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BackgroundSafe and potent antiretroviral medications in child-friendly formulations are needed to treat young children living with HIV-1. We aimed to select dosing for a dispersible tablet formulation of dolutegravir that achieved pharmacokinetic exposures similar to those in adults, and was safe and well tolerated in young children.MethodsInternational Maternal Pediatric Adolescent AIDS Clinical Trial (IMPAACT) P1093 is a phase 1-2 ongoing multicentre, open-label, non-comparative study of dolutegravir. A 5 mg dispersible tablet formulation of dolutegravir was studied in children aged 4 weeks to less than 6 years old, weighing at least 3 kg, with HIV RNA of greater than 1000 copies per mL and no previous treatment with integrase strand transfer inhibitor recruited from IMPAACT clinical research sites in Africa, the Americas, and Asia. Doses were selected on the basis of intensive pharmacokinetic evaluation on days 5-10, with safety and tolerability assessed up to 48 weeks. The primary objectives of this study are to evaluate the pharmacokinetics of dolutegravir in combination with optimised background therapy and to establish the dose of dolutegravir that achieves the targeted 24-h trough concentration and 24-h area under the curve for infants, children, and adolescents with HIV-1, to establish the safety and tolerability of dolutegravir at 24 and 48 weeks, and to select a dose that achieves similar exposure to the dolutegravir 50 mg once daily dose in adults. This analysis included participants treated with the proposed dose of dolutegravir dispersible tablets in two stages for each of three age cohorts. This trial is registered at ClinicalTrials.gov (NCT01302847) and is ongoing.FindingsWe recruited 181 participants from April 20, 2011, to Feb 19, 2020; of these, 96 received dolutegravir dispersible tablets. This analysis included 73 (35, 48% female) participants who received the final proposed dose with median (range) age of 1 year (0·1 to 6·0), weight (minimum-maximum) of 8·5 kg (3·7 to 18·5), plasma HIV-1 RNA concentration of 4·2 log10 copies per mL (2·1 to 7·0), and CD4% of 24·0% (0·3 to 49·0); 64 (87·7%) were treatment-experienced. The selected dose within each age cohort (≥2 years to

Resumo Neste estudo investigamos como vivências de estigma do HIV se expressam entre jovens soropositivos, em transição para a clínica de adultos, no serviço de saúde, na família e nas interações afetivos-sexuais e sua relação com as desigualdades e hierarquias sociais. O estudo envolveu 31 jovens (idade mediana 21) em transição para a clínica de adultos (G1) e 12 jovens (idade mediana 30) que já fizeram essa transição (G2), ambos atendidos num serviço de saúde do Rio de Janeiro. Dentre os 43 jovens, 70% eram mulheres e 65% foi infectado por transmissão vertical. Os jovens responderam a questionários e participaram de grupos focais sobre estigma da aids e passagem para a vida adulta. A maioria relatou situações de discriminação associadas ao estigma do HIV na vida cotidiana e no cuidado em saúde. Os jovens do G1 revelaram maior preocupação com as consequências da revelação do HIV e dificuldades com o tratamento. Os relatos do G2 sugerem que a constituição de relações conjugais, incluindo parceiro/a e filhos soronegativos e o acesso ao tratamento, possibilitaram resignificar o receio da estigmatização. Os achados visam orientar a formação e ação de profissionais envolvidos na prevenção e cuidado de jovens vivendo com HIV. Abstract This study analyzes how experiences of HIV-related stigma are expressed among HIV-positive young people transitioning to an adult clinic, the health service, the family, the affective-sexual interactions, and their relationship with inequalities and social hierarchies. This research included 31 young people (median age 21) transitioning to an adult clinic (G1) and 12 young people (median age 30) who had already made this transition (G2), both monitored at a health service in Rio de Janeiro. Seventy percent of the 43 young people were women and 65% were infected by mother-to-child transmission. Young people answered questionnaires and participated in focus groups on AIDS stigma and transition to adulthood. Most reported discrimination associated with HIV stigma in daily life and health care. G1 young people showed more significant concern about the consequences of HIV disclosure and difficulties with treatment. The G2 accounts suggest that establishing marital relationships, including HIV-negative partners and children, linked to treatment access allowed resignifying the fear of stigmatization. The findings aim to guide the training and action of professionals involved in the prevention and care of young people living with HIV.

Few studies have compared the clinical efficacy and adverse events of combined antiretroviral therapy (cART) regimens in pregnant women seeking obstetrical care. The objective of this study was to compare the efficacy (virus load response), adverse events, and obstetrical and neonatal outcomes of three different regimens of cART in HIV-infected pregnant women initiating treatment in Rio de Janeiro, Brazil. This was a retrospective cohort study of cART-naive pregnant women who initiated either ritonavir-boosted protease inhibitors (atazanavir or lopinavir), efavirenz, or raltegravir plus a backbone regimen. From 2014 to 2018, 390 pregnant women were followed over time. At baseline, the median viral load (VL) for HIV was 4.1 log copies/ml. Among participants who received cART for 2 to 7 weeks, the VL decline was greater for raltegravir (2.24 log copies/ml) than for efavirenz or protease inhibitors (P < 0.001). Virologic suppression was achieved in 87% of women on raltegravir near delivery versus 73% on efavirenz and 70% on protease inhibitors (P = 0.011). Patients on raltegravir achieved virologic suppression faster than those on other regimens (P = 0.019). Overall, the HIV perinatal infection rate was 1.5%. This clinical study compared three potent and well-tolerated cART regimens and demonstrated that a higher proportion of participants on raltegravir achieved an undetectable HIV VL near delivery (P = 0.011) compared to the other arms. These findings suggest that raltegravir-containing regimens are optimal regimens for women with HIV initiating treatment late in pregnancy.

