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Summary Background Drug-drug interactions between orally administered antiretroviral therapy (ART) and hormones released from an intravaginal ring are not known. We hypothesised that ART containing either efavirenz or ritonavir-boosted atazanavir would alter plasma concentrations of vaginally administered etonogestrel and ethinylestradiol but that ART concentrations would be unchanged during use of an intravaginal ring. Methods We did a parallel, three-group, pharmacokinetic evaluation at HIV clinics in Asia (two sites), South America (five), sub-Saharan Africa (three), and the USA (11) between Dec 30, 2014, and Sept 12, 2016. We enrolled women with HIV who were either ART-naive (control group; n=25), receiving efavirenz-based ART (n=25), or receiving atazanavir–ritonavir-based ART (n=24). Women receiving ART were required to be on the same regimen for at least 30 days, with 400 copies or less per mL of plasma HIV-1 RNA; women not receiving ART had CD4 counts of 350 cells per μL or less. We excluded participants who had a bilateral oophorectomy or conditions that were contraindicated in the intravaginal ring product labelling. An intravaginal ring releasing etonogestrel and ethinylestradiol was inserted at entry (day 0). Single plasma samples for hormone concentrations were collected on days 7, 14, and 21 after intravaginal ring insertion. The primary outcome was the plasma concentration of etonogestrel and ethinylestradiol on day 21. Etonogestrel and ethinylestradiol concentrations were compared between each ART group and the control group by geometric mean ratio (GMR) with 90% CIs and Wilcoxon rank-sum test. As secondary outcomes, efavirenz or ritonavir-boosted atazanavir concentrations were assessed by 8-h intensive pharmacokinetic sampling at entry before intravaginal ring insertion and before intravaginal ring removal on day 21. Antiretroviral areas under the concentration-time curve (AUC0–8 h) were compared before and after intravaginal ring insertion by GMR (90% CI) and Wilcoxon signed-rank test. This study is registered with ClinicalTrials.gov , number NCT01903031 . Findings Between Dec 30, 2014, and Sept 12, 2016, we enrolled 84 participants in the study; ten participants were excluded from the primary hormone analysis. 74 participants met the primary endpoint: 25 in the control group, 25 in the efavirenz group, and 24 in the atazanavir group. On day 21 of intravaginal ring use, participants receiving efavirenz had 79% lower etonogestrel (GMR 0·21, 90% CI 0·16–0·28; p Interpretation Hormone exposure was significantly lower when an intravaginal ring contraceptive was combined with efavirenz-based ART. Further studies designed to examine pharmacodynamic endpoints, such as ovulation, when intravaginal ring hormones are combined with efavirenz are warranted. Funding National Institutes of Health, through the AIDS Clinical Trials Group and the International Maternal Pediatric Adolescent AIDS Clinical Trials Network, National Institute of Allergy and Infectious Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute of Mental Health.

Summary Objectives HIV-infected women are at increased risk of human papillomavirus (HPV) infection. Time trends in annual prevalences of cervical high-risk human papillomavirus (HR-HPV) genotypes among a non-vaccinated, HIV-infected female cohort in urban Brazil were assessed for the period 2006–2012. Methods Cervical specimens were collected for HPV genotyping yearly between January 2006 and December 2012 in a cross-sectional analysis of participants aged ≥18 years enrolled in the Women's HIV Cohort at Fiocruz in Rio de Janeiro, Brazil. Age-adjusted generalized estimating equation models with an exchangeable matrix were used to estimate odds ratios (OR) and 95% confidence intervals (CI) for annual HPV positivity (reference year: 2006). Results Among the 590 participants, the median age across all study years ranged from 35.5 to 40.0 years. The prevalence of any HR-HPV was ≥53% every year; prevalences of HR-HPV 16, 58, 59, and 68 were ≥24% in at least 1 year. The odds of HPV 16 and 68 decreased in 2012. HPV 58 prevalence followed a U-shape, beginning and ending at >20%. HPV 59 prevalence followed a linear trend, with increased odds in 2012 (OR 16.0, 95% CI 3.8–67.3; Bonferroni-adjusted p -value Conclusions The prevalences of HR-HPV 58, 59, and 68 were high in this cohort. Given current HR-HPV vaccine coverage and availability, further investigations are needed to optimize vaccine recommendations for this population.

Information on vaccine-type HPV seroprevalence is essential for vaccine strategies; however, limited data are available on past exposure to HPV-quadrivalent vaccine types in HIV-infected woman in Brazil.To assess the seroprevalence for HPV types 6, 11, 16 and 18 in HIV-infected and uninfected women, from Rio de Janeiro, Brazil and to investigate potential associations with age and pregnancy status.1100-sera were tested by virus-like particle (VLPs)-based ELISA for antibodies to HPV types 16, 18, 6 and 11. Statistical analysis was carried out by STATA/SE 10.1 and comparisons among HIV-infected and HIV-uninfected women were assessed by Poisson regression models with robust variance.HPV-6, 11, 16 and 18 seroprevalence was significantly higher among HIV-positive women (29.9%, 8.5%, 56.2% and 38.0%, respectively) compared to HIV-negative women (10.9%, 3.5%, 30.8% and 21.7%, respectively), when adjusted by age and pregnancy status. Overall, 69.4% of HIV-infected and 41.5% of HIV-uninfected women tested positive for any HPV quadrivalent vaccine type. However 4.7% and 1.1%, respectively, tested positive for all HPV vaccine type. In HIV-uninfected women who were pregnant, we found a higher HPV-11 seroprevalence (8.5% vs. 1.5%; P0.001) and a lower HPV 16 seroprevalence (22.6% vs. 34.2%; P = 0.010) compared to not pregnant women. HIV-uninfected women, aged 40 or more years old had a higher HPV 16 seroprevalence compared to women aged less than 40 years old.We did not observe a strong association between age and positive HPV antibodies nor an association between pregnancy and HPV seroprevalence. HPV seroprevalence was significantly higher among HIV-infected women compared to HIV negative women. In both populations the seroprevalence to all four HPV vaccine types was low suggesting that women may potentially benefit from the HPV vaccines.

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.

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. STUDYDESIGN:HIV-infectedwomen � 30yearsofagewereincluded. 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:Atotal of 667 women were included, and the median age at baseline was 34.9 years (interquartile range, 30.9e40.5 years). In all, 507 (76%) women were premenopausal, and 160 (24%) reached menopause during the observational period; of these, 36 of160 (27%) had early menopause. The median age at natural menopause was 48 years (interquartile range, 45e50 years). Menarche at

a Instituto de Pesquisa Clinica Evandro Chagas (IPEC), Fundacao Oswaldo Cruz, Av. Brasil, 4365, Manguinhos, Rio de Janeiro, RJ, 21045-900, Brasil b Laboratorio de Virologia, Instituto de Medicina Tropical, Universidade de Sao Paulo, Sao Paulo, Brasil c Instituto Fernandes Figueira (IFF), Fundacao Oswaldo Cruz, Manguinhos, Rio de Janeiro, RJ, Brasil d Instituto de Comunicacao e Informacao Cientifica e Tecnologica em Saude (ICICT), Fundacao Oswaldo Cruz, Manguinhos, Rio de Janeiro, RJ, Brasil University of California at San Francisco, San Francisco, CA, USA International Journal of Infectious Diseases (2009) 13, 655—656