Ruth Khalili Friedman

Early mortality and cause of deaths in patients using HAART in Brazil and the United States.

Objective:To compare the early mortality pattern and causes of death among patients starting HAART in Brazil and the United States. Methods:We analyzed the combined data from two clinical cohorts followed at the Johns Hopkins AIDS Service in Baltimore, United States, and the Evandro Chagas Clinical Research Institute AIDS Clinic in Rio de Janeiro, Brazil. Participants included those who entered either cohort between 1999 and 2007 and were antiretroviral naive. Follow-up was at 1 year since HAART initiation. Cox proportional hazards regression analysis was used to assess the role of the city on the risk of death. Results:A total of 859 and 915 participants from Baltimore and Rio de Janeiro, respectively, were included. In Rio de Janeiro, 64.7% of deaths occurred within 90 days of HAART initiation; in Baltimore, 48.9% occurred between 180 and 365 days. AIDS-defining illness (61.8%) and non-AIDS-defining illness (55.6%) predominated as causes of death in Rio de Janeiro and Baltimore, respectively. Risk of death was similar in both cities (hazard ratio 1.04; P value = 0.95) after adjusting for CD4+ T cell count, age, sex, HIV risk group, prior AIDS-defining illness, and Pneumocystis jirovecii pneumonia and Mycobacterium avium prophylaxis. Individuals with CD4+ T cell count less than or equal to 50 cells/μl (hazard ratio 4.36; P = 0.001) or older (hazard ratio, 1.03; P = 0.03) were more likely to die. Conclusion:Although late HIV diagnosis is a problem both in developed and developing countries, differences in the timing and causes of deaths clearly indicate that, besides interventions for early HIV diagnosis, different strategies to curb early mortality need to be tailored in each country.

Factors associated with increased prevalence of human papillomavirus infection in a cohort of HIV-infected Brazilian women

OBJECTIVES Human papillomavirus (HPV) infection is a major risk factor for cervical disease. Using baseline data from the HIV-infected cohort of Evandro Chagas Clinical Research Institute at Fiocruz, Rio de Janeiro, Brazil, factors associated with an increased prevalence of HPV were assessed. METHODS Samples from 634 HIV-infected women were tested for the presence of HPV infection using hybrid capture II and polymerase chain reaction. Prevalence ratios (PR) were estimated using Poisson regression analysis with robust variance. RESULTS The overall prevalence of HPV infection was 48%, of which 94% were infected with a high-risk HPV. In multivariate analysis, factors independently associated with infection with high-risk HPV type were: younger age (<30 years of age; PR 1.5, 95% confidence interval (CI) 1.1-2.1), current or prior drug use (PR 1.3, 95% CI 1.0-1.6), self-reported history of HPV infection (PR 1.2, 95% CI 0.96-1.6), condom use in the last sexual intercourse (PR 1.3, 95% CI 1.1-1.7), and nadir CD4+ T-cell count <100cells/mm(3) (PR 1.6, 95% CI 1.2-2.1). CONCLUSIONS The estimated prevalence of high-risk HPV-infection among HIV-infected women from Rio de Janeiro, Brazil, was high. Close monitoring of HPV-related effects is warranted in all HIV-infected women, in particular those of younger age and advanced immunosuppression.

Systematic review of the effectiveness and safety of assisted reproduction techniques in couples serodiscordant for human immunodeficiency virus where the man is positive

OBJECTIVE To evaluate the effectiveness and safety of assisted reproduction techniques (ART) in human immunodeficiency virus (HIV) serodiscordant couples. DESIGN Systematic review of five databases of noncomparative open intervention and observational studies of serodiscordant couples undergoing ART, with study selection and data extraction performed independently and in duplicate. SETTING Tertiary fertility centers. PATIENT(S) HIV serodiscordant couples where the man is HIV positive. INTERVENTION(S) Intrauterine insemination (IUI), in vitro fertilization (IVF), or intracytoplasmic injection (ICSI) performed after washed semen viral testing. MAIN OUTCOME MEASURE(S) Pregnancy rates per cycle, cumulative pregnancy, abortion rate, and HIV seroconversion in newborns or women. RESULT(S) Of the 658 abstracts retrieved, 41 were selected for review, and 17 full articles were included (3,900 IUI cycles in 1,184 couples in 11 aggregated studies and 738 ICSI/IVF cycles in 579 couples across 10 studies). The IUI and ICSI results were, respectively: pregnancy rates per cycle, 18% and 38.1%; cumulative pregnancy, 50% and 52.9%; and abortion rate, 15.6% and 20.6%. No seroconversions in women or newborns were detectable at birth or after 3 to 6 months. CONCLUSION(S) Cumulative evidence suggests that ART is safe and effective for avoiding horizontal and vertical transmission in HIV serodiscordant couples.

