Differential gene expression of cytokines, receptors, and miRNAs in individuals living with HIV-1 and vaccinated against yellow fever.

Between 2016 and 2018, Brazil faced a yellow fever (YF) outbreak, which led to an expansion of vaccination coverage. The coexistence of the YF outbreak and the HIV-1 epidemic in Brazil raised concerns regarding the immune response and vaccine effectiveness in individuals living with HIV (PLWH). The aim of this study was to investigate the immune response to YF vaccination in PLWH and HIV-uninfected individuals as controls. Transcript levels of immunomodulatory molecules, including IL-6, IL-10, IL-21, TGF-ß, CD19, CD163, miR-21, miR-146, and miR-155, were measured using RTqPCR. TCD4+ cells were evaluated by cytometry, and neutralizing antibody (Nab) titers were detected by a micro plaque-reduction neutralization test. The findings of our study revealed several noteworthy observations. First, there was a notable reduction in the circulation of TCD4+ cells postvaccination. Among people living with HIV (PLWH), we observed an increase in the expression of IL-10 following vaccination, while IL-6 expression was diminished in PLWH with lower TCD4+ counts. Furthermore, we identified the downregulation of CD19 and TGF-ß, along with the upregulation of IL-21 and CD163. Notably, we observed positive correlations between the levels of IL-10/IL-21, IL-10/CD163, and IL-6/CD19. Additionally, there was a positive correlation between miRNAs 146 and 155. It is important to emphasize that all participants exhibited robust neutralizing antibody responses after receiving 17DD YF vaccination. In this context, the gene expression data presented can be useful for biomarker studies of protective antibodies induced by YF vaccination. This study sheds light on immune mechanisms in individuals living with HIV and YF vaccination.

The impact of early anti-SARS-CoV-2 antibody production on the length of hospitalization stay among COVID-19 patients.

IMPORTANCE: The study provides valuable insights into the sociodemographic characteristics, clinical outcomes, and humoral immune response of those affected by the virus that has devastated every field of human life since 2019; the COVID-19 patients. Firstly, the association among clinical manifestations, comorbidities, and the production of neutralizing antibodies (Nabs) against SARS-CoV-2 is explored. Secondly, varying levels of Nabs among patients are revealed, and a significant correlation between the presence of Nabs and a shorter duration of hospitalization is identified, which highlights the potential role of Nabs in predicting clinical outcomes. Lastly, a follow-up conducted 7 months later demonstrates the progression and persistence of Nabs production in recovered unvaccinated individuals. The study contributes essential knowledge regarding the characteristics of the study population, the early humoral immune response, and the dynamics of Nabs production over time. These findings have significant implications for understanding the immune response to COVID-19 and informing clinical management approaches.

Pregnancy incidence, outcomes and associated factors in a cohort of women living with HIV/AIDS in Rio de Janeiro, Brazil, 1996-2016.

The aim of this research was to analyze pregnancy incidence and associated factors in a cohort of 753 women living with HIV/AIDS (WLWHA) in Rio de Janeiro, Brazil, from 1996 to 2016. Women aged 18-49 years who were not on menopause (surgical or natural) and did not have a tubal ligation were eligible for the study. Data were collected by medical professionals during initial and follow-up visits. Person-time pregnancy incidence rates were calculated throughout the follow-up period. Pregnancy incidence-associated factors were investigated by univariate and multiple analyzes, using an extension of the Cox survival model. Follow-up visits recorded 194 pregnancies, with an incidence rate of 4.01/100 person-years (95% CI: 3.47; 4.60). A higher pregnancy incidence was associated with CD4 nadir ≥ 350 cells/mm³, use of an antiretroviral regimen not containing Efavirenz, and prior teenage pregnancy. In turn, women with a viral load ≥ 50 copies/mL, age ≥ 35 years old, with two or more children and using a highly effective contraceptive method showed a lower incidence. Results showed a significant reduction in pregnancy incidence after 2006, a significant reduction in female sterilization from 1996 to 2016, and a high rate of cesarean sections. The association found between pregnancy incidence and the use of contraceptive methods and virological control markers suggests a good integration between HIV/AIDS and reproductive health services. The high rate of cesarean section delivery indicates the need to improve childbirth care.

Pregnancy incidence, outcomes and associated factors in a cohort of women living with HIV/AIDS in Rio de Janeiro, Brazil, 1996-2016 / Incidência, desfechos e fatores associados à gravidez em uma coorte de mulheres vivendo com HIV/aids no Rio de Janeiro, Brasil, 1996-2016 / Incidencia, resultados y factores asociados con el embarazo en una cohorte de mujeres que viven con VIH/SIDA en Río de Janeiro, Brasil, 1996-2016

Abstract The aim of this research was to analyze pregnancy incidence and associated factors in a cohort of 753 women living with HIV/AIDS (WLWHA) in Rio de Janeiro, Brazil, from 1996 to 2016. Women aged 18-49 years who were not on menopause (surgical or natural) and did not have a tubal ligation were eligible for the study. Data were collected by medical professionals during initial and follow-up visits. Person-time pregnancy incidence rates were calculated throughout the follow-up period. Pregnancy incidence-associated factors were investigated by univariate and multiple analyzes, using an extension of the Cox survival model. Follow-up visits recorded 194 pregnancies, with an incidence rate of 4.01/100 person-years (95% CI: 3.47; 4.60). A higher pregnancy incidence was associated with CD4 nadir ≥ 350 cells/mm³, use of an antiretroviral regimen not containing Efavirenz, and prior teenage pregnancy. In turn, women with a viral load ≥ 50 copies/mL, age ≥ 35 years old, with two or more children and using a highly effective contraceptive method showed a lower incidence. Results showed a significant reduction in pregnancy incidence after 2006, a significant reduction in female sterilization from 1996 to 2016, and a high rate of cesarean sections. The association found between pregnancy incidence and the use of contraceptive methods and virological control markers suggests a good integration between HIV/AIDS and reproductive health services. The high rate of cesarean section delivery indicates the need to improve childbirth care.

