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This phase IIa, randomised, single‐blind, placebo‐controlled study was conducted to determine the dose of recombinant human granulocyte colony‐stimulating factor (lenograstim) suitable for use in AIDS patients. The study was conducted at 27 European AIDS/HIV centres, and recruited 69 AIDS patients with an initial episode or relapse of cytomegalovirus infection (neurological site excluded) and an absolute neutrophil count (ANC) ≤1.0×109/L upon diagnosis or between days 1 and 12 of ganciclovir (GCV) treatment. The patients were randomised to placebo (n=14) or one of four lenograstim arms: 150 µg/m2/d (the standard onco‐haematology dose, n=13) or 100 (n=13), 50 (n=15), or 25 µg/m2/d (n=14). In all groups, the planned dose of GCV was 10mg/kg/d for 21 d. Median ANC at weeks 2 and 3 was significantly higher in each lenograstim group than in the placebo group (p=0.05). At week 3, median ANC (×109/L) was 0.7 in the placebo group, compared with 6.0, 7.4, 4.5, and 2.0 in the 150, 100, 50, and 25 µg2/d lenograstim groups, respectively. Median ANC was not significantly different between the 150, 100, and 50 µg/m2/d lenograstim groups at any time point, but significantly higher in the 50 than in the 25 µg/m2/d group at weeks 2 (p=0.05) and 3 (p=0.02). Lenograstim was generally well tolerated, leading to no severe adverse events. In conclusion, lenograstim 50µg/m2/d is suitable for the treatment of ganciclovir‐induced neutropenia and is safe. These results should help the physician choose an optimal and cost‐efficient regimen for patients with AIDS‐related neutropenia when rHuG‐CSF support is indicated. [ABSTRACT FROM AUTHOR]

AIM: To measure serum androgen concentrations in men with HIV related Kaposi's sarcoma (KS) who had been treated with recombinant interferon (IFN) alpha-2a to determine the role of androgens on the development of KS lesions. METHODS: 32 men with HIV related KS who had been treated with IFN were studied: 24 men in complete KS remission and eight not in remission. Serum androgen concentrations were determined before, during, and after IFN treatment and correlated with clinical remission. RESULTS: All patients in complete KS remission had lower serum androgen concentrations following IFN treatment: -51% for dehydroepiandrosterone (DHEA) (p < 0.0001); -38% for DHEA sulphate (p < 0.002);-39% for androstenedione (p < 0.002); and -44% for testosterone (p < 0.007). These decreases brought the serum concentrations to about normal levels. However, IFN had varying effects on serum androgen concentrations in the men not in remission: a small decrease, a large increase in one androgen, or no change in serum androgens. CONCLUSIONS: The association between serum androgen levels and the progression or remission of HIV associated KS suggests that androgens affect the development of KS lesions. A clear understanding of the changes in the androgen environment may provide a sound basis for the development of new therapeutic strategies. [ABSTRACT FROM PUBLISHER]

Introduction – objectifs VAC-3S est un vaccin dirigé contre le motif 3S très conservé de la gp41 du VIH-1. 3S induit l’externalisation de NKp44L sur les CD4 non infectés et leur destruction par les NK. Les anticorps anti-3S (Ac-3S), sans effet direct sur la charge virale (CV), protègent de l’inflammation et de la déplétion CD4, comme démontré dans un modèle primate non-humain. Chez des patients VIH-1, la présence naturelle d’Ac-3S est corrélée à un ralentissement de la progression clinique et à une protection des CD4, indépendamment de la CV. Matériels et méthodes La phase I randomisée, en double-insu vs placebo a évalué la tolérance, l’immunogénicité (ELISA) et la différenciation/activation lymphocytaire (cytométrie) de 4 doses (0,1/1/10/20μg) injectées 3 fois en IM à 4 semaines d’intervalle chez des patients (pts) traités avec des CV < 50 c/mL. Les derniers résultats du bras 20 μg seront présentés [ doses 0,1–10 μg, cf. JNI 2013, M40 ]. Résultats Le bras 20 μg comprend 8 pts (dont 2 placebos) sur 33 inclus. Leurs caractéristiques (en médiane) sont : âge 43,5 ans (36–53) ; CD4 569 c/mm 3 (427–811) ; ratio CD4/CD8 1,1 (0,8–1,6) ; nadir CD4 331 c/mm 3 (150–437). Aucun effet indésirable (EI) grave, ni rebond viral n’ont été observés. Les EI de grades 1–2 sont : asthénie, fièvre, céphalée, réactions locales. Grade 3 : céphalée (N = 1), ténosynovite (N = 1). Cinq patients sur 6 présentent une réponse Ac-3S. Conclusion VAC-3S aux doses testées est bien toléré. La majorité des pts à 20 μg présentent une réponse Ac-3S. Une étude internationale de phase II est en cours [NCT02041247]. Elle évaluera l’effet d’un schéma d’administration intensifié, avec des doses de 20/40/80 μg, sur l’immunogénicité et un panel complet de marqueurs immunitaires, dont les sous-populations lymphocytaires, l’inflammation chronique et l’ADN-VIH. [ABSTRACT FROM AUTHOR]