Transgender People and HIV Prevention: What We Know and What We Need to Know, a Call to Action

Abstract: Transgender people have been disproportionally affected by HIV, particularly transgender women. Their increased vulnerability to HIV is due to multiple issues, including biological (eg, increased efficiency of HIV transmission through receptive anal sex), epidemiological (eg, increased likelihood of having HIV-infected partners), structural (eg, social stigma limiting employment options), and individual factors (eg, internalized stigma leading to depression and substance use and risk-taking behaviors). There have been limited culturally appropriate HIV prevention interventions for transgender people, with many key prevention studies (eg, the iPrEx PrEP study) enrolling transgender women in a study focusing on men who have sex with men. This has resulted in limited understanding of the optimal ways to decrease transgender people's risk for HIV acquisition. The current supplement of JAIDS is designed to review what is known about HIV prevention for transgender people and to highlight new insights and best practices. The study reviews recent epidemiologic data, the pharmacology of HIV prophylactic agents in individuals who may be using exogenous hormones, and several recent multi-component interventions designed to address the lived experience of transgender people. Additionally, the study reviews the work going on at the NIH to address transgender health in general and HIV prevention in specific, as well as two important papers related to clinical trial design issues and the ethical conduct of research in this frequently disenfranchised population. It is the hope of the HIV Prevention Trials Network (HPTN) that this supplement will promote new knowledge around transgender health and the requisite issues that need to be addressed in order to conduct optimal clinical trials. The ultimate hope is that the information distilled in this supplement will inform investigators, clinicians, and public health officials in order to design further research to develop optimal prevention interventions for transgender people and to implement these interventions in ways that are culturally congruent and health promoting

Testing for Network and Spatial Autocorrelation

Testing for dependence has been a well-established component of spatial statistical analyses for decades. In particular, several popular test statistics have desirable properties for testing for the presence of spatial autocorrelation in continuous variables. In this paper we propose two contributions to the literature on tests for autocorrelation. First, we propose a new test for autocorrelation in categorical variables. While some methods currently exist for assessing spatial autocorrelation in categorical variables, the most popular method is unwieldy, somewhat ad hoc, and fails to provide grounds for a single omnibus test. Second, we discuss the importance of testing for autocorrelation in network, rather than spatial, data, motivated by applications in social network data. We demonstrate that existing tests for autocorrelation in spatial data for continuous variables and our new test for categorical variables can both be used in the network setting

Predictors and outcomes of Mycobacterium tuberculosis bacteremia among patients with HIV and tuberculosis co-infection enrolled in the ACTG A5221 STRIDE study

Background: We evaluated predictors and outcomes of Mycobacterium tuberculosis bacteremia among participants undergoing baseline mycobacterial blood culture in the ACTG A5221 STRIDE study, a randomized clinical trial comparing earlier with later ART among HIV-infected patients suspected of having tuberculosis with CD4-positive T-lymphocyte counts (CD4 counts) <250 cells/mm3. We conducted a secondary analysis comparing participants with respect to presence or absence of M. tuberculosis bacteremia. Methods: Participants with a baseline mycobacterial blood culture were compared with respect to the presence or absence of M. tuberculosis bacteremia. Baseline predictors of M. tuberculosis bacteremia were identified and participant outcomes were compared by mycobacteremia status. Results: Of 90 participants with baseline mycobacterial blood cultures, 29 (32.2%) were female, the median (IQR) age was 37 (31–45) years, CD4 count was 81 (33–131) cells/mm3, HIV-1 RNA level was 5.39 (4.96–5.83) log10 copies/mL, and 18 (20.0%) had blood cultures positive for M. tuberculosis. In multivariable analysis, lower CD4 count (OR 0.85 per 10-cell increase, p = 0.012), hemoglobin ≤8.5 g/dL (OR 5.8, p = 0.049), and confirmed tuberculosis (OR 17.4, p = 0.001) were associated with M. tuberculosis bacteremia. There were no significant differences in survival and AIDS-free survival, occurrence of tuberculosis immune reconstitution inflammatory syndrome (IRIS), or treatment interruption or discontinuation by M. tuberculosis bacteremia status. IRIS did not differ significantly between groups despite trends toward more virologic suppression and greater CD4 count increases at week 48 in the bacteremic group. Conclusions: Among HIV-infected tuberculosis suspects, lower CD4 count, hemoglobin ≤8.5 g/dL, and the presence of microbiologically confirmed pulmonary tuberculosis were associated with increased adjusted odds of mycobacteremia. No evidence of an association between M. tuberculosis bacteremia and the increased risk of IRIS was detected. Trial registration ClinicalTrials.gov: NCT00108862

Predictors and outcomes of Mycobacterium tuberculosis bacteremia among patients with HIV and tuberculosis co-infection enrolled in the ACTG A5221 STRIDE study.