The aim of this study was to evaluate the concordance between two versions of the scoring system (2011 and 2019), recommended by the Brazilian Ministry of Health, for the diagnosis of pulmonary tuberculosis (PTB) in children and adolescents. A retrospective descriptive study was performed to assess the medical records of children and adolescents with PTB, in TB units from Brazilian cities located in Rio de Janeiro, Minas Gerais, and Parana States, from January 1 st , 2004, to December 1 st , 2018. Patients aged 0 to 18 years old with a diagnosis of PTB were included. The comparison between the two scoring systems showed a moderate concordance according to the κ coefficient value = 0.625. Fourteen patients showed a reduction in the TB score, going from 30 points in the 2011, to 25 points or less in the 2019 one. Seventy one percent of these 14 patients had radiological changes suggestive of PTB and 86% had tuberculin skin tests greater than 10 mm. The study concluded that a moderate agreement was observed between the 2011 and 2019 scoring systems, with an increase in the number of patients scoring 25 points or less in 2019, which can eventually hinder the diagnosis of PTB.

Despite the investment in prevention of mother-to-child transmission of HIV, there is still little data about the proportion of women that are retained in treatment after pregnancy in Brazil. Research worldwide shows that a significant proportion of women drop out of treatment after pregnancy. The aim of this study was to identify factors associated with treatment dropout of women that received prenatal care at a federal hospital in Rio de Janeiro between 2016 and 2017 and abandoned treatment after pregnancy. This was a retrospective cohort study using data on prescription refills and hospital medical records. Cross-sectional analysis of data from 454 women showed that 18% were not on cART after pregnancy. Illicit drug use during pregnancy, being less than 35 years old, and being aware of HIV diagnosis before conceiving but not taking cART were factors associated with treatment interruption postpartum. The high prevalence of interruption of HIV treatment after pregnancy suggests that there is a need for better post-natal care to increase adherence in this population.

This study analyzes how experiences of HIV-related stigma are expressed among HIV-positive young people transitioning to an adult clinic, the health service, the family, the affective-sexual interactions, and their relationship with inequalities and social hierarchies. This research included 31 young people (median age 21) transitioning to an adult clinic (G1) and 12 young people (median age 30) who had already made this transition (G2), both monitored at a health service in Rio de Janeiro. Seventy percent of the 43 young people were women and 65% were infected by mother-to-child transmission. Young people answered questionnaires and participated in focus groups on AIDS stigma and transition to adulthood. Most reported discrimination associated with HIV stigma in daily life and health care. G1 young people showed more significant concern about the consequences of HIV disclosure and difficulties with treatment. The G2 accounts suggest that establishing marital relationships, including HIV-negative partners and children, linked to treatment access allowed resignifying the fear of stigmatization. The findings aim to guide the training and action of professionals involved in the prevention and care of young people living with HIV.Neste estudo investigamos como vivências de estigma do HIV se expressam entre jovens soropositivos, em transição para a clínica de adultos, no serviço de saúde, na família e nas interações afetivos-sexuais e sua relação com as desigualdades e hierarquias sociais. O estudo envolveu 31 jovens (idade mediana 21) em transição para a clínica de adultos (G1) e 12 jovens (idade mediana 30) que já fizeram essa transição (G2), ambos atendidos num serviço de saúde do Rio de Janeiro. Dentre os 43 jovens, 70% eram mulheres e 65% foi infectado por transmissão vertical. Os jovens responderam a questionários e participaram de grupos focais sobre estigma da aids e passagem para a vida adulta. A maioria relatou situações de discriminação associadas ao estigma do HIV na vida cotidiana e no cuidado em saúde. Os jovens do G1 revelaram maior preocupação com as consequências da revelação do HIV e dificuldades com o tratamento. Os relatos do G2 sugerem que a constituição de relações conjugais, incluindo parceiro/a e filhos soronegativos e o acesso ao tratamento, possibilitaram resignificar o receio da estigmatização. Os achados visam orientar a formação e ação de profissionais envolvidos na prevenção e cuidado de jovens vivendo com HIV.

BackgroundDespite great progress made in methods to prevent mother-to-child transmission of HIV (MTCT), delivery and uptake of these measures remains a challenge in many countries. Although the Brazilian Ministry of Health aimed to eliminate MTCT by 2015, infection still occured in 15-24% of infants born to HIV-infected mothers. We sought to identify remaining factors that constrain MTCT elimination.MethodsWe conducted a retrospective, matched case-control study by reviewing hospital charts of infants born to HIV-infected mothers between 1997 and 2014 at three MTCT reference hospitals in the Rio de Janeiro metropolitan area. Cases were defined as HIV-exposed children with two positive HIV tests before 18months of age; controls were defined as HIV-exposed children with two negative HIV tests before 18months of age. We performed bivariate and MTCT cascade analyses to identify risk factors for MTCT and gaps in prevention services.ResultsWe included 435 infants and their mothers (145 cases, 290 controls). Bivariate analyses of MTCT preventative care (PMTCT) indicated that cases were less likely to complete all individual measures in the antenatal, delivery, and postnatal period (p

