Thalita F. Abreu

Pregnancy outcome in women infected with HIV-1 receiving combination antiretroviral therapy before versus after conception

Objective: The potential adverse effects of antiretroviral drugs during pregnancy are discrepant and few studies, mostly from Europe, have provided information about pregnancy outcomes of those already on treatment at conception. The aim of this study was to investigate the impact of antiretrovirals (ARVs) on pregnancy outcome according to the timing of treatment initiation in a cohort of pregnant women from Brazil infected with HIV. Methods: A prospective cohort of 696 pregnant women followed up in one single centre between 1996 and 2006 was studied. Patients who had ARV treatment before pregnancy were compared with those treated after the first trimester. The outcomes evaluated were preterm delivery (PTD) (<37 weeks), severe PTD (<34 weeks), low birth weight (LBW) (<2500 g) and very LBW (<1500 g). Results: Patients who were using ARVs pre-conception had higher rates of LBW (33.3% vs 16.5%; p<0.001) and a similar trend for PTD (26.3% vs 17.7%; p = 0.09). Stratification by type of therapy (dual vs highly active antiretroviral therapy (HAART)) according to timing of initiation of ARVs showed that patients who use HAART pre-conception have a higher rate of PTD (20.2% vs 10.2%; p = 0.03) and LBW (24.2% vs 10.2%; p = 0.002). After adjusting for several factors, HAART used pre-conception was associated with an increased risk for PTD (AOR 5.0; 95% CI 1.5 to 17.0; p = 0.009) and LBW (OR 3.6; 95% CI 1.7 to 7.7; p = 0.001). Conclusions: We identified an increased risk for LBW and PTD in patients who had HAART prior to pregnancy.

Successful prevention of HIV transmission from mother to infant in Brazil using a multidisciplinary team approach

OBJECTIVES To determine the HIV vertical transmission rate (VTR) and associated risk factors by use of zidovudine and infant care education in Brazil. METHODS Since 1995, a prospective cohort of HIV infected pregnant women has been followed at the Federal University of Rio de Janeiro. A multidisciplinary team was established to implement the best available strategy to prevent maternal-infant HIV transmission. Patients with AIDS or low CD(4) and high viral load received anti-retroviral drugs in addition to zidovudine. Children were considered infected if they had 2 positive PCR-RNA tests between 1 and 4 months of age, or were HIV antibody positive after 18 months. Education regarding infant treatment and use of formula instead of breast feeding was provided. RESULTS Between 1995 and August, 2000, HIV status was determined for 145 infants. Compliance with intra-partum treatment, infant treatment and use of formula was 88.2%. Intra-partum zidovudine treatment was completed in 134/145 (92.6%) of patients; 88.1% had rupture of membranes < 4 hours; 85.4% of mothers were asymptomatic. The mean CD(4) count was 428.4 cells and mean viral load 39,050 copies. HIV vertical transmission rate was 4/145 (2.75%; CI: 0.1%-5.4%). The only risk factor significantly associated with transmission was a failure to use zidovudine intra-partum in 2 of the 4 mothers (50% versus 6.4% in non-transmitting mothers). A trend toward low CD(4) and high viral load at entry, and rupture of membranes > 4 hours were associated with increased HIV transmission. CONCLUSION HIV vertical transmission in Brazil was reduced to a level similar to other countries with the most effective prevention programs using a multidisciplinary team approach. A high level of compliance for use of anti-retroviral drugs, the provision of health education to mothers, and use of formula for all exposed infants.

Osteomyelitis caused by Paracoccidioides brasiliensis in a child from the metropolitan area of Rio de Janeiro.

The authors describe a case of paracoccidioidomycosis in a 7-year-old girl from the city of Rio de Janeiro who initially presented to her physician with a lesion in her calcaneous which was misdiagnosed and treated as bacterial osteomyelitis. Later, cutaneous manifestations, lymph node enlargement, and hepatosplenomegaly developed and biopsy of the skin and cervical lymph nodes showed the fungus which was also present in the sputum. It is emphasized that Paracoccidioides brasiliensis can be the cause of bone lesions in endemic areas of Latin America and that response to treatment with amphotercin B is good.

Pregnancy in HIV vertically infected adolescents and young women: a new generation of HIV-exposed infants.

Background:Vertically infected individuals are reaching childbearing age and the new generation of HIV-exposed infants is coming to pediatric care. Methods:Chart review of pregnancies among HIV vertically infected adolescents and young women. Results:Fifteen pregnancies were reviewed. Girls had HIV diagnosis at median age 10.1 years (range 1.3–20). They started sexual life at median age 15 years (range 13–19); median age at pregnancy was 16.9 years (range 14–21.5); 36.4% 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/μl and median viral load was 4800 copies/ml (range 50–100 000); 54% had undetectable viral load near delivery. All patients delivered 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 of life and none was breastfed. Fourteen (93%) infants were considered HIV-uninfected; one was lost to follow-up. Conclusions:This group of adolescents seems to have sexual behavior similar to that of HIV-uninfected. Since this is an experimented antiretroviral population, new drugs may be necessary for adequate viral suppression to avoid HIV mother-to-child transmission. Follow-up of this third generation of HIV-exposed infants needs to be addressed within HIV adolescent care.

