Fabiana Maria Kakehasi

Antiretroviral adherence during pregnancy and postpartum in Latin America

Adherence to antiretrovirals by pregnant women (and postpartum women if breastfeeding) is crucial to effectively decrease maternal viral load and decrease the risk of mother-to-child transmission of HIV. Our objectives were to describe self-reported adherence to antiretrovirals during the antepartum (after 22 weeks of pregnancy) and postpartum periods (6-12 weeks and 6 months), and identify predictors of adherence among HIV-infected women enrolled and followed in a prospective cohort study from June 2008 to June 2010 at multiple sites in Latin America. Adherence was evaluated using the number of missed and expected doses during the 3 days before the study visit. At the pre-delivery visit, 340 of 376 women (90%) reported perfect adherence. This rate significantly decreased by 6-12 weeks (171/214 [80%]) and 6 months postpartum (163/199 [82%], p<0.01). The odds for less than perfect adherence at the pre-delivery visit was significantly higher for pregnant women with current tobacco use (odds ratio [OR]=2.9, 95% confidence interval [CI]: 1.46-6.14; p=0.0029). At 6-12 weeks postpartum, the probability of non-perfect adherence increased by 6% for each 1 year increase in age (OR=1.06, 95% CI: 1.00-1.12, p=0.0497). At 6 months postpartum, the odds of nonperfect adherence was higher for those who were currently using alcohol (OR=3.04, 95% CI: 1.34-6.90; p=0.0079). Although a self-report measure of adherence based on only 3 days may lead to overestimation of actual adherence over time, women with perfect adherence had lower viral loads and higher CD4 counts. Adherence to antiretrovirals decreased significantly postpartum. Interventions should target women at high risk for lower adherence during pregnancy and postpartum, including tobacco and alcohol users.

Prevalence of primary drug resistance-associated mutations among HIV type 1 vertically Infected children in Belo Horizonte, Brazil.

In the past few years there has been increasing concern about the transmission of drug-resistant HIV. This study aimed to describe the frequency of primary mutations associated with HIV-1 drug resistance and the prevalence of genetic HIV subtypes in a population of vertically infected children before the initiation of HAART. At the time of genotypic testing, the median age was 6.0 years (IQR 25-75%: 3.8-9.2) and the median age at admission was 3.84 years (IQR 25-75%: 1.23-6.11). Antepartum maternal ARV exposure for PMTCT occurred for three (7.3%) mothers. According to the WHO criteria, primary ARV resistance mutations were detected in four out of 41 (9.8%) children. Subtype B was the most prevalent (63.4%). The relatively high prevalence of primary HIV-1 DRMs in this cohort of perinatally infected children in Brazil supports the local recommendation to perform resistance testing in all newly diagnosed children, regardless of age at diagnosis and antenatal ARV exposure.

Maternal antiretrovirals and hepatic enzyme, hematologic abnormalities among human immunodeficiency virus type 1-uninfected infants: the NISDI perinatal study.

Objectives: To assess hepatic enzyme (HE) and hematologic abnormalities among human immunodeficiency virus-1-uninfected infants according to maternal antiretroviral regimen during pregnancy. Study Design: In a prospective cohort, HE and hematologic values of human immunodeficiency virus-1-uninfected, term infants with hospital discharge (HD) within 6 days after birth were evaluated. Maternal antiretroviral regimens were categorized as: 1 or 2 nucleoside reverse transcription inhibitors (NRTIs), highly active antiretroviral therapy (HAART)/protease inhibitor (PI), or HAART/non-NRTI. Results: Among 503 infants, 63% and 24% had HE and hemoglobin abnormalities, respectively, at HD. Most or all HE and hemoglobin abnormalities (96–100%) were grade 1 or 2. At HD, infants with maternal HAART/PI or HAART/non-NRTI were more likely to have elevated HE [adjusted odds ratio (AOR): 1.9, 2.4, respectively] compared with infants whose mothers received 1 or 2 NRTIs. Infants with maternal HAART/PI were less likely to have abnormal hemoglobin values at HD (AOR, 0.5) when compared with those whose mothers received 1 or 2 NRTIs. Persistently abnormal hemoglobin and HE values decreased with time, such that <10% of infants had abnormalities at 6 months of age. Conclusions: Maternal receipt of HAART regimens was associated with an increased risk of HE abnormalities, and maternal HAART/PI was associated with a lower risk of abnormal hemoglobin values, at HD. Abnormalities of HE and hemoglobin were generally mild and transient.