Hospital Federal dos Servidores do Estado. Infectious Diseases Department. Rio de Janeiro, RJ, Brazil. Universidade Federal do Rio de Janeiro. Instituto de Biologia. Departamento de Gen?tica. Laborat?rio de Biologia Molecular. Rio de Janeiro, RJ, Brazil. Hospital Federal dos Servidores do Estado. Infectious Diseases Department. Rio de Janeiro, RJ, Brazil / Funda??o Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brazil. Hospital Federal dos Servidores do Estado. Infectious Diseases Department. Rio de Janeiro, RJ, Brazil / Funda??o Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brazil. Universidade Federal do Rio de Janeiro. Instituto de Biologia. Departamento de Gen?tica. Laborat?rio de Biologia Molecular. Rio de Janeiro, RJ, Brazil. Universidade Federal do Rio de Janeiro. Instituto de Biologia. Departamento de Gen?tica. Laborat?rio de Biologia Molecular. Rio de Janeiro, RJ, Brazil. Universidade Federal do Rio de Janeiro. Instituto de Biof?sica Carlos Chagas Filho. Laborat?rio de Gen?mica Estrutural. Rio de Janeiro, RJ, Brazil. Universidade Federal do Rio de Janeiro. Instituto de Biof?sica Carlos Chagas Filho. Laborat?rio de Gen?mica Estrutural. Rio de Janeiro, RJ, Brazil. Universidade Federal do Rio de Janeiro. Instituto de Biologia. Departamento de Gen?tica. Laborat?rio de Biologia Molecular. Rio de Janeiro, RJ, Brazil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Hospital Federal dos Servidores do Estado. Infectious Diseases Department. Rio de Janeiro, RJ, Brazil. Hospital Federal dos Servidores do Estado. Maternal-Fetal Unit. Rio de Janeiro, RJ, Brazil. University of California at San Francisco. Department of Epidemiology and Biostatistics. San Francisco, California, United States of America. BACKGROUND: Zika virus (ZIKV) was first isolated in Uganda in 1947. In Brazil, the first reported case of ZIKV infection was in May 2015. Additionally, dengue (DENV) is endemic and there has been a recent outbreak of chikungunya (CHIKV). Since the clinical manifestations of different arboviral infections (AI) can be similar, definitive diagnosis requires laboratory testing. OBJECTIVES: To determine the prevalence of ZIKV, DENV, and CHIKV infections in a Brazilian cohort of HIV-infected pregnant women, to assess clinical/immunological characteristics and pregnancy outcomes of women with evidence of recent AI. STUDY DESIGN: Laboratory diagnosis of ZIKV, DENV and CHIKV infections utilized serological assays, RT-PCR and PRNT. The tests were performed at the first visit, 34-36 weeks of gestation and at any time if a woman had symptoms suggestive of AI. Mann-Whitney tests were used for comparison of medians, Chi-square or Fisher's to compare proportions; p< 0.05 was considered statistically significant. Poisson regression was used to analyze risk factors for central nervous system (CNS) malformations in the infant according to maternal symptomatology. RESULTS: Of 219 HIV-infected pregnant women enrolled, 92% were DENV IgG+; 47(22%) had laboratory evidence of recent AI. Of these, 34 (72%) were ZIKV+, nine (19%) CHIKV+, and two (4%) DENV+. Symptoms consistent with AI were observed in 23 (10%) women, of whom 10 (43%) were ZIKV+, eight (35%) CHIKV+. No CNS abnormalities were observed among infants of DENV+ or CHIKV+ women; four infants with CNS abnormalities were born to ZIKV+ women (three symptomatic). Infants born to ZIKV+ women had a higher risk of CNS malformations if the mother was symptomatic (RR = 7.20), albeit not statistically significant (p = 0.066). CONCLUSIONS: Among HIV-infected pregnant women with laboratory evidence of a recent AI, 72% were ZIKV-infected. In this cohort, CNS malformations occurred among infants born to both symptomatic and asymptomatic pregnant women with Zika infection.

Objective The aim of the current study was to evaluate the safety of a new reduced protein (2.1 g/100 kcal) infant formula containing 4 g/L of 90% galacto-oligosaccharides (GOS) and 10% fructo-oligosaccharides (FOS). Methods Healthy term infants from Brazil were enrolled. Those born to human immunodeficiency virus (HIV)-positive mothers were randomized to a test ( n = 65) or control ( n = 63) formula group. Infants born to HIV-negative mothers were either exclusively breast-fed ( n = 79) or received a mixed diet (breast milk and test formula, n = 65). Between 2 weeks and 4 months of age, infants were exclusively fed according to their assigned group. Anthropometric measurements were taken at baseline, 1, 2, 3, 4, 6, 8, 10, and 12 months. Digestive tolerance was evaluated during the first 4 months. The primary outcome was mean daily weight gain between 2 weeks and 4 months in the test formula and breast-fed groups. Results Data from all infants ( N = 272) were used in the intention-to-treat (ITT) analysis and data from 230 infants were used in the per-protocol (PP) analysis. The difference in mean daily weight gain between 2 weeks and 4 months in the test formula and breast-fed groups was 1.257 g/day (onesided 95% confidence interval [CI]: -0.705 to inf, P < 0.001) in the PP analysis, showing that the lower bound of the 95% CI was above the -3.0 g/day non-inferiority margin. Results were similar in the ITT analysis. Symptoms of digestive tolerance and frequency of adverse events were similar in the two groups. Conclusions The formula containing 2.1 g/100 kcal protein and GOS and FOS was safe and tolerated well.

Introduction : The HIV epidemics in the Caribbean, Central America and South America (CCASA), Eastern Europe (EE) and Asia and Pacific (AP) regions are diverse epidemics affecting different key populations in predominantly middle-income countries. This narrative review describes the populations of HIV-positive youth approaching adolescence and adulthood in CCASA, EE and AP, what is known of their outcomes in paediatric and adult care to date, ongoing research efforts and future research priorities. Methods : We searched PubMed and abstracts from recent conferences and workshops using keywords including HIV, transition and adolescents, to identify published data on transition outcomes in CCASA, EE and AP. We also searched within our regional clinical/research networks for work conducted in this area and presented at local or national meetings. To give insight into future research priorities, we describe published data on characteristics and health status of young people as they approach age of transition, as a key determinant of health in early adulthood, and information available on current transition processes. Results and discussion : The perinatally HIV-infected populations in these three regions face a range of challenges including parental death and loss of family support; HIV-related stigma and socio-economic disparities; exposure to maternal injecting drug use; and late disclosure of HIV status. Behaviourally HIV-infected youth often belong to marginalized sub-groups, with particular challenges accessing services and care. Differences between and within countries in characteristics of HIV-positive youth and models of care need to be considered in comparisons of outcomes in young adulthood. The very little data published to date on transition outcomes across these three regions highlight some emerging issues around adherence, virological failure and loss to follow-up, alongside examples of programmes which have successfully supported adolescents to remain engaged with services and virologically suppressed. Conclusions : Limited data available indicate uneven outcomes in paediatric services and some shared challenges for adolescent transition including retention in care and adherence. The impact of issues specific to low prevalence, concentrated epidemic settings are poorly understood to date. Outcome data are urgently needed to guide management strategies and advocate for service provision in these regions. Keywords HIV; transition; youth; adolescents; loss to follow-up; adherence; outcomes; paediatric (Published: 16 May 2017) Bailey H et al. Journal of the International AIDS Society 2017, 20(suppl 3) :21475 http://www.jiasociety.org/index.php/jias/article/view/21475 | http://dx.doi.org/10.7448/IAS.20.4.21475

