Reproductive health syndemics impact retention in care among women living with HIV in Rio de Janeiro, Brazil.

Syndemic psychosocial and reproductive factors affecting women's retention in HIV care remain understudied. We analyzed correlates of non-retention in a cohort of women with HIV in Brazil from 2000‒2015. Participants self-reported exposure to physical/sexual violence, illicit drug use, adolescent pregnancy, or induced abortion. Lifetime history of these psychosocial stressors were used to create a syndemic score based on the presence or absence of these conditions. All dichotomous variables were summed (range 0 to 4), with greater scores indicating more syndemic factors experienced. Logistic regression models identified predictors of non-retention, defined as < 2 HIV viral load or CD4 results within the first year of enrollment. Of 915 women, non-retention was observed for 18%. Prevalence of syndemic factors was adolescent pregnancy (53.2%), physical/sexual violence (38.3%), induced abortion (27.3%), and illicit drug use (17.2%); 41.2% experienced ≥ 2 syndemic conditions. Syndemic scores of 2 and 3 were associated with non-retention, as well as low education, years with HIV and seroprevalent syphilis. Psychosocial and reproductive syndemics can limit women's retention in HIV care. Syphilis infection predicted non-retention and could be explored as a syndemic factor in future studies.

Agreements, Behaviour, and Change: Sex Outside the Relationship in Male HIV-negative Partners in HIV Serodiscordant Relationships in Australia, Brazil, and Thailand.

Male HIV serodiscordant couples have diverse relationship agreements regarding sex outside the relationship. We examined the relationship agreements as described by 343 male HIV-negative partners in HIV serodiscordant relationships in Australia, Brazil and Thailand participating in a multi-year cohort study. At baseline, 125 (34.1%) HIV-negative partners reported no agreement, 115 (33.5%) had a monogamous agreement, and 103 (37.9%) had an open agreement allowing sex outside the relationship. Relationship agreements were largely stable over time, with 76% of HIV-negative men reporting the same agreement across follow up, while changes were predominantly towards having an open agreement. Behaviour largely matched relationship agreements, and the predictors of breaking an agreement by having condomless anal intercourse (CLAI) with an outside partner were CLAI within the relationship (OR = 3.17, 95%CI: 1.64-6.14, p < 0.001) and PrEP use in the last three months (OR = 3.42, 95%CI: 1.48-7.92, p = 0.004). When considering HIV transmission risk for HIV-negative men in serodiscordant relationships, greater focus needs to be placed on sex that is occurring outside the relationship and the agreements that facilitate this.

Reproductive health syndemics impact retention in care among women living with HIV in Rio de Janeiro, Brazil

ABSTRACT Syndemic psychosocial and reproductive factors affecting women's retention in HIV care remain understudied. We analyzed correlates of non-retention in a cohort of women with HIV in Brazil from 2000-2015. Participants self-reported exposure to physical/sexual violence, illicit drug use, adolescent pregnancy, or induced abortion. Lifetime history of these psychosocial stressors were used to create a syndemic score based on the presence or absence of these conditions. All dichotomous variables were summed (range 0 to 4), with greater scores indicating more syndemic factors experienced. Logistic regression models identified predictors of non-retention, defined as < 2 HIV viral load or CD4 results within the first year of enrollment. Of 915 women, non-retention was observed for 18%. Prevalence of syndemic factors was adolescent pregnancy (53.2%), physical/sexual violence (38.3%), induced abortion (27.3%), and illicit drug use (17.2%); 41.2% experienced > 2 syndemic conditions. Syndemic scores of 2 and 3 were associated with non-retention, as well as low education, years with HIV and seroprevalent syphilis. Psychosocial and reproductive syndemics can limit women's retention in HIV care. Syphilis infection predicted non-retention and could be explored as a syndemic factor in future studies.

Characteristics of Agreements to have Condomless Anal Intercourse in the Presence of an Undetectable Viral Load Among HIV Serodiscordant Male Couples in Australia, Brazil and Thailand.