Resumo O objetivo deste estudo foi analisar a incidência de gravidez e fatores associados em uma coorte de mulheres vivendo com HIV/aids (MVHA) no Rio de Janeiro, Brasil. Foi realizada uma coorte clínica com 753 MVHA entre 1996 e 2016. Mulheres com idade entre 18-49 anos que não estavam na menopausa natural ou cirúrgica e que não tinham laqueadura tubária foram elegíveis para o estudo. Os dados foram coletados durante as consultas iniciais e de acompanhamento por profissionais médicos. As taxas de incidência por pessoa-tempo foram calculadas durante todo o período de acompanhamento. Análises univariadas e múltiplas foram realizadas para investigar fatores associados à incidência de gravidez, utilizando uma extensão do modelo de sobrevida de Cox. Foram registradas 194 gestações durante as consultas de acompanhamento, com uma taxa de incidência de 4,01/100 pessoas-ano (IC95%: 3,47-4,60). Uma maior incidência de gravidez foi associada a nadir CD4 ≥ 350 células/mm³, terapia antirretroviral sem Efavirenz e gravidez anterior na adolescência, enquanto uma menor incidência foi observada em mulheres com carga viral ≥ 50 cópias/mL, idade ≥ 35 anos, com dois ou mais filhos e que usavam um método contraceptivo altamente eficaz. Houve uma redução significativa na incidência de gestações após 2006, uma redução significativa na esterilização feminina entre 1996 e 2016 e uma alta taxa de cesarianas. A associação entre a incidência de gestações e o uso de métodos contraceptivos e marcadores de controle virológico sugere uma boa integração entre HIV/aids e serviços de saúde reprodutiva. A alta taxa de cesarianas indica a necessidade de melhoria na assistência ao parto.

Resumen El objetivo de este estudio fue analizar la incidencia del embarazo y los factores asociados en una cohorte de mujeres que viven con VIH/SIDA (MVHA) en Río de Janeiro, Brasil. Se realizó una cohorte clínica con 753 MVHA entre 1996 y 2016. Las mujeres de 18-49 años que no estaban en la menopausia natural o quirúrgica y que no tenían ligadura de trompas fueron elegibles para el estudio. Los datos se recopilaron durante las consultas iniciales y de seguimiento por parte de profesionales médicos. Las tasas de incidencia por persona-tiempo se calcularon durante todo el período de seguimiento. Se realizaron análisis univariados y múltiples para investigar los factores asociados con la incidencia del embarazo utilizando una extensión del modelo de supervivencia de Cox. Se registraron 194 embarazos durante las consultas de seguimiento, con una tasa de incidencia de 4,01/100 personas-año (IC95%: 3,47-4,60). Una mayor incidencia de embarazo se asoció con nadir CD4 ≥ 350 células/mm3, terapia antirretroviral sin Efavirenz y embarazo previo en la adolescencia, mientras que una menor incidencia se observó en mujeres con carga viral ≥ 50 copias/mL, edad ≥ 35 años, con dos o más hijos y que usaban un método anticonceptivo muy eficaz. Hubo una reducción significativa en la incidencia de embarazos después de 2006, una reducción significativa en la esterilización femenina entre 1996 y 2016 y una alta tasa de cesáreas. La asociación entre la incidencia de embarazos y el uso de métodos anticonceptivos y marcadores de control virológico sugiere una buena integración entre el VIH/SIDA y los servicios de salud reproductiva. La alta tasa de cesáreas indica la necesidad de mejorar la asistencia al parto.

Comparing Web-Based Venues to Recruit Gay, Bisexual, and Other Cisgender Men Who Have Sex With Men to a Large HIV Prevention Service in Brazil: Evaluation Study.

