O415 Efficacy and safety of 48-week maintenance with QD ATV vs ATV/r (both + 2NRTIs) in patients with VL <50 c/mL after induction with ATV/r + 2NRTIs: study AI424136

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Cellular Immune Responses Induced with Dose-Sparing Intradermal Administration of HIV Vaccine to HIV-Uninfected Volunteers in the ANRS VAC16 Trial

The objective was to compare the safety and cellular immunogenicity of intradermal versus intramuscular immunization with an HIV-lipopeptide candidate vaccine (LIPO-4) in healthy volunteers.A randomized, open-label trial with 24 weeks of follow-up was conducted in France at six HIV-vaccine trial sites. Sixty-eight healthy 21- to 55-year-old HIV-uninfected subjects were randomized to receive the LIPO-4 vaccine (four HIV lipopeptides linked to a T-helper-stimulating epitope of tetanus-toxin protein) at weeks 0, 4 and 12, either intradermally (0.1 ml, 100 microg of each peptide) or intramuscularly (0.5 ml, 500 microg of each peptide). Comparative safety of both routes was evaluated. CD8+ T-cell immune responses to HIV epitopes (ELISpot interferon-gamma assay) and tetanus toxin-specific CD4+ T-cell responses (lymphoproliferation) were assessed at baseline, two weeks after each injection, and at week 24.No severe, serious or life-threatening adverse events were observed. Local pain was significantly more frequent after intramuscular injection, but local inflammatory reactions were more frequent after intradermal immunization. At weeks 2, 6, 14 and 24, the respective cumulative percentages of induced CD8+ T-cell responses to at least one HIV peptide were 9, 33, 39 and 52 (intradermal group) or 14, 20, 26 and 37 (intramuscular group), and induced tetanus toxin-specific CD4+ T-cell responses were 6, 27, 33 and 39 (intradermal), or 9, 46, 54 and 63 (intramuscular). In conclusion, intradermal LIPO-4 immunization was well tolerated, required one-fifth of the intramuscular dose, and induced similar HIV-specific CD8+ T-cell responses. Moreover, the immunization route influenced which antigen-specific T-cells (CD4+ or CD8+) were induced.ClinicalTrials.gov NCT00121121

Long-term efficacy and safety of fostemsavir among subgroups of heavily treatment-experienced adults with HIV-1

Objectives: The aim of this study was to understand how demographic and treatment-related factors impact responses to fostemsavir-based regimens. Design: BRIGHTE is an ongoing phase 3 study evaluating twice-daily fostemsavir 600 mg and optimized background therapy (OBT) in heavily treatment-experienced individuals failing antiretroviral therapy with limited treatment options (Randomized Cohort 1-2 and Nonrandomized Cohort 0 fully active antiretroviral classes). Methods: Virologic response rates (HIV-1 RNA <40 copies/ml, Snapshot analysis) and CD4+ T-cell count increases in the Randomized Cohort were analysed by prespecified baseline characteristics (age, race, sex, region, HIV-1 RNA, CD4+ T-cell count) and viral susceptibility to OBT. Safety results were analysed by baseline characteristics for combined cohorts (post hoc). Results: In the Randomized Cohort, virologic response rates increased between Weeks 24 and 96 across most subgroups. Virologic response rates over time were most clearly associated with overall susceptibility scores for new OBT agents (OSS-new). CD4+ T-cell count increases were comparable across subgroups. Participants with baseline CD4+ T-cell counts less than 20 cells/μl had a mean increase of 240 cells/μl. In the safety population, more participants with baseline CD4+ T-cell counts less than 20 vs. at least 200 cells/μl had grade 3/4 adverse events [53/107 (50%) vs. 24/96 (25%)], serious adverse events [58/107 (54%) vs. 25/96 (26%)] and deaths [16/107 (15%) vs. 2/96 (2%)]. There were no safety differences by other subgroups. Conclusion: Week 96 results for BRIGHTE demonstrate comparable rates of virologic and immunologic response (Randomized Cohort) and safety (combined cohorts) across subgroups. OSS-new is an important consideration when constructing optimized antiretroviral regimens for heavily treatment-experienced individuals with limited remaining treatment options