The use of undetectable viral load (VL) to negotiate condomless anal intercourse (CLAI) in HIV serodiscordant male relationships has become more common as more data regarding the effectiveness of antiretroviral treatments for the prevention of HIV transmission has been described. We examined viral load agreements (VLAs) for condomless sex in the presence of an undetectable VL in 343 HIV serodiscordant male couples in Australia, Brazil and Thailand. Factors associated with having a VLA included having agreements for the HIV-positive partner to report his VL result (p < 0.001), agreeing that VL affects agreements about sexual practice (p < 0.001), the HIV-negative partner's perception of his partner's undetectable VL (p < 0.001), the couple's belief in the efficacy of undetectable VL in preventing HIV transmission (p < 0.001), and the couple engaging in CLAI with each other (p < 0.001). Over time, these agreements became more common although 49.3% of couples in the sample never had a viral load agreement. As these agreements become more common, further education is required to support male couples in using them safely.

Timing of HIV diagnosis relative to pregnancy and postpartum HIV care continuum outcomes among Latin American women, 2000 to 2017.

BACKGROUND: HIV incidence among women of reproductive age and vertical HIV transmission rates remain high in Latin America. We, therefore, quantified HIV care continuum barriers and outcomes among pregnant women living with HIV (WLWH) in Latin America. METHODS: WLWH (aged ≥16 years) enrolling at Caribbean, Central and South America network for HIV epidemiology (CCASAnet) sites from 2000 to 2017 who had HIV diagnosis, pregnancy and delivery dates contributed. Logistic regression produced adjusted odds ratios (aOR) and 95% confidence intervals (CI) for retention in care (≥2 visits ≥3 months apart) and virological suppression (viral load <200 copies/mL) 12 months after pregnancy outcome. Cumulative incidences of loss to follow-up (LTFU) postpartum were estimated using Cox regression. Evidence of HIV status at pregnancy confirmation was the exposure. Covariates included pregnancy outcome (born alive vs. others); AIDS diagnosis prior to delivery; CD4, age, HIV-1 RNA and cART regimen at first delivery and CCASAnet country. RESULTS: Among 579 WLWH, median postpartum follow-up was 4.34 years (IQR 1.91, 7.35); 459 (79%) were HIV-diagnosed before pregnancy confirmation, 445 (77%) retained in care and 259 (45%) virologically suppressed at 12 months of postpartum. Cumulative incidence of LTFU was 21% by 12 months and 40% by five years postpartum. Those HIV-diagnosed during pregnancy had lower odds of retention (aOR = 0.58, 95% CI: 0.35 to 0.97) and virological suppression (aOR = 0.50, 95% CI: 0.31 to 0.82) versus those HIV-diagnosed before. CONCLUSION: HIV diagnosis during pregnancy was associated with poorer 12-month retention and virological suppression. Young women should be tested and linked to HIV care earlier to narrow these disparities.

Outcomes After Second-Line Antiretroviral Therapy in Children Living With HIV in Latin America.

BACKGROUND: Little is known about the long-term outcomes of children living with HIV in Latin America. Few studies have examined antiretroviral therapy (ART) regimen switches in the years after the introduction of ART in this population. This study aimed to assess clinical outcomes among children who started second-line ART in the Caribbean, Central and South America network for HIV epidemiology. METHODS: Children (<18 years old) with HIV who switched to second-line ART at sites within Caribbean, Central and South America network for HIV epidemiology were included. The cumulative incidence and relative hazards of virologic failure while on second-line ART, loss to follow-up, additional major ART regimen changes, and all-cause mortality were evaluated using competing risks methods and Cox models. RESULTS: A total of 672 children starting second-line ART were included. Three years after starting second-line ART, the cumulative incidence of death was 0.10 [95% confidence interval (CI) 0.08 to 0.13], loss to follow-up was 0.14 (95% CI: 0.11 to 0.17), and major regimen change was 0.19 (95% CI: 0.15 to 0.22). Of those changing regimens, 35% were due to failure and 11% due to toxicities/side effects. Among the 312 children with viral load data, the cumulative incidence of virologic failure at 3 years was 0.62 (95% CI: 0.56 to 0.68); time to virologic failure and regimen change were uncorrelated (rank correlation -0.001; 95% CI -0.18 to 0.17). CONCLUSIONS: Poor outcomes after starting second-line ART in Latin America were common. The high incidence of virologic failure and its poor correlation with changing regimens was particularly worrisome. Additional efforts are needed to ensure children receive optimal ART regimens.