BACKGROUND: Internet and mobile phones, widely available in Brazil, could be used to disseminate information about HIV prevention and to recruit gay, bisexual, and other cisgender men who have sex with men (MSM) to HIV prevention services. Data evaluating the characteristics of MSM recruited through different web-based strategies and estimating their cost and yield in the country are not available. OBJECTIVE: We aimed to describe a web-based recruitment cascade, compare the characteristics of MSM recruited to a large HIV prevention service in Rio de Janeiro according to web-based venues, and estimate the cost per participant for each strategy. METHODS: We promoted advertisements on geosocial networking (GSN) apps (Hornet and Grindr) and social media (Facebook and Instagram) from March 2018 to October 2019. The advertisements invited viewers to contact a peer educator to schedule a visit at the HIV prevention service. Performance of web-based recruitment cascade was based on how many MSM (1) were reached by the advertisement, (2) contacted the peer educator, and (3) attended the service. We used chi-square tests to compare MSM recruited through GSN apps and social media. The estimated advertisement cost to recruit a participant was calculated by dividing total advertisement costs by number of participants who attended the service or initiated preexposure prophylaxis (PrEP). RESULTS: Advertisement reached 1,477,344 individuals; 1270 MSM contacted the peer educator (86 contacts per 100,000 views)-564 (44.4%), 401 (31.6%) and 305 (24.0%)-through social media, Grindr, and Hornet. Among the 1270 individuals who contacted the peer educator, 36.3% (n=461) attended the service with similar proportion for each web-based strategy (social media: 203/564, 36.0%; Grindr: 152/401, 37.9%; and Hornet: 107/305, 35.1%). MSM recruited through GSN apps were older (mean age 30 years vs 26 years; P<.001), more frequently self-reported as White (111/247, 44.9% vs 62/191, 32.5%; P=.03), and had higher schooling level (postsecondary: 157/254, 61.8% vs 94/194, 48.5%; P=.007) than MSM recruited through social media. GSN apps recruited MSM with higher HIV risk as measured by PrEP eligibility (207/239, 86.6% vs 133/185, 71.9%; P<.001) compared with social media, but there was no difference in PrEP uptake between the two strategies (P=.22). The estimated advertisement costs per participant attending the HIV prevention service were US $28.36 for GSN apps and US $12.17 for social media. The estimated advertisement costs per participant engaging on PrEP were US $58.77 for GSN apps and US $27.75 for social media. CONCLUSIONS: Social media and GSN app advertisements were useful to disseminate information on HIV prevention strategies and to recruit MSM to a large HIV prevention service in Brazil. Compared to GSN apps, social media advertisements were less expensive and reached more vulnerable and younger MSM. Digital marketing campaigns should use different and complementary web-based venues to reach a plurality of MSM.

A Technology-Based Intervention Among Young Men Who Have Sex With Men and Nonbinary People (The Conectad@s Project): Protocol for A Vanguard Mixed Methods Study.

BACKGROUND: In many parts of the world, including Brazil, uptake for biomedical interventions has been insufficient to reverse the HIV epidemic among key populations at high risk for HIV, including men who have sex with men. Young MSM (YMSM), particularly Black YMSM, have high HIV incidence, low viral suppression, and low preexposure prophylaxis (PrEP) uptake and adherence. Therefore, novel approaches to increase the HIV biomedical interventions uptake by YMSM are urgently needed. OBJECTIVE: We describe the Conectad@s Project, which aims to: (1) estimate the prevalence and incidence of HIV and other sexually transmitted infections, the onset of sexual risk behavior, and barriers to biomedical interventions among YMSM aged 18 to 24 years in Rio de Janeiro, Brazil; and (2) conduct a technology-based adherence intervention study to promote a rapid linkage of YMSM to HIV care or prevention, and support and sustain adherence. METHODS: A cross-sectional survey will be conducted with 400 YMSM recruited using respondent-driven sampling (RDS) adapted for social media-based sampling, preceded by a formative phase. HIV and sexually transmitted infections testing will be conducted, including early HIV infection biomarker detection. Behavioral, partnership, network, and structural measures will be collected through structured questionnaires. All individuals recruited for the survey will have access to HIV risk assessment, antiretroviral therapy (ART), PrEP, prevention counseling, and a technology-based adherence intervention. Those who accept the adherence intervention will receive weekly text messages via a social networking app (WhatsApp) for 24 weeks, with follow-up data collected over 48 weeks. RESULTS: The Conectad@s project has been approved by our local institutional review board (#CAAE 26086719.0.0000.4262) in accordance with all applicable regulations. Questionnaires for the RDS survey and intervention were developed and tested in 2020, formative interviews were conducted in January and February 2021 to guide the development of the RDS, and enrollment is planned to begin in early 2022. CONCLUSIONS: The Conectad@s Project is a vanguard study that, for the first time, will apply digital RDS to sample and recruit YMSM in Brazil and rapidly connect them to ART, PrEP, or prevention counseling through a technology-based adherence intervention. RDS will allow us to estimate HIV prevalence among YMSM and measure HIV infection biomarkers in the context of the onset of risky behavior. The data will lay the groundwork to adapt and implement HIV prevention strategies, identify barriers to the earliest HIV infection diagnosis, immediate ART or PrEP initiation, and detect new clusters of HIV transmission. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/34885.

Global estimates of viral suppression in children and adolescents and adults on antiretroviral therapy adjusted for missing viral load measurements: a multiregional, retrospective cohort study in 31 countries.