A pilot study to evaluate the safety and feasibility of the administration of AZT/3TC fixed dose combination to HIV infected pregnant women and their infants in Rio de Janeiro, Brazil

Objectives: To evaluate the safety and feasibility of zidovudine and lamivudine (AZT/3TC) given to HIV infected pregnant women and their infants in Rio de Janeiro, Brazil. Methods: This open label phase II study enrolled 40 HIV infected antiretroviral naive women ⩾20 weeks gestation, CD4 <500 cells ×106/l, from two public hospitals. Treatment: fixed dose AZT 300 mg/3TC 150 mg by mouth every 12 hours until labour; AZT 300 mg by mouth every 3 hours until delivery; infants: AZT 4 mg/kg every 12 hours plus 3TC 2 mg/kg every 12 hours for 6 weeks. Blood haematology and chemistry were monitored; adherence evaluated by pills count; efficacy measured by changes in lymphocyte (CD4) and viral load, and by HIV RNA-PCR tests performed at birth, 6 and 12 weeks, to diagnose infant infection. No women breast fed. Results: Patient characteristics: mean age 24.48 (SD 3.5) years; gestational age 24.5 (4.5) weeks; AZT/3TC duration 14.4 (4.4) weeks; vaginal delivery: 11/39; caesarean section: 28/39. Entry and pre-labour CD4: 310/486 cells ×106/l (p<0.001); entry and pre-labour viral load: 53 818/2616 copies/ml (p<0.001). Thirty nine women tolerated treatment with >80% adherence; one was lost to follow up. Five newborns were excluded from 3TC receipt. All 39 babies were uninfected. Haematological toxicity in newborns was common: anaemia in 27; neutropenia in five (two severe); platelets counts <100 000 in two. All values recovered on study completion. Conclusions: Fixed dose AZT/3TC is well accepted, gives improvements in CD4 and viral load; no infants were HIV infected. Haematological toxicity in infants needs careful monitoring.

Factors associated with lack of antiretroviral adherence among adolescents in a reference centre in Rio de Janeiro, Brazil

The objective of this study was to describe the adherence to antiretroviral therapy (ART) among adolescents followed-up in Rio de Janeiro. This cross-sectional study included all adolescents (aged 10–19 years) followed at Instituto de Puericultura e Pediatria Martagão Gesteira and Hospital Universitário Clementino Fraga Filho. Adherence was determined by self-report (number of missed ART doses in three days prior to the interview). Adherence was categorized as taking ≥95% of the ARTs (adherent), or <95% (non-adherent). Variables related to demographics and treatment were evaluated and if P value ≤0.15, they were selected for a logistic regression analysis. One hundred and one adolescents were interviewed. The mean time on ART was 91 months and the mean adherence was 94% of this, 21 were non-adherent, and 80 adherent. The risk factors associated with non-adherence were: if the patient was not concerned about ART, odds ratio (OR) = 3.47 (95% confidence interval [CI] = 1.13–10.68); if they do not carry an extra dose of ART, OR = 6.63 (95% CI = 1.73–25.47); if a healthcare worker taught them how to take ART, OR = 0.27 (95% CI = 0.08–0.93). Adherence among adolescents was higher than expected. Factors associated with lack of adherence were: interviewees being unaware of ARTs and lack of commitment to the treatment. Interventions involving these factors must be evaluated.

Immunogenicity and safety of meningococcal C conjugate vaccine in children and adolescents infected and uninfected with HIV in Rio de Janeiro, Brazil.

Background: We aimed to evaluate the Meningococcal (Neisseria meningitidis) C conjugated (MCC) vaccine seroconversion and adverse events (AEs) in HIV-infected and HIV-uninfected children and adolescents in Rio de Janeiro, Brazil. Methods: HIV-infected or HIV-uninfected subjects, 2–18 years old, with CD4+ T-lymphocyte cell (CD4) percentage >15%, without active infection or antibiotic use, were enrolled. All patients were evaluated before and 1–2 months after immunization for seroconversion (defined as ≥4-fold titer increase in human serum bactericidal activity) and at 20 minutes, 3 and 7 days after immunization for AEs. Factors associated with seroconversion among HIV-infected group were studied. Results: Two hundred four subjects were enrolled: 154 HIV-infected and 50 HIV-uninfected. Median age was 12 years, and 53% were female. Among the HIV-infected group, 82 (53%) had a history of at least 1 C clinical category of Centers for Diseases Control and Prevention event, and 134 (87%) were using combination antiretroviral therapy. The median nadir CD4 percentage was 13% (0–47%). Seventy-six (37.3%) experienced mild AEs. Seroconversion occurred in 46 of 154 (30%) in the HIV-infected group and in 38 of 50 (76%) in the uninfected group (P < 0.01). Factors associated with seroconversion in the HIV-infected group were as follows: never had a C clinical category event [odds ratio (OR) = 2.1, 95% confidence interval (CI): 1.0–4.4]; undetectable viral load at immunization (OR: 2.4, 95% CI: 1.1–5.2) and higher CD4 nadir/100 cells (OR: 1.1, 95% CI: 1.0–1.2). Conclusion: MCC vaccine should be administered to HIV-infected children and adolescents after maximum immunologic and virologic benefits have been achieved with combination antiretroviral therapy. Our data suggest that a single dose of MCC vaccine is insufficient for HIV-infected individuals 2–18 years of age.