BACKGROUND: We evaluated predictors and outcomes of Mycobacterium tuberculosis bacteremia among participants undergoing baseline mycobacterial blood culture in the ACTG A5221 STRIDE study, a randomized clinical trial comparing earlier with later ART among HIV-infected patients suspected of having tuberculosis with CD4-positive T-lymphocyte counts (CD4 counts)/mm(3). We conducted a secondary analysis comparing participants with respect to presence or absence of M. tuberculosis bacteremia. METHODS: Participants with a baseline mycobacterial blood culture were compared with respect to the presence or absence of M. tuberculosis bacteremia. Baseline predictors of M. tuberculosis bacteremia were identified and participant outcomes were compared by mycobacteremia status. RESULTS: Of 90 participants with baseline mycobacterial blood cultures, 29 (32.2%) were female, the median (IQR) age was 37 (31-45) years, CD4 count was 81 (33-131) cells/mm(3), HIV-1 RNA level was 5.39 (4.96-5.83) log10 copies/mL, and 18 (20.0%) had blood cultures positive for M. tuberculosis. In multivariable analysis, lower CD4 count (OR 0.85 per 10-cell increase, p = 0.012), hemoglobin ≤8.5 g/dL (OR 5.8, p = 0.049), and confirmed tuberculosis (OR 17.4, p = 0.001) were associated with M. tuberculosis bacteremia. There were no significant differences in survival and AIDS-free survival, occurrence of tuberculosis immune reconstitution inflammatory syndrome (IRIS), or treatment interruption or discontinuation by M. tuberculosis bacteremia status. IRIS did not differ significantly between groups despite trends toward more virologic suppression and greater CD4 count increases at week 48 in the bacteremic group. CONCLUSIONS: Among HIV-infected tuberculosis suspects, lower CD4 count, hemoglobin ≤8.5 g/dL, and the presence of microbiologically confirmed pulmonary tuberculosis were associated with increased adjusted odds of mycobacteremia. No evidence of an association between M. tuberculosis bacteremia and the increased risk of IRIS was detected. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00108862

Participation of women in HIV clinical trials: the IPEC-FIOCRUZ experience

Jordan E Lake1, Ruth K Friedman2, Cynthia B Cunha2, Sandra W Cardoso2, Valdilea G Veloso2, Judith S Currier1, Beatriz Grinsztejn21Division of Infectious Diseases, University of California at Los Angeles, Los Angeles, CA, USA; 2Funda&amp;ccedil;&amp;atilde;o Oswaldo Cruz &amp;ndash; Instituto de Pesquisa Cl&amp;iacute;nica Evandro Chagas/IPEC, Rio de Janeiro, State of Rio de Janeiro, BrazilBackground: Fifty percent of people living with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) worldwide are female. In Brazil, for example, 240,000 women are infected with HIV, rates of infection in women have increased over the last two decades, and addressing HIV prevention and treatment for women at risk for, or living with, HIV/AIDS remains a challenge. To better address the needs of women living with HIV in Brazil, the Instituto de Pesquisa Cl&amp;iacute;nica Evandro Chagas &amp;ndash; Funda&amp;ccedil;&amp;atilde;o Oswaldo Cruz (IPEC-FIOCRUZ) HIV Women&amp;rsquo;s Cohort was established in 1996 to study the natural history of women seeking HIV care. This analysis describes the characteristics of women in the cohort who participated in HIV clinical trials between 1999 and 2008.Methods: A total of 736 Women&amp;rsquo;s Cohort participants were in active follow-up and 665 participants from the Women&amp;rsquo;s Cohort were included in univariable and multivariable analyses to determine socioeconomic and sociodemographic factors associated with women&amp;rsquo;s participation in HIV clinical trials at our site.Results: Of the complete cohort, 23% participated in a clinical trial between January 1999 and July 2008. Odds of participation decreased for women who were younger than 35 years old, currently employed, had an HIV-positive sexual partner, and/or who reported a lifetime history of illicit drug use. Alternatively, the odds of participation increased for women who had more than 8 years of formal education, were living independently, and/or were married or cohabitating.Conclusion: The rate of participation in HIV clinical trials by women in the IPEC-Fiocruz Cohort was similar to other published cohorts, but identification of local risk factors and barriers to participation remains important. Our analysis offers a novel description of the factors associated with participation in HIV clinical trials among women in care at IPEC-FIOCRUZ in Rio de Janeiro, Brazil.Keywords: AIDS, Brazil, South America, clinical trial participation&amp;nbsp

