Tim-3+ T-bet+ Tumor-Specific Th1 Cells Colocalize with and Inhibit Development and Growth of Murine Neoplasms

Abstract Although T cells infiltrate many types of murine and human neoplasms, in many instances tumor-specific cytotoxicity is not observed. Strategies to stimulate CTL-mediated antitumor immunity have included in vitro stimulation and/or genetic engineering of T cells, followed by adoptive transfer into tumor-bearing hosts. In this model of B cell lymphoma in SJL/J mice, we used Tim-3+ T-bet+ Th1 cells to facilitate the development of tumor-specific CTL. Tumor-specific Th1 cell lines were polarized with IL-12 during in vitro stimulation and long term maintenance. As few as 5 million Tim-3+ T-bet+ Th1 cells enabled recipients to resist growth of malignant transplantable cells. In addition, similar numbers of Th1 cells injected into 2- to 3-mo-old mice inhibited development of the spontaneous primary lymphomas, which normally arise in 90% of aging mice. CFSE+ Th1 cells colocalized with injected tumor cells in vivo and formed conjugates with the tumor cells within follicles, whereas in nontumor-challenged recipients the CFSE+ Th1 cells localized only within the T cell zones of the spleen. These results provide evidence that adoptive immunotherapy with Tim-3+ T-bet+ tumor-specific Th1 cells can be used to induce host cytotoxic responses that inhibit the development and growth of neoplastic cells

Beyond the Biomedical: Preexposure Prophylaxis Failures in a Cohort of Young Black Men Who Have Sex With Men in Atlanta, Georgia

In a cohort of young black men who have sex with men, we observed high human immunodeficiency virus incidence despite education and access to preexposure prophylaxis (PrEP). Although PrEP has efficacy in clinical trials, we identify barriers to real-world effectiveness. Human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP) has high biomedical efficacy; however, awareness, access, uptake, and persistence on therapy remain low among black men who have sex with men (BMSM), who are at highest risk of HIV in the United States. To date, discussions of “PrEP failure” have focused on one typology: rare, documented HIV acquisitions among PrEP users with adequate serum drug levels (ie, biomedical failure). In our cohort of HIV-negative young BMSM in Atlanta, Georgia, we continue to observe a high HIV incidence (6.2% annually at interim analysis) despite access to free PrEP services. Among 14 seroconversions, all were offered PrEP before acquiring HIV. Among these participants, we identified 4 additional typologies of PrEP failure that expand beyond biomedical failure: low PrEP adherence, PrEP discontinuation, PrEP contemplation without initiation, and PrEP refusal. We describe the 5 typologies and suggest interventions to improve PrEP effectiveness among those at highest risk

Pre-exposure Prophylaxis Uptake and Discontinuation Among Young Black Men Who Have Sex With Men in Atlanta, Georgia: A Prospective Cohort Study

Human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP) has great potential to reduce HIV incidence among young black men who have sex with men (YBMSM); however, initiation and persistence for this group remain low. We sought to understand the patterns and predictors of PrEP uptake and discontinuation among YBMSM in Atlanta, Georgia. PrEP was offered to all participants in a prospective cohort of YBMSM aged 18-29 years not living with HIV. Time to PrEP uptake, first discontinuation, and final discontinuation were assessed using the Kaplan-Meier method. Cox proportional hazard models were used to identify predictors of uptake and discontinuation. After 440 person-years of follow-up, 44% of YBMSM initiated PrEP through the study after a median of 122 days. Of PrEP initiators, 69% had a first discontinuation and 40% had a final discontinuation during the study period. The median time to first PrEP discontinuation was 159 days. Factors associated with PrEP uptake included higher self-efficacy, sexually transmitted infection (STI), and condomless anal intercourse. Factors associated with discontinuation included younger age, cannabis use, STI, and fewer sex partners. HIV incidence was 5.23/100 person-years (95% confidence interval [CI], 3.40-7.23), with a lower rate among those who started PrEP (incidence rate ratio, 0.39; 95% CI, .16-.92). Persistent PrEP coverage in this cohort of YBMSM was suboptimal, and discontinuations were common despite additional support services available through the study. Interventions to support PrEP uptake and persistence, especially for younger and substance-using YBMSM, are necessary to achieve full PrEP effectiveness. NCT02503618