PubMed · 8217645
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HIV guidelines under attack.. https://pubmed.ncbi.nlm.nih.gov/8217645/
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BACKGROUND: Estimating the time since HIV infection (TSI) at population level is essential for tracking changes in the global HIV epidemic. Most methods for determining TSI give a binary classification of infections as recent or non-recent within a window of several months, and cannot assess the cumulative impact of an intervention. RESULTS: We developed a Random Forest Regression model, HIV-phyloTSI, which combines measures of within-host diversity and divergence to generate continuous TSI estimates directly from viral deep-sequencing data, with no need for additional variables. HIV-phyloTSI provides a continuous measure of TSI up to 9 years, with a mean absolute error of less than 12 months overall and less than 5 months for infections with a TSI of up to a year. It performs equally well for all major HIV subtypes based on data from African and European cohorts. CONCLUSIONS: We demonstrate how HIV-phyloTSI can be used for incidence estimates on a population level.
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We have previously demonstrated that immunization of HIV-1-infected individuals with the common recall antigen, tetanus, induced transient increases in plasma viremia as well as an increased ability to isolate virus from CD8+ T cell-depleted peripheral blood mononuclear cells (PBMCs) under minimally stimulated culture conditions (IL-2 plus IL-4) postimmunization. In this study, HIV-1-infected individuals were immunized with tetanus toxoid and PBMCs were examined at multiple time points following immunization. Tetanus-induced production of virus was defined as an increased ability to isolate HIV-1 from CD8+ T cell-depleted PBMCs in vitro in the presence of tetanus antigen as opposed to no antigen or control antigen alone. Following immunization, in vitro tetanus-induced production of HIV-1 was observed in 8 of 13 (62%) patients compared to 2 of 13 (15%) patients prior to immunization. In four of these patients, virus could also be isolated from CD8+ T cell-depleted PBMCs in the presence of tetanus without the addition of any exogenous IL-2. Furthermore, virus could be isolated from the unfractionated PBMCs of two patients when tetanus antigen alone was added to the culture in the absence of added PHA or PHA blasts. HIV-1 was isolated predominantly from CD4+ T cells with a CD45RO+, CD25+ phenotype and was associated with a trend to elevated levels in culture supernatants of IFN-gamma, IL-6, TNF-alpha, and IL-4. These findings have important implications with regard to the role of ongoing antigen-specific immune responses in the induction of HIV-1 expression in vivo.