Evaluating the impact of policies recommending PrEP to subpopulations of men and transgender women who have sex with men based on demographic and behavioral risk factors.

IntroductionDeveloping guidelines to inform the use of antiretroviral pre-exposure prophylaxis (PrEP) for HIV prevention in resource-limited settings must necessarily be informed by considering the resources and infrastructure needed for PrEP delivery. We describe an approach that identifies subpopulations of cisgender men who have sex with men (MSM) and transgender women (TGW) to prioritize for the rollout of PrEP in resource-limited settings.MethodsWe use data from the iPrEx study, a multi-national phase III study of PrEP for HIV prevention in MSM/TGW, to build statistical models that identify subpopulations at high risk of HIV acquisition without PrEP, and with high expected PrEP benefit. We then evaluate empirically the population impact of policies recommending PrEP to these subpopulations, and contrast these with existing policies.ResultsA policy recommending PrEP to a high risk subpopulation of MSM/TGW reporting condomless receptive anal intercourse over the last 3 months (estimated 3.3% 1-year HIV incidence) yields an estimated 1.95% absolute reduction in 1-year HIV incidence at the population level, and 3.83% reduction over 2 years. Importantly, such a policy requires rolling PrEP out to just 59.7% of MSM/TGW in the iPrEx population. We find that this policy is identical to that which prioritizes MSM/TGW with high expected PrEP benefit. It is estimated to achieve nearly the same reduction in HIV incidence as the PrEP guideline put forth by the US Centers for Disease Control, which relies on the measurement of more behavioral risk factors and which would recommend PrEP to a larger subset of the MSM/TGW population (86% vs. 60%).ConclusionsThese findings may be used to focus future mathematical modelling studies of PrEP in resource-limited settings on prioritizing PrEP for high-risk subpopulations of MSM/TGW. The statistical approach we took could be employed to develop PrEP policies for other at-risk populations and resource-limited settings

Los ensayos clínicos y su situación actual en Perú: Oportunidades para la acción

GEsTión es un grupo de sitios de investigación en la ciudad de Lima, que están dedicados exclusivamente a implementar ensayos clínicos auspiciados por la Industria Farmacéutica Internacional (IFI). Nos hemos asociado para divulgar, explorar y desarrollar procesos operativos consistentes en el marco de la investigación clínica y nuevas formas de reclutamiento de pacientes. Es nuestra intención difundir estos avances a la comunidad de investigadores y a todos aquellos que están involucrados de una u otro forma en procesos de investigación. Esta contribución tomará la forma de artículos publicados en medios sociales, publicaciones impresas, reuniones públicas de trabajo, eventos públicos, congresos, talleres y otros por definir.&nbsp

Syphilis Predicts HIV Incidence Among Men and Transgender Women Who Have Sex With Men in a Preexposure Prophylaxis Trial

Background. Syphilis infection may potentiate transmission of human immunodeficiency virus (HIV). We sought to determine the extent to which HIV acquisition was associated with syphilis infection within an HIV preexposure prophylaxis (PrEP) trial and whether emtricitabine/tenofovir (FTC/TDF) modified that association. Methods. The Preexposure Prophylaxis Initiative (iPrEx) study randomly assigned 2499 HIV-seronegative men and transgender women who have sex with men (MSM) to receive oral daily FTC/TDF or placebo. Syphilis prevalence at screening and incidence during follow-up were measured. Hazard ratios for the effect of incident syphilis on HIV acquisition were calculated. The effect of FTC/TDF on incident syphilis and HIV acquisition was assessed. Results. Of 2499 individuals, 360 (14.4%) had a positive rapid plasma reagin test at screening; 333 (92.5%) had a positive confirmatory test, which did not differ between the arms (FTC/TDF vs placebo, P = .81). The overall syphilis incidence during the trial was 7.3 cases per 100 person-years. There was no difference in syphilis incidence between the study arms (7.8 cases per 100 person-years for FTC/TDF vs 6.8 cases per 100 person-years for placebo, P = .304). HIV incidence varied by incident syphilis (2.8 cases per 100 person-years for no syphilis vs 8.0 cases per 100 person-years for incident syphilis), reflecting a hazard ratio of 2.6 (95% confidence interval, 1.6–4.4; P < .001). There was no evidence for interaction between randomization to the FTC/TDF arm and incident syphilis on HIV incidence. Conclusions. In HIV-seronegative MSM, syphilis infection was associated with HIV acquisition in this PrEP trial; a syphilis diagnosis should prompt providers to offer PrEP unless otherwise contraindicated

