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AbstractIntroductionAlthough pre‐exposure prophylaxis (PrEP) is a remarkable biomedical advance to prevent HIV, ongoing research on PrEP contributes to and interacts with a legacy of HIV experimentation on marginalized communities in resource‐limited settings. This paper explores the complexity of PrEP research mistrust among Peruvian transgender (trans) women who completed a PrEP adherence intervention and those who refused participation (i.e. declined to enrol, voluntarily withdrew, and/or were lost to follow‐up).MethodsData were derived from 86 trans women (mean age 29 years) participants in the formative (four focus groups (n = 32), 20 interviews) and the evaluation stages (34 interviews) of a social network‐based PrEP intervention for trans women in Lima, Peru. The formative stage took place from May to July 2015, while the evaluative stage took place from April to May 2018. Audio files were transcribed verbatim and analysed via an immersion crystallization approach using Dedoose (v.6.1.18).ResultsThree paradoxes of trans women's participation in PrEP science as a "key" population emerged as amplifying mistrust: (1) increases in PrEP research targeting trans women but limited perceived improvements in HIV outcomes; (2) routine dismissal by research physicians and staff of PrEP‐related side effects and the social realities of taking PrEP, resulting in questions about who PrEP research is really for and (3) persistent limitations on PrEP access for trans women despite increasing involvement in clinical trials, fostering feelings of being a "guinea pig" to advance PrEP science.ConclusionsFindings highlight the wisdom inherent in PrEP mistrust as a reflection of trans women's experiences that underscore the broken bonds of trust between communities, researchers and the research enterprise. PrEP mistrust is amplified through perceived paradoxes that suggest to trans women that they are key experimental participants but not target PrEP users outside of research settings. Findings highlight the urgent need to reframe mistrust not as a characteristic of trans women to be addressed through education and outreach, but as a systemic institutional‐ and industry‐level problem replicated, manifested and ultimately to be corrected, through global HIV science.

AbstractIntroductionTransmitted, or any pretreatment drug resistance (TDR, PDR) can compromise efficacy of first‐line antiretroviral therapy (ART). In Peru, genotypic resistance testing is not routinely performed before ART initiation, and estimated PDR prevalence prior to 2012 ranged from 1.0% to 4.7%. We aimed to update estimates of PDR prevalence in men who have sex with men (cis‐MSM) and transgender women (TW).MethodsWe obtained HIV sequences from three studies of ART‐naïve cisgender‐MSM and TW (n = 470) in Lima, Peru from 2013 to 2017, almost two‐thirds of whom had acute or recent infections. Sanger sequences of HIV pol were interrogated for surveillance drug resistance mutations (SDRM) using the Stanford Calibrated Population Resistance (CPR) tool and scored for resistance to nucleoside reverse transcriptase inhibitors (NRTIs) and non‐nucleoside reverse transcriptase inhibitors (NNRTIs) with the HIVdb programme. We calculated binomial proportions and 95% confidence intervals. χ2 and exact or trend tests were used to examine predictors of PDR.ResultsSeventy‐seven (16.4%) individuals had PDR (95% CI: 13.2 to 20.0); most resistance was likely TDR since 63% were incident infections. SDRM were present in 9.8% (7.3 to 12.9). Resistance to any NRTI was present in <1% of individuals, while efavirenz resistance was present in 10% (6.9% to 12.4%). TW were not statistically more likely than cis‐MSM to have PDR (11.4% vs. 9.1%, p = 0.54). Age, incident versus prevalent infection, or residence district did not predict PDR. Prevalence of SDRM increased from 3% in 2013 to 21% 2017 within incident infections (p = 0.04), but not when including prevalent infections.ConclusionsPrevalence of NNRTI resistance in three studies of ART‐naïve MSM and TW in Lima, Peru reaches 10%. Because our study reports PDR in a population in which most acquired HIV recently, the overall prevalence of PDR, including previously treated persons, is likely underestimated. These results underscore the need for a nationally representative survey of PDR in Peru and consideration of non‐NNRTI anchored first‐line ART options. This study also represents the first evaluation of PDR in cis‐MSM versus TW in South America, and demonstrates that, although TW are at higher risk of acquiring HIV, they are at similar risk of acquiring a virus with resistance mutations.

