First HIV prevalence estimates of a representative sample of adult sub-Saharan African migrants in a European city. Results of a community-based, cross-sectional study in Antwerp, Belgium.

INTRODUCTION: While sub-Saharan African migrants are the second largest group affected by HIV in Europe, sound HIV prevalence estimates based on representative samples of these heterogeneous communities are lacking. Such data are needed to inform prevention and public health policy. METHODS: This community-based, cross-sectional study combined oral fluid HIV testing with an electronic behavioral survey. Adopting a two-stage time location sampling HIV prevalence estimates for a representative sample of adult sub-Saharan African migrants in Antwerp, Belgium were obtained. Sample proportions and estimated adjusted population proportions were calculated for all variables. Univariable and multivariable logistic regression analysis explored factors independently associated with HIV infection. RESULTS: Between December 2013 and October 2014, 744 sub-Saharan African migrants were included (37% women). A substantial proportion was socially, legally and economically vulnerable: 21% were probably of undocumented status, 63% had financial problems in the last year and 9% lacked stable housing. Sexual networks were mostly African and crossed national borders, i.e. sexual encounters during travels within Europa and Africa. Concurrency is common, 34% of those in a stable relationship had a partner on the side in the last year. HIV prevalence was 5.9%(95%CI:3.4%-10.1%) among women and 4.2% (95%CI:1.6%-10.6%) among men. Although high lifetime HIV testing was reported at community level (73%), 65.2% (CI95%:32.4%-88.0%) of sub-Saharan African migrants were possibly undiagnosed. Being 45 years or older, unprotected sex when travelling within Europe in the last year, high intentions to use condoms, being unaware of their last sexual partners' HIV status, recent HIV testing and not having encountered partner violence in the last year were independently associated with HIV infection in multivariable logical regression. In univariable analysis, HIV infection was additionally associated to unemployment. CONCLUSIONS: This is the first HIV prevalence study among adult sub-Saharan African migrants resettling in a European city based on a representative sample. HIV prevalence was high and could potentially increase further due to the high number of people with an undiagnosed HIV infection, social vulnerability, high levels of concurrency and mainly African sexual networks. Given this population's mobility, an aligned European combination prevention approach addressing these determinants is urgently needed.

TOGETHER Project to Increase Understanding of the HIV Epidemic Among Sub-Saharan African Migrants: Protocol of Community-Based Participatory Mixed-Method Studies.

BACKGROUND: Sub-Saharan African Migrants (SAM) are the second largest group affected by HIV/AIDS in Belgium and the rest of Western Europe. Increasing evidence shows that, more than previously thought, SAM are acquiring HIV in their host countries. This calls for a renewed focus on primary prevention. Yet, knowledge on the magnitude of the HIV epidemic among SAM (HIV prevalence estimates and proportions of undiagnosed HIV infections) and underlying drivers are scarce and limit the development of such interventions. OBJECTIVE: By applying a community-based participatory and mixed-methods approach, the TOGETHER project aims to deepen our understanding of HIV transmission dynamics, as well as inform future primary prevention interventions for this target group. METHODS: The TOGETHER project consists of a cross-sectional study to assess HIV prevalence and risk factors among SAM visiting community settings in Antwerp city, Belgium, and links an anonymous electronic self-reported questionnaire to oral fluid samples. Three formative studies informed this method: (1) a social mapping of community settings using an adaptation of the PLACE method; (2) a multiple case study aiming to identify factors that increase risk and vulnerability for HIV infection by triangulating data from life history interviews, lifelines, and patient files; and (3) an acceptability and feasibility study of oral fluid sampling in community settings using participant observations. RESULTS: Results have been obtained from 4 interlinked studies and will be described in future research. CONCLUSIONS: Combining empirically tested and innovative epidemiological and social science methods, this project provides the first HIV prevalence estimates for a representative sample of SAM residing in a West European city. By triangulating qualitative and quantitative insights, the project will generate an in-depth understanding of the factors that increase risk and vulnerability for HIV infection among SAM. Based on this knowledge, the project will identify priority subgroups within SAM communities and places for HIV prevention. Adopting a community-based participatory approach throughout the full research process should increase community ownership, investment, and mobilization for HIV prevention.

Efficient in vitro expansion of human immunodeficiency virus (HIV)-specific T-cell responses by gag mRNA-electroporated dendritic cells from treated and untreated HIV type 1-infected individuals.

Developing an immunotherapy to keep human immunodeficiency virus type 1 (HIV-1) replication suppressed while discontinuing highly active antiretroviral therapy (HAART) is an important challenge. In the present work, we evaluated in vitro whether dendritic cells (DC) electroporated with gag mRNA can induce HIV-specific responses in T cells from chronically infected subjects. Monocyte-derived DC, from therapy-naïve and HAART-treated HIV-1-seropositive subjects, that were electroporated with consensus codon-optimized HxB2 gag mRNA efficiently expanded T cells, secreting gamma interferon (IFN-gamma) and interleukin 2 (IL-2), as well as other cytokines and perforin, upon restimulation with a pool of overlapping Gag peptides. The functional expansion levels after 1 week of stimulation were comparable in T cells from HAART-treated and treatment-naïve patients and involved both CD4(+) and CD8(+) T cells, with evidence of bifunctionality in T cells. Epitope mapping of p24 showed that stimulated T cells had a broadened response toward previously nondescribed epitopes. DC, from HAART-treated subjects, that were electroporated with autologous proviral gag mRNA equally efficiently expanded HIV-specific T cells. Regulatory T cells did not prevent the induction of effector T cells in this system, whereas the blocking of PD-L1 slightly increased the induction of T-cell responses. This paper shows that DC, loaded with consensus or autologous gag mRNA, expand HIV-specific T-cell responses in vitro.

Simultaneous activation of viral antigen-specific memory CD4+ and CD8+ T-cells using mRNA-electroporated CD40-activated autologous B-cells.

Recently, it has become obvious that not only CD8 T-cells, but also CD4 T-helper cells are required for the induction of an effective, long-lasting cellular immune response. In view of the clinical importance of cytomegalovirus (CMV) and human immunodeficiency virus (HIV) infection, we developed 2 strategies to simultaneously reactivate viral antigen-specific memory CD4 and CD8 T-cells of CMV-seropositive and HIV-seropositive subjects using mRNA-electroporated autologous CD40-activated B cells. In the setting of HIV, we provide evidence that CD40-activated B cells can be cultured from HAART-naive HIV-1 seropositive patients. These cells not only express and secrete the HIV p24 antigen after electroporation with codon-optimized HIV-1 gag mRNA, but can also be used to in vitro reactivate Gag antigen-specific interferon-gamma-producing CD4 and CD8 autologous T-cells. For the CMV-specific approach, we applied mRNA coding for the pp65 protein coupled to the lysosomal-associated membrane protein-1 to transfect CD40-activated B cells to induce CMV antigen-specific CD4 and CD8 T-cells. More detailed analysis of the activated interferon-gamma-producing CMV pp65 tetramer positive CD8 T-cells revealed an effector memory phenotype with the capacity to produce interleukin-2. Our findings clearly show that the concomitant activation of both CD4 and CD8 (memory) T-cells using mRNA-electroporated CD40-B cells is feasible in CMV and HIV-1-seropositive persons, which indicates the potential value of this approach for application in cellular immunotherapy of infectious diseases.