Contribution of syphilis to adverse pregnancy outcomes in people living with and without HIV in south Brazil: 2008-2018.

BACKGROUND: Syphilis co-infection among pregnant people living with HIV (PLH) may worsen pregnancy outcomes. We evaluated the impact of syphilis co-infection on pregnancies in south Brazil. METHODS: Data was extracted from hospital records between 1/1/2008 -12/31/2018. Preterm birth (PTB), low birth weight (LBW < 2500 g), and a composite adverse infant outcome [AIO: HIV vertical transmission, loss to follow-up before HIV diagnosis (LTFU), stillbirth, congenital syphilis] were evaluated among pregnancies without HIV and syphilis (PWOH+S), PLH mono-infection, syphilis mono-infection (PLS), and PLH with syphilis (PLH + S). RESULTS: Among 48,685 deliveries where patients were tested for HIV and syphilis, 1,353 (2.8%) occurred in PLH; of these, 181 (13.4%) were HIV/syphilis co-infected (PLH + S). Among PLH, 2.4% of infants acquired HIV and 13.1% were LTFU. Among all PLS, 70.5% of infants acquired congenital syphilis. Across the cohort, 1.2% stillbirths/neonatal deaths occurred. 37.0% of PLH + S did not initiate ART versus 15.4% of PLH mono-infection (p < 0.001). 37.6% of PLH + S had VDRL titers > 1:16 compared to 21.7% of PLS only (p < 0.001). Among PLH, syphilis co-infection and unknown/high VDRL titers ( > 1:16) increased AIO risk more (aRR:3.96, 95%CI:3.33-4.70) compared to low VDRL titers ( < 1:8) (aRR:3.51, 95%CI:2.90-4.25). Unsuppressed viremia ( > 50 copies/mL) was associated with risk of PTB (aRR:1.43, 95%CI:1.07-1.92) and AIO (aRR:1.38, 95%CI:1.11-1.70) but not LBW. Lack of prenatal care was significant in predicting PTB and LBW in all PLH and PLS mono-infection. CONCLUSION: Syphilis co-infection worsens adverse infant outcomes in all women and compounds negative effects of HIV infection during pregnancy. Effective syphilis treatment and HIV VL suppression are paramount for optimal obstetric care.

Single High Dose of Liposomal Amphotericin B in Human Immunodeficiency Virus/AIDS-Related Disseminated Histoplasmosis: A Randomized Trial.

BACKGROUND: Histoplasmosis is a major AIDS-defining illness in Latin America. Liposomal amphotericin B (L-AmB) is the drug of choice for treatment, but access is restricted due to the high drug and hospitalization costs of the conventional long regimens. METHODS: Prospective randomized multicenter open-label trial of 1- or 2-dose induction therapy with L-AmB versus control for disseminated histoplasmosis in AIDS, followed by oral itraconazole therapy. We randomized subjects to: (i) single dose 10 mg/kg of L-AmB; (ii) 10 mg/kg of L-AmB on D1, and 5 mg/kg of L-AmB on D3; (iii) 3 mg/kg of L-AmB daily for 2 weeks (control). The primary outcome was clinical response (resolution of fever and signs/symptoms attributable to histoplasmosis) at day 14. RESULTS: A total of 118 subjects were randomized, and median CD4+ counts, and clinical presentations were similar between arms. Infusion-related toxicity, kidney toxicity at multiple time-points, and frequency of anemia, hypokalemia, hypomagnesemia, and liver toxicity were similar. Day 14 clinical response was 84% for single-dose L-AmB, 69% 2-dose L-AmB, and 74% for control arm (P = .69). Overall survival on D14 was 89.0% (34/38) for single-dose L-AmB, 78.0% (29/37) for 2-dose L-AmB, and 92.1% (35/38) for control arm (P = .82). CONCLUSIONS: One day induction therapy with 10 mg/kg of L-AmB in AIDS-related histoplasmosis was safe. Although clinical response may be non-inferior to standard L-AmB therapy, a confirmatory phase III clinical trial is needed. A single induction dose would markedly reduce drug-acquisition costs (>4-fold) and markedly shorten and simplify treatment, which are key points in terms of increased access.

Pregnancy rates and clinical outcomes among women living with HIV enrolled in HPTN 052.