Viral Load Predicts New World Health Organization Stage 3 and 4 Events in HIV-Infected Children Receiving Highly Active Antiretroviral Therapy, Independent of CD4 T Lymphocyte Value

BACKGROUND Many resource-limited countries rely on clinical and immunological monitoring without routine virological monitoring for human immunodeficiency virus (HIV)-infected children receiving highly active antiretroviral therapy (HAART). We assessed whether HIV load had independent predictive value in the presence of immunological and clinical data for the occurrence of new World Health Organization (WHO) stage 3 or 4 events (hereafter, WHO events) among HIV-infected children receiving HAART in Latin America. METHODS The NISDI (Eunice Kennedy Shriver National Institute of Child Health and Human Development International Site Development Initiative) Pediatric Protocol is an observational cohort study designed to describe HIV-related outcomes among infected children. Eligibility criteria for this analysis included perinatal infection, age <15 years, and continuous HAART for ≥6 months. Cox proportional hazards modeling was used to assess time to new WHO events as a function of immunological status, viral load, hemoglobin level, and potential confounding variables; laboratory tests repeated during the study were treated as time-varying predictors. RESULTS The mean duration of follow-up was 2.5 years; new WHO events occurred in 92 (15.8%) of 584 children. In proportional hazards modeling, most recent viral load >5000 copies/mL was associated with a nearly doubled risk of developing a WHO event (adjusted hazard ratio, 1.81; 95% confidence interval, 1.05-3.11; P = .033), even after adjustment for immunological status defined on the basis of CD4 T lymphocyte value, hemoglobin level, age, and body mass index. CONCLUSIONS Routine virological monitoring using the WHO virological failure threshold of 5000 copies/mL adds independent predictive value to immunological and clinical assessments for identification of children receiving HAART who are at risk for significant HIV-related illness. To provide optimal care, periodic virological monitoring should be considered for all settings that provide HAART to children.

Paracoccidioidomycosis in children in the state of Rio de Janeiro (Brazil): Geographic distribution and the study of a "reservarea"

Thirty six cases of acute disseminated paracoccidioidomycosis in 3 to 12 year-old children, natives of the state of Rio de Janeiro, were seen in the period 1981-1996. All patients were residents in the rural region of 15 counties, scattered on the Southwestern part of this state. The rural region of two neighboring counties, where 16 cases (44.4%) occurred, was visited. It exhibited the environmental conditions that are considered favorable to the survival of P. brasiliensis. The most important of these conditions, abundant watercourses and autochthonous forest, are distributed on well defined and limited areas, in which the dwellings are also localized. Probably, a careful epidemiological study of forthcoming cases of the disease in children may facilitate the search for the micro-niche of the fungus.

AIDS in childhood: cardiac involvement with and without triple combination antiretroviral therapy

OBJECTIVE To describe the prevalence of cardiac abnormalities in the echocardiogram of children with AIDS followed up in a reference service at 18+/-6 months of AIDS confirmed diagnosis. METHODS A cross-section study with a cohort after 18+/-6 months of AIDS diagnosis. The study included a total of 93 children with a confirmed diagnosis of AIDS with vertical transmission, with no malignancies and who underwent echocardiogram (echo) during cardiologic evaluation. Cardiac abnormalities were assessed in patients who were not treated (G1) and patients who were treated (G2) with combination antiretroviral therapy. RESULTS When diagnosed with AIDS, the children were on average 3.07 years old and 50.50% were female. The combination regimen with antiretroviral agents was used by 47 patients (G2). Cardiac involvement was present in 40 children (43.00%). The presence of left ventricular dysfunction (G1: 39.10%; G2: 10.60%) and the isolated enlargement of left ventricle (G1: 6.60%; G2: 14.90%) were the most frequent findings. We observed a significant association between the groups without and with combination antiretroviral therapy asregards the presence of left ventricular dysfunction (PR= 3.42; [1.41-8.26]; p = 0.02) and malnutrition (PR = 1.79; [1.00-3.20]; p = 0.04). CONCLUSION Cardiac involvement was frequent in children with AIDS and left ventricular dysfunction was the most common abnormality on echocardiogram. There was a statistically significant difference between the groups with and without triple combination treatment as regards the presence of left ventricular dysfunction and malnutrition.