High prevalence of anal high-risk HPV infection among transwomen: estimates from a Brazilian RDS study.

INTRODUCTION: As the leading sexually transmitted infection worldwide, human papillomavirus (HPV) may disproportionately affect transwomen. We aimed to estimate anal HPV prevalence, especially focusing on high-risk (hr)-HPV types and evaluate their associated factors among transwomen living in Rio de Janeiro, Brazil. METHODS: Transwomen enrolled in a respondent-driven sampling (RDS)-based survey conducted between August 2015 and January 2016 self-collected anal samples, which were promptly stored at minus 80°C. After DNA extraction, HPV detection and genotyping were performed using the PapilloCheck test. We estimated HPV prevalences and evaluated the correlates of anal hr-HPV infection using a regression logistic model. RESULTS: Out of 345 transwomen, 272 (78.8%) were included in this analysis (122 [44.9%] HIV-positive). No participant had ever received HPV vaccination. Among participants enrolled, 212 (77.9%) were positive for any anal HPV type and 165 (60.7%) for hr-HPV. Most common hr-HPV were as follows: HPV16 (17.6%), HPV68 (14.7%), HPV39 (14.3%), HPV56 (12.5%), HPV51 (11.4%) and HPV52 (11.0%). HIV-positive transwomen had three times the odds of having an hr-HPV compared to HIV-negative transwomen. Participants who had a current rectal Neisseria gonorrhoeae infection had 3.7 times the odds of being coinfected with hr-HPV. Among HIV-positive transwomen, neither antiretroviral therapy use, undetectable viral load, current and nadir CD4 counts were associated with anal hr-HPV infection. CONCLUSIONS: Brazilian transwomen in our study exhibit some of the highest population-specific rates of HPV and hr-HPV. There is an urgent need to elucidate the burden of HPV infection, prevalence of HPV-related diseases and access to and uptake of HPV vaccination among transwomen, especially from low- and middle-income settings.

Depression, sexual behavior, and HIV treatment outcomes among transgender women, cisgender women and men who have sex with men living with HIV in Brazil and Thailand: a short report.

One in five transgender women (TW) are living with HIV, yet little has been published about their health outcomes. We analyzed data from TW (n = 37), cisgender women (CW, n = 165), and cisgender men who have sex with men (MSM, n = 151) in Thailand and Brazil. We hypothesized: (1) TW will have higher odds of depressive symptoms, lower odds of condom use and greater odds of a detectable viral load compared to MSM and CW; and (2) TW will have lower odds of condom use and higher odds of detectable viral load. We found that TW had higher odds of depression (OR 2.2, 95%CI: 1.0, 4.8, p = 0.04) and were less likely than MSM (22% v. 42%, p = 0.01) to use condoms with partners of unknown serostatus. In multivariable models, TW had lower odds than MSM of using condoms with partners with unknown serostatus (OR 0.38, 95%CI: 0.15, 0.90) and CW had lower odds than MSM of using condoms with HIV-negative partners (0.60 [0.38, 0.95], p = 0.029). We found no significant differences in detectable viral load. Disaggregating data by gender is important to understand factors that contribute to viral suppression and HIV transmission risk among people living with HIV.

Antiretroviral therapy and vaginally administered contraceptive hormones: a three-arm, pharmacokinetic study.

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<0·0001) and 59% lower ethinylestradiol (0·41, 0·32-0·52; p<0·0001) concentrations compared with the control group. By contrast, participants receiving ritonavir-boosted atazanavir had 71% higher etonogestrel (1·71, 1·37-2·14; p<0·0001), yet 38% lower ethinylestradiol (0·62, 0·49-0·79; p=0·0037) compared with the control group. The AUC0-8 h of efavirenz or atazanavir did not differ between the groups. 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.

Transcendendo: A Cohort Study of HIV-Infected and Uninfected Transgender Women in Rio de Janeiro, Brazil.