HPTN 052 was a multi-country clinical trial of cART for preventing heterosexual HIV-1 transmission. The study allowed participation of pregnant women and provided access to cART and contraceptives. We explored associations between pregnancy and clinical measures of HIV disease stage and progression. Of 869 women followed for 5.70 (SD = 1.62) years, 94.7% were married/cohabitating, 96% initiated cART, and 76.3% had >2 past pregnancies. Of 337 women who experienced pregnancy, 89.3% were from countries with lower contraceptive coverage, 56.1% first started cART with PI-based regimens and 57.6% were 25-34 years old. Mean cART duration and condom use were similar among pregnant and nonpregnant individuals. Adjusting for confounders, viral load suppression (VLS) was not (aHR(CI) = 0.82(0.61, 1.08)) and CD4 was slightly associated with decreased rates of first pregnancy over time (aHR(CI) = 0.9(0.84, 0.95)); baseline VLS was associated with increased (aRR(CI) = 2.48(1.71, 3.59)) and baseline CD4 was slightly associated with decreased number of pregnancies (aRR(CI) = 0.9(0.85,0.96)) over study duration. Partner seroconversion was univariably associated with higher rates of first pregnancy (HR(CI) = 2.02(1.32,3.07)). Despite a background of higher maternal morbidity and mortality rates, our findings suggest that becoming pregnant does not pose a threat to maternal health in women with HIV when there is access to medical care and antiretroviral treatment.

The Effect of Partnership Presence and Support on HIV Viral Suppression Among Serodiscordant Partnered and Single Heterosexual HIV-Positive Individuals in Brazil.

HIV-negative individuals in serodiscordant partnerships experience reduced risk of HIV acquisition when their partners adhere to ART and achieve undetectable viral loads. Partnership support may encourage ART adherence, reducing viral load and the risk of HIV transmission. This study aims to determine whether HIV viral suppression is associated with partnership status and partnership support among 201 HIV positive (HIV+ individuals in serodiscordant partnerships and 100 HIV+ unpartnered individuals receiving care at Hospital Nossa Senhora da Conceição in Porto Alegre, Brazil between 2014 and 2016. Clinical data and patient-reported questionnaire data were assessed, and propensity scores were used to control for confounding variables in adjusted logistic regression models. Viral suppression did not significantly differ between HIV+ partnered (78.5% virally suppressed) and unpartnered (76.0% virally suppressed) individuals. Among individuals in partnerships, viral suppression was significantly associated with having a partner who attended monthly clinic visits (AOR 2.99; 95% CI 1.00-8.93). Instrumental social support-attending monthly visits-may improve the odds of viral suppression among HIV+ individuals in serodiscordant relationships.

Association of NR1I2 gene polymorphisms and time of progression to AIDS.

BACKGROUND: The time of progression towards AIDS can vary greatly among seropositive patients, and may be associated with host genetic variation. The NR1I2 (PXR) gene, a ligand-activated transcription factor, regulates the transcription immune pathway genes and can therefore be targets of viral replication mechanisms influencing time of progression to AIDS. OBJECTIVE: To verify the association of single nucleotide polymorphisms (SNPs) rs3814057, rs6785049, rs7643645, and rs2461817 in the NR1I2 (PXR) gene with progression to AIDS in HIV-1 infected patients. METHODS: Blood samples were obtained from 96 HIV-1 positive individuals following informed consent. DNA was isolated and genotyped through real time polymerase chain reaction (PCR) for the presence of SNPs in the NR1I2. Questionnaires on socio-demographic features and behaviors were answered and time of progression to AIDS was estimated based on medical chart analysis. FINDINGS: Patients with the GG genotype for rs7643645 were shown to be related with a more rapid disease progression when compared to GA and AA genotypes. This result was maintained by the Multivariate Cox Regression considering sex, ethnicity, and presence of HLA-B*57, HLA-B*27, and CCR5del32 polymorphisms. MAIN CONCLUSIONS: Recent studies reported the expression of the nuclear receptors in T-Lymphocytes, suggesting their possible role in the immune response. In addition, nuclear receptors have been shown to inhibit the HIV replication, although no such mechanism has been thoroughly elucidated to date. This is the first time an association between NR1I2 polymorphism and time of progression to AIDS is reported and supports an apparent relationship between the gene in the immune response and identifies another genetic factor influencing AIDS progression.

HIV testing of male partners of pregnant women in Porto Alegre, Brazil: a potential strategy for reduction of HIV seroconversion during pregnancy.

