IntroductionWe describe temporal trends in the mortality rates and factors associated with AIDS and non-AIDS related mortality at the Evandro Chagas Clinical Research Institute (IPEC), Oswaldo Cruz Foundation (FIOCRUZ).MethodsAdult patients enrolling from 1986 through 2009 with a minimum follow up of 60 days were included. Vital status was exhaustively checked using patients’ medical charts, through active contact with individuals and family members and by linkage with the Rio de Janeiro Mortality database using a previously validated algorithm. The CoDe protocol was used to establish the cause of death. Extended Cox proportional hazards models were used for multivariate modeling.ResultsA total of 3530 individuals met the inclusion criteria, out of which 868 (24.6%) deceased; median follow up per patient was 3.9 years (interquartile range 1.7–9.2 years). The dramatic decrease in the overall mortality rates was driven by AIDS-related causes that decreased from 9.19 deaths/100PYs n 1986–1991 to 1.35/100PYs in 2007–2009. Non-AIDS related mortality rates remained stable overtime, at around 1 death/100PYs. Immunodeficiency significantly increased the hazard of both AIDS-related and non-AIDS-related causes of death, while HAART use was strongly associated with a lower hazard of death from either cause.ConclusionsOur results confirm the remarkable decrease in AIDS-related mortality as the HIV epidemic evolved and alerts to the conditions not traditionally related to HIV/AIDS which are now becoming more frequent, needing careful monitoring.

Background The burden of HIV in transgender women (transwomen) in Brazil remains unknown. We aimed to estimate HIV prevalence among transwomen, and identify the factors associated with newly diagnosed HIV infections. Methods “Transcender” was a respondent driven sampling study of transwomen in Rio de Janeiro, Brazil, conducted from August 2015 to January 2016. Twelve seeds were recruited from social movements and formative phase. Eligibility criteria were: self-identification as transwomen, being 18 years of age or older, living in Rio de Janeiro or metropolitan area, and having a valid peer recruitment coupon. Participants were categorized as HIV-negative, known HIV infected, or newly diagnosed as HIV infected. Predictors of newly diagnosed HIV infections were assessed by comparing the newly diagnosed with the HIV-negative. Population estimates were adjusted using the RDSII estimator. Findings In total, 345 eligible transwomen were enrolled. The study sample was young and diverse on gender identity. Population estimates of no prior HIV testing, HIV-infection and newly diagnosed as HIV-infected were 29·1%, 32·1% and 7·0%, respectively (based on n=60 with no prior testing, n=141 HIV-infected, n=40 newly diagnosed). Syphilis, rectal chlamydia and gonorrhea infection were diagnosed in 28·9%, 14·6%, and 13·5%, respectively. Newly diagnosed HIV infections were associated with black race (22·8; 95%CI 2·9–178·9), travesti (34·1; 95%CI 5·8–200·2) or transsexual woman (41·3; 95%CI 6·3–271·2) gender identity, history of sex work (30·7; 95%CI 3·5–267·3), and history of sniffing cocaine (4·4; 95%CI 1·4–14·1). Interpretation Our results suggest that transwomen bear the largest burden of HIV among any population at risk in Brazil. The high proportion of HIV diagnosis among young participants points to the need for tailored long-term health care and prevention services in order to curb the HIV epidemic and improve the quality-of-life of transwomen in Brazil. Funding This work was supported by Brazilian Research Council (470056/2014-2) and NIAID-NIH (UM1AI069496).

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.

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 Cox's 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.

BackgroundTransposable elements (TEs), both DNA transposons and retrotransposons, are genetic elements with the main characteristic of being able to mobilize and amplify their own representation within genomes, utilizing different mechanisms of transposition. An almost universal feature of TEs in eukaryotic genomes is their inability to transpose by themselves, mainly as the result of sequence degeneration (by either mutations or deletions). Most of the elements are thus either inactive or non-autonomous. Considering that the bulk of some eukaryotic genomes derive from TEs, they have been conceived as “TE graveyards.” It has been shown that once an element has been inactivated, it progressively accumulates mutations and deletions at neutral rates until completely losing its identity or being lost from the host genome; however, it has also been shown that these “neutral sequences” might serve as raw material for domestication by host genomes.ResultsWe have analyzed the sequence structural variations, nucleotide divergence, and pattern of insertions and deletions of several superfamilies of TEs belonging to both class I (long terminal repeats [LTRs] and non-LTRs [NLTRs]) and II in the genome of Anopheles gambiae, aiming at describing the landscape of deterioration of these elements in this particular genome. Our results describe a great diversity in patterns of deterioration, indicating lineage-specific differences including the presence of Solo-LTRs in the LTR lineage, 5′-deleted NLTRs, and several non-autonomous and MITEs in the class II families. Interestingly, we found fragments of NLTRs corresponding to the RT domain, which preserves high identity among them, suggesting a possible remaining genomic role for these domains.ConclusionsWe show here that the TEs in the An. gambiae genome deteriorate in different ways according to the class to which they belong. This diversity certainly has implications not only at the host genomic level but also at the amplification dynamic and evolution of the TE families themselves.