Testagem anti-HIV em mulheres grávidas no Brasil: taxas e preditores

OBJETIVO: Estimar las tasas de oferta y realización de la prueba anti-HIV y sus predictivos entre mujeres que recibieron atención prenatal. MÉTODOS: Se realizó un estudio transversal, de base poblacional, con 2.234 puérperas en 12 ciudades de Brasil. Las muestras probabilísticas fueron seleccionadas independientemente por ciudad, entre puérperas que asistieron a por lo menos una visita prenatal. Se colectaron datos sociodemográficos, informaciones sobre cuidado prenatal y acceso a intervenciones de prevención del HIV durante el embarazo, con la utilización de una encuesta. Se realizaron análisis bivariadas y multivariadas para verificar los efectos independientes de las co-variables en la oferta y realización de la prueba anti-HIV. Los datos fueron colectados en el período de noviembre de 1999 a abril de 2000. RESULTADOS: La realización de la prueba anti-HIV durante el embarazo fue realizada por el 77,5% de las encuestadas. La oferta de la prueba fue positivamente asociada con: el conocimiento previo sobre la prevención de la transmisión materno-infantil del HIV; mayor número de visitas prenatal; mayor nivel de escolaridad y presencia de color blanco de piel. La tasa de aceptación de la prueba anti-HIV fue de 92,5%. CONCLUSIONES: Los resultados indican que La diseminación de la información sobre prevención de la transmisión materno-infantil del HIV puede contribuir para aumentar la cobertura de la evaluación anti-HIV durante el embarazo. Las mujeres no-blancas con menores niveles de educación deben ser priorizadas. La estrategias para aumentar la participación de poblaciones vulnerables al cuidado prenatal y la sensibilización de trabajadores de la salud son de gran importancia.OBJETIVO: Estimar as taxas de oferta e realização do teste anti-HIV e seus preditores entre mulheres que receberam atendimento pré-natal. MÉTODOS: Foi conduzido estudo transversal, de base populacional, com 2.234 puérperas em 12 cidades do Brasil. Amostras probabilísticas foram selecionadas independentemente por cidade, entre puérperas que compareceram a pelo menos uma visita pré-natal. Foram coletados dados sociodemográficos, informações sobre cuidado pré-natal e acesso a intervenções de prevenção do HIV durante a gravidez corrente, com a utilização de um questionário. Foram realizadas análises bivariadas e multivariadas para verificar os efeitos independentes das covariáveis na oferta e realização do teste anti-HIV. Os dados foram coletados no período de novembro de 1999 a abril de 2000. RESULTADOS: A realização do teste na gravidez foi relatada por 77,5% das entrevistadas. A oferta do teste anti-HIV foi positivamente associada a: conhecimento prévio sobre a prevenção da transmissão materno-infantil do HIV; maior número de visitas pré-natal; maior nível de escolaridade e ter cor da pele branca. A taxa de aceitação do teste anti-HIV foi de 92,5%. CONCLUSÕES: Os resultados indicam que a disseminação da informação sobre prevenção da transmissão materno-infantil do HIV pode contribuir para aumentar a cobertura da testagem anti-HIV durante a gravidez. Mulheres não-brancas com menores níveis educacionais devem ser priorizadas. Estratégias para aumentar a participação de populações vulneráveis ao cuidado pré-natal e a sensibilização de trabalhadores de saúde são de grande importância.OBJECTIVE: To assess rates of offering and uptake of HIV testing and their predictors among women who attended prenatal care. METHODS: A population-based cross-sectional study was conducted among postpartum women (N=2,234) who attended at least one prenatal care visit in 12 cities. Independent and probabilistic samples were selected in the cities studied. Sociodemographic data, information about prenatal care and access to HIV prevention interventions during the current pregnancy were collected. Bivariate and multivariate analyses were carried out to assess independent effects of the covariates on offering and uptake of HIV testing. Data collection took place between November 1999 and April 2000. RESULTS: Overall, 77.5% of the women reported undergoing HIV testing during the current pregnancy. Offering of HIV testing was positively associated with: previous knowledge about prevention of mother-to-child transmission of HIV; higher number of prenatal care visits; higher level of education and being white. HIV testing acceptance rate was 92.5%. CONCLUSIONS: The study results indicate that dissemination of information about prevention of mother-to-child transmission among women may contribute to increasing HIV testing coverage during pregnancy. Non-white women with lower level of education should be prioritized. Strategies to increase attendance of vulnerable women to prenatal care and to raise awareness among health care workers are of utmost importance