Purpose: Worldwide, the burden of adverse health conditions is substantial among travestis and transgender women (trans women). Transcendendo, the first trans-specific cohort in a low- or middle-income country, is an open cohort established in August 2015 to longitudinally evaluate the health aspects of trans women aged ≥18 years in Rio de Janeiro, Brazil. Methods: Study visits occur on an annual basis. Data on sociodemographics, behavioral, gender transition, affirmation procedures, hormone use, discrimination, violence, clinical and mental health, HIV prevention, and care (for those HIV-infected) are collected. Physical examination, anthropometric measurements, and laboratory tests are performed. Results: As of July 2017, 322 trans women were enrolled in the cohort with a median age of 31.5 years (interquartile range 25.7-39.5), of whom 174 (54%) were HIV-infected. The Transcendendo baseline information reinforces the scenario of marginalization and deprivation surrounding trans women. Most participants had low income (62.0% were living with below US$ 10.00/day), showed a very high engagement in sex work (78.6%), and reported increased occurrence of sexual (46.3%) and physical (54.0%) violence. Pre-exposure peophylaxis (PReP) was used by 18.8% of the HIV-uninfected trans women, only through research participation. Positive screening for depression (57.8%) and problematic use of tobacco (56.6%), cannabis (28.9%), cocaine (23.8%), and alcohol (21.5%) were high. Almost all participants (94.8%) reported hormone use at some point, mostly without medical supervision (78.7%). Conclusion: Our results describe a context of exclusion experienced by trans women, exposing vulnerabilities of this population in a middle-income country, with poor access to trans-specific care, HIV prevention and care, and mental health care. Addressing transgender experiences and needs can help the development of strategies to diminish stigma, improve health care environment, guide future research on trans morbidities, substance use, and trans-specific interventions to support health-related recommendations. Ultimately, it contributes to close the gaps concerning transgender health and reinforces that trans care cannot be disentangled from the social environment that surrounds trans women.

The Longitudinal Effects of Non-injection Substance Use on Sustained HIV Viral Load Undetectability Among MSM and Heterosexual Men in Brazil and Thailand: The Role of ART Adherence and Depressive Symptoms (HPTN 063).

The effect of non-injection substance use on HIV viral load (VL) is understudied in international settings. Data are from HPTN063, a longitudinal observational study of HIV-infected individuals in Brazil, Thailand, and Zambia, with focus on men with VL data (Brazil = 146; Thailand = 159). Generalized linear mixed models (GLMM) assessed whether non-injection substance use (stimulants, cannabis, alcohol, polysubstance) was associated with VL undetectability. ART adherence and depressive symptoms were examined as mediators of the association. In Thailand, substance use was not significantly associated with VL undetectability or ART adherence, but alcohol misuse among MSM was associated with increased odds of depression (AOR = 2.75; 95% CI 1.20, 6.32, p = 0.02). In Brazil, alcohol misuse by MSM was associated with decreased odds of undetectable VL (AOR = 0.34; 95% CI 0.13, 0.92, p = 0.03). Polysubstance use by heterosexual men in Brazil was associated with decreased odds of ART adherence (AOR = 0.25; 95% CI 0.08, 0.78, p = 0.02). VL suppression appears attainable among non-injection substance users. Substance use interventions among HIV-positive men should address depression, adherence, and VL undetectability.

The Intersection of HIV, Social Vulnerability, and Reproductive Health: Analysis of Women Living with HIV in Rio de Janeiro, Brazil from 1996 to 2016.

Comprehensive care for sexual and reproductive health (SRH) and social needs for women living with HIV remains limited globally. We aimed to assess trends in baseline sociodemographic, clinical, sexual, and reproductive characteristics among a cohort of HIV-infected women in Rio de Janeiro from 1996 to 2016. Participants were stratified into four time periods based on year of enrollment; we compared cross-sectional data from each period. Of 1361 participants (median age 36), most were black or mixed race (60.1%), unemployed (52.1%), and without secondary education (54%). Adolescent pregnancy was common (51.5%), and 18.3% reported sexual debut at < 15 years old. Nearly half (45.2%) had < 5 lifetime sexual partners, yet prior syphilis and oncogenic human papillomavirus prevalence were 10.9% and 43.1%, respectively. Lifetime prevalence of induced abortion was 30.3%, and 16% used no contraceptive method. Future research should explore interactions between social vulnerability, HIV, and poor SRH outcomes and healthcare models to alleviate these disparities.