BACKGROUND: As countries move towards the UNAIDS's 95-95-95 targets and with strong evidence that undetectable equals untransmittable, it is increasingly important to assess whether those with HIV who are receiving antiretroviral therapy (ART) achieve viral suppression. We estimated the proportions of children and adolescents and adults with viral suppression at 1, 2, and 3 years after initiating ART. METHODS: In this retrospective cohort study, seven regional cohorts from the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium contributed data from individuals initiating ART between Jan 1, 2010, and Dec 31, 2019, at 148 sites in 31 countries with annual viral load monitoring. Only people with HIV who started ART after the time a site started routine viral load monitoring were included. Data up to March 31, 2020, were analysed. We estimated the proportions of children and adolescents (aged <18 years at ART initiation) and adults (aged ≥18 years at ART initiation) with viral suppression (viral load <1000 copies per mL) at 1, 2, and 3 years after ART initiation using an intention-to-treat approach and an adjusted approach that accounted for missing viral load measurements. FINDINGS: 21 594 children and adolescents (11 812 [55%] female, 9782 [45%] male) from 106 sites in 22 countries and 255 662 adults (163 831 [64%] female, 91 831 [36%] male) from 143 sites in 30 countries were included. Using the intention-to-treat approach, the proportion of children and adolescents with viral suppression was 7303 (36%) of 20 478 at 1 year, 5709 (30%) of 19 135 at 2 years, and 4287 (24%) of 17 589 at 3 years after ART initiation; the proportion of adults with viral suppression was 106 541 (44%) of 240 600 at 1 year, 79 141 (36%) of 220 925 at 2 years, and 57 970 (29%) of 201 124 at 3 years after ART initiation. After adjusting for missing viral load measurements among those who transferred, were lost to follow-up, or who were in follow-up without viral load testing, the proportion of children and adolescents with viral suppression was 12 048 (64% [plausible range 43-81]) of 18 835 at 1 year, 10 796 (62% [41-77]) of 17 553 at 2 years, and 9177 (59% [38-91]) of 15 667 at 3 years after ART initiation; the proportion of adults with viral suppression was 176 964 (79% [53-80]) of 225 418 at 1 year, 145 552 (72% [48-79]) of 201 238 at 2 years, and 115 260 (65% [43-69]) of 178 458 at 3 years after ART initiation. INTERPRETATION: Although adults with HIV are approaching the global target of 95% viral suppression, progress among children and adolescents is much slower. Substantial efforts are still needed to reach the viral suppression target for children and adolescents. FUNDING: US National Institutes of Health.

Prevalence of induced abortion and associated factors in a cohort of women living with HIV/AIDS, Rio de Janeiro, Brazil, 1996-2016. / Prevalência e fatores associados ao aborto induzido no ingresso em uma coorte de mulheres vivendo com HIV/aids, Rio de Janeiro, Brasil, 1996-2016.

The aim of this study was to verify the prevalence of induced abortion and associated factors at the time of inclusion in a cohort of women living with HIV/AIDS in the city of Rio de Janeiro, Brazil, from 1996 to 2016. Eligibility criteria for inclusion in the cohort were female sex at birth, age 18 years and older, and confirmed HIV infection. At the baseline visit, data on sexual, reproductive, and behavioral aspects and HIV infection were obtained through a face-to-face interview with the attending physician. Lifetime prevalence of induced abortion was calculated, and factors associated with induced abortion were verified by multiple logistic regression for all the women and for those with previous pregnancy. In the entire cohort of women, 30.4% reported a history of induced abortion, compared to 33.5% in women with previous pregnancy. Frequency of reported induced abortion showed a significant reduction during the period (41.7% in 1996-2000 versus 22.5% in 2011-2016, p < 0.001). Factors associated with induced abortion, both for the entire cohort and for the women with previous pregnancy, were age, schooling, ≥ 5 lifetime sexual partners, teenage pregnancy, lifetime use of any illicit drug, and inclusion in the cohort after the year 2005. Changes in the socioeconomic, sexual, reproductive, and HIV infection profile are possible explanations for the reduction in abortions during the period. Studies that use direct methods to measure abortion should be conducted in other populations to confirm the downward trend in induced abortion and its determinants in Brazil.

O objetivo deste estudo é verificar a prevalência e os fatores associados ao aborto induzido no ingresso em uma coorte de mulheres vivendo com HIV/aids, no Município do Rio de Janeiro, Brasil, no período 1996-2016. O critério de elegibilidade para o ingresso na coorte era ser do sexo feminino ao nascimento, ter mais de 18 anos de idade e ter infecção comprovada pelo HIV. Na visita inicial, dados sobre aspectos sexuais, reprodutivos, comportamentais e da infecção pelo HIV foram obtidos durante entrevista face a face com o médico assistente. Foi calculada a prevalência de aborto induzido na vida e verificados os fatores associados ao aborto induzido por meio de regressão logística múltipla, para o total de mulheres e entre aquelas com gestação prévia. Do total de mulheres, 30,4% referiram algum aborto induzido na vida, sendo este valor de 33,5% em mulheres com gestação prévia. A frequência de aborto induzido relatado apresentou queda significativa no período analisado (41,7% de 1996-2000 vs. 22,5% de 2011-2016, p < 0,001). Os fatores associados ao aborto induzido, tanto para o total de mulheres quanto para aquelas com gestação prévia, foram o aumento da idade, escolaridade mais elevada, número de parceiros sexuais na vida ≥ 5, gestação na adolescência, uso de qualquer droga ilícita na vida e período de ingresso na coorte após 2005. Mudanças no perfil socioeconômico, sexual, reprodutivo e da infecção pelo HIV são explicações possíveis para a redução da prática do aborto no período. Estudos que utilizem métodos de aferição direta do aborto devem ser conduzidos em outras populações, para confirmar a tendência de queda do aborto induzido no país e seus determinantes.