Quality of Life Among Individuals with HIV Starting Antiretroviral Therapy in Diverse Resource-Limited Areas of the World

As Antiretroviral Therapy (ART) is scaled up in low- and middle-income countries, it is important to understand Quality of Life (QOL) correlates including disease severity and person characteristics and to determine the extent of between-country differences among those with HIV. QOL and medical data were collected from 1,563 of the 1,571 participants at entry into a randomized clinical trial of ART conducted in the U.S. (n = 203) and 8 resource-limited countries (n = 1,360) in the Caribbean, South America, Asia, and Africa. Participants were interviewed prior to initiation of ART using a modified version of the ACTG SF-21, a health-related QOL measure including 8 subscales: general health perception, physical functioning, role functioning, social functioning, cognitive functioning, pain, mental health, and energy/fatigue. Other measures included demographics, CD4+ lymphocyte count, plasma HIV-1 RNA viral load. Higher quality of life in each of the 8 QOL subscales was associated with higher CD4+ lymphocyte category. General health perception, physical functioning, role functioning, and energy/fatigue varied by plasma HIV-1 RNA viral load categories. Each QOL subscale included significant variation by country. Only the social functioning subscale varied by sex, with men having greater impairments than women, and only the physical functioning subscale varied by age category. This was the first large-scale international ART trial to conduct a standardized assessment of QOL in diverse international settings, thus demonstrating that implementation of the behavioral assessment was feasible. QOL indicators at study entry varied with disease severity, demographics, and country. The relationship of these measures to treatment outcomes can and should be examined in clinical trials of ART in resource-limited settings using similar methodologies

Same-day initiation of oral pre-exposure prophylaxis among gay, bisexual, and other cisgender men who have sex with men and transgender women in Brazil, Mexico, and Peru (ImPrEP): a prospective, single-arm, open-label, multicentre implementation study.