"I Wasn't in My Right Mind": Qualitative Findings on the Impact of Alcohol on Condom Use in Patients Living with HIV/AIDS in Brazil, Thailand, and Zambia (HPTN 063).

PURPOSE: There have been significant biomedical improvements in the treatment and prevention of HIV over the past few decades. However, new transmissions continue to occur. Alcohol use is a known barrier to medication adherence and consistent condom use and therefore may affect treatment as prevention (TasP) efforts. The purpose of this study was to further explore how alcohol is associated with condom use and sexual transmission behavior in three international cities. METHOD: HIV Prevention Trials Network 063 was an observational mixed-methods study of HIV-infected patients currently in care in Rio de Janeiro, Brazil; Chiang Mai, Thailand; and Lusaka, Zambia. Across these three global cities, 80 qualitative interviews were conducted from 2010 to 2012. From these interviews, quotes related to substance use, almost all of which were alcohol, were analyzed using thematic analysis to identify how the use was related to sexual transmission behaviors. RESULTS: Overall, the theme that alcohol impairs cognitive abilities emerged from the data and included the following subthemes: expectancies, impaired decision-making, loss of control, and less concern for others. Themes specific to international settings and risk subgroups were also identified. CONCLUSION: Our analysis identified how alcohol influences sexual transmission behavior in HIV patients in three international settings. These findings may provide direction for content development for future secondary prevention interventions to effectively implement TasP internationally.

The Role of Religious Service Attendance, Psychosocial and Behavioral Determinants of Antiretroviral Therapy (ART) Adherence: Results from HPTN 063 Cohort Study.

Early and sustained antiretroviral therapy (ART) adherence can suppress the HIV virus in individuals and reduce onward transmission of HIV in the population. Religiosity has been associated with better HIV clinical outcomes. Data are from a longitudinal, observational study of 749 HIV-infected individuals from Brazil, Zambia, and Thailand (HPTN 063). Ordered logistic regression assessed whether religious service attendance was associated with ART adherence (self-reported and plasma HIV-RNA) and moderated the association between alcohol problems and ART adherence. In each country, > 80% of participants reported high self-reported ART adherence (good/very good/excellent). Religious service attendance exceeded 85% but was statistically unrelated to adherence. In combined-country models, (p = 0.03) as alcohol problems increased, the probability of high self-reported ART adherence, as well as viral-load, became weaker at higher compared to low service attendance frequency. Future studies should evaluate spirituality variables and replicate the moderation analyses between religious attendance and alcohol problems.

Health-related quality of life assessment among people living with HIV in Rio de Janeiro, Brazil: a cross-sectional study.

PURPOSE: To assess health-related quality of life (HRQoL) and its associated factors among people living with HIV/AIDS (PLWHA) in Rio de Janeiro, Brazil. METHODS: A cross-sectional study including PLWHA receiving usual HIV-care at Instituto Nacional de Infectologia Evandro Chagas (INI/Fiocruz) was conducted between 2014 and 2016 in Rio de Janeiro, Brazil. The EQ-5D-3L assessed HRQoL; PHQ-2 and ASSIST were used for screening depression and substance use, respectively. Clinical variables were obtained from the INI/Fiocruz cohort database, and structured questions evaluated intimate partner violence, sexual abstinence and relationship status. Data were analysed using multivariable Tobit regression model. RESULTS: A total of 1480 PLWHA were included: 64.7% were male at birth (38.4% men who have sex with men [MSM], 24.3% heterosexual men and 2% transgender women [TGW]); median age was 43.1 years, and 95.8% were receiving antiretroviral therapy. The median EQ-5D-3L utility score was 0.801. Results showed that the following factors: MSM and women; older age; lower educational level; no engagement in a relationship; depression screening positive; polysubstance use; and, detectable viral load were independently associated with worse HRQoL. CONCLUSIONS: PLWHA under care at INI/Fiocruz presented good HRQoL. Polysubstance use, depression and lower educational level were among the factors negatively associated with HRQoL. This was the first time that the EQ-5D-3L utility scores were calculated for a considerable number of PLWHA in Brazil, which is a fundamental piece of information for future cost-effectiveness analysis.