El objetivo de este estudio es verificar la prevalencia y los factores asociados al aborto inducido en el ingreso en una cohorte de mujeres, que viven con VIH/sida, en el municipio de Rio de Janeiro, durante el período 1996-2016. El criterio de elegibilidad para el ingreso en la cohorte era ser del sexo femenino al nacer, tener más de 18 años de edad y sufrir una infección comprobada por VIH. En la visita inicial, datos sobre aspectos sexuales, reproductivos, comportamentales y de infección por el VIH se obtuvieron durante la entrevista cara a cara con el médico asistente. Se calculó la prevalencia del aborto inducido en la vida y se verificaron los factores asociados al aborto inducido mediante regresión logística múltiple, para el total de mujeres y entre aquellas con gestación previa. Del total de mujeres, un 30,4% refería algún aborto inducido en la vida, siendo ese valor de un 33,5% en mujeres con gestación previa. La frecuencia de aborto inducido relatado presentó una caída significativa durante el período analizado (un 41,7% en el período 1996-2000 vs. 22,5% en el período 2011-2016, p < 0,001). Los factores asociados al aborto inducido, tanto para el total de mujeres, como para aquellas con gestación previa, fueron el aumento de la edad de la mujer, escolaridad más elevada, número de parejas sexuales en la vida ≥ 5, gestación en la adolescencia, consumo de cualquier droga ilícita en la vida y período de ingreso en la cohorte tras 2005. Cambios en el perfil socioeconómico, sexual, reproductivo y de infección por VIH son explicaciones posibles para la reducción de la realización de abortos durante el período. Se deben llevar a cabo estudios que utilicen métodos de medición directa del aborto en otras poblaciones para confirmar la tendencia de caída del aborto inducido en el país y sus determinantes.

Prevalência e fatores associados ao aborto induzido no ingresso em uma coorte de mulheres vivendo com HIV/aids, Rio de Janeiro, Brasil, 1996-2016 / Prevalencia y factores asociados al aborto inducido en el ingreso en una cohorte de mujeres que viven con VIH/SIDA, Río de Janeiro, Brasil, 1996-2016 / Prevalence of induced abortion and associated factors in a cohort of women living with HIV/AIDS, Rio de Janeiro, Brazil, 1996-2016

O objetivo deste estudo é verificar a prevalência e os fatores associados ao aborto induzido no ingresso em uma coorte de mulheres vivendo com HIV/aids, no Município do Rio de Janeiro, Brasil, no período 1996-2016. O critério de elegibilidade para o ingresso na coorte era ser do sexo feminino ao nascimento, ter mais de 18 anos de idade e ter infecção comprovada pelo HIV. Na visita inicial, dados sobre aspectos sexuais, reprodutivos, comportamentais e da infecção pelo HIV foram obtidos durante entrevista face a face com o médico assistente. Foi calculada a prevalência de aborto induzido na vida e verificados os fatores associados ao aborto induzido por meio de regressão logística múltipla, para o total de mulheres e entre aquelas com gestação prévia. Do total de mulheres, 30,4% referiram algum aborto induzido na vida, sendo este valor de 33,5% em mulheres com gestação prévia. A frequência de aborto induzido relatado apresentou queda significativa no período analisado (41,7% de 1996-2000 vs. 22,5% de 2011-2016, p < 0,001). Os fatores associados ao aborto induzido, tanto para o total de mulheres quanto para aquelas com gestação prévia, foram o aumento da idade, escolaridade mais elevada, número de parceiros sexuais na vida ≥ 5, gestação na adolescência, uso de qualquer droga ilícita na vida e período de ingresso na coorte após 2005. Mudanças no perfil socioeconômico, sexual, reprodutivo e da infecção pelo HIV são explicações possíveis para a redução da prática do aborto no período. Estudos que utilizem métodos de aferição direta do aborto devem ser conduzidos em outras populações, para confirmar a tendência de queda do aborto induzido no país e seus determinantes.

El objetivo de este estudio es verificar la prevalencia y los factores asociados al aborto inducido en el ingreso en una cohorte de mujeres, que viven con VIH/sida, en el municipio de Rio de Janeiro, durante el período 1996-2016. El criterio de elegibilidad para el ingreso en la cohorte era ser del sexo femenino al nacer, tener más de 18 años de edad y sufrir una infección comprobada por VIH. En la visita inicial, datos sobre aspectos sexuales, reproductivos, comportamentales y de infección por el VIH se obtuvieron durante la entrevista cara a cara con el médico asistente. Se calculó la prevalencia del aborto inducido en la vida y se verificaron los factores asociados al aborto inducido mediante regresión logística múltiple, para el total de mujeres y entre aquellas con gestación previa. Del total de mujeres, un 30,4% refería algún aborto inducido en la vida, siendo ese valor de un 33,5% en mujeres con gestación previa. La frecuencia de aborto inducido relatado presentó una caída significativa durante el período analizado (un 41,7% en el período 1996-2000 vs. 22,5% en el período 2011-2016, p < 0,001). Los factores asociados al aborto inducido, tanto para el total de mujeres, como para aquellas con gestación previa, fueron el aumento de la edad de la mujer, escolaridad más elevada, número de parejas sexuales en la vida ≥ 5, gestación en la adolescencia, consumo de cualquier droga ilícita en la vida y período de ingreso en la cohorte tras 2005. Cambios en el perfil socioeconómico, sexual, reproductivo y de infección por VIH son explicaciones posibles para la reducción de la realización de abortos durante el período. Se deben llevar a cabo estudios que utilicen métodos de medición directa del aborto en otras poblaciones para confirmar la tendencia de caída del aborto inducido en el país y sus determinantes.

