Calendar trends in sexual behaviours in a cohort of HIV-infected MSM at the era of treatment as prevention of HIV infection.

BACKGROUND: With the advent of treatment as prevention of HIV infection (TasP), we assessed trends in sexual behaviours between 2000 and 2017 among HIV-infected MSM enrolled in the French ANRS PRIMO cohort. METHODS: At each cohort visit, a clinical questionnaire including laboratory values was completed and a self-administered questionnaire was used to collect sexual behaviours, that is, the number, type (steady/casual) and HIV status (positive or negative/unknown) of partners, and condom use. The possible influence of viral load (undetectable/detectable) measured at the preceding visit on the evolution over time of sexual behaviour was assessed with logistic regression models fitted by generalized estimating equations (GEE), taking into account longitudinal data. RESULTS: We analyzed data from 10657 follow-up visits by 1364 MSM. Overall, whatever the considered behavioural variable: at least one sexual partner, steady and/or casual, condomless sex with steady, casual partners, serodiscordant or not, we observed a calendar increase with a particularly more marked rise from 2010 (P < 0.0001). Inconsistent condom use did not differ according to the viral load status (detectable vs. undetectable). Trends in inconsistent condom use increased across different generations of MSM, as defined by the year they were diagnosed with HIV infection. CONCLUSIONS: 'Having a sexual partner' and condomless sex, both increased in frequency between 2000 and 2017. Viral load status did not influence condom use as could have been expected from the 2008 Swiss Statement.

Cohort Profile: French hospital database on HIV (FHDH-ANRS CO4).

The French Hospital Database on HIV (FHDH) is a hospital-based multicentre open cohort with inclusions ongoing since 1989. The research objectives focus mainly on mid- and long-term clinical outcomes and therapeutic strategies, as well as severe AIDS and non-AIDS morbidities, and public health issues relative to HIV infection. FHDH also serves to describe HIV-infected patients receiving hospital care in France. FHDH includes data on more than 120,000 HIV-infected patients from 70 French general or university hospitals distributed throughout France. Patients are eligible for inclusion if they are infected by HIV-1 or HIV-2 and give their written informed consent. Standardized variables are collected at each outpatient visit or hospital admission during which a new clinical manifestation is diagnosed, a new treatment is prescribed or a change in biological markers is noted, and/or at least every 6 months. Since its inception, variables collected in FHDH include demographic characteristics, HIV-related biological markers, the date and type of AIDS and non AIDS-defining events, antiretroviral treatments and the date and causes of death, as reported in the medical records. Since 2005, data have also been collected on: co-infection with hepatitis B or C virus; alcohol and tobacco use; and non HIV-related biomarkers. Anyone can submit a research project by completing a standardized form available on the FHDH website (http://www.ccde.fr/_fold/fl-1385734776-429.pdf) or from the corresponding author, describing the context and objectives of the study. All projects are reviewed by the scientific committee.

Ribosomal protein SA haploinsufficiency in humans with isolated congenital asplenia.

Isolated congenital asplenia (ICA) is characterized by the absence of a spleen at birth in individuals with no other developmental defects. The patients are prone to life-threatening bacterial infections. The unbiased analysis of exomes revealed heterozygous mutations in RPSA in 18 patients from eight kindreds, corresponding to more than half the patients and over one-third of the kindreds studied. The clinical penetrance in these kindreds is complete. Expression studies indicated that the mutations carried by the patients-a nonsense mutation, a frameshift duplication, and five different missense mutations-cause autosomal dominant ICA by haploinsufficiency. RPSA encodes ribosomal protein SA, a component of the small subunit of the ribosome. This discovery establishes an essential role for RPSA in human spleen development.

Severe X-linked chronic granulomatous disease in two unrelated females.

Chronic granulomatous disease (CGD) is a rare primary immunodeficiency caused by mutations of one of the subunits of phagocyte reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase leading to decreased or complete absence of neutrophil oxidative burst. We report the clinical and laboratory findings in two young unrelated females 14 and 9 years of age and natives of Tahiti and Reunion Islands, respectively, with severe X-linked granulomatous disease. In both cases, the infectious pattern was unusual, with convergent symptoms suggesting underlying mycobacterial infection. Functional analysis revealed low residual NADPH oxidase activity with about 5-10% of normal neutrophil population. De novo null mutations affecting the CYBB gene that encodes the gp91 protein were found in both cases in the heterozygous state (in patient 1, p.Arg130X in exon 5, and in patient 2, a novel insertion in exon 6, c.632_633insCATC). Methylation analysis confirmed that phenotype expression was linked to skewed X inactivation and showed that the de novo mutation arose on the maternally inherited chromosome in one case and on the paternally inherited chromosome in the other case. In conclusion, X-linked CGD carriers could therefore be at risk for severe infectious diseases depending on the skewed X inactivation pattern and the infectious context.