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; 2Fundação Oswaldo Cruz – Instituto de Pesquisa Clínica 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 Clínica Evandro Chagas – Fundação Oswaldo Cruz (IPEC-FIOCRUZ) HIV Women’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’s Cohort participants were in active follow-up and 665 participants from the Women’s Cohort were included in univariable and multivariable analyses to determine socioeconomic and sociodemographic factors associated with women’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&nbsp

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

Incidência e preditores de gestação em mulheres com HIV/Aids no Rio de Janeiro

OBJETIVO: Identificar incidencia y predictores de la primera gestación entre mujeres con VIH/Sida. MÉTODOS: Estudio prospectivo de cohorte conducido en Rio de Janeiro, Sureste de Brasil, entre 1996 y 2003. El estudio incluyó 225 mujeres acompañadas hasta la primera gestación o hasta el primer evento considerado censura (histerectomía, ligadura tubárica, menopausia, 50 años de edad, pérdida de acompañamiento, óbito o final de diciembre de 2003). Se estimaron las tasas de incidencia de gestación y de aborto, y se usaron modelos de riesgos proporcionales de Cox para identificar las características de la visita de inclusión asociadas con el riesgo de gestación. RESULTADOS: Las mujeres fueron acompañadas por 565 persona/años, con promedio de acompañamiento de 3 años por mujer. La edad promedio fue de 32 años (DP:7), y 54,7% eran blancas. Sesenta gestaciones fueron observadas en 39 mujeres y 18 resultaron en abortos inducidos (tasas de incidencia de 6,9% y 2,1% mujeres/año, respectivamente). Las gestaciones repetidas ocurrieron en 33,3% de las mujeres (13/39). Fue observado el mayor riesgo de gestación entre mujeres jóvenes (HR=3,42; IC 95%:1,69;6,95) y entre aquellas que vivían con sus parejas (HR=1,89; IC 95%: 1,00;3,57). El menor riesgo de gestación estuvo asociado a la mayor escolaridad (HR=0,43; IC95%:0,19;0,99) y al uso de terapia antirretroviral (HR=0,61; IC95%:0,31;1,17). CONCLUSIONES: La incidencia de gestación en la cohorte fue menor al compararse con aquella observada en la población general. Características sociodemográficas deben ser consideradas en el manejo de los deseos reproductivos de mujeres VIH-positivas en edad reproductiva. Los programas de VIH/SIDA deben incluir consejos reproductivos y contraceptivos para prevenir la transmisión del VIH para sus parejas y prole.OBJETIVO: Identificar incidência e preditores incidência da primeira gestação entre mulheres com HIV/Aids. MÉTODOS: Estudo prospectivo de coorte conduzido entre 1996 e 2003 no Rio de Janeiro, RJ, com 225 mulheres acompanhadas até a primeira gestação ou até o primeiro evento considerado censura (histerectomia, ligadura tubárea, menopausa, 50 anos de idade, perda de acompanhamento, óbito ou final de dezembro de 2003). Taxas de incidência de gestação e de aborto foram estimadas e modelos de riscos proporcionais de Cox foram usados para identificar as características da visita de inclusão associadas com o risco de gestação. RESULTADOS: As mulheres foram acompanhadas por 565 pessoas/ano, com média de acompanhamento de 3 anos por mulher. A idade média foi de 32 anos (DP: 7) e 54,7% eram brancas. Sessenta gestações foram observadas em 39 mulheres e 18 resultaram em abortos induzidos (taxas de incidência de 6,9% e 2,1% mulheres/ano, respectivamente). Gestações repetidas ocorreram em 33,3% das mulheres (13/39). Maior risco de gestação foi observado entre mulheres jovens (HR = 3,42; IC95%:1,69;6,95) e entre aquelas vivendo com seus parceiros (HR = 1,89; IC95%:1,00;3,57). Menor risco de gestação esteve associado à maior escolaridade (HR = 0,43; IC95%:0,19;0,99) e ao uso de terapia anti-retroviral (HR = 0,61; IC95%:0,31;1,17). CONCLUSÕES: A incidência de gestação na coorte foi menor se comparada àquela observada na população geral. Características sociodemográficas devem ser consideradas no manejo dos desejos reprodutivos de mulheres HIV-positivas em idade reprodutiva. Os programas de HIV/Aids devem incluir aconselhamento reprodutivo e contraceptivo para prevenir a transmissão do HIV para seus parceiros e prole.OBJECTIVE: To assess incidence and predictors of first pregnancy among women with HIV/AIDS. METHODS: Prospective cohort study was conducted in Rio de Janeiro, southeastern Brazil, between 1996 and 2003. This study comprised 225 women with HIV/AIDS followed up until their first pregnancy or first censored event (hysterectomy, tubal ligation, menopause, 50 years of age, loss to follow-up, death or the end of December 2003). Pregnancy and abortion rates were estimated, and Cox proportional hazards models were used to identify baseline characteristics associated with pregnancy risk. RESULTS: The women were followed up for 565 person/years with a median follow-up of 3 years per women. The mean age was 32 years (SD: 7), and 54.7% were white. There were 60 pregnancies in 39 women, and 18 were terminated (induced abortions), accounting for a rate of 6.9% and 2.1% women/year, respectively. Repeated pregnancies occurred in 33.3% of the women (13/39). Higher pregnancy risk was seen among younger women (HR=3.42; 95%CI: 1.69;6.95) and those living with their partners (HR=1.89; 95%CI: 1.00;3.57). Lower pregnancy risk was associated with higher education level (HR=0.43; 95%CI: 0.19;0.99) and use of antiretroviral therapy (HR=061; 95%CI: 0.31;1.17). CONCLUSIONS: Lower pregnancy rates were found in our cohort than in the general population. Sociodemographic characteristics should be taken into consideration in the management of reproductive health in HIV-positive childbearing age women. Reproductive and family planning counseling must be incorporated into HIV/AIDS programs for women to help preventing HIV transmission to their partners and offspring