BACKGROUND: Although gay, bisexual, and other cisgender men who have sex with men (MSM) and transgender women have the highest HIV burden in Latin America, pre-exposure prophylaxis (PrEP) implementation is poor. We aimed to assess the feasibility of same-day oral PrEP delivery in Brazil, Mexico, and Peru. METHODS: Implementation PrEP (ImPrEP) was a prospective, single-arm, open-label, multicentre PrEP implementation study conducted in Brazil (14 sites), Mexico (four sites), and Peru (ten sites). MSM and transgender women were eligible to participate if they were aged 18 years or older, HIV-negative, and reported one or more prespecified criteria. Enrolled participants received same-day initiation of daily oral PrEP (tenofovir disoproxil fumarate [300 mg] coformulated with emtricitabine [200 mg]). Follow-up visits were scheduled at week 4 and quarterly thereafter. We used logistic regression models to identify factors associated with early loss to follow-up (not returning after enrolment), PrEP adherence (medication possession ratio ≥0·6), and long-term PrEP engagement (attending three or more visits within 52 weeks). This study is registered at the Brazilian Registry of Clinical Trials, U1111-1217-6021. FINDINGS: From Feb 6, 2018, to June 30, 2021, 9979 participants were screened and 9509 were enrolled (Brazil n=3928, Mexico n=3288, and Peru n=2293). 543 (5·7%) participants were transgender women, 8966 (94·3%) were cisgender men, and 2481 (26·1%) were aged 18-24 years. There were 12 185·25 person-years of follow-up. 795 (8·4%) of 9509 participants had early loss to follow-up, 6477 (68·1%) of 9509 were adherent to PrEP, and 5783 (70·3%) of 8225 had long-term PrEP engagement. Transgender women (adjusted odds ratio 1·60, 95% CI 1·20-2·14), participants aged 18-24 years (1·80, 1·49-2·18), and participants with primary education (2·18, 1·29-3·68) had increased odds of early loss to follow-up. Transgender women (0·56, 0·46-0·70), participants aged 18-24 years (0·52, 0·46-0·58), and those with primary education (0·60, 0·40-0·91) had lower odds of PrEP adherence. Transgender women (0·56, 0·45-0·71), participants aged 18-24 years (0·56, 0·49-0·64), and those with secondary education (0·74, 0·68-0·86) had lower odds of long-term PrEP engagement. HIV incidence was 0·85 per 100 person-years (95% CI 0·70-1·03) and was higher for transgender women, participants from Peru, those aged 18-24 years, Black and mixed-race participants, and participants who were non-adherent to PrEP. INTERPRETATION: Same-day oral PrEP is feasible for MSM and transgender women in Latin America. Social and structural determinants of HIV vulnerability need to be addressed to fully achieve the benefits of PrEP. FUNDING: Unitaid, WHO, and Ministries of Health in Brazil, Mexico, and Peru. TRANSLATIONS: For the Portuguese and Spanish translations of the abstract see Supplementary Materials section

Factores determinantes de la respuesta insulínica en sujetos con pruebas normales de tolerancia oral a la glucosa

Insulin resistance (IR) has been associated to the plurimetabolic syndrome, a know risk factor for coronary heart disease. Fasting plasma insulin and the 120 minutes insulin response to an oral glucose tolerance test (OGTT), are both widely used in clinical practice and indirectly estimate IR. The aim of this study is to determine insulin levels in our population, both fasting and at 2 hours after 75 g oral glucose load, and the factors conditioning them. 92 normotensives subjects (65 females), aged 42.1 ± 13.9 years, with a mean body mass index (BMI) of 31.8 ± 7.6 kg/m² and whit normal OGTT (WHO 1997) were studied. Median of serum fasting  insulin and the values of the upper (UQ) and lower quartiles (LQ) were; 11.85 uU/ml (26.3-93.3). Grouping subjects by the BMI, as normal, overweight and o base (WHO 1997), the median of the basal insulin and the UQ and LQ values were 6.6 (5.6-8.7), 11.5 (7.4-34.5) and 16.3 (9.4-27.4), respectively (p<0.00001) and after 120 minutes post glucose oral load were: 31.5 (19.2-34.4), 76.5 (30.1-76.8) and 96.9 (35.8-138) (p<0.00001). there was no difference in basal or 120 minutes insulin, nor by sex, neither by diabetic antecedent  in relatives. Basal insulin correlated significantly with weight (r=0.52), BMI (r=0.57), waist circumference (WC) and triglycerides (r=0.469). multiple regression analysis disclosed BMI as the only variable related to basal insulin (p<0.0212). Insulin after 120 minutes glucose loas correlated significantly with basal insulin (r=0.339) and triglycerides (r=0.36). Multiple regression analysis and showed basal independently related to it (p<0.00001).La resistencia a la insulina (RI) es una alteración que ha sido relacionada al sindrome plurimetabólico y conlleva mayor riesgo de enfermedad coronaria. La respuesta de insulina durante el test de tolerancia oral a la glucosa (TTOG), puede indirectamente valorar la RI en un paciente. Con el objeto de determinar en nuestro medio los valores de insulina sérica basal y a los 120 minutos después del TTOG con 75 gramos y los factores condicionantes de esta respuesta, se han estudiado 92 sujetos (65 mujeres) normotensos, con un TTGO normal (OMS 1997) de 42.1 ± 13.9 años de edad, con índici de masa corporal (IMC) de 31.8 ± 7.6 kg/m². La mediana de la insulina basal y los valores del cuartil inferior (CI) y superior (CS) fueron 11.8 uUI/ml (6.92-18.51)y a los 120 minutos 41.7 (26.3-93.3). Al agrupar a los sujetos de acuerdo al IMC (OMS 1997), en normales, con sobrepeso y obesos, las medianas de insulina basal y los valores del CS y CI fueron: 6.6 (5,6-8.7), 11.5(7.4-13.5) y 16.3 (9.4-27.4), respectivamente (p<0.00001) y a los 120 minutos: 31.5 (19.2-34.4), 76.5(30.1-76.8) y 96.9 (35.8-138) (p<0.00001). No hubo diferencia en la respuesta entre sexos ni con el antecendente damiliar de diabetes. La insulina basal correlacionó significativamente con el peso (r=0.52),IMC(r=0.57), perímetro de la cintura (r=0.48) y triglicéridos (r=0.469). En el análisis de regresión múltiple, el IMC fue la única variable adociada independientemente a la insulina basal (p<0.0212). La insulina a los 120 minutos correlacionó en forma significativa con el valor de insulina basal (r=0.77), el índice de HOMA (r=0.75), el IMC(r=0.44),el perímetro de la cintura (r=0.339) y los triglicéridos (r=0.36). En el análisis de regresión múltiple la única variable asociada independientemente fue la insulina basal (p<0.00001)