The aim of this study was to verify the prevalence of induced abortion and associated factors at the time of inclusion in a cohort of women living with HIV/AIDS in the city of Rio de Janeiro, Brazil, from 1996 to 2016. Eligibility criteria for inclusion in the cohort were female sex at birth, age 18 years and older, and confirmed HIV infection. At the baseline visit, data on sexual, reproductive, and behavioral aspects and HIV infection were obtained through a face-to-face interview with the attending physician. Lifetime prevalence of induced abortion was calculated, and factors associated with induced abortion were verified by multiple logistic regression for all the women and for those with previous pregnancy. In the entire cohort of women, 30.4% reported a history of induced abortion, compared to 33.5% in women with previous pregnancy. Frequency of reported induced abortion showed a significant reduction during the period (41.7% in 1996-2000 versus 22.5% in 2011-2016, p < 0.001). Factors associated with induced abortion, both for the entire cohort and for the women with previous pregnancy, were age, schooling, ≥ 5 lifetime sexual partners, teenage pregnancy, lifetime use of any illicit drug, and inclusion in the cohort after the year 2005. Changes in the socioeconomic, sexual, reproductive, and HIV infection profile are possible explanations for the reduction in abortions during the period. Studies that use direct methods to measure abortion should be conducted in other populations to confirm the downward trend in induced abortion and its determinants in Brazil.

Pre-exposure prophylaxis 2.0: new drugs and technologies in the pipeline.

Pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate and emtricitabine was adopted by WHO as a strategy to reduce HIV incidence. Although shown to be highly effective in reducing HIV acquisition, the protective efficacy of oral tenofovir disoproxil fumarate and emtricitabine relies on optimal adherence, which poses a challenge for a key portion of the most at-risk populations (women, young individuals [15-24 years], racial and ethnic minority men who have sex with men, and transgender women). New PrEP agents in clinical development include novel oral agents (eg, tenofovir alafenamide and islatravir [also known as MK-8591]), long-acting injectables (eg, cabotegravir), vaginal rings, broadly neutralising monoclonal antibodies, topical products (including gels, films, and enemas), and multipurpose technologies. In addition, new drug delivery systems, such as implants and transdermal devices, are promising strategies that are being developed for HIV prevention. The ultimate goal of this new PrEP research agenda is to expand the available PrEP regimens and offer preventive technologies that will appeal to a wide variety of individuals with different needs over the course of their sexually active lifespan.

Severe infection increases cardiovascular risk among HIV-infected individuals.

BACKGROUND: The identification and management of cardiovascular risk factors became a major clinical issue among HIV-infected individuals in the post-cART era. As in the past decades the link between acute infections and cardiovascular diseases became clear in the general population, we sorted to investigate the role of severe infections on incident cardiovascular diseases (CVDs) among HIV-infected individuals. METHODS: HIV-infected individuals aged ≥18 years, with no history of CVD were followed from January 2000 to December 2013 until the occurrence of the first CVD event, death or end of study, whichever occurred first. To explore the effect of severe infections on the incidence of CVD we used extended Cox regression models and stratified post-hospitalization follow-up time into three periods: < 3 months, 3-12 months and > 12 months post discharge. RESULTS: One hundred-eighty four persons from 3384 HIV-infected individuals developed incident CVD events during the follow-up (incidence rate = 11.10/1000 PY (95%CI: 9.60-12.82)). Risk of an incident CVD was 4-fold higher at < 3 months post-hospitalization for severe infections (adjusted hazard ratio [aHR], 4.52; 95% confidence interval [CI] 2.46-8.30), after adjusting for sociodemographic and clinical factors as well as comorbidities. This risk remained significant up to one year (3-12 months post hospital discharge aHR 2.39, 95% CI 1.30-4.38). Additionally, non-white race/ethnicity (aHR 1.49, 95% CI 1.10-2.02), age ≥ 60 years (aHR 2.01, 95% CI 1.01-3.97) and hypertension (aHR 1.90, 95% CI 1.38-2.60) were associated with an increased risk of CVD events. High CD4 (≥ 500 cells/mm3: aHR 0.41, 95% CI 0.27-0.62) and cART use (aHR 0.21, 95% CI 0.14-0.31) reduced the risk of CVD events. CONCLUSIONS: We provide evidence for a time-dependent association between severe infection and incident cardiovascular disease in HIV-infected individuals. cART use, and high CD4 count were significantly associated with reduced hazards of CVD.

Transcendendo: A Cohort Study of HIV-Infected and Uninfected Transgender Women in Rio de Janeiro, Brazil.