Pregnant women have a significantly higher risk of HIV acquisition during gestation than their non-pregnant counterparts due to behavioral and biological factors. Acute seroconversion during gestation results in increased HIV mother-to-child transmission rates and has been identified as a major public health challenge. In order to address potential HIV seroconversion in our pregnant patients, we conducted a prospective cohort study to evaluate the acceptability of offering HIV testing to sexual partners of HIV-negative pregnant women receiving antenatal care at two hospitals in Porto Alegre, Brazil. Over a 14-month study period, HIV-negative pregnant women at two hospital-based clinic sites were encouraged to bring their stable sexual partner for HIV voluntary counseling and testing during prenatal care. Women were re-interviewed following delivery to measure success of the intervention. Of the 1223 HIV-negative pregnant women enrolled in the study, 663 (54%) of their male sexual partners received HIV testing during antenatal care and 4 (0.6%) were diagnosed with HIV infection. A total of 645 women were interviewed at the time of delivery, with 620 (97%) confirming that HIV testing was suggested to their partner. The most common reason provided by women as to why partners did not come for testing was work (69%) and lack of perceived risk (14%). Independent predictors of successful partner testing included being white (odds ratio [OR] 1.59, 95% confidence interval [CI] 1.18-2.12), married (OR 1.78, 95% CI 1.08-2.94), having an older age of sexual debut (OR 0.94, 95% CI 0.9-0.98), and being recruited at Hospital Conceiçao (OR 2.1, 95% CI 1.52-2.88). We conclude that HIV partner testing during prenatal care is acceptable, rendering this intervention attractive to public health programs targeting prevention of sexually transmitted infections.

HIV voluntary counseling and testing of couples during maternal labor and delivery: the TRIPAI Couples study.

BACKGROUND: Women in Brazil are routinely tested for HIV-1 during pregnancy with rapid testing repeated during labor in some settings. Partner testing is not routinely offered. The peripartum period provides opportunity for HIV testing of couples. METHODS: A cross-sectional study was conducted in a large public hospital in southern Brazil. HIV rapid testing was offered to all pregnant women in labor. Male partners of women who consented to partner inclusion were offered testing. Within HIV-serodiscordant couples, HIV-negative individuals were evaluated for the delta-32 base-pair CCR5 deletion allele. RESULTS: From February to September 2009, 2888 women delivered, with 1729 eligible women approached for study participation; 1648 (95%) HIV-negative women consented to partner testing and 66% of partners accepted testing. Seven HIV-infected men (0.6%) with no prior diagnosis were identified. Testing strategies uncovered 7 additional serodiscordant couples, 4 HIV-infected women diagnosed at delivery, and 3 HIV-infected men who had not disclosed their status to their partners, for a total serodiscordance rate of 1.3% in 1101 couples. No cases of acute maternal or infant infection were noted. No delta-32 base-pair deletions were identified in 14 HIV-negative partners in serodiscordant relationships. Parameters associated with increased acceptance of partner testing included higher income (P = 0.003), education (P < 0.0001), stable relationships of longer duration (P = 0.001), and female support of partner testing (P < 0.0001). CONCLUSIONS: Testing of couples at the time of labor and delivery is a feasible public health strategy in areas of moderate-to-high HIV prevalence, which can potentially prevent acute infections in men, women, and infants.

Cesarean delivery and risk of HIV vertical transmission in Southern Brazil, 2008-2018.

BACKGROUND: Childbirth via cesarean delivery can prevent intrapartum vertical transmission for women who are not virally suppressed at the time of delivery. Few studies have compared cesarean delivery trends between women living with HIV and women without HIV and have examined the role of cesarean delivery in the prevention of vertical transmission in the era of potent combination antiretroviral therapy. OBJECTIVE: We hypothesized that the cesarean delivery rate is high in women living with HIV compared with women without HIV and that cesarean delivery usage decreases over time among women living with HIV with advances in combined antiretroviral therapy in a country with a high national cesarean delivery rate. This study aimed (1) to evaluate cesarean delivery trends in women with and without HIV and (2) to examine its role in preventing vertical transmission among women living with HIV in a setting of free, universal combined antiretroviral therapy coverage in a retrospective cohort of nearly 56,000 deliveries at a major referral institution in a city with the highest prevalence of maternal HIV in Brazil. STUDY DESIGN: Data from maternal-infant pairs from January 1, 2008, to December 31, 2018, were extracted. Cesarean delivery rates were compared using the Pearson chi-square test. Cesarean delivery predictors were evaluated by multivariate log-linear Poisson regression using a generalized estimating equations approach. HIV viral suppression was defined as a viral load of <1000 copies/ml at delivery. HIV vertical transmission was determined following national guidelines. RESULTS: Over 11 years, 48,688 pregnancies occurred in 40,375 women; HIV seroprevalence was 2.7%; 18,886 cesarean deliveries (38.8%) were performed; 47.7% of women living with HIV and 38.6% of women without HIV underwent cesarean delivery (P<.001). Although HIV was associated with cesarean delivery (adjusted relative risk, 1.17 [95% confidence interval, 1.05-1.29]), women living with HIV with vertical transmission achieved similar cesarean delivery rates (36.7%) as women without HIV (39.8%) in 2018. Cesarean delivery in women living with HIV with an unknown viral load at delivery (42.6%) did not increase over time. HIV vertical transmission rate was 2.2%, the highest in women living with HIV with an unknown viral load (8.4%) vs women living with HIV without vertical transmission (4.1%) and women living with HIV with vertical transmission (0.5%) (P<.001). CONCLUSION: In the HIV epicenter of Brazil, women living with HIV with vertical transmission had fewer surgical deliveries, likely because of the use of potent combination antiretroviral therapy. Nearly half of the women living with HIV with an unknown viral load did not undergo cesarean delivery, a potential missed opportunity for the prevention of HIV vertical transmission.

