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An understanding of how broadly neutralizing activity develops in HIV-1-infected individuals is needed to guide vaccine design and immunization strategies. Here we used a large panel of 44 HIV-1 envelope variants (subtypes A, B, and C) to evaluate the presence of broadly neutralizing antibodies in serum samples obtained 3 years after seroconversion from 40 women enrolled in the CAPRISA 002 acute infection cohort. Seven of 40 participants had serum antibodies that neutralized more than 40% of viruses tested and were considered to have neutralization breadth. Among the samples with breadth, CAP257 serum neutralized 82% (36/44 variants) of the panel, while CAP256 serum neutralized 77% (33/43 variants) of the panel. Analysis of longitudinal samples showed that breadth developed gradually starting from year 2, with the number of viruses neutralized as well as the antibody titer increasing over time. Interestingly, neutralization breadth peaked at 4 years postinfection, with no increase thereafter. The extent of cross-neutralizing activity correlated with CD4+ T cell decline, viral load, and CD4+ T cell count at 6 months postinfection but not at later time points, suggesting that early events set the stage for the development of breadth. However, in a multivariate analysis, CD4 decline was the major driver of this association, as viral load was not an independent predictor of breadth. Mapping of the epitopes targeted by cross-neutralizing antibodies revealed that in one individual these antibodies recognized the membrane-proximal external region (MPER), while in two other individuals, cross-neutralizing activity was adsorbed by monomeric gp120 and targeted epitopes that involved the N-linked glycan at position 332 in the C3 region. Serum antibodies from the other four participants targeted quaternary epitopes, at least 2 of which were PG9/16-like and depended on the N160 and/or L165 residue in the V2 region. These data indicate that fewer than 20% of HIV-1 subtype C-infected individuals develop antibodies with cross-neutralizing activity after 3 years of infection and that these antibodies target different regions of the HIV-1 envelope, including as yet uncharacterized epitopes. [ABSTRACT FROM AUTHOR]

Background: Nyaope is a strongly addictive novel psychoactive substance that is commonly used in predominantly black townships in South Africa. The undesired behaviours of the users result in family members developing mental health challenges. Nyaope users often commit petty crimes, including stealing from families and neighbours., Aim: The aim of this study was to quantify anxiety symptoms among family members of nyaope users in Tshwane, South Africa., Setting: Data were collected from nine townships within Tshwane Metropolitan Municipality., Methods: The quantitative cross-sectional survey used the General Anxiety Disorder (GAD-7) tool to quantify anxiety symptoms, and a questionnaire was used to collect sociodemographic data from a sample of 390 participants., Results: The ages of the participants ranged from 18 years to 87 years, with a mean of 47 years. The mothers to the nyaope users were the biggest group at 35% ( n = 138). The prevalence of anxiety symptoms was 73% ( n = 286) of the total sample and ranged from mild (41.8, n = 163), moderate (14.62, n = 57) and severe (16.92%, n = 66). The Pearson chi-square test identified significant associations between anxiety symptoms and the gender of the participant ( p = 0.001), the age of the nyaope user and the period of nyaope use ( p = 0.008). Multivariate regression model indicated gender and place of residence as a significant variable in the development of anxiety symptoms ( p = 0.01)., Conclusion: Nyaope use is a risk factor for the development of anxiety for family members of nyaope users with the highest proportion reporting mild symptoms., Contribution: There is a need to develop interventions for mental health support for families of nyaope users., Competing Interests: The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this article., (© 2023. The Authors.)