We describe a case of Zika virus infection acquired during the first trimester in a HIV-infected pregnant woman that led to multiple fetal malformations and fetal demise in Rio de Janeiro, Brazil.

Background Low maternal vitamin D has been associated with preterm birth (PTB). Human immunodeficiency virus (HIV)-infected pregnant women are at risk for PTB, but data on maternal vitamin D and PTB in this population are scarce. Methods In a cohort of Latin American HIV-infected pregnant women from the National Institute of Child Health and Human Development International Site Development Initiative protocol, we examined the association between maternal vitamin D status and PTB. Vitamin D status was defined as the following 25-hydroxyvitamin D levels: severe deficiency ( Results Of 715 HIV-infected pregnant women, 13 (1.8%) were severely vitamin D deficient, 224 (31.3%) were deficient, and 233 were (32.6%) insufficient. Overall, 23.2% (166/715) of pregnancies resulted in PTB (median GA of PTBs = 36 weeks [interquartile range: 34–36]). In multivariate analysis, severe vitamin D deficiency was associated with PTB (odds ratio = 4.7, 95% confidence interval: 1.3–16.8]). Conclusion Severe maternal vitamin D deficiency is associated with PTB in HIV-infected Latin American pregnant women. Further studies are warranted to determine if vitamin D supplementation in HIV-infected women may impact PTB.

Methicillin-resistant Staphylococcus aureus (MRSA) colonization has been linked to HIV-related sexual and social behaviors. MRSA risk factors may be different for HIV-infected children, adolescents and young adults. We investigated the association of MRSA colonization, persistent colonization and genotypes with potential risk factors among HIV-infected youth.For this case-control study, patients 24 years of age or younger attending 2 HIV reference centers were recruited from February to August 2012 and followed for 1 year. Nasal swabs were collected at enrollment and every 3 months. MRSA clones were characterized by staphylococcal chromosomal cassette mec typing, spa typing and multilocus sequence typing. We compared MRSA colonization and persistent colonization with patient demographic and clinical characteristics.Among 117 participants, MRSA colonization frequency (calculated for each collection based on the number of positive cultures per patient) was 12.8% at the first collection. The average MRSA colonization frequency was 10.4%. Our results showed 11.1% were persistent carriers (subjects with more than 1 positive culture in at least 3). Crowding was the only factor associated with MRSA colonization (P = 0.018). Persistent carriers had significantly higher (4.2 times) odds of living in a crowded household (95% confidence interval-1.1-16.2). We observed high genetic diversity among MRSA isolates, with t002/ST5 and t318/ST30 being the most frequent.MRSA colonization among HIV-infected youth is more closely related to living in a low-income or slum community than to HIV-related clinical factors. High genetic MRSA isolate diversity in our population suggests frequent transmission.

Challenges to the adherence to combination antiretroviral therapy among the pediatric population should be understood in the context of the trajectories of families, their interaction with healthcare services, and their access to material and symbolic goods. The present study analyzed individual, institutional and social factors that might be associated with the caregivers' role in the treatment adherence of children and adolescents living with HIV (CALHIV). Based on semi-structured interviews and questionnaires applied to 69 caregivers seen at pediatric AIDS services of five Brazilian macro-regions, we observed that adherent caregivers had better acceptance of diagnosis and treatment, were less likely to face discrimination and social isolation secondary to AIDS-related stigma and tended to believe in the efficacy of treatment, and to be more optimistic about life perspectives of CALHIV. Interventions aiming to improve adherence and to promote the health of CALHIV should take in consideration the interplay of such different factors.

Our objective was to describe viral suppression and antiretroviral (ARV) resistance mutations in an ongoing cohort of perinatally-infected HIV+ (PHIV+) pregnant women. Descriptive analysis was performed using SPSS 18.0. From 2011 to 2014, we followed 22 PHIV+ pregnant women. Median age at prenatal entry was 19 years (Interquartile range (IQR) 17.6–21.0); 86% had an AIDS diagnosis; 81% had disclosed their HIV status to partner 11. The median age at HIV diagnosis was 8.3 y (IQR 4.0–13.6), the median age at sexual debut was 16 years (IQR 14–18). At the time of prenatal care initiation, four (18%) were on their first antiretroviral treatment (ART), eight (36%) in their second regimen and nine (41%) in their third regimen or beyond, and one had no data. Seventeen of 22 (77%) had HIV-viral load (VL) > 50 copies/mL at prenatal care entry, 16 had a genotyping exam performed. Seventeen of 22 PHIV+ had VL results near delivery: 7/17 (41%) had VL < 50 copies/mL. Among those who had genotyping at prenatal entry, 11/16 (69%) had mutations associated with ARV resistance. The most frequent major mutations were K103N, M184V, T215, M41L, D67N at reverse transcriptase gene and M46, I54V and V82A at protease gene. No vertical transmissions occurred. Management of pregnancy among PHIV+ is challenging. Individualized ART are needed to achieve viral suppression in a highly ART-exposed subpopulation.

