on the relationship between changes in the gut microbiota and human disease, including AIDS, is a growing field. However, studies on the eukaryotic component of the intestinal microbiota have just begun and have not yet been conducted in HIV-infected patients. Moreover, eukaryotic community profiling is influenced by the use of different methodologies at each step of culture-independent techniques. Herein, initially, four DNA extraction protocols were compared to test the efficiency of each method in recovering eukaryotic DNA from fecal samples. Our results revealed that recovering eukaryotic components from fecal samples differs significantly among DNA extraction methods. Subsequently, the composition of the intestinal eukaryotic microbiota was evaluated in HIV-infected patients and healthy volunteers through clone sequencing, high-throughput sequencing of nuclear ribosomal internal transcribed spacers 1 (ITS1) and 2 (ITS2) amplicons and real-time PCRs. Our results revealed that not only richness (Chao-1 index) and alpha diversity (Shannon diversity) differ between HIV-infected patients and healthy volunteers, depending on the molecular strategy used, but also the global eukaryotic community composition, with little overlapping taxa found between techniques. Moreover, our results based on cloning libraries and ITS1/ITS2 metabarcoding sequencing showed significant differences in fungal composition between HIV-infected patients and healthy volunteers, but without distinct clusters separating the two groups. Malassezia restricta was significantly more prevalent in fecal samples of HIV-infected patients, according to cloning libraries, whereas operational taxonomic units (OTUs) belonging to Candida albicans and Candida tropicalis were significantly more abundant in fecal samples of HIV-infected patients compared to healthy subjects in both ITS subregions. Finally, real-time PCR showed the presence of Microsporidia, Giardia lamblia, Blastocystis and Hymenolepis diminuta in different proportions in fecal samples from HIV patients as compared to healthy individuals. Our work revealed that the use of different sequencing approaches can impact the perceived eukaryotic diversity results of the human gut. We also provide a more comprehensive view of the eukaryotic community in the gut of HIV-infected patients through the complementarity of the different molecular techniques used. Combining these various methodologies may provide a gold standard for a more complete characterization of the eukaryotic microbiome in future studies

Neuropsychiatric adverse effects on dolutegravir: an emerging concern in Europe

International audienceno abstrac

First-line highly active antiretroviral regimens in 2001-2002 in the French Hospital Database on HIV: combination prescribed and biological outcomes.: First-line haart : combination prescribed and biological outcomes.

INTRODUCTION: We compared biological outcomes in antiretroviral-naive patients with viral load (VL) > 5,000 copies/ml starting combivir-based, three-drug highly active antiretroviral therapy regimens in 2001-2002 according to the third component, namely abacavir (ABC), nelfinavir (NFV), indinavir/ritonavir (IDV/r), lopinavir/ritonavir (LPV/r), nevirapine (NVP) or efavirenz (EFV). METHODS: We evaluated virological response (HIV RNA or = 50 CD4+ T-cells/microl) separately in patients with baseline VL or = 100,000 copies/ml, the virological efficacy of EFV was similar to that of NVP (0.90) and LPV/r (0.97) and better than that of NFV (0.62), ABC (0.75) and IDV/r (0.78). The immunological results found in these patients were similar to those observed in patients with baseline VL < 100,000 copies/ml. CONCLUSIONS: For first-line therapy, in this observational setting, EFV, LPV/r and NVP, when added to the combivir backbone, were more likely to drive viral load < 500 copies/ml. LPV/r showed the best immunological effectiveness

Concentration–response model of rilpivirine in a cohort of HIV-1-infected naive and pre-treated patients

International audienceRilpivirine is widely prescribed in people living with HIV. Although trough plasma concentrations have been associated with virological response, the drug pharmacodynamics remain incompletely characterized

Gut microbiota associated with HIV infection is significantly enriched in bacteria tolerant to oxygen

International audienceObjectives Gut microbiota modifications occurring during HIV infection have recently been associated with inflammation and microbial translocation. However, discrepancies between studies justified a comprehensive analysis performed on a large sample size.Design and methods In a case–control study, next-generation sequencing of the 16S rRNA gene was applied to the faecal microbiota of 31 HIV-infected patients, of whom 18 were treated with antiretroviral treatment (ART), compared with 27 healthy controls. 21 sera samples from HIV-infected patients and 7 sera samples from control participants were used to test the presence of 25 markers of inflammation and/or immune activation.Results Diversity was significantly reduced in HIV individuals when compared with controls and was not restored in the ART group. The relative abundance of several members of Ruminococcaceae such as Faecalibacterium prausnitzii was critically less abundant in the HIV-infected group and inversely correlated with inflammation/immune activation markers. Members of Enterobacteriaceae and Enterococcaceae were found to be enriched and positively correlated with these markers. There were significantly more aerotolerant species enriched in HIV samples (42/52 species, 80.8%) when compared with the control group (14/87 species, 16.1%; χ2 test, p<10−5, conditional maximum-likelihood estimate (CMLE) OR=21.9).Conclusions Imbalance between aerobic and anaerobic flora observed in HIV faecal microbiota could be a consequence of the gut impairment classically observed in HIV infection via the production of oxygen. Overgrowth of proinflammatory aerobic species during HIV infection raises the question of antioxidant supplementation, such as vitamin C, E or N-acetylcysteine

The distribution of the major fungal OTUs recovered from the amplification of the ITS2 region in the fecal samples of HIV-infected patients and healthy subjects.

<p>The heatmap shows read counts for the 13 OTUs identified as contributing most to the variance (up to 86% across all samples) as determined by SIMPER analysis. The dendrogram shows the clustering of samples based on Bray-Curtis similarity distance.</p

The distribution of the major eukaryotic MOTUs detected in the fecal samples of HIV-infected patients and healthy subjects using cloning and sequencing methods.

<p>The heatmap shows read counts for the 33 MOTUs identified as contributing most to the variance (up to 86% across all samples) as determined by Similarity Percentage (SIMPER) analysis. The dendrogram shows the clustering of samples based on Bray-Curtis similarity distance.</p