Efficacy and safety of three antiretroviral regimens for initial treatment of HIV-1: a randomized clinical trial in diverse multinational settings.

BACKGROUND: Antiretroviral regimens with simplified dosing and better safety are needed to maximize the efficiency of antiretroviral delivery in resource-limited settings. We investigated the efficacy and safety of antiretroviral regimens with once-daily compared to twice-daily dosing in diverse areas of the world. METHODS AND FINDINGS: 1,571 HIV-1-infected persons (47% women) from nine countries in four continents were assigned with equal probability to open-label antiretroviral therapy with efavirenz plus lamivudine-zidovudine (EFV+3TC-ZDV), atazanavir plus didanosine-EC plus emtricitabine (ATV+DDI+FTC), or efavirenz plus emtricitabine-tenofovir-disoproxil fumarate (DF) (EFV+FTC-TDF). ATV+DDI+FTC and EFV+FTC-TDF were hypothesized to be non-inferior to EFV+3TC-ZDV if the upper one-sided 95% confidence bound for the hazard ratio (HR) was ≤1.35 when 30% of participants had treatment failure. An independent monitoring board recommended stopping study follow-up prior to accumulation of 472 treatment failures. Comparing EFV+FTC-TDF to EFV+3TC-ZDV, during a median 184 wk of follow-up there were 95 treatment failures (18%) among 526 participants versus 98 failures among 519 participants (19%; HR 0.95, 95% CI 0.72-1.27; p = 0.74). Safety endpoints occurred in 243 (46%) participants assigned to EFV+FTC-TDF versus 313 (60%) assigned to EFV+3TC-ZDV (HR 0.64, CI 0.54-0.76; p<0.001) and there was a significant interaction between sex and regimen safety (HR 0.50, CI 0.39-0.64 for women; HR 0.79, CI 0.62-1.00 for men; p = 0.01). Comparing ATV+DDI+FTC to EFV+3TC-ZDV, during a median follow-up of 81 wk there were 108 failures (21%) among 526 participants assigned to ATV+DDI+FTC and 76 (15%) among 519 participants assigned to EFV+3TC-ZDV (HR 1.51, CI 1.12-2.04; p = 0.007). CONCLUSION: EFV+FTC-TDF had similar high efficacy compared to EFV+3TC-ZDV in this trial population, recruited in diverse multinational settings. Superior safety, especially in HIV-1-infected women, and once-daily dosing of EFV+FTC-TDF are advantageous for use of this regimen for initial treatment of HIV-1 infection in resource-limited countries. ATV+DDI+FTC had inferior efficacy and is not recommended as an initial antiretroviral regimen. TRIAL REGISTRATION: www.ClinicalTrials.gov NCT00084136. Please see later in the article for the Editors' Summary.

Risk-taking behavior for HIV acquisition during pregnancy in Porto Alegre, Brazil.

Recent studies suggest that acquisition of HIV-1 infection during pregnancy and breastfeeding is associated with a high risk of HIV mother-to-child transmission. This study evaluates risk factors associated with HIV acquisition during pregnancy in women delivering at a large metropolitan medical facility located in the south of Brazil. From February to August 2009, our group conducted a cross-sectional study assessing women's risk for HIV acquisition by administering an oral survey to peripartum women. Of 2465 participants, 42% (n = 1046) knew that partner had been tested for HIV. During pregnancy, 82% (n = 2022) of participants never used condoms; yet 97% (n = 2399) practiced vaginal sex. Multivariate logistic regression analysis showed that patients with more years of education, in a relationship for more than 1 year, and who knew their own HIV status were more likely to know their partners' HIV status (P < 0.05). Those who were in relationship for more than 1 year and were married/living together were more likely to be comfortable discussing HIV testing with partners (P < 0.05). In conclusion, women in Brazil are at risk of HIV-infection during pregnancy as they remain sexually active, often do not know their sexual partner's HIV status, and have minimal condom use.

Patterns of pregnancy loss among women living with and without HIV in Brazil, 2008-2018.