Effectiveness of first-line antiretroviral therapy in the IPEC cohort, Rio de Janeiro, Brazil

Background: While Brazil has had a long-standing policy of free access to antiretroviral therapy (ART) for all in need, the epidemiological impact of ART on human immunodeficiency virus (HIV) RNA suppression in this middle-income country has not been well evaluated. We estimate first-line ART effectiveness in a large Brazilian cohort and examine the socio-demographic, behavioral, clinical and structural factors associated with virologic suppression. Methods: Virologic suppression on first-line ART at 6, 12, and 24 months from start of ART was defined as having a viral load measurement ≤400 copies/mL without drug class modification and/or discontinuation. Drug class modification and/or discontinuation were defined based on the class of a particular drug. Quasi-Poisson regression was used to quantify the association of factors with virologic suppression. Results: From January 2000 through June 2010, 1311 patients started first-line ART; 987 (75%) patients used NNRTI-based regimens. Virologic suppression was achieved by 77%, 76% and 68% of patients at 6, 12 and 24 months, respectively. Factors associated with virologic suppression at 12 months were: >8 years of formal education (compared to <4 years, risk ratio (RR) 1.13, 95% confidence interval (95% CI) 1.03-1.24), starting ART in 2005-2010 (compared to 2000-2004, RR 1.25 95% CI 1.15-1.35), and clinical trial participation (compared to no participation, RR 1.08 95% CI 1.01-1.16). Also at 12 months, women showed less virologic suppression compared to heterosexual men (RR 0.90 95% CI 0.82-0.99). For the 24-month endpoint, in addition to higher education, starting ART in the later period, and clinical trial participation, older age and an NNRTI-based regimen were also independently associated with virologic suppression. Conclusions: Our results show that in Brazil, a middle-income country with free access to treatment, over three-quarters of patients receiving routine care reached virologic suppression on first-line ART by the end of the first year. Higher education, more recent ART initiation and clinical trial participation were associated with improved outcomes both for the 12-month and the 24-month endpoints, suggesting that further studies are needed to understand what aspects relating to these factors lead to higher virologic suppression

What Drives the US and Peruvian HIV Epidemics in Men Who Have Sex with Men (MSM)?

In this work, we estimate the proportions of transmissions occurring in main vs. casual partnerships, and by the sexual role, infection stage, and testing and treatment history of the infected partner, for men who have sex with men (MSM) in the US and Peru. We use dynamic, stochastic models based in exponential random graph models (ERGMs), obtaining inputs from multiple large-scale MSM surveys. Parallel main partnership and casual sexual networks are simulated. Each man is characterized by age, race, circumcision status, sexual role behavior, and propensity for unprotected anal intercourse (UAI); his history is modeled from entry into the adult population, with potential transitions including HIV infection, detection, treatment, AIDS diagnosis, and death. We implemented two model variants differing in assumptions about acute infectiousness, and assessed sensitivity to other key inputs. Our two models suggested that only 4–5% (Model 1) or 22–29% (Model 2) of HIV transmission results from contacts with acute-stage partners; the plurality (80–81% and 49%, respectively) stem from chronic-stage partners and the remainder (14–16% and 27–35%, respectively) from AIDS-stage partners. Similar proportions of infections stem from partners whose infection is undiagnosed (24–31%), diagnosed but untreated (36–46%), and currently being treated (30–36%). Roughly one-third of infections (32–39%) occur within main partnerships. Results by country were qualitatively similar, despite key behavioral differences; one exception was that transmission from the receptive to insertive partner appears more important in Peru (34%) than the US (21%). The broad balance in transmission contexts suggests that education about risk, careful assessment, pre-exposure prophylaxis, more frequent testing, earlier treatment, and risk-reduction, disclosure, and adherence counseling may all contribute substantially to reducing the HIV incidence among MSM in the US and Peru