Assessing sexually transmitted infections in a cohort of women living with HIV/AIDS, in Rio de Janeiro, Brazil

A cohort of 458 HIV-positive women under antiretroviral therapy has been followed at a reference hospital in Rio de Janeiro, Brazil. Most of them belong to impoverished social strata. Patients were screened for sexually transmitted infections (STIs) and gynaecologic conditions. Some STIs were found to be uncommon (e.g. chlamydial and gonococcal infections), while some conditions (bacterial vaginosis) and STIs, e.g. hepatitis B and human papilloma virus (HPV) infection, were found to be quite prevalent. The latter is of special concern, due to the high prevalence of HIV/HPV co-infection (∼51%) and its association with severe immunodeficiency, in a context of unacceptable high levels of uterine cancer and uneven gynaecological care. HIV-positive women are in need of comprehensive health services, including high-quality, regular, gynaecologic care in order to diagnose and treat lower genital tract infections and prevent the evolution of HPV-related lesions. Reproductive counselling should be a part of this approach.

Incidence of Modifying or Discontinuing First HAART Regimen and Its Determinants in a Cohort of HIV-Infected Patients from Rio de Janeiro, Brazil

Studies on the long-term safety and tolerability of HAART are scarce in developing countries. HAART has been universally available in Brazil since 1997, providing a unique opportunity to evaluate the incidence and risk factors for HAART discontinuation or modification. We analyzed retrospective data from 670 treatment-naive patients followed at the HIV cohort of Evandro Chagas Clinical Research Institute, Oswaldo Cruz Foundation, in Rio de Janeiro, Brazil, who first received HAART between January 1996 and December 2006. Our four outcomes of interest were treatment failure (TF-MOD), short-term toxicity (ST-MOD), long-term toxicity (LT-MOD), and overall modification/discontinuation (MOD, composed of TF-MOD, ST-MOD, LT-MOD, and other reasons). Risk factors were assessed using Coxs proportional hazards regression. Incidences of MOD, ST-MOD, LT-MOD, and TF-MOD were 28.3, 24.0, 4.0, and 5.6 per 100 persons-years, respectively. MOD was observed in 69% of the patients; 40% of the MODs were toxicity related. The risk of MOD in the first year of treatment was 32% (95% CI: 28.3-35.5%); the median time from HAART initiation to MOD was 14 months (IQR: 3.0-29.5). The most frequent reasons for ST-MOD were gastrointestinal; women had a higher hazard for ST-MOD. Metabolic toxicity was the most frequent reason for LT- MOD, particularly dislipidemia and lipodystrophy. Increased hazard of TF-MOD was observed among those with lower CD4(+) lymphocyte counts (<200 cells/mm(3)). Our results indicate that toxicities can compromise adherence and thus impact future treatment options. This is especially relevant in the context of limited access to second and third line treatment regimens.

Factors associated with colposcopy-histopathology confirmed cervical intraepithelial neoplasia among HIV-infected women from Rio De Janeiro Brazil.

Introduction Despite the availability of preventive strategies (screening tests and vaccines), cervical cancer continues to impose a significant health burden in low- and medium-resourced countries. HIV-infected women are at increased risk for infection with human papillomavirus (HPV) and thus development of cervical squamous intraepithelial neoplasia (CIN). Methods Study participants included HIV-infected women enrolling the prospective open cohort of Evandro Chagas Clinical Research Institute, Oswaldo Cruz Foundation (IPEC/FIOCRUZ). At cohort entry, women were subjected to conventional Papanicolaou test, HPV-DNA test and colposcopy; lesions suspicious for CIN were biopsied. Histopathology report was based on directed biopsy or on specimens obtained by excision of the transformation zone or cervical conization. Poisson regression modeling was used to assess factors associated with CIN2+ diagnosis. Results The median age of the 366 HIV-infected women included in the study was 34 years (interquartile range: 28–41 years). The prevalence of CIN1, CIN2 and CIN3 were 20.0%, 3.5%, and 2.2%, respectively. One woman was found to have cervical cancer. The prevalence of CIN2+ was 6.0%. Factors associated with CIN2+ diagnosis in the multivariate model were age < years compared to ≥35 years (aPR  =  3.22 95%CI 1.23–8.39), current tobacco use (aPR  =  3.69 95%CI 1.54–8.78), nadir CD4 T-cell count <350 cells/mm3 when compared to ≥ 350 cells/mm3 (aPR  =  6.03 95%CI 1.50–24.3) and concomitant diagnosis of vulvar and/or vaginal intraepithelial lesion (aPR  =  2.68 95%CI 0.99–7.24). Discussion Increased survival through wide-spread use of highly active antiretroviral therapy might allow for the development of cervical cancer. In Brazil, limited cytology screening and gynecological care adds further complexity to the HIV-HPV co-infection problem. Integrated HIV care and cervical cancer prevention programs are needed for the prevention of cervical cancer mortality in this group of women.