Group B Streptococcus (GBS) is a leading cause of infectious morbidity in newborns. We describe the prevalence of GBS colonization and the serotypes and antibiotic susceptibility profiles of isolates obtained from a cohort of human immunodeficiency virus (HIV)-infected pregnant women. This was a cross-sectional study at a centre for the prevention of mother-to-child transmission of HIV. Vaginal and rectal swabs were collected at 35-37 weeks of gestation from 158 eligible women. GBS isolates were serotyped and antimicrobial susceptibility tests performed. Patient sociodemographic characteristics, CD4 counts and viral loads were abstracted from records. The overall anogenital prevalence of GBS colonization was 49/158 (31.0%): 40/158 (25.3%) for vagina, 19/158 (12.0%) for rectum and 10/158 (6.3%) for both. Predominant serotypes were Ib (34.9%) and Ia (25.6%). All were penicillin-susceptible. Two were resistant to erythromycin (4.0%) and one to clindamycin (2.0%). The colonization rate by GBS was high in this cohort. Serotype Ib was the most frequently identified.

Vertically infected individuals are reaching childbearing age and the new generation of HIV-exposed infants is coming to pediatric care. The authors conducted chart reviews of 15 pregnancies among HIV vertically infected adolescents and young women. Girls were diagnosed with HIV at median age of 10.1 years (range 1.3-20). They started sexual life at a median age of 15 years (range 13-19); median age at pregnancy was 16.9 years (range 14-21.5). Slightly more than 36% had presented an AIDS-defining clinical event have been followed for median 8.5 years (range 2.9-15.8) and had used median two antiretroviral regimens (range 0-7). Fourteen (93.3%) received antiretroviral drugs during pregnancy; median CD4 cell count during pregnancy was 394 (range 117-651) cells/mul and median viral load was 4800 copies/ml (range 50-100 000); 54% had undetectable viral load near delivery. All patients delivered their babies by elective c-section. Median birth weight was 2650 g (range 2085-3595) median length was 47.3 cm (range 42-51) and median gestational age 38 weeks (range 37-39). All newborn received zidovudine for 6 weeks and none was breastfed. Fourteen (93%) infants were considered HIV-uninfected; one was lost to follow-up. The authors concluded that this group of adolescents seems to have sexual behavior similar to that of HIV-uninfected youth. Since this is an experimented antiretroviral population new drugs may be necessary for adequate viral suppression to avoid mother-to-child transmission of HIV. Follow-up of this third generation of HIV-exposed infants needs to be addressed within HIV adolescent care.

This study assessed the relationship between the body mass index (BMI) of HIV-1-infected women and their infants' perinatal outcomes. The study population consisted of women enrolled in the NICHD International Site Development Initiative (NISDI) Perinatal Study with data allowing calculation of the BMI adjusted for length of gestation (adjBMI), who delivered singleton infants. Outcome variables included infant growth parameters at birth (weight, BMI, length and head circumference) and gestational age. Of 697 women from Argentina, the Bahamas, Brazil and Mexico who were included in the analysis, the adjBMI was classified as underweight for 109 (15.6%), normal for 418 (60.0%), overweight for 88 (12.6%) and obese for 82 (11.8%). Median infant birth weight, BMI, birth length and head circumference differed significantly according to maternal adjBMI (P

OBJECTIVE: To describe trends in sociodemographic, immunological and virological profiles and interventions to decrease the risk of mother-to-child HIV transmission. METHODS: Retrospective cohort study conducted at a tertiary institution in Rio de Janeiro, Brazil from January 1996 to December 2004. Analysis was performed by stratification in three time periods: 1996-1998 (P1), 1999-2001 (P2) and 2002-2004 (P3). RESULTS: In 9 years, 622 pregnancies occurred. Complications included: maternal mortality 0.3%, stillbirths 2.5%, miscarriages 0.6%, neonatal mortality 1.1%, prematurity 9.9%, low birth weight (LBW) 16.5%, congenital malformations 2.2%. The number of HIV-infected pregnant patients grew threefold over time reflecting increased prevalence of disease and patient identification. HIV diagnosis before pregnancy increased from 30% in P1 to 45% in P3. The proportion of pregnant women receiving highly active antiretroviral therapy increased from none (P1) to 88% (P3) with a significant trend towards women delivering at undetectable viral loads in later years despite a higher frequency of advanced disease. Scheduled cesarean deliveries increased from 35% in P1 to 48% in P3. Perinatal transmission rates were 2.4% with a decline from 3.5% in P1 to 1.6% in P3. Neonatal outcomes tended to remain constant or improve with time. A slight rise in LBW and congenital malformations were observed. CONCLUSIONS: During the observational period, HIV+ pregnant women presented with more advanced disease and lower socio-economic status. However, improved management of HIV-infected patients (associated with increased identification and increased availability of treatment) resulted into very low transmission rates similar to those of developed countries with overall improvement of patient outcomes. OBJETIVOS: Descrever as tendências temporais nas características sociodemográficas, imunológicas e virológicas e as das condutas utilizadas para reduzir o risco da transmissão mãe-filho do HIV. MÉTODOS: Estudo de coorte retrospectivo em uma instituição de saúde terciária no Rio de Janeiro de janeiro de 1996 a dezembro de 2004. A análise utilizou a estratificação em três períodos de tempo: 1996-1998 (P1), 1999-2001 (P2) e 2002-2004 (P3). RESULTADOS: Em 9 anos, 622 gestações foram acompanhadas. As complicações foram: mortalidade materna 0,3%, natimortos 2,5%, abortos 0,6%, mortalidade neonatal 1,1%, prematuridade 9,9%, baixo peso ao nascer (BPN) 16,5%, malformações congênitas 2,2%. O número de gestantes HIV positivo triplicou ao longo do tempo, refletindo o aumento da prevalência da doença e a melhor identificação das pacientes. O diagnóstico da infecção pelo HIV antes da gestação aumentou de 30% em P1 para 45% em P3. A proporção de gestantes recebendo o tratamento combinado potente aumentou de zero em P1 para 88% em P3 com uma tendência significativa a ter uma carga viral abaixo do limite de detecção no parto nos últimos anos apesar de uma maior proporção de pacientes com doença mais avançada. O índice de cesarianas eletivas aumentou de 35% em P1 para 48% em P3. A taxa de transmissão perinatal global foi de 2,4% caindo de 3,5% em P1 para 1,6% em P3. Os desfechos neonatais tenderam a permanecer constantes ou a melhorar ao longo do tempo. Um discreto aumento dos índices de BPN e de malformações congênitas foi observado. CONCLUSÕES: Ao longo do período de estudo aumentou a proporção de gestantes HIV positivo com doença mais avançada e com padrão socioeconômico mais baixo. Por outro lado, a melhora da abordagem terapêutica dos pacientes infectados pelo HIV, associada a uma maior detecção de casos e maior acesso ao tratamento, resultou em uma redução da taxa de transmissão igualando-se à observada em países desenvolvidos com melhora concomitante de outros desfechos.