A lopinavir-ritonavir (LPV/r)-based regimen is recommended during pregnancy to reduce the risk of HIV mother-to-child transmission, but the appropriate dose is controversial. We compared the pharmacokinetics of standard and increased LPV/r doses during pregnancy. This randomized, open-label prospective study enrolled 60 pregnant women between gestational weeks 14 and 30. The participants received either the standard dose (400/100 mg twice a day [BID]) or increased dose (600/150 mg BID) of LPV/r tablets during pregnancy and the standard dose for 6 weeks after childbirth. Pharmacokinetics analysis was performed using a high-performance liquid chromatography-tandem mass spectrometry method. Adherent participants who received the standard dose presented minimum LPV concentrations of 4.4, 4.3, and 6.1 g/ml in the second and third trimesters and postpartum, respectively. The increased-dose group exhibited values of 7.9, 6.9, and 9.2 g/ml at the same three time points. Although LPV exposure was significantly higher in the increased-dose group, the standard dose produced therapeutic levels of LPV against wild-type virus in all adherent participants, except one patient in the third trimester; 50%, 37.5%, and 25%, and 0%, 15%, and 0% of the participants in the standard-and increased-dose groups failed to achieve therapeutic levels against resistant viruses during the second and third trimesters and after childbirth, respectively. After 12 weeks of treatment and after childbirth, all adherent participants achieved undetectable HIV viral loads, and their babies (49/54) were uninfected. No serious drug-related adverse events were observed. We conclude that the standard dose is appropriate for use during pregnancy and that an increased dose may be necessary for women harboring resistant HIV. (This study has been registered at ClinicalTrials.gov under registration no. NCT00605098.)

Background: The oncoproteins of human papillomavirus (HPVs) directly effect cell-cycle control. We hypothesize that regulatory and cell cycle protein expression might be additionally modified in the cervix of HIV/HPV co-infected women.

Introduction: Evidence suggests that, of all affected populations, transgender women (transwomen) may have the heaviest HIV burden worldwide. Little is known about HIV linkage and care outcomes for transwomen. We aimed to estimate population-level indicators of the HIV cascade of care continuum, and to evaluate factors associated with viral suppression among transwomen in Rio de Janeiro, Brazil. Methods: We conducted a respondent-driven sampling (RDS) study of transwomen from August 2015 to January 2016 in Rio de Janeiro, Brazil and collected data on linkage and access to care, antiretroviral treatment and performed HIV viral load testing. We derived population-based estimates of cascade indicators using sampling weights and conducted RDS-weighted logistic regression analyses to evaluate correlates of viral suppression (viral load ≤50 copies/mL). Results: Of the 345 transwomen included in the study, 89.2% (95% CI 55–100%) had been previously tested for HIV, 77.5% (95% CI 48.7–100%) had been previously diagnosed with HIV, 67.2% (95% CI 39.2–95.2) reported linkage to care, 62.2% (95% CI 35.4–88.9) were currently on ART and 35.4% (95% CI 9.5–61.4%) had an undetectable viral load. The final adjusted RDS-weighted logistic regression model for viral suppression indicated that those who self-identified as black (adjusted odds ratio [aOR] 0.06, 95% CI 0.01–0.53, p < 0.01), reported earning ≤U$160/month (aOR 0.11, 95% CI 0.16–0.87, p = 0.04) or reported unstable housing (aOR 0.08, 95% CI 0.01–0.43, p < 0.01) had significantly lower odds of viral suppression. Conclusions: Our cascade indicators for transwomen showed modest ART use and low viral suppression rates. Multi-level efforts including gender affirming care provision are urgently needed to decrease disparities in HIV clinical outcomes among transwomen and reduce secondary HIV transmission to their partners.