Online self-sampling kits for human immunodeficiency virus and other sexually transmitted infections: Feasibility, positivity rates, and factors associated with infections in France.

BACKGROUND: Men who have sex with men are increasingly diagnosed with sexually transmitted infections (STI) in France. To address this situation, quarterly screening for HIV combined with hepatitis B (HBV) and hepatitis C (HCV), as well as annual screening for C.trachomatis (CT) and N.gonorrhoeae (NG) are recommended. The MemoDepistages program offered an at-home screening solution for these infections. This study describes the feasibility of this screening process, the rate of positive test results, and the factors associated with positivity. METHODS: Participants were recruited online. Laboratories verified the quantity and quality of the samples. Logistic regression was used to determine the associated factors for infection. RESULTS: Overall, 1556 out of 1908 (81.6%) blood samples were tested for at least HIV. A total of eight participants (0.5%) were newly diagnosed with HIV and four with HCV (0.3%). No new infection was confirmed for HBV. Overall positivity was 9.3% for CT and 9.6% for NG. The highest positivity was reported in rectal swabs for CT (7.3%) and in pharyngeal swabs for NG (7.2%). Factors associated with extragenital CT/NG were age under 30 years (for pharyngeal and rectal infections) and having at least 10 partners in the past 6 months (p<0.001) (for pharyngeal infections only). CONCLUSIONS: The self-sampling kit for multiple STIs can perform comprehensive tests and identify new infections in young people, especially in extragenital sites.

Online self-sampling kits to screen multipartner MSM for HIV and other STIs: participant characteristics and factors associated with kit use in the first 3 months of the MemoDepistages programme, France, 2018.

OBJECTIVES: In 2017, to reduce the proportion of men who have sex with men (MSM) in the undiagnosed HIV population in France (38%), HIV screening is advised each 3 months and STI screening is advised each year in multipartner MSM. Despite the range of testing solutions, over 40% of MSM were not tested for HIV and over 50% for STIs in the past year. Based on international experiments that offer screening solutions via online advertising, the French National Health Agency launched a programme (MemoDepistages) to provide a free self-sampling kit (SSK) for HIV and STIs. This article analyses the sociodemographic and behavioural characteristics of MSM in terms of kit acceptance and sample return. METHODS: Participants were registered for the programme online after ordering an SSK. The study included men aged over 18 years, living in one of the four selected French regions, and willing to disclose their postal and email address; they had health insurance, acknowledged more than one male partner in the past year, indicated a seronegative or unknown HIV status and were not taking medically prescribed pre-exposure prophylaxis drugs. Samples were collected by users and posted directly to the laboratory. Characteristics associated with kit acceptance and sample return were analysed using logistic regression. RESULTS: Overall, 7158 eligible MSM were offered to participate in the programme, with 3428 ordering the kit (47.9%) and 1948 returning their sample, leading to a return rate of 56.8% and an overall participation rate of 27.2%. Acceptance and return rates were strongly associated with sociodemographic characteristics, mainly education level but not with behavioural characteristics. Non-college graduates had lower acceptance (44.2%) and return rates (47.7%). CONCLUSION: The programme rapidly recruited a large number of MSM. It removed geographical inequalities related to screening access.

The MEC1 and MEC2 lines represent two CLL subclones in different stages of progression towards prolymphocytic leukemia.

The EBV carrying lines MEC1 and MEC2 were established earlier from explants of blood derived cells of a chronic lymphocytic leukemia (CLL) patient at different stages of progression to prolymphocytoid transformation (PLL). This pair of lines is unique in several respects. Their common clonal origin was proven by the rearrangement of the immunoglobulin genes. The cells were driven to proliferation in vitro by the same indigenous EBV strain. They are phenotypically different and represent subsequent subclones emerging in the CLL population. Furthermore they reflect the clinical progression of the disease. We emphasize that the support for the expression of the EBV encoded growth program is an important differentiation marker of the CLL cells of origin that was shared by the two subclones. It can be surmised that proliferation of EBV carrying cells in vitro, but not in vivo, reflects the efficient surveillance that functions even in the severe leukemic condition. The MEC1 line arose before the aggressive clinical stage from an EBV carrying cell within the subclone that was in the early prolymphocytic transformation stage while the MEC2 line originated one year later, from the subsequent subclone with overt PLL characteristics. At this time the disease was disseminated and the blood lymphocyte count was considerably elevated. The EBV induced proliferation of the MEC cells belonging to the subclones with markers of PLL agrees with earlier reports in which cells of PLL disease were infected in vitro and immortalized to LCL. They prove also that the expression of EBV encoded set of proteins can be determined at the event of infection. This pair of lines is particularly important as they provide in vitro cells that represent the subclonal evolution of the CLL disease. Furthermore, the phenotype of the MEC1 cells shares several characteristics of ex vivo CLL cells.

Soluble factors produced by activated CD4+ T cells modulate EBV latency.

Following infection with Epstein-Barr virus (EBV), the virus is carried for life in the memory B-cell compartment in a silent state (latency I/0). These cells do not resemble the proliferating lymphoblastoid cells (LCLs) (latency III) that are generated after infection. It is of fundamental significance to identify how the different EBV expression patterns are established in the latently infected cell. In view of the prompt activatability of CD4(+) T cells in primary EBV infection, and their role in B-cell differentiation, we studied the involvement of CD4(+) T cells in the regulation of EBV latency. Lymphoblastoid cell lines (LCLs) were cocultured with autologous or allogeneic CD4(+) T cells. Activated T cells influenced the expression of two key viral proteins that determine the fate of the infected B cell. EBNA2 was down-regulated, whereas LMP1 was unregulated and the cells proliferated less. This was paralleled by the down-regulation of the latency III promoter (Cp). Experiments performed in the transwell system showed that this change does not require cell contact, but it is mediated by soluble factors. Neutralizing experiments proved that the up-regulation of LMP1 is, to some extent, mediated by IL21, but this cytokine was not responsible for EBNA2 down-regulation. This effect was partly mediated by soluble CD40L. We detected similar regulatory functions of T cells in in vitro-infected lymphocyte populations. In conclusion, our results revealed an additional mechanism by which CD4(+) T cells can control the EBV-induced B-cell proliferation.

Type I interferons directly down-regulate BCL-6 in primary and transformed germinal center B cells: differential regulation in B cell lines derived from endemic or sporadic Burkitt's lymphoma.

Type I interferons (IFN) exert multiple effects on both the innate and adaptive immune system in addition to their antiviral and antiproliferative activities. Little is known, however about the direct effects of type I IFNs on germinal center (GC) B cells, the central components of adaptive B cell responses. We used Burkitt's lymphoma (BL) lines, as a model system of normal human GC B cells, to examine the effect of type I IFNs on the expression of BCL-6, the major regulator of the GC reaction. We show that type I IFNs, but not IFNγ, IL-2 and TNFα rapidly down-regulate BCL-6 protein and mRNA expression, in cell lines derived from endemic, but not from sporadic BL. IFNα-induced down-regulation is specific for BCL-6, independent of Epstein-Barr virus and is not accompanied by IRF-4 up-regulation. IFNα-induced BCL-6 mRNA down-regulation does not require de novo protein synthesis and is specifically inhibited by piceatannol. The proteasome inhibitor MG132 non-specifically prevents, while inhibitors of alternate type I IFN signaling pathways do not inhibit IFNα-induced BCL-6 protein downregulation. We validate our results with showing that IFNα rapidly down-regulates BCL-6 mRNA in purified mouse normal GC B cells. Our results identify type I IFNs as the first group of cytokines that can down-regulate BCL-6 expression directly in GC B cells.