The availability of highly potent antiretroviral treatment during the last decades has transformed human immunodeficiency virus (HIV) infection into a chronic disease. Children that were diagnosed during the first months or years of life and received treatment, are living longer and better and are presently reaching adolescence and adulthood. Perinatally HIV-infected adolescents (PHIV) and young adults may present specific clinical, behavior and social characteristics and demands. We have performed a literature review about different aspects that have to be considered in the care and follow-up of PHIV. The search included papers in the MEDLINE database via PubMed, located using the keywords "perinatally HIV-infected" AND "adolescents". Only articles published in English or Portuguese from 2003 to 2014 were selected. The types of articles included original research, systematic reviews, and quantitative or qualitative studies; case reports and case series were excluded. Results are presented in the following topics: "Puberal development and sexual maturation", "Growth in weight and height", "Bone metabolism during adolescence", "Metabolic complications", "Brain development, cognition and mental health", "Reproductive health", "Viral drug resistance" and "Transition to adult outpatient care". We hope that this review will support the work of pediatricians, clinicians and infectious diseases specialists that are receiving these subjects to continue treatment.

To evaluate the prevalence and predictors of low vitamin D status among pregnant women with HIV infection.The present cross-sectional study analyzed repository specimens collected at 12-34 weeks of pregnancy among women enrolled across 17 sites in Latin America and the Caribbean between 2002 and 2009. Logistic regression modeling was used to identify factors associated with low vitamin D status (25-hydroxyvitamin D30 ng/mL).Among 715 women, 218 (30.5%) were vitamin D deficient (20 ng/mL) and 252 (35.2%) were insufficient (21- /mL). Factors associated with low vitamin D status included residence in subtropical latitudes (adjusted odds ratio [aOR] 1.97, 95% confidence interval [CI] 1.35-2.88), assessment during non-summer seasons (autumn: aOR 1.85, 95% CI 1.20-2.86; spring: 4.3, 2.65-6.95; winter: 10.82, 5.74-20.41), employment (aOR 1.56, 95% CI 1.06-2.38), and assessment before 20 weeks of pregnancy (aOR 1.89, 95% CI 1.18-3.06). Factors protective against low vitamin D status were CD4 count below 200 cells per mm(3) (aOR 0.45, 95% CI 0.26-0.77) and protease inhibitors (aOR 0.62, 95% CI 0.40-0.95).Low vitamin D status was prevalent among pregnant women with HIV infection. Further studies are warranted to identify the impact of low maternal vitamin D status.

Objective The purpose of this study was to complete an evaluation of nevirapine (NVP) toxicity in a cohort of HIV+ pregnant women. Study design This was a retrospective study of 611 women followed from January 1996 to December 2003. All women who used NVP for >7 days were included. Multivariate logistic regression was used to test independent association of CD4 and hepatitis C virus (HCV) infection related to the outcome of toxic effects of NVP. Results One hundred ninety-seven women were exposed to NVP for >7 days, and toxicity occurred in 11 (5.6%), leading to drug discontinuation in 7 patients. One case of Stevens-Johnson syndrome occurred. No serious liver toxicity occurred except for 1 grade 4 cholestasis. Median CD4 was 344 in women without toxicities and 298 in women with toxicities. HCV was the only significant factor associated to toxicity by logistic regression (odds ratio [OR] 15.61, P = .001). Conclusion NVP toxicities occurred in a very small fraction of patients and were not associated with fatalities.

In order to understand antiretroviral resistance during pregnancy and its impact on HIV vertical transmission, we performed a cross-sectional analysis of 231 HIV-infected pregnant women who fulfilled Brazilian guidelines for antiretroviral testing and had antiretroviral genotypic testing performed between April 2010 and October 2012. At entry into prenatal care, the mean CD4 cell count for this cohort of patients was 406 cells/mm3 (95% CI: 373–438 cells/mm3), while the mean HIV RNA was 24,394 copies/ml (95% CI: 18,275–30,513 copies/ml). Thirty-six women (16%) had detectable antiretroviral-resistant mutations. By 34 weeks gestation, 75% had achieved HIV RNA 3 was eight times that of subjects with CD4 cell counts >500 CD4 cells/mm3 (95% CI 1.5–42.73). Six infants were HIV infected, four born to mothers with detectable viraemia at 34 weeks and two born to mothers who were lost to follow up. Antiretroviral resistance is common in prenatal care but did not increase vertical transmission if viral load was appropriately suppressed. Genotyping should be considered in Brazil in order to assist initiation of appropriate combination antiretroviral therapy during pregnancy to suppress viral load to avoid vertical transmission.