HIV Infection Is Not Associated with Carotid Intima-Media Thickness in Brazil: A Cross-Sectional Analysis from the INI/ELSA-Brasil Study.

BACKGROUND: Carotid intima-media thickness (cIMT) has been used as an early marker of atherosclerotic disease in the general population. Recently its role among HIV-infected patients has been questioned. To date, no Brazilian study has compared cIMT in respect to HIV status. METHODS: We compared data from 535 patients actively followed in a prospective cohort in Rio de Janeiro (HIV group); 88 HIV-negative individuals who were nominated by patients (friend controls-FCs); and 10,943 participants of the ELSA-Brasil study. Linear regression models were used to study associations of the 3 groups and several covariables with cIMT. Propensity scores weighting (PSW) were also employed to balance data. RESULTS: Median thickness in mm (IQR) were 0.54 (0.49,0.62); 0.58 (0.52,0.68); and 0.57 (0.49,0.70), HIV, FCs and ELSA-Brasil groups, respectively (p-value<0.001). The best linear model chosen did not include the group variables, after adjusting for all the variables chosen, showing no difference of cIMT across groups. Similar results were obtained with PSW. Several traditional CVD risk factors were also significantly associated with cIMT: female gender, higher education and higher HDL were negatively associated while risk factors were older age, current/former smoker, AMI/stroke family history, CVD history, hypertension, DM, higher BMI and total cholesterol. CONCLUSIONS: We show for the first time in a middle-income setting that cIMT, is not different in HIV-infected patients in Rio de Janeiro compared with 2 different groups of non-HIV-infected individuals. Traditional CVD risk factors are associated with this outcome. Our results point out that high standards of care and prevention for CVD risk factors should always be sought both in the HIV-infected and non-infected populations to prevent CVD-related events.

Secretory Leukocyte Protease Inhibitor Expression and High-Risk HPV Infection in Anal Lesions of HIV-Positive Patients.

OBJECTIVE: The aim of this study was to evaluate secretory leukocyte protease inhibitor (SLPI) expression in anal biopsies from HIV-positive (HIV+) individuals, and compare that to anal intraepithelial neoplasia (AIN) diagnoses and human papillomavirus (HPV) status. DESIGN: This is a cross-sectional study of a cohort of 54 HIV+ (31 males and 23 females) from an AIDS clinic in Rio de Janeiro, Brazil. METHODS: The study material consisted of anorectal tissue biopsies obtained from HIV+ subjects, which were used to construct tissue microarray paraffin blocks for immunohistochemical analysis of SLPI expression. Biopsies were evaluated by an expert pathologist and classified as low-grade AIN1, high-grade AIN2/3, or normal squamous epithelium. In addition, DNA from the biopsies was extracted and analyzed for the presence of low- or high-risk HPV DNA. RESULTS: Histologically, normal squamous epithelium from the anorectal region showed strong positive SLPI staining in 17/20 (85%) samples. In comparison, 9/17 (53%) dysplastic squamous epithelial samples from AIN1 patients showed strong SLPI staining, and only 5/17 (29%) samples from AIN2/3 patients exhibited strong SPLI staining, which both were significantly fewer than those from normal tissue (P = 0.005). Furthermore, there was a significantly higher proportion of samples in which oncogenic high-risk HPV genotypes were detected in low SLPI-expressing tissues than that in tissues with high SLPI expression (P = 0.040). CONCLUSIONS: Taken together these results suggest that low SLPI expression is associated with high-risk HPV infections in the development of AIN.

Time trend analysis of cervical high-risk human papillomavirus (HPV) in HIV-infected women in an urban cohort from Rio de Janeiro, Brazil: the rise of non-16/18 HPV.

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 <0.01). 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.

Polymorphism in apoptotic BAX (-248G>A) gene but not in anti-apoptotic BCL2 (-938C>A) gene and its protein and mRNA expression are associated with cervical intraepithelial neoplasia.