AbstractIntroduction: In Peru, transgender women (TW) experience unique vulnerabilities for HIV infection due to factors that limit access to, and quality of, HIV prevention, treatment and care services. Yet, despite recent advances in understanding factors associated with HIV vulnerability among TW globally, limited scholarship has examined how Peruvian TW cope with this reality and how existing community‐level resilience strategies are enacted despite pervasive social and economic exclusion facing the community. Addressing this need, our study applies the understanding of social capital as a social determinant of health and examines its relationship to HIV vulnerabilities to TW in Peru.Methods: Using qualitative methodology to provide an in‐depth portrait, we assessed (1) intersections between social marginalization, social capital and HIV vulnerabilities; and (2) community‐level resilience strategies employed by TW to buffer against social marginalization and to link to needed HIV‐related services in Peru. Between January and February 2015, 48 TW participated (mean age = 29, range = 18–44) in this study that included focus group discussions and demographic surveys. Analyses were guided by an immersion crystallization approach and all coding was conducted using Dedoose Version 6.1.18.Results: Themes associated with HIV vulnerability included experiences of multilevel stigma and limited occupational opportunities that placed TW at risk for, and limited their engagement with, existing HIV services. Emergent resiliency‐based strategies included peer‐to‐peer and intergenerational knowledge sharing, supportive clinical services (e.g. group‐based clinic attendance) and emotional support through social cohesion (i.e. feeling part of a community).Conclusion: This study highlights the importance of TW communities as support structures that create and deploy social resiliency‐based strategies aimed at deterring and mitigating the impact of social vulnerabilities to discrimination, marginalization and HIV risk for individual TW in Peru. Public health strategies seeking to provide HIV prevention, treatment and care for this population will benefit from recognizing existing social capital within TW communities and incorporating its strengths within HIV prevention interventions. At the intersection of HIV vulnerabilities and collective agency, dimensions of bridging and bonding social capital emerged as resiliency strategies used by TW to access needed healthcare services in Peru. Fostering TW solidarity and peer support are key components to ensure acceptability and sustainability of HIV prevention and promotion efforts.

© 2020 Sanchez, Gonçalves, Llano, Gonzáles, Fernández-Maldonado, Vogt, Soria, Perez, Cedeño, Fernández, Nourikyan, de Bernard, Ganoza, Pedruzzi, Bonduelle, Mothe, Gòmez, Esteban, Garcia, Lama, Brander and Combadiere. ; [Background]: Our previous work has demonstrated the benefits of transcutaneous immunization in targeting Langerhans cells and preferentially inducing CD8 T-cell responses. ; [Methods]: In this randomized phase Ib clinical trial including 20 HIV uninfected volunteers, we compared the safety and immunogenicity of the MVA recombinant vaccine expressing HIV-B antigen (MVA-B) by transcutaneous and intramuscular routes. We hypothesized that the quality of innate and adaptive immunity differs according to the route of immunization and explored the quality of the vector vaccine-induced immune responses. We also investigated the early blood transcriptome and serum cytokine levels to identify innate events correlated with the strength and quality of adaptive immunity. ; [Results]: We demonstrate that MVA-B vaccine is safe by both routes, but that the quality and intensity of both innate and adaptive immunity differ significantly. Transcutaneous vaccination promoted CD8 responses in the absence of antibodies and slightly affected gene expression, involving mainly genes associated with metabolic pathways. Intramuscular vaccination, on the other hand, drove robust changes in the expression of genes involved in IL-6 and interferon signalling pathways, mainly those associated with humoral responses, and also some levels of CD8 response. ; [Conclusion]: Thus, vaccine delivery route perturbs early innate responses that shape the quality of adaptive immunity. ; This project has received funding from the European Union's Seventh Programme for research, technological development and demonstration under grant agreement No 241904, the European Union's Horizon 2020 Research, Innovation Programme under grant agreement No. 681137, NIH grant P01-AI131568 and La Fondation pour la Recherche Medicale.