Chagas Disease, France

Chagas Disease, Franc

Nutrients

BACKGROUND: Coffee intake has been shown to modulate both the effect of ethanol on serum GGT activities in some alcohol consumers and the risk of alcoholic cirrhosis in some patients with chronic diseases. This study aimed to analyze the impact of coffee intake and alcohol consumption on advanced liver fibrosis (ALF) in HIV-HCV co-infected patients. METHODS: ANRS CO13-HEPAVIH is a French, nationwide, multicenter cohort of HIV-HCV-co-infected patients. Sociodemographic, behavioral, and clinical data including alcohol and coffee consumption were prospectively collected using annual self-administered questionnaires during five years of follow-up. Mixed logistic regression models were performed, relating coffee intake and alcohol consumption to ALF. RESULTS: 1019 patients were included. At the last available visit, 5.8% reported high-risk alcohol consumption, 27.4% reported high coffee intake and 14.5% had ALF. Compared with patients with low coffee intake and high-risk alcohol consumption, patients with low coffee intake and low-risk alcohol consumption had a lower risk of ALF (aOR (95% CI) 0.24 (0.12(-)0.50)). In addition, patients with high coffee intake had a lower risk of ALF than the reference group (0.14 (0.03(-)0.64) in high-risk alcohol drinkers and 0.11 (0.05(-)0.25) in low-risk alcohol drinkers). CONCLUSIONS: High coffee intake was associated with a low risk of liver fibrosis even in HIV-HCV co-infected patients with high-risk alcohol consumption

The F4/AS01B HIV-1 Vaccine Candidate Is Safe and Immunogenic, But Does Not Show Viral Efficacy in Antiretroviral Therapy-Naive, HIV-1-Infected Adults: A Randomized Controlled Trial

The impact of the investigational human immunodeficiency virus type 1 (HIV-1) F4/AS01(B) vaccine on HIV-1 viral load (VL) was evaluated in antiretroviral therapy (ART)-naive HIV-1 infected adults.This phase IIb, observer-blind study (NCT01218113), included ART-naive HIV-1 infected adults aged 18 to 55 years. Participants were randomized to receive 2 (F4/AS01(B)_2 group, N=64) or 3 (F4/AS01(B)_3 group, N=62) doses of F4/AS01(B) or placebo (control group, N=64) at weeks 0, 4, and 28. Efficacy (HIV-1 VL, CD4(+) T-cell count, ART initiation, and HIV-related clinical events), safety, and immunogenicity (antibody and T-cell responses) were evaluated during 48 weeks.At week 48, based on a mixed model, no statistically significant difference in HIV-1 VL change from baseline was demonstrated between F4/AS01(B)_2 and control group (0.073 log(10)copies/mL [97.5% confidence interval (CI): -0.088; 0.235]), or F4/AS01(B)_3 and control group (-0.096 log(10)copies/mL [97.5% CI: -0.257; 0.065]). No differences between groups were observed in HIV-1 VL change, CD4(+) T-cell count, ART initiation, or HIV-related clinical events at intermediate timepoints. Among F4/AS01(B) recipients, the most frequent solicited symptoms were pain at injection site (252/300 doses), fatigue (137/300 doses), myalgia (105/300 doses), and headache (90/300 doses). Twelve serious adverse events were reported in 6 participants; 1 was considered vaccine-related (F4/AS01(B)_2 group: angioedema). F4/AS01(B) induced polyfunctional F4-specific CD4(+) T-cells, but had no significant impact on F4-specific CD8(+) T-cell and anti-F4 antibody levels.F4/AS01(B) had a clinically acceptable safety profile, induced F4-specific CD4(+) T-cell responses, but did not reduce HIV-1 VL, impact CD4(+) T-cells count, delay ART initiation, or prevent HIV-1 related clinical events

OA04-01. Safety and immunogenicity of LIPO-5, a HIV-1 lipopeptide vaccine: results of ANRS VAC18, a phase 2, randomized, double-blind, placebo-controlled trial

International audiencen.

Essais vaccinaux anti VIH 1 de phase I chez l'homme (approche comparative de la réponse immune induite par un vecteur recombinant canarypox et par des lipopeptides)

PARIS5-BU Méd.Cochin (751142101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF