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

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

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Case Report: Longitudinal follow-up and testicular sperm extraction in a patient with a pathogenic NR5A1 (SF-1) frameshift variant: p.(Phe70Serfs*5)

BackgroundSteroidogenic factor 1 (SF-1), encoded by the nuclear receptor subfamily 5 group A member 1 (NR5A1) gene, is a transcriptional factor crucial for adrenal and gonadal organogenesis. Pathogenic variants of NR5A1 are responsible for a wide spectrum of phenotypes with autosomal dominant inheritance including disorders of sex development and oligospermia–azoospermia in 46,XY adults. Preservation of fertility remains challenging in these patients.ObjectiveThe aim was to offer fertility preservation at the end of puberty in an NR5A1 mutated patient.Case reportThe patient was born of non-consanguineous parents, with a disorder of sex development, a small genital bud, perineal hypospadias, and gonads in the left labioscrotal fold and the right inguinal region. Neither uterus nor vagina was detected. The karyotype was 46,XY. Anti-Müllerian hormone (AMH) and testosterone levels were low, indicating testicular dysgenesis. The child was raised as a boy. At 9 years old, he presented with precocious puberty treated by triptorelin. At puberty, follicle-stimulating hormone (FSH), luteinising hormone (LH), and testosterone levels increased, whereas AMH, inhibin B, and testicular volume were low, suggesting an impaired Sertoli cell function and a partially preserved Leydig cell function. A genetic study performed at almost 15 years old identified the new frameshift variant NM_004959.5: c.207del p.(Phe70Serfs*5) at a heterozygous state. He was thus addressed for fertility preservation. No sperm cells could be retrieved from three semen collections between the ages of 16 years 4 months and 16 years 10 months. A conventional bilateral testicular biopsy and testicular sperm extraction were performed at 17 years 10 months of age, but no sperm cells were found. Histological analysis revealed an aspect of mosaicism with seminiferous tubules that were either atrophic, with Sertoli cells only, or presenting an arrest of spermatogenesis at the spermatocyte stage.ConclusionWe report a case with a new NR5A1 variant. The fertility preservation protocol proposed at the end of puberty did not allow any sperm retrieval for future parenthood

Routine testing to reduce late HIV diagnosis in France.

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Routine testing to reduce late HIV diagnosis in France

Although around half the French population has had an HIV test, many people are still not diagnosed until the disease is advanced. Cyrille Delpierre and colleagues believe the answer is to expand routine testin

Challenges of providing HIV pre-exposure prophylaxis in Martinique, French West Indies

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Apport du logiciel Nadis

Objectifs. Nous avons étudié l’intérêt du module « pharmacovigilance » du dossier médical informatisé Nadis® dans la collecte des effets indésirables (EIs) survenus chez les patients exposés aux antirétroviraux. Méthodes. Nous avons recueilli les EIs notifiés durant 17 mois (novembre 2010−mars 2012). Les caractéristiques du patient, des EIs et des antirétroviraux suspects ont été relevés. Les EIs recueillis ont été recensés et comparés au nombre de notifications spontanées sur une période similaire avant l’exploitation du Nadis®. Résultats. Au total, 119 EIs ont été recueillis (soit une augmentation de 183 %) concernant les EIs gastro-intestinaux (21,8 %), rénaux (20,2 %), neuropsychiatriques (16,8 %), hépatiques (13,5 %), cutanés (8,4 %), métaboliques (6,7 %), chez 109 patients exposés aux inhibiteurs nucléosidiques (31,8 %) / nucléotidiques (13,6 %) de la réverse transcriptase, inhibiteurs non nucléosidiques de la réverse transcriptase (13,1 %), inhibiteurs des protéases (36,4 %) et inhibiteurs d’intégrase (5,1 %). Conclusion. L’exploitation du logiciel Nadis® a permis une amélioration de la notification des EIs chez les patients exposés aux antirétroviraux

Experiences of HIV postexposure prophylaxis (PEP) among highly exposed men who have sex with men (MSM)

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