Impact of Point-of-Care Testing on the Management of Sexually Transmitted Infections in South Africa: Evidence from the HVTN702 Human Immunodeficiency Virus Vaccine Trial.

BACKGROUND: Alternative approaches to syndromic management are needed to reduce rates of sexually transmitted infections (STIs) in resource-limited settings. We investigated the impact of point-of-care (POC) versus central laboratory-based testing on STI treatment initiation and STI adverse event (STI-AE) reporting. METHODS: We used Kaplan-Meier and Cox regression models to compare times to treatment initiation and STI-AE reporting among HVTN702 trial participants in South Africa. Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) were diagnosed POC at eThekwini clinic and in a central laboratory at Verulam/Isipingo clinics. All clinics used POC assays for Trichomonas vaginalis (TV) testing. RESULTS: Among 959 women (median age, 23 [interquartile range, 21-26] years), median days (95% confidence interval [95%CI]) to NG/CT treatment initiation and NG/CT-AE reporting were 0.20 (.16-.25) and 0.24 (.19-.27) at eThekwini versus 14.22 (14.12-15.09) and 15.12 (13.22-21.24) at Verulam/Isipingo (all P < .001). Median days (95%CI) to TV treatment initiation and TV-AE reporting were 0.17 (.12-.27) and 0.25 (.20-.99) at eThekwini versus 0.18 (.15-.2) and 0.24 (.15-.99) at Verulam/Isipingo (all P > .05). Cox regression analysis revealed that NG/CT treatment initiation (adjusted hazard ratio [aHR], 39.62 [95%CI, 15.13-103.74]) and NG/CT-AE reporting (aHR, 3.38 [95%CI, 2.23-5.13]) occurred faster at eThekwini versus Verulam/Isipingo, while times to TV treatment initiation (aHR, 0.93 [95%CI, .59-1.48]) and TV-AE reporting (aHR, 1.38 [95%CI, .86-2.21]) were similar. CONCLUSIONS: POC testing led to prompt STI management with potential therapeutic and prevention benefits, highlighting its utility as a diagnostic tool in resource-limited settings.

Deep sequencing of the human TCRγ and TCRß repertoires suggests that TCRß rearranges after αß and γδ T cell commitment.

T lymphocytes respond to a broad array of pathogens with the combinatorial diversity of the T cell receptor (TCR). This adaptive response is possible because of the unique structure of the TCR, which is composed of two chains, either αß or γδ, that undergo genetic rearrangement in the thymus. αß and γδ T cells are functionally distinct within the host but are derived from a common multipotent precursor. The canonical model for T cell lineage commitment assumes that the γ, δ, and ß chains rearrange before αß or γδ T cell commitment. To test the standard model in humans, we used high-throughput sequencing to catalog millions of TCRγ and TCRß chains from peripheral blood αß and γδ T cells from three unrelated individuals. Almost all sampled αß and γδ T cells had rearranged TCRγ sequences. Although sampled αß T cells had a diverse repertoire of rearranged TCRß chains, less than 4% of γδ T cells in peripheral blood had a rearranged TCRß chain. Our data suggest that TCRγ rearranges in all T lymphocytes, consistent with TCRγ rearranging before T cell lineage commitment. However, rearrangement of the TCRß locus appears to be restricted after T cell precursors commit to the αß T cell lineage. Indeed, in T cell leukemias and lymphomas, TCRγ is almost always rearranged and TCRß is only rearranged in a subset of cancers. Because high-throughput sequencing of TCRs is translated into the clinic for monitoring minimal residual for leukemia/lymphoma, our data suggest the sequencing target should be TCRγ.