BACKGROUND: Pregnancy loss is poorly understood, but infection may be a risk factor. Few studies have evaluated pregnancy loss among women living with HIV in the era of potent combination antiretroviral therapy. OBJECTIVE: We hypothesize that maternal HIV and syphilis infection lead to increased risk of pregnancy loss, including both miscarriage and stillbirth. This study aimed to assess trends and possible predictors of spontaneous miscarriage and stillbirth among women living with HIV in a cohort of nearly 56,000 deliveries at a major referral institution in a city with the highest prevalence of HIV in Brazil. STUDY DESIGN: Data from hospital records for women delivering from January 1, 2008 to December 31, 2018 were reviewed. Rates of stillbirth, miscarriage, and any pregnancy loss were compared using the Pearson chi-square test. Predictors of pregnancy loss were evaluated by robust univariate log-linear Poisson regression using a generalized estimating equations approach. RESULTS: A total of 55,844 pregnancies were included in the analysis, with 54,308 pregnancies from 43,502 women without HIV and 1536 pregnancies from 1186 women living with HIV (seroprevalence of maternal HIV: 2.7%). Overall, 1130 stillbirths (2.0%) and 6558 miscarriages (11.7%) occurred. Any pregnancy loss was similar in both groups (13.8% in women without and 14.1% in women with HIV; P=.733). Stillbirth was higher among women living with HIV (3.4%) than among women without HIV (2.0%; P<.001), but there was no difference in overall miscarriage rates (10.7% in women with vs. 11.8% in women without HIV; P=.188). Women living with HIV had higher miscarriage rates between 12 and 20 weeks than women without HIV (34.8% vs 23.7%; P=.001), likely because of syphilis coinfection. Stillbirth rates were higher for women living with HIV from 2008 to 2014; however, a steady plateau was reached from 2014 to 2018, mirroring stillbirth rates in women without HIV. Maternal HIV infection did not increase the risk of miscarriage (relative risk, 0.90; 95% confidence interval, 0.77-1.05) or any pregnancy loss (relative risk, 1.00; 95% confidence interval, 0.88-1.15), but was associated with stillbirth (relative risk, 1.65; 95% confidence interval, 1.23-2.21). Maternal syphilis was associated with any pregnancy loss (relative risk, 1.24; 95% confidence interval, 1.11-1.38) and stillbirth (relative risk, 3.39; 95% confidence interval, 2.77-4.14), but not miscarriage (relative risk, 0.91; 95% confidence interval, 0.80-1.04). CONCLUSION: In the era of combination antiretroviral therapy, there was no difference in miscarriage rates between women with and without HIV. HIV was associated with stillbirth risk but improved over time. Maternal syphilis was significantly associated with any pregnancy loss and stillbirth in all women. Syphilis is likely the main driver of pregnancy loss in women living with HIV in Brazil.

Ineffective penicillin treatment and absence of partner treatment may drive the congenital syphilis epidemic in Brazil.

BACKGROUND: Reducing congenital syphilis has been the focus of Brazilian health programs for decades, yet the cases continue to increase. Although health interventions have targeted HIV screening and treatment, syphilis management continues to be challenging. Syphilis during pregnancy may enhance the HIV maternal seroconversion risk. The potential factors fueling the syphilis epidemic were evaluated in south Brazil, an area of high HIV or syphilis endemicity. OBJECTIVE: We hypothesized that ineffective treatment because of a lack of partner treatment, late presentation to care, and reinfection of previously treated mothers were potential drivers of syphilis mother-to-child transmission. STUDY DESIGN: Data on women diagnosed with syphilis during pregnancy between January 1, 2008 and December 31, 2018 were obtained from a large urban hospital in Porto Alegre, Brazil. The patients were stratified into effective vs ineffective treatment groups according to the World Health Organization guidelines. Crude and adjusted risk ratios for the prediction of congenital syphilis and adverse fetal or neonatal outcomes were computed using Poisson regression. RESULTS: Nearly 56,000 pregnant women delivered over the 11-year period; 1541 (2.8%) had confirmed syphilis during pregnancy, with 934 (61%) receiving ineffective syphilis treatment because of late presentation and diagnosis, delayed treatment initiation, and loss to follow-up with no treatment recorded. Ineffective treatment was associated with maternal education, prenatal care, timing of syphilis diagnosis, venereal diseases research laboratory titers, and maternal HIV coinfection. On multivariate regression analysis, ineffective treatment (adjusted risk ratio, 4.52; 95% confidence interval, 2.35-8.69), absence of prenatal care (adjusted risk ratio, 9.31; 95% confidence interval, 3.77-23.0), syphilis diagnosis at delivery (adjusted risk ratio, 3.08; 95% confidence interval, 2.07-4.58), and maternal nontreponemal titers ≥1:64 (1.09-1.93) were associated with an increased risk of fetal loss. Ineffective treatment (adjusted risk ratio, 1.71; 95% confidence interval, 1.59-1.84), year of diagnosis 2014 to 2016 (adjusted risk ratio, 1.07; 95% confidence interval, 1.02-1.13), absence of prenatal care (adjusted risk ratio, 1.44; 95% confidence interval, 1.17-1.76), and maternal nontreponemal titers >1:4 were associated with an increased risk of congenital syphilis. Although partner treatment reduced the congenital syphilis risk (adjusted risk ratio, 0.60; 95% confidence interval, 0.55-0.66), only 31.8% of partners received treatment. Maternal HIV coinfection was not associated with an increased risk of fetal loss, low birthweight, preterm birth, congenital syphilis, or symptomatic neonatal infection. CONCLUSION: Public health initiatives promoting effective syphilis treatment in pregnancy, increased access to high-quality prenatal care, and partner treatment should be considered to reduce congenital syphilis.

