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Background Pre-exposure prophylaxis (PrEP) is the first biomedical intervention with proven efficacy to reduce human immunodeficiency virus (HIV) acquisition in men who have sex with men (MSM) and transgender women (TGW). Little is known about levels of interest and characteristics of individuals who elect to take PrEP in real-world clinical settings. Methods The US PrEP Demonstration Project is a prospective, open-label cohort study assessing PrEP delivery in municipal STD clinics in San Francisco and Miami and a community health center in Washington, DC. HIV-uninfected MSM and TGW seeking sexual health services at participating clinics were assessed for eligibility and offered up to 48 weeks of emtricitabine/tenofovir for PrEP. Predictors of enrollment were assessed using a multivariable Poisson regression model, and characteristics of enrolled participants are described. Results Of 1069 clients assessed for participation, 921 were potentially eligible and 557 (60.5%) enrolled. In multivariable analysis, participants from Miami (aRR 1.53; 95% CI 1.33-1.75) or DC (aRR 1.33; 95% CI 1.2-1.47), those who were self-referred (aRR 1.48; 95% CI 1.32-1.66), with prior PrEP awareness (aRR 1.56; 95% CI 1.05-2.33) and those reporting >1 episode of anal sex with an HIV-infected partner in the last 12 months (aRR 1.20; 95% CI 1.09-1.33) were more likely to enroll. Almost all (98%) of enrolled participants were MSM, and at baseline, 63.5% reported condomless receptive anal sex in the prior three months. Conclusions Interest in PrEP is high among a diverse population of MSM at risk for HIV infection when offered in STD and community health clinics.

IntroductionConvincing evidence exists for a protective role of cellular immunity in HIV infection. For example, virologic control and detection of HIV-specific cytotoxic T lymphocytes (CTLs) are temporally related during primary HIV infection, 1 and CD8 T-cell depletion results in widespread virus replication and disease progression in the simian immunodeficiency virus (SIV)-infected nonhuman primate model. In HIV infection, the failure of antiviral immunity has been attributed in part to qualitative CTL defects 2-4 such as decreased perforin in total-and HIV-specific CD8 T cells in peripheral blood and lymphoid tissue, including gutassociated lymphoid tissues. [5][6][7][8] Perforin defects are also evident in CTLs of patients who are on highly active antiretroviral therapy (HAART). 2,9 The inability of most patients to keep HIV under control in the absence of potent antiretroviral therapy 10,11 has led to the quest for immunotherapeutic approaches to augment antiviral cellular immunity.CD8 T cells can be identified phenotypically for their maturation status based upon expression of cell-surface maturation markers. For example, naive, central memory, effector memory, and effector subsets manifest differential expression of CD45RA and CD62L or CCR7, 12 and perturbations in their distribution have been identified in HIV infection. Typically, naive and effector CD8 T cells are reduced, and effector memory subsets are expanded in patients with HIV who have only partial restoration with HAART. [1][2][3] The major mechanism by which effector CD8 T cells kill virusinfected targets and tumor cells is via secretion of lytic molecules, namely perforin and granzymes. 13,14 Lytic granules in CTLs are stored in a dense core within secretory lysosomes, 15 and the membrane that encloses the granules contains lysosomal glycoproteins such as lysosome-associated membrane protein-1 (LAMP-1; CD107a), LAMP-2 (CD107b), and CD63. 16 Soluble granule contents are released during exocytosis, and the incorporation of granule membrane proteins such as CD107a into the plasma membrane serve as markers of degranulation.Preservation of memory and effector CD8 T-cell pools in vivo depends in part upon homeostatic proliferation which is regulated by cytokines and self-peptide MHC ligands for the T-cell receptor (TCR). It is now widely accepted that generation of long-term memory CD4 and CD8 T cells is dependent upon antigenic stimulation, but their survival is antigen independent and requires peripherally produced cytokines, particularly those that use the common ␥-chain for signaling, such as interleukin (IL)-15. [17][18][19] Another more recently described pleiotropic cytokine that uses the common ␥-chain is IL-21, which is produced only by activated CD4 T lymphocytes and has significant sequence similarity to cytokines IL-2, Based on the known T-cell-potentiating properties of IL-21 in tumor models, 26,27 we hypothesized that IL-21 could augment the effector function of CD8 T cells in patients with HIV. Patients, materials, and methods Stu...

Pre-exposure prophylaxis (PrEP) for prevention of HIV infection has demonstrated efficacy in randomized controlled trials as well as in demonstration projects. For PrEP implementation to result in significant reductions in HIV incidence for men who have sex with men (MSM) in the United States, sufficient access to PrEP care and continued engagement outside of demonstration projects is required. We report the results of a follow-up survey of 173 former participants from the Miami and San Francisco sites of the U.S. PrEP Demo Project, administered 4–6 months after study completion. Survey respondents continued to frequently access medical care and had a high incidence of sexually transmitted infections after completion of the Demo Project, indicating ongoing sexual risk behavior. Interest in continuing PrEP was high, with 70.8% indicating they were “very interested” in continuing PrEP. Among respondents, 39.9% reported continuation of PrEP following completion of the Demo Project, largely through their primary care providers and frequently at low or no cost. Variability in access and engagement was seen, with participants from the San Francisco site, those with medical insurance, and those with a primary care provider at the end of the Demo Project more likely to successfully obtain PrEP medication. Two respondents reported HIV seroconversion in the period between study completion and the follow-up survey. Additional effort to increase equitable access to PrEP outside of demonstration projects is needed to realize the potential impact of this evidence-based prevention intervention.