HIV-infected children usually live in vulnerable situations, experiencing discrimination and stigma commonly felt by other people living with HIV/AIDS. The present study aims to analyse primary socialisation of HIV-infected children and adolescents recruited from a public health service in Rio de Janeiro (Brazil) as a social process that shapes a new generation of stigmatised and vulnerable persons. Research was informed by an interactionist perspective, focusing on key aspects of HIV-infected children and adolescents life histories under the conceptual frame of Erving Goffman's theories regarding "moral careers". Goffman defines the making of a moral career as the process through which a person learns that she/he possesses a particular attribute, which may lead her/him to be discredited by members of the surrounding society. We have identified aspects of life histories of HIV-vertically infected children and adolescents for each aspect of "moral career" as described by Goffman, relating them to as family structure, the experience of living HIV within the family, and the position and family role of a given subject. The patterns of "moral career" proposed by Goffman in 1963 were useful in identifying components of HIV-related stigma among children and adolescents. These include gender and social disadvantages, difficulty in coping with a child with a potentially severe disease, orphanhood, abandonment, adoption and disclosure of one's HIV serostatus. Primary socialisation of HIV-infected children and adolescents is a key piece of the complex HIV/AIDS-labelling process that could be targeted by interventions aiming to decrease stigma and marginalisation. Health care workers and stakeholders should be committed to ensuring education and guaranteeing the legal rights of this specific population, including the continuous provision of quality health care, full access to school and support to full disclosure of HIV diagnosis.

Highly active antiretroviral therapy (HAART) has resulted in dramatic decreases in morbidity and improved survival for adults and children with HIV infection [1–3]. However, even as the risk of AIDS-defining illness has decreased, other complications have become more significant causes of morbidity and mortality in long-term survivors. Liver failure and cirrhosis have emerged as leading non-AIDS causes of illness and death in HIV-infected adults, especially in those with hepatitis B (HBV) or C (HCV) co-infection [4]. While co-infections, hepatotoxic antiretroviral medications (ARVs) and other drugs, severe immunosuppression, alcohol use and other traditional (non-HIV-specific) risk factors for hepatic dysfunction have been implicated, hepatic fibrosis and dysfunction also occur in adults with longstanding HIV infection and no other specific risk factors [5–6]. Hepatitis and liver dysfunction are recognized complications of perinatal HIV infection, but the prevalence of clinically recognized disease appears to be much lower than that in adults [7–9]. However, as these children now survive into adulthood and face lifelong HIV infection and treatment, hepatic dysfunction may emerge as an important cause of morbidity and even mortality. The standard for assessing presence and degree of liver inflammation, fibrosis and cirrhosis is examination of a liver biopsy, but this diagnostic approach is highly invasive and unsuitable for potential hepatic fibrosis screening. The aspartate aminotransferase [AST]-to-platelet ratio index (APRI) is a non-invasive measure of significant hepatic fibrosis that has been used in studies of HIV-mono-infected and HIV/HCV co-infected adults [10–18]. An APRI >1.5 has been validated as evidence of significant liver fibrosis in HIV-HCV co-infected adults [12–14]. In studies of HIV-uninfected children with chronic viral hepatitis and other liver conditions, elevated APRI has been shown to be associated with liver fibrosis - including validation with liver biopsy findings - especially with more advanced stages of liver fibrosis [19–22]. The best APRI cutoff for children has not been established; the adult APRI cutoff of 1.5 appears to be highly specific but relatively insensitive for detection of liver fibrosis in children [19]. APRI has not been previously studied in HIV-infected children. The purpose of this study is to estimate the rate of elevated APRI, as a marker of potential liver fibrosis, in a cohort of perinatally HIV- infected Latin American children.

Viral load (VL) near delivery is a determinant of mother-to-child transmission (MTCT) of HIV. To evaluate factors associated with an undetectable VL near delivery in HIV-infected pregnant women receiving highly active antiretroviral therapy (HAART) and non-HAART regimens, HIV-infected pregnant women with a detectable VL at entry and having used antiretrovirals for ≥4 weeks before delivery were selected. Multivariate analysis was employed using binary logistic unconditional models; the dependent variable was having a VL

OBJECTIVE: HIV-infected adolescents are a heterogeneous population; source of infection immunodeficiency severity and antiretroviral (ARV) experience vary. Here we describe youth followed in an observational study at Latin American sites of the NICHD International Site Development Initiative (NISDI). METHODS: The NISDI pediatric protocol is an ongoing prospective cohort study that collects demographic clinical immunologic virologic and medication data. Youth were enrolled at 15 sites in Brazil Argentina and Mexico between 2002 and 2006. HIV-infected subjects aged 12-21 years at the time of enrollment were analyzed. RESULTS: Data from 120 HIV-infected youth were analyzed. Sixty-nine (58%) had acquired HIV through vertical transmission (VT); 51(42%) via horizontal transmission (HT). Twenty-eight percent of the VT group were not diagnosed until they were >/=10 years of age. Ninety-one percent of the VT group and 46% of the HT were receiving ARV at enrollment. Modes of HT included sexual (ST) blood product transfusion (BPT) and unknown (U). Severe immunodeficiency was frequent (21%) in the ST group. Low BMI was frequent in the VT and BPT sub-groups. Utilization of HAART increased over the course of the study but viral suppression was present in only 38% of the VT group and 37% of the HT group at study end. CONCLUSIONS: This cohort of HIV-infected adolescents in Latin America displayed a diverse epidemiologic pattern. Care providers must be prepared to address the diverse needs and challenges of this population. The levels of virologic suppression achieved were inadequate. Further research into appropriate interventions for this population is urgently needed.