Prospective cohort study of children exposed to hepatitis C virus through a pregnancy screening program.

OBJECTIVES: Porto Alegre, in south Brazil, has one of the highest hepatitis C virus (HCV) infection rates in the country (84.4 cases/100 000 in 2018). Prenatal screening of HCV, however, has not been routinely offered. METHODS: A longitudinal study of pregnant women with HCV and their infants was conducted between January 2014 and December 2018. Screening for HCV antibodies was offered to all women delivering at the study tertiary institution. HCV RT-PCR was performed if the woman was seropositive. Infants were followed prospectively. RESULTS: Among 18 953 pregnant women delivering infants during the study period, 17 810 were screened for HCV antibodies (93.9%) with 130 positive results (HCV seroprevalence 0.7%). HCV-RNA was detectable in 57/117 cases (48.7%). HCV viremia was associated with the use of injectable drugs (P = 0.03), inhaled/crack drug use (P = 0.02), having an HCV-seropositive partner, and ≥3 lifetime sexual partners (P < 0.01). Genotype 1 was most prevalent (68%) during pregnancy. Among 43 children with follow-up, six (13%) were HCV-infected (transmission rate 13.9%); 50% were infected with genotype 3. Two infants (33%) cleared their infection; the mothers had genetic polymorphisms associated with clearance. CONCLUSION: HCV vertical transmission was high in the study population, with HCV infection during pregnancy being vastly underdiagnosed. Public health efforts must focus on this vulnerable population for disease prevention and early treatment.

Increased IL-8 levels in HIV-infected individuals who initiated ART with CD4+ T cell counts <350 cells/mm3 - A potential hallmark of chronic inflammation.

The identification of inflammatory markers in HIV+ individuals on ART is fundamental since chronic ART-controlled HIV infection is linked to an increased inflammatory state. In this context, we assessed plasma levels of pro-inflammatory cytokines (IL-1ß, IL-8, and IL-12p70) of HIV+ individuals who initiated ART after immunosuppression (CD4+ T cell counts <350 cells/mm3). HIV+ individuals were stratified according to two extreme phenotypes: Slow Progressors (SPs; individuals with at least 8 years of infection before ART initiation) and Rapid Progressors (RPs; individuals who needed to initiate ART within 1-4 years after infection). A control group was composed of HIV-uninfected individuals. We found increased IL-8 levels (median: 5.13 pg/mL; SPs and RPs together) in HIV-infected individuals on ART as compared to controls (median: 3.2 pg/mL; p = 0.04), although no association with the progression profile (slow or rapid progressors) or CD4+ T cell counts at sampling was observed. This result indicates that IL-8 is a general marker of chronic inflammation in HIV+ individuals on ART, independently of CD4+ T cell counts at the beginning of the treatment or of the potential progression profile of the patient. In this sense, IL-8 may be considered a possible target for novel therapies focused on reducing inflammation in chronic HIV infection.

Delayed diaphragmatic hernia after open trauma with unusual content: Case report.

INTRODUCTION: Post-traumatic diaphragmatic hernias are not commonly diagnosed immediately after the initial trauma. There is a greater prevalence of left hernias due to the fragility or injury in diaphragm muscle and the lack of solid and fixed structures on the left side. PRESENTATION OF CASE: A male patient, 30 years old, he was admitted to the emergency department presenting diffuse abdominal pain, vomiting, dyspnea, pain in the left hemithorax with worsening during forced inspiration. After performing X-ray and computed tomography (CT), the presence of organs in the abdominal cavity outside the usual position was evidenced and with discrete deviation. Immediate surgery was performed with posterolateral thoracic access through the sixth left intercostal space combined with left subcostal access. Initially, it was found jejunum, ileum and left colonic flexure and accessory spleen filling the hernial sac. DISCUSSION: This report is the first case to report two accessory spleens in manual reduction of herniation between thoracic and abdominal cavities after trauma and percutaneous perforation. The splenectomy performed in both organs occurred due to their advanced ischemia that was due to reduced vascularity. CONCLUSION: The presence of the reported accessory spleen inside the thoracic cavity is only a possible variation within the possibilities in cases of diaphragmatic hernias, which does not modify the surgical procedure in a relevant way.