HPV is associated with cervical cancer and plays a crucial role in tumor formation. Apoptosis is regulated by different pathways involving genes that either promote (BCL2 gene) or inhibit (BAX gene) cell death. Our goal was to determine whether the BCL2-938C>A (rs2279115) and BAX-248G>A (rs4645878) single nucleotide polymorphisms (SNPs) are associated with squamous intraepithelial neoplasia (SIL) risk, and whether their phenotypic expression was impaired in these lesions. Two hundred and thirty-one cases showing SIL were classified as low SIL (LSIL, n = 101) or high SIL (HSIL, n = 130), and control subjects (n = 266) with no gynecologically proven SIL were recruited. No statistical difference in the genotype and allelic frequency of the BCL-2-938C>A polymorphism was observed among the groups. BCL2-938C/A and A/A homozygotes carriers had higher distribution of BCL-2-expressing cells in stroma in the SIL group. BCL2 mRNA-expression was not correlated with BCL2-938C>A SNPs in both groups. We did find a strong association of the BAX GG genotype and risk for SIL. No difference was observed between LSIL and HSIL groups. In BAX-248G/A and A/A homozygote carriers, the number of BAX-expressing cells was lower the epithelium area in SIL. However, mRNA expression was higher in SIL patients than in the control group. In conclusion, our data provide evidence that allele G carriers in the BAX-248G>A promoter SNP may influence the development of SIL. However, this genotype does not influence the SIL outcome. Additionally, we suggest a possible role of HPV infection in the inhibition of the expression of BAX protein, decreasing cell death, and favoring cervical carcinogenesis.

Chlamydia trachomatis, Neisseria gonorrhoeae and syphilis among men who have sex with men in Brazil.

BACKGROUND: Sexually transmitted diseases (STD) are frequently asymptomatic and increase the likelihood of transmitting and acquiring HIV. In Brazil, the guidelines for STDs diagnosis and treatment are based on the syndromic approach. Nucleic acid amplification tests (NAAT) has been recommended as routine STDs screening in some countries, especially for men who have sex with men (MSM). Limited data are available about how to best define target groups for routine screening by NAATs within this population. We aimed to assess the prevalence of rectal and urethral Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections and syphilis, and the factors associated with having at least one STD among HIV-infected and uninfected MSM in Rio de Janeiro, Brazil. METHODS: From August 2010 to June 2012, 391 MSM were enrolled into the Evandro Chagas National Institute of Infectious Diseases-INI-Fiocruz cohort, and 292 MSM (HIV-infected:211 and HIV-uninfected:81) were included in this study. NAATs were performed on the rectal swabs and urine for CT and NG. The rapid plasma reagin test and microhemagglutination assay for Treponema pallidum were performed for syphilis diagnosis. RESULTS: The overall prevalence of STD was 20.0% (95%CI:15.7-25.1): 10% anorectal chlamydia; syphilis 9.9%; anorectal gonorrheae 2.5%; and urethral chlamydia 2.2%; no case of urethral gonorrheae was detected. The proportion of HIV-positive MSM who had at least one STD was nearly two times that of HIV-negative MSM (22.6% vs 13.2%; P = 0.09). The frequency of each STD, except for anorectal NG (1.5% vs.5.2%), was higher among HIV-positive than HIV-negative individuals. Among the 211 asymptomatic participants, 17.5% (n = 37) were identified as having at least one STD; 10.4% (n = 22/211) tested positive for anorectal chlamydia. Sixty five percent of HIV-positive MSM were asymptomatic at the time of the STD diagnosis, while 100.0% of the HIV-negative MSM. Age (APR = 0.78; 95%CI:0.60-1.00 for each additional ten years) and a positive-HIV serostatus (APR = 2.05; 95%CI:1.03-4.08) were significantly associated with STD diagnosis. CONCLUSION: An overall high STD-prevalence rate was observed, especially among HIV-infected and in younger individuals, and the majority of STDs were asymptomatic. STD screening using NAATs among asymptomatic MSM is a potentially cost-effective intervention for the prevention of HIV infection among MSM.