Patients with insulin-dependent diabetes are prone to infection, possibly related to poor metabolic control. Relative immune deficiency exists in pregnancy. We hypothesized that pregnant patients with insulin-dependent diabetes are at an increased risk for infection and that infection is related to poor glycemic control. We matched 65 pregnant women with insulin-dependent diabetes to 65 nondiabetic pregnant controls. At least one episode of infection before delivery occurred in 83% of the women with insulin-dependent diabetes (26% in control group). The rate of postpartum infection was five times higher in the group with insulin-dependent diabetes and they were susceptible to more kinds of infections. Although there was no overall difference among the indices of glycemic control, hemoglobin A1 obtained before the infection was higher than during infection. We conclude that a high rate of infection exists in pregnant women with diabetes; infection and poor glycemic control may be associated, but it is unclear whether improvement in metabolic control will reduce this high infection rate.

Seven Brazilian sites participating in the Pediatric AIDS Clinical Trials Group international cryopreservation quality assurance pilot program cryopreserved and shipped peripheral blood mononuclear cells (PBMC) to a central U.S. laboratory for analysis. Cell viability and recovery significantly increased over time. A wet-laboratory training session conducted at the central laboratory significantly improved the quality of the cryopreserved PBMC.

OBJECTIVE. The goal was to describe the frequency, characteristics, and correlates of infectious disease morbidity during the first 6 months of life among HIV-1–exposed but uninfected infants.METHODS. The study population consisted of infants enrolled in the National Institute of Child Health and Human Development International Site Development Initiative Perinatal Study who were HIV-1 uninfected and had follow-up data through the 6-month study visit. Definitive and presumed infections were recorded at study visits (birth, 6–12 weeks, and 6 months).RESULTS. Of 462 HIV-1–uninfected infants with 11644 child-weeks of observation, 283 experienced ≥1 infection. These 283 infants experienced 522 infections (1.8 infections per infant). The overall incidence rate of infections was 4.5 cases per 100 child-weeks of observation. Overall, the most common infections were skin or mucous membrane infections (1.9 cases per 100 child-weeks) and respiratory tract infections (1.7 cases per 100 child-weeks). Thirty-six percent of infants had >1 respiratory tract infection (1.8 cases per 100 child-weeks). Incidence rates of upper and lower respiratory tract infections were similar (0.89 cases per 100 child-weeks and 0.9 cases per 100 child-weeks, respectively). Cutaneous and/or oral candidiasis occurred in 48 neonates (10.3%) and 92 older infants (19.3%). Early neonatal sepsis was diagnosed in 12 infants (26.0 cases per 1000 infants). Overall, 81 of 462 (17.5%) infants were hospitalized with an infection. Infants with lower respiratory tract infections were hospitalized frequently (40.7%). The occurrence of ≥1 neonatal infection was associated with more-advanced maternal HIV-1 disease, tobacco use during pregnancy, infant anemia, and crowding. Lower maternal CD4+ cell counts, receipt of intrapartum antibiotic treatment, and country of residence were associated with postneonatal infections.CONCLUSIONS. Close monitoring of HIV-1–exposed infants, especially those who are anemic at birth or whose mothers have more-advanced HIV-1 disease or who smoked during pregnancy, remains important.

A cohort of 297 HIV-infected pregnant women was followed from January 1996 to December 2001. The overall transmission rate was 3.57% and remained constant over time. Low birth-weight was independently associated with a higher risk of vertical transmission (P=0.0072), whereas a longer duration of antiretroviral drugs during pregnancy was independently associated with a lower risk of transmission (P = 0.0084). Further decreases in transmission should be obtained by initiating prophylaxis earlier in pregnancy.

We report the occurrence of congenital toxoplasmosis in an infant born to an HIV infected mother who had high anti-toxoplasma IgG and negative IgM at nine weeks of gestation. We briefly review available literature and discuss the possible mechanisms of transmission of congenital toxoplasmosis among HIV infected pregnant women.

Afim de obter dados sobre as manifestações clínicas da leptospirose em crianças, foram revistos 188 exames sorológicos realizados em pacientes com idade entre 0 e 12 anos no Laboratório de Referência Nacional para Leptospirose (FIOCRUZ-RJ) no período de janeiro de 1983 ajunho de 1991. Cinquenta e dois (27,6%) soros eram reagentes. Vinte etrês (12,2%) crianças tinham evidênciasorológica de infecção aguda. Os sinais e sintomas mais freqüentemente encontrados nestes casos foram: febre (100%); mialgias (69,5%); cefaléia (52,1%); icterícia (47,8%); vômitos (34,8%); dores abdominais, manifestações hemorrágicas e disfunção renal (17,4%); conjuntivite (13%); hepatomegalia (4,3%).In order to obtain data about clinical manifestations of symptomatic leptospiral infection in children, the authors reviewed 188 microscopic agglutination tests performed on sera of patients aged 0 to 12 years, made at the National Reference Laboratory of Leptospirosis (FIOCRUZ-RJ) from January 1983 to June 1991. Fifty two (27.6%) sera were positive. Twenty three (12.2%) children had serological evidence of acute infection. The mostfrequent signs and symptoms of these 23 cases were: fever (100%); myalgia (69.5%); headache (52.1%); jaundice (47.8%); vomit (34.8%); abdominal pain, hemorrhagic manifestations and impaired renal function (17.4%); conjunctivitis (13%); hepatomegaly (4.3%).

Objective: To evaluate treatment adherence among perinatally-infected pediatric human immunodeficiency virus (HIV) patients followed in pediatric centers in Brazil. Methods: This was a cross-sectional multicenter study. Medical records were reviewed and adherence scale, assessment of caregivers’ quality of life (WHOQOL-BREF), anxiety, depression, and alcohol/substances use/abuse were assessed. Outcomes included self-reported 100% adherence in the last three days and HIV viral load (VL)