HIV-1 heterosexual transmission and association with sexually transmitted infections in the era of treatment as prevention.

OBJECTIVES: HIV-1 heterosexual transmission among individuals on antiretroviral treatment (ART) with undetectable viremia is extremely rare. The aim of this study was to evaluate the risk of sexual HIV-1 transmission and other sexually transmitted infections (STIs) in HIV-1 serodifferent couples while the index partner is on ART. METHODS: HIV transmission was evaluated in 200 HIV-1 heterosexual serodifferent couples in a stable relationship (≥3 months). All HIV-positive individuals had been on ART for ≥3 months and had been followed up for a median preceding time of 4.5 years (range 0.3-16 years) at the HIV couples clinic at Hospital Nossa Senhora da Conceição in Porto Alegre, Brazil. Following written informed consent, participants responded to demographic/behavioral questionnaires. Quantitative PCR for HIV RNA, T-cell subsets, and STI testing (syphilis, herpes, human papillomavirus, gonorrhea, and bacterial vaginosis) were performed. Self-collected vaginal swabs were obtained for quantitative HIV genital viral load testing. RESULTS: Among 200 couples, 70% of index partners were female. Five seroconversions were observed; the HIV infection incidence was 2.5% (95% confidence interval 0.8% to 5.7%). Mean plasma viral load results were higher in HIV transmitters compared to non-transmitters (p=0.02). The presence of STIs was significantly greater in couples who seroconverted (60.0% vs. 13.3%; odds ratio 9.75, 95% confidence interval 1.55-61.2; p=0.023). The duration of undetectable HIV viremia and presence of STIs were associated with HIV transmission. CONCLUSIONS: Undetectable viremia was the main factor associated with non-transmissibility of HIV in this setting.

Antiretroviral adherence and virologic suppression in partnered and unpartnered HIV-positive individuals in southern Brazil.

BACKGROUND: An undetectable serum HIV-1 load is key to effectiveness of antiretroviral (ARV) therapy, which depends on adherence to treatment. We evaluated factors possibly associated with ARV adherence and virologic response in HIV-infected heterosexual individuals. METHODS: A cross-sectional study was conducted in 200 HIV-1 serodiscordant couples and 100 unpartnered individuals receiving ARV treatment at a tertiary hospital in southern Brazil. All subjects provided written informed consent, answered demographic/behavioral questionnaires through audio computer-assisted self-interviews (ACASI), and collected blood and vaginal samples for biological markers and assessment of sexually transmitted infections (STIs). HIV-negative partners were counseled and tested for HIV-1. RESULTS: The study population mean age was 39.9 years, 53.6% were female, 62.5% were Caucasian, 52.6% had incomplete or complete elementary education, 63.1% resided in Porto Alegre. Demographic, behavioral and biological marker characteristics were similar between couples and single individuals. There was an association between adherence reported on ACASI and an undetectable serum viral load (P<0.0001). Logistic regression analysis demonstrated that single-tablet ARV-regimens were independently associated with adherence (OR = 2.3; 95CI%: 1.2-4.4; P = 0.011) after controlling for age, gender, education, marital status, personal income, ARV regimen, and median time of ARV use. A positive correlation between genital secretion PCR results and serum viral load was significant in the presence of STIs (r = 0.359; P = 0.017). Although HIV PCR detection in vaginal secretions was more frequent in women with detectable viremia (9/51, 17.6%), it was also present in 7 of 157 women with undetectable serum viral loads (4.5%), p = 0.005. CONCLUSIONS: ARV single tablet regimens are associated with adherence. Detectable HIV-1 may be present in the genital secretions of women with undetectable viremia which means there is potential for HIV transmission in adherent individuals with serologic suppression.

Histoplasmosis, An Underdiagnosed Disease Affecting People Living With HIV/AIDS in Brazil: Results of a Multicenter Prospective Cohort Study Using Both Classical Mycology Tests and Histoplasma Urine Antigen Detection.