Purpose: Worldwide, the burden of adverse health conditions is substantial among travestis and transgender women (trans women). Transcendendo, the first trans-specific cohort in a low- or middle-income country, is an open cohort established in August 2015 to longitudinally evaluate the health aspects of trans women aged ≥18 years in Rio de Janeiro, Brazil. Methods: Study visits occur on an annual basis. Data on sociodemographics, behavioral, gender transition, affirmation procedures, hormone use, discrimination, violence, clinical and mental health, HIV prevention, and care (for those HIV-infected) are collected. Physical examination, anthropometric measurements, and laboratory tests are performed. Results: As of July 2017, 322 trans women were enrolled in the cohort with a median age of 31.5 years (interquartile range 25.7-39.5), of whom 174 (54%) were HIV-infected. The Transcendendo baseline information reinforces the scenario of marginalization and deprivation surrounding trans women. Most participants had low income (62.0% were living with below US$ 10.00/day), showed a very high engagement in sex work (78.6%), and reported increased occurrence of sexual (46.3%) and physical (54.0%) violence. Pre-exposure peophylaxis (PReP) was used by 18.8% of the HIV-uninfected trans women, only through research participation. Positive screening for depression (57.8%) and problematic use of tobacco (56.6%), cannabis (28.9%), cocaine (23.8%), and alcohol (21.5%) were high. Almost all participants (94.8%) reported hormone use at some point, mostly without medical supervision (78.7%). Conclusion: Our results describe a context of exclusion experienced by trans women, exposing vulnerabilities of this population in a middle-income country, with poor access to trans-specific care, HIV prevention and care, and mental health care. Addressing transgender experiences and needs can help the development of strategies to diminish stigma, improve health care environment, guide future research on trans morbidities, substance use, and trans-specific interventions to support health-related recommendations. Ultimately, it contributes to close the gaps concerning transgender health and reinforces that trans care cannot be disentangled from the social environment that surrounds trans women.

Reduction of inflammation and T cell activation after 6 months of cART initiation during acute, but not in early chronic HIV-1 infection.

OBJECTIVES: To investigate the impact of early combined antiretroviral therapy (cART) on inflammation biomarkers and immune activation during acute and early chronic HIV-1 infection. METHODS: We included 12 acute (AHI), 11 early chronic (EcHI), and 18 late chronic HIV-1-infected (LcHI) individuals who were treated with cART and 18 HIV-1-uninfected (HIV-neg) individuals. Plasmatic levels of inflammation biomarkers, CD8+CD38+HLA-DR+ T cell frequencies, CD4 T cell counts, CD4/CD8 ratio, total HIV-1 DNA and plasmatic viral load were evaluated. Mann-Whitney test, Pearson and Spearman correlation, and linear regression models were used for statistical analyses. RESULTS: IP-10, IL-18, and sCD163 were significantly elevated at pre-ART in the AHI and EcHI groups, showing a significant reduction after 6 months of cART in the AHI group, achieving similar levels to the HIV-neg group. For the EcHI group, the IP-10 and sCD163 levels were also significantly reduced on M6-ART; however, IP-10 levels remained higher than in the HIV-neg group, and no significant reduction of IL-18 levels was observed. The CD8+ T cell activation levels were elevated in the AHI and EcHI groups at pre-ART and showed a significant reduction on M6-ART, but they were similar to levels seen for HIV-neg only after 12 months of cART. At pre-ART, IP-10 levels but not IL-18 levels were positively correlated with HIV-1 viral load in the AHI group. CONCLUSIONS: Early initiation of cART in HIV infection can reduce systemic inflammation, but the earlier normalization of the inflammation markers was only observed when cART was initiated in the acute phase of infection. A slower dynamic of reduction was observed for CD8+ T cell activation.

Adherence to antiretroviral therapy for HIV/AIDS in Latin America and the Caribbean: Systematic review and meta-analysis.

INTRODUCTION: Optimal adherence to antiretroviral therapy is closely related with suppression of the HIV viral load in plasma, slowing disease progression and decreasing HIV transmission rates. Despite its importance, the estimated proportion of people living with HIV in Latin America and the Caribbean with optimal adherence has not yet been reported in a meta-analysis. Moreover, little is known of the factors leading to poor adherence which may be setting-specific. We present a pooled estimate of adherence to antiretroviral therapy (ART) of people living with HIV in Latin America and Caribbean, report the methods used to measure adherence and describe the factors associated with poor adherence among the selected studies. METHODS: We electronically searched published studies up to July 2016 on the PubMed, Web of Science and Virtual Health Library (Latin America and the Caribbean Regional Portal); considering the following databases: MEDLINE, LILACS, PAHO and IBECS. Two independent reviewers selected and extracted data on ART adherence and study characteristics. Pooled estimate of adherence was derived using a random-effects model. Risk of bias in individual studies was assessed independently by two investigators using the Risk of Bias Assessment tool for Non-randomized Studies (RoBANS). RESULTS AND DISCUSSION: The meta-analysis included 53 studies published between 2005 and 2016, which analysed 22,603 people living with HIV in 25 Latin America and Caribbean countries. Overall adherence in Latin America and Caribbean was 70% (95% CI: 63-76; I2  = 98%), similar to levels identified by studies conducted in high-income regions. Self-report was the most frequently used method to measure adherence. Subgroup analysis showed that adherence was higher for the shortest recall time frame used, as well as in countries with lower income level, Gross National Income (GNI) per capita and Human Development Index (HDI). Studies reported diverse adherence barriers, such as alcohol and substance misuse, depression, unemployment and pill burden. CONCLUSIONS: Our study suggests that adherence to ART in Latin America and Caribbean may be below the sufficient levels required for a successful long-term viral load suppression.

Screening for decreased glomerular filtration rate and associated risk factors in a cohort of HIV-infected patients in a middle-income country.