HIV rapid testing as a key strategy for prevention of mother-to-child transmission in Brazil

OBJECTIVE To assess the feasibility of HIV rapid testing for pregnant women at maternity hospital admission and of subsequent interventions to reduce perinatal HIV transmission. METHODS Study based on a convenience sample of women unaware of their HIV serostatus when they were admitted to delivery in public maternity hospitals in Rio de Janeiro and Porto Alegre, Brazil, between March 2000 and April 2002. Women were counseled and tested using the Determine HIV1/2 Rapid Test. HIV infection was confirmed using the Brazilian algorithm for HIV infection diagnosis. In utero transmission of HIV was determined using HIV-DNA-PCR. There were performed descriptive analyses of sociodemographic data, number of previous pregnancies and abortions, number of prenatal care visits, timing of HIV testing, HIV rapid test result, neonatal and mother-to-child transmission interventions, by city studied. RESULTS HIV prevalence in women was 6.5% (N=1,439) in Porto Alegre and 1.3% (N=3.778) in Rio de Janeiro. In Porto Alegre most of women were tested during labor (88.7%), while in Rio de Janeiro most were tested in the postpartum (67.5%). One hundred and forty-four infants were born to 143 HIV-infected women. All newborns but one in each city received at least prophylaxis with oral zidovudine. It was possible to completely avoid newborn exposure to breast milk in 96.8% and 51.1% of the cases in Porto Alegre and Rio de Janeiro, respectively. Injectable intravenous zidovudine was administered during labor to 68.8% and 27.7% newborns in Porto Alegre and Rio de Janeiro, respectively. Among those from whom blood samples were collected within 48 hours of birth, in utero transmission of HIV was confirmed in 4 cases in Rio de Janeiro (4/47) and 6 cases in Porto Alegre (6/79). CONCLUSIONS The strategy proved feasible in maternity hospitals in Rio de Janeiro and Porto Alegre. Efforts must be taken to maximize HIV testing during labor. There is a need of strong social support to provide this population access to health care services after hospital discharge.OBJETIVO: Analisar a viabilidade da testagem rapida para o HIV entre gestantes na admissao a maternidade e de intervencoes para reduzir a transmissao perinatal do HIV. METODOS: Amostra de conveniencia de mulheres que desconheciam sua situacao sorologica para o HIV quando admitidas para o parto em maternidades publicas do Rio de Janeiro, RJ, e de Porto Alegre, RS, entre marco de 2000 e abril de 2002. As mulheres foram aconselhadas e testadas com teste rapido Determine HIV1/2 na maternidade. Infeccao pelo HIV foi confirmada pelo algoritmo brasileiro para o diagnostico da infeccao pelo HIV. A transmissao intra-utero foi determinada pelo PCR-DNA-HIV. Foram realizadas analises descritivas dos dados sociodemograficos, numero de gestacoes e de abortos previos, numero de visitas de pre-natal, momento da testagem para o HIV, resultado do teste rapido para o HIV, intervencoes recebidas pelos recem-natos e de transmissao vertical do HIV, de acordo com cada cidade. RESULTADOS: A prevalencia de HIV entre as mulheres foi 6,5% (N=1.439) em Porto Alegre e 1,3% (N=3.778) no Rio de Janeiro. A maioria foi testada durante o trabalho de parto em Porto Alegre e no pos-parto, no Rio de Janeiro. Cento e quarenta e quatro criancas nasceram de 143 mulheres infectadas pelo HIV. Todos os recem-natos receberam ao menos a profilaxia com zidovudina oral, exceto um em cada cidade. Foi possivel evitar qualquer exposicao ao leite materno em 96,8% e 51,1% dos recem-natos em Porto Alegre e no Rio de Janeiro, respectivamente. A zidovudina injetavel foi administrada durante o trabalho de parto para 68,8% dos recem-natos em Porto Alegre e 27,7% no Rio de Janeiro. Entre aqueles com amostras de sangue coletadas ate 48 horas do nascimento, a transmissao intra-utero foi confirmada em quatro casos no Rio de Janeiro (4/47) e em seis casos em Porto Alegre (6/79). CONCLUSOES: A estrategia mostrou-se factivel nas maternidades do Rio de Janeiro e de Porto Alegre. Esforcos devem ser empreendidos para maximizar a testagem durante o trabalho de parto. Forte suporte social precisa ser acoplado a essa estrategia para garantir o acesso dessa populacao ao sistema de saude apos a alta da maternidade.