BACKGROUND: Histoplasmosis is highly endemic in the American continent. This condition is associated with a high mortality, particularly in people living with HIV/AIDS (PLWHA). Diagnosis of histoplasmosis is usually late in South America, as Histoplasma antigen detection is rarely available. Here we determined the prevalence, risk factors, and outcome of histoplasmosis in PLWHA in Brazilian hospitals. METHODS: This was a prospective cohort study (2016-2018) involving 14 tertiary medical centers in Brazil. We included hospitalized PLWHA presenting with fever and additional clinical findings. Patients were investigated at each participant center with classical mycology methods. Also, Histoplasma antigen detection was performed in urine samples (IMMY). Probable/proven histoplasmosis was defined according to European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group/National Institute of Allergy and Infectious Diseases Mycoses Study Group criteria. RESULTS: From 616 eligible patients, 570 were included. Histoplasmosis was identified in 21.6% (123/570) of patients. Urine antigen testing increased the diagnostic yield in 53.8%, in comparison with standard mycology methods. Variables independently associated with histoplasmosis were CD4+ count <50 cells/mm3, use of an antiretroviral (protective effect), and sample collection in the Northeast region of Brazil. Dyspnea at presentation was independently associated with death. Histoplasmosis was more frequent than tuberculosis in patients with low CD4+ counts. Overall 30-day mortality was 22.1%, decreasing to 14.3% in patients with antigen-based diagnosis. CONCLUSIONS: Histoplasmosis is a very frequent condition affecting PLWHA in Brazil, particularly when CD4+ counts are lower than 50 cells/mm3. Antigen detection may detect earlier disease, with a probable impact on outcomes. Access to this diagnostic tool is needed to improve clinical management of PLWHA in endemic countries.

Sexual transmission of HIV-1 among serodiscordant couples in Porto Alegre, southern Brazil.

BACKGROUND: A cohort of 93 heterosexual HIV serodiscordant couples with no prior antiretroviral use were identified in a large referral center from February 2000 to January 2006 in southern Brazil. METHODS: Review of clinic records retrospectively identified 56 cases of untreated index cases whereas 37 couples were identified prospectively. Demographics, medical, and laboratory data were obtained. During follow-up, 41/93 index cases (44%) initiated antiretrovirals (ARVs) and from 52 without ARV use, 4 were lost to follow-up. Median viral loads were used to compare transmitters versus nontransmitters (Mann-Whitney test). RESULTS: Sixty-seven (72%) index cases were female (49% identified during ante-natal care). Unprotected sexual intercourse as a risk factor for HIV-1 infection was significantly higher as compared to intravenous drug use (P < 0.0001) in female index partners but not in male index cases. Sexually transmitted diseases were identified in 22 cases (24%). Six HIV-1 seroconversions occurred (6.5%). In all cases index partners were not using ARVs at the time of seroconversion. Among 26 couples with a male index case, there were 4 seroconversions (15%) and among 67 female index cases there were 2 seroconversions (3%). All seroconversions occurred with virus loads >1000 copies/mL. Eight female index cases (22%) reported no condom use. CONCLUSIONS: Heterosexual transmission occurred more frequently from HIV-infected males to females (rate ratio 3.5; CI, 95% 0.8-16.5 P = 0.259), although without statistical significance, probably because of the small sample. Transmitters showed significantly higher median viral loads (P = 0.042) suggesting that heterosexual transmission of HIV is more a function of viral load than gender of index case. ARV use may play a role in the prevention of HIV-1 heterosexual transmission. Other factors may be involved and should be further evaluated in larger cohorts.

High CXCL10/IP-10 levels are a hallmark in the clinical evolution of the HIV infection.

The aim of this study was to investigate the modulation of plasma CXCL10, CCL20, CCL22, CCL2, CCL17 and CCL24 levels in HIV-positive patients grouped according to extreme phenotypes of progression to AIDS, and at different stages of HIV infection. HIV-positive individuals with extreme phenotypes of AIDS progression (n=58) at different clinical stages (chronic individuals, both pre-HAART and under-HAART) and HIV-negative controls (n=20) were evaluated. Additionally, HIV-positive individuals that initiated HAART with >350CD4+T-cells/mm3 were compared with those who initiated treatment with <350CD4+T-cells/mm3. Plasma levels of six chemokines were quantified by a Luminex assay. Higher CXCL10 levels were observed in individuals immediately before their CD4+T-cell levels were indicative for HAART (pre-HAART), independently of their progressor status, i.e. slow (SPs) or rapid progressors (RPs). SPs pre-HAART showed higher CXCL10 levels compared to elite controllers and RPs under HAART (pc=0.009 and pc=0.007, respectively). CXCL10 levels were higher in SPs HAART CD4<350 (initiated HAART with <350 CD4+T-cells) when compared with SPs HAART CD4>350 (initiated HAART with >350 CD4+T-cells) (1096 vs. 360.33pg/mL, p=0.0101). Normalisation of CXCL10 levels seems to depend on the CD4+T-cell nadir at HAART initiation. CCL20 levels were higher in chronic SPs, SPs pre-HAART, SPs HAART and RPs HAART compared with the HIV-negative controls, indicating persistent CCL20 expression. In conclusion, our results indicate that CXCL10 levels are a hallmark in the clinical evolution of HIV infection. However, our results must be verified in a study evaluating a larger number of AIDS progressors.