Brazilian network for HIV Drug Resistance Surveillance (HIV-BresNet): a survey of treatment-naive individuals

Introduction: In Brazil, more than 487,450 individuals are currently undergoing antiretroviral treatment. In order to monitor the transmission of drug-resistant strains and HIV subtype distribution in the country, this work aimed to estimate its prevalence and to characterize the nationwide pretreatment drug resistance in individuals recently diagnosed with HIV between 2013 and 2015. Methods: The HIV threshold survey methodology (HIV-THS, WHO) targeting antiretroviral-naive individuals with recent HIV diagnosis was utilized, and subjects were selected from 51 highly populated cities in all five Brazilian macroregions. The HIV pol genotypic test was performed by genomic sequencing. Results: We analysed samples from 1568 antiretroviral-naive individuals recently diagnosed with HIV, and the overall transmitted drug resistance (TDR) prevalence was 9.5% (150 sequences). The regional prevalence of resistance according to Brazilian geographical regions was 9.4% in the northeast, 11.2% in the southeast, 6.8% in the central region, 10.2% in the north and 8.8% in the south. The inhibitor-specific TDR prevalence was 3.6% for nucleoside reverse transcriptase inhibitors (NRTIs), 5.8% for non-nucleoside reverse transcriptase inhibitors (NNRTIs) and 1.6% for protease inhibitors (PIs)1.0% of individuals presented resistance to more than one class of inhibitors. Overall, subtype B was more prevalent in every region except for the southern, where subtype C prevails. Conclusions: To the best of our knowledge, this is the first TDR study conducted in Brazil with nationwide representative sampling. The TDR prevalence revealed a moderate rate in the five Brazilian geographical regions, although some cities presented higher TDR prevalence rates, reaching 14% in Sao Paulo, for example. These results further illustrate the importance of surveillance studies for designing future strategies in primary antiretroviral therapy, aiming to mitigate TDR, as well as for predicting future trends in other regions of the globe where mass antiretroviral (ARV) treatment was implemented.Brazilian Ministry of HealthUniv Fed Rio de Janeiro, Lab Virol Mol, Dept Genet IB, Rio De Janeiro, RJ, BrazilFdn Med Trop Amazonas, Manaus, Amazonas, BrazilLAPI Univ Fed Bahia, Hosp Univ Prof Edgar Santos, Lab Pesquisa, Salvador, BA, BrazilLab Cent Saude Publ Ceara Lacen CE, Fortaleza, Ceara, BrazilLab Cent Saude Publ Dist Fed, Setor Grandes Areas Norte SGAN 601, Brasilia, DF, BrazilUniv Fed Minas Gerais UFMG, Fac Med, Lab Imunol & Biol Mol DIP, Belo Horizonte, MG, BrazilLab Cent Saude Publ Mato Grosso Sul, Campo Grande, MS, BrazilLab Cent Saude Publ Pernambuco, Recife, PE, BrazilLab Municipal Curitiba, Curitiba, PR, BrazilFiocruz MS, Lab AIDS & Imunol Mol, Dept Imunol, Rio De Janeiro, RJ, BrazilUniv Fed Rio de Janeiro, Hosp Univ Clementino Fraga Filho, Lab Carga Viral, Rio de Janeiro, RJ, BrazilInst Biol Exercito, Rio De Janeiro, RJ, BrazilLab Cent Saude Publ Rio Grande Sul, Porto Alegre, RS, BrazilLab Hosp Nossa Senhora Conceicao, Porto Alegre, RS, BrazilLab Cent Saude Publ Santa Catarina, Florianopolis, SC, BrazilUNESP, Lab Biol Mol Hemocentro Botucatu, Fac Med, Botucatu, SP, BrazilUniv Estadual Campinas, Lab Pesquisa AIDS, Hosp Clin, Campinas, SP, BrazilInst Adolfo Lutz Sao Jose do Rio Preto, Lab Biol Mol, Sao Jose Do Rio Preto, SP, BrazilUniv Fed Sao Paulo UNIFESP, Escola Paulista Med, Lab Retrovirol, Sao Paulo, SP, BrazilInst Adolfo Lutz Cent, Lab Retrovirus, Ctr Virol, Nucleo Doencas Sanguineas & Sexuais, Sao Paulo, SP, BrazilMinist Saude, Dept Vigilancia Prevencao & Controle DST AIDS & H, Setor Adm Fed Sul SAFS 02, Secretaria Vigilancia Saude, Brasilia, DF, BrazilUniv Brasilia, Programa Pos Grad Saude Colet, Fac Med, Fac Ciencias Saude, Brasilia, DF, BrazilUniv Sao Paulo, Fac Med, Sao Paulo, SP, BrazilUniv Fed Sao Paulo UNIFESP, Escola Paulista Med, Lab Retrovirol, Sao Paulo, SP, BrazilBMH: TC 298/12Web of Scienc