Towards a fair consideration of PrEP as part of combination HIV prevention in Latin America

Submitted by Fábio Marques ([email protected]) on 2018-09-20T18:59:40Z No. of bitstreams: 1 Towards a fair consideration of PrEP as part of combination HIV prevention_Beatriz_Grinsztejn_etal_INI_Lapclin-AIDS_2016.pdf: 231546 bytes, checksum: a85fa3b286d4b42f0f852a5759955d26 (MD5)Approved for entry into archive by Regina Costa ([email protected]) on 2018-09-27T18:38:51Z (GMT) No. of bitstreams: 1 Towards a fair consideration of PrEP as part of combination HIV prevention_Beatriz_Grinsztejn_etal_INI_Lapclin-AIDS_2016.pdf: 231546 bytes, checksum: a85fa3b286d4b42f0f852a5759955d26 (MD5)Made available in DSpace on 2018-09-27T18:38:51Z (GMT). No. of bitstreams: 1 Towards a fair consideration of PrEP as part of combination HIV prevention_Beatriz_Grinsztejn_etal_INI_Lapclin-AIDS_2016.pdf: 231546 bytes, checksum: a85fa3b286d4b42f0f852a5759955d26 (MD5) Previous issue date: 2016Pan American Health Organization (PAHO), Washington, DC, USA.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, Brasil.Instituto Nacional de Salud Pública. Cuernavaca, México.Investigaciones Medicas en Salud. Lima, Peru.Ministerio de Salud y Protección Social. Bogotá, Colombia.Centro de Investigación Interdisciplinaria en Sexualidad, SIDA y Sociedad, Universidad Peruana Cayetano Heredia. Lima, Peru.Pan American Health Organization (PAHO). Washington, DC, USA.Despite progress in scaling up antiretroviral treatment, HIV prevention strategies have not been successful in significantly curbing HIV incidence in Latin America. HIV prevention interventions need to be expanded to target the most affected key populations with a combination approach, including new high impact technologies. Oral pre-exposure prophylaxis (PrEP) is recommended as additional prevention choice for individuals at higher risk of infection and could become a cost-effective prevention tool. We discuss the barriers and solutions for a fair consideration of PrEP as part of combination HIV prevention strategies in Latin America