With the introduction of combined active antiretroviral therapy and the improved survival of HIV-infected patients, degenerative diseases and drug toxicity have emerged as long-term concerns. We studied the prevalence of decreased glomerular filtration rate (GFR) and associated risk factors in a cohort of HIV-infected patients from a middle-income country. Our cross-sectional study included all adult patients who attended an urban outpatient clinic in 2008. GFR was estimated using the CKD-EPI equation. The prevalence ratio (PR) of decreased GFR (defined as <60 mL/min/1.73 m(2)) was estimated using generalizing linear models assuming a Poisson distribution. We analyzed data from 1,970 patients, of which 82.9% had been exposed to ART. A total of 249 patients (12.6%) had a GFR between 60 and 89 mL/min/1.73 m(2), 3.1% had a GFR between 30 and 59, 0.3% had a GFR between 15 and 29, and 0.4% had a GFR <15. Decreased GFR was found in only 74 patients (3.8%). In the multivariate regression model, the factors that were independently associated with a GFR below 60 mL/min/1.73 m(2) were as follows: age ≥ 50 years (PR = 3.4; 95% CI: 1.7-6.8), diabetes (PR = 2.0; 95% CI: 1.2-3.4), hypertension (PR = 2.0; 95% CI: 1.3-3.2), current CD4+ cell count <350 cells/mm3 (PR = 2.1; 95% CI: 1.3-3.3), past exposure to tenofovir (PR = 4.7; 95% CI: 2.3-9.4) and past exposure to indinavir (PR =1.7; 95% CI: 1.0-2.8). As in high-income countries, CKD was the predominant form of kidney involvement among HIV-infected individuals in our setting. The risk factors associated with decreased glomerular filtration were broad and included virus-related factors as well as degenerative and nephrotoxic factors. Despite the potential for nephrotoxicity associated with some antiretroviral drugs, in the short-term, advanced chronic renal disease remains very rare.

Avaliação da incidência de doenças oportunistas na coorte de pacientes infectados pelo HIV em acompanhamento no Instituto de Pesquisa Clínica Evandro Chagas – IPEC/Fiocruz / Opportunistic illnesses incidence evaluation in IPEC cohort of HIV infected patients

O advento da terapia antirretroviral de alta potência (ARTc) modificou dramaticamente a história natural de infecção pelo HIV. O aumento da sobrevida e qualidade de vida dos pacientes infectados pelo HIV foi acompanhado por um aumento gradual da ocorrência de doenças não diretamente relacionadas à Aids. No entanto, as doenças oportunistas persistem como uma das principais causas de morte e hospitalização nesta população. A ocorrência de doenças oportunistas na era pós-ARTc está na maior parte das vezes associada ao diagnóstico tardio e à falha virológica em pacientes em uso de cART.Artigo 1: Revisão sistemática sobre a incidência de doenças oportunistas e suas tendências temporais, comparando resultados publicados de países de alta renda e de países de baixa/média renda. Foi realizada busca sistemática de publicações sobre doenças oportunistase infecção pelo HIV nas seguintes bases de dados: Pubmed, Web of Science, Lilacs e Google scholar. 37 publicações foram incluídas, sendo 25 estudos conduzidos em países de alta rendae 12 estudos conduzidos em países de baixa/média renda. Conclusões: Foi observada redução da taxas de incidência de doenças oportunistas tanto em países de alta quanto em países de baixa/média renda. A maior parte dos estudos é oriunda de países de alta renda. Não foram encontrados estudos brasileiros que reportassem taxas anuais de incidência de doençasoportunistas. Artigo 2:Estimar a incidência de doenças oportunistas na coorte de pacientes infectados pelo HIV do IPEC no período de 1987-2012, determinar variáveis associadas aincidência de doenças oportunistas na era pós-ARTc. 3.378 pacientes com idade superior a 18 anos foram incluídos, destes, 1.119 (33 por cento) apresentaram doença oportunista durante o estudo...

The advent of highly active antiretroviral therapy (cART) dramatically changed the natural history of HIV infection . The gain in survival and quality of life of HIVinfectedpatients were accompanied by a gradual increase in incidence of diseases not directly related to AIDS. However, opportunistic illnesses remain the main cause of hospitalizationand death in this population. The occurrence of opportunistic diseases in the post-cART era ismainly associated with late HIV diagnosis and linkage to care and to virological failure incART experimented patients. Article 1: Systematic review of the incidence of opportunisticillnesses and their temporal trends, comparing published results of high-income and low/middle-income settings. We performed a systematic search of publications onopportunistic infections and HIV infection in the following databases: PubMed, Web ofScience, Lilacs and Google scholar. 37 publications were included, 25 studies conducted in high-income settings and 12 studies in low/middle-income settings. Conclusions: Weobserved a reduction in the incidence rates of opportunistic diseases both in high and low/middle-income settings. Most of the studies are from high-income settings. No Brazilianstudies were found that reported on annual incidence rates of opportunistic illnesses. Article2: To estimate the incidence of opportunistic illnesses in the IPEC cohort of HIV-infectedpatients in the period of 1987-2012; to determine variables associated with the incidence of opportunistic illnesses in the post-cART. 3,378 patients aged 18 years or older were included, of whom 1,119 (33 percent) had an opportunistic illness during follow-up...