Predictors of early menopause in HIV-infected women: a prospective cohort study.

OBJECTIVE This study sought to investigate the age at natural menopause and its predictors in a cohort of human immunodeficiency virus (HIV)-infected women in Rio de Janeiro, Brazil. STUDY DESIGN HIV-infected women ≥30 years of age were included. Menopause was defined as having ≥1 year since the last menstrual period. Early age at natural menopause was defined as the onset of menopause at ≤45 years of age. Multivariate Cox proportional hazards analysis was applied. RESULTS A total of 667 women were included, and the median age at baseline was 34.9 years (interquartile range, 30.9-40.5 years). In all, 507 (76%) women were premenopausal, and 160 (24%) reached menopause during the observational period; of these, 36 of 160 (27%) had early menopause. The median age at natural menopause was 48 years (interquartile range, 45-50 years). Menarche at <11 years of age (hazard ratio [HR], 2.03; 95% confidence interval [CI], 1.23-3.37), cigarette smoking during the observational period (HR, 1.59; 95% CI, 1.08-2.33), chronic hepatitis C virus (HCV) infection (HR, 2.53; 95% CI, 1.27-5.07), and CD4 count <50 cells/mm(3) (HR, 3.07; 95% CI, 1.07-8.80) were significantly associated with an earlier age at natural menopause. The magnitudes of the effects of menarche at <11 years of age (HR, 2.7; 95% CI, 1.23-5.94), cigarette smoking during the observational period (HR, 3.00; 95% CI, 1.39-6.45), chronic HCV infection (HR, 6.26; 95% CI, 2.12-18.52), and CD4 count <50 cells/mm(3) (HR, 6.64; 95% CI, 1.91-23.20) were much higher and significantly associated with early natural menopause. CONCLUSION Early natural menopause was frequent among the HIV-infected women. In addition to menarche and cigarette smoking, which are menopausal factors among women in general, HIV-related immunodeficiency and chronic HCV were additional predictors for an earlier age at natural menopause. Adequate management of HIV in women is critical, as early onset of menopause has been associated with increased morbidity and mortality.

Cervical cytological abnormalities and factors associated with high-grade squamous intraepithelial lesions among HIV-infected women from Rio de Janeiro, Brazil:

Although cervical cancer remains a major public health problem in Brazil, knowledge of cervical cytological abnormalities among HIV-infected women remains scarce. At baseline evaluation of a cohort followed in Rio de Janeiro, Brazil, 703 HIV-infected women underwent cytology-based cervical cancer screening and human papillomavirus (HPV) DNA testing. Poisson regression analysis was used to evaluate the association of factors with the presence of high-grade squamous intraepithelial lesions (HSIL). Cervical cytology was abnormal in 24.3% of the women; 4.1% had HSIL. Beyond HPV infection, factors independently associated with the presence of HSIL was age (≥25 and ≤40 years, prevalence ratio [PR] 2.60, 95% confidence interval [CI] 1.11–6.10), and more than three pregnancies was protective (PR 0.33, 95% CI 0.11–0.94). High coverage of cervical cancer screening is warranted to prevent morbidity and mortality from cervical cancer in this population.

Pregnancy rates and predictors in women with HIV/AIDS in Rio de Janeiro, Southeastern Brazil

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.OBJETIVO: Identificar incidencia e preditores incidencia da primeira gestacao entre mulheres com HIV/Aids. METODOS: Estudo prospectivo de coorte conduzido entre 1996 e 2003 no Rio de Janeiro, RJ, com 225 mulheres acompanhadas ate a primeira gestacao ou ate o primeiro evento considerado censura (histerectomia, ligadura tubarea, menopausa, 50 anos de idade, perda de acompanhamento, obito ou final de dezembro de 2003). Taxas de incidencia de gestacao e de aborto foram estimadas e modelos de riscos proporcionais de Cox foram usados para identificar as caracteristicas da visita de inclusao associadas com o risco de gestacao. RESULTADOS: As mulheres foram acompanhadas por 565 pessoas/ano, com media de acompanhamento de 3 anos por mulher. A idade media foi de 32 anos (DP: 7) e 54,7% eram brancas. Sessenta gestacoes foram observadas em 39 mulheres e 18 resultaram em abortos induzidos (taxas de incidencia de 6,9% e 2,1% mulheres/ano, respectivamente). Gestacoes repetidas ocorreram em 33,3% das mulheres (13/39). Maior risco de gestacao 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 gestacao esteve associado a 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). CONCLUSOES: A incidencia de gestacao na coorte foi menor se comparada aquela observada na populacao geral. Caracteristicas sociodemograficas 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 transmissao do HIV para seus parceiros e prole.