Perfil das gestantes infectadas pelo HIV atendidas em pré-natal de alto risco de referência de Belo Horizonte

OBJECTIVES: identify HIV infected pregnant women in a referral center and investigate characteristics related to infection and parity. METHODS: a cross-sectional study comprising all HIV infected women treated at the High Risk Prenatal Care in the Hospital das Clinicas da Universidade Federal de Minas Gerais, in 2004. Demographic data, HIV epidemiology infection and obstetrical history were collected. For statistical analysis SPSS 12.0 was used. RESULTS: eighty five women median aged 29.1 and 90 pregnancies were followed-up. In 55 pregnancies (61.1%) women had prior information of the infection. Sixty four (71.1%) informed they lived together. Probably they all acquired HIV in heterosexual relations. Fifty four (60%) were diagnosed during one of the pregnancies. The global pregnancies median was 3.5, and 1.71 following diagnosis. Patients with prior diagnosis had a higher pregnancy median as compared to those who were diagnosed during their pregnancies (p = 0.002). Eighty six pregnant women made use of anti-retroviral medication, 56.7% through therapeutic indication. No vertical transmission cases were determined. CONCLUSIONS: new pregnancies in HIV infected women are not rare notwithstanding contraceptive resources offered. Therefore, further investigations are necessary to identify what difficulties not previously approached they have during routine medical assistance.

Predictors of postpartum viral load rebound in a cohort of HIV-infected Brazilian women

To assess the postpartum viral load of HIV‐infected women treated with potent antiretrovirals (ARVs) during pregnancy, and look for predictors of viral load rebound.

Evaluation of hematological, virologic and anthropometric parameters as progression markers in HIV-1 infected children

OBJECTIVE To analyze total lymphocyte count, total leukocyte count, hemoglobin levels, nutritional status, CD4+ T-lymphocyte count and viral load as markers of disease progression and/or death in HIV-infected children. METHODS This retrospective cohort study assessed antiretroviral naïve HIV-infected children who were asymptomatic or had mild and/or moderate symptoms. The events of interest were: progression to clinical category C (according to the classification of the Centers for Disease Control and Prevention - CDC, 1994) or death. Values of total leukocyte count, total lymphocyte count, hemoglobin, weight-for-age z score, CD4+ T-lymphocyte count and plasma viral load obtained at admission were considered in the risk analysis of events of interest. The population was stratified into age groups: < 12, >or= 12 to < 36, >or= 36 to < 60 months. RESULTS One hundred and twenty patients, admitted between 1997 and 2003, met the inclusion criteria for the present study. The total median of follow-up duration was 7.4 months (25-75% interquartile range = 3.8-21.1). In the multivariate analysis, only CD4+ T-lymphocytes count, according to the categories of the World Health Organization, and weight-for-age z score <or= -2 were predictors of risk for disease progression in children older than 12 months. In children younger than 12 months, none of the variables was associated with risk of progression. CONCLUSION Nutritional status is an important aspect in the assessment of risk of disease progression in HIV-infected children older than 12 months.

HIV-1 RNA detection in the amniotic fluid of HIV-infected pregnant women.

This study is aimed at evaluating the potential to detect human immunodeficiency virus (HIV) in amniotic fluid (AF) collected at delivery from 40 HIV-positive pregnant women. Thirty patients had a plasma viral load (VL) below 1,000 copies/mL at delivery. VL was positive in three AF samples. No significant association was found between the HIV-1 RNA in AF and the maternal plasma samples. There was no HIV vertical transmission detected.

Avaliação dos parâmetros hematológicos, virológicos e antropométricos como marcadores de progressão em crianças infectadas pelo HIV-1

OBJECTIVE: To analyze total lymphocyte count, total leukocyte count, hemoglobin levels, nutritional status, CD4+ T-lymphocyte count and viral load as markers of disease progression and/or death in HIV-infected children. METHODS: This retrospective cohort study assessed antiretroviral naive HIV-infected children who were asymptomatic or had mild and/or moderate symptoms. The events of interest were: progression to clinical category C (according to the classification of the Centers for Disease Control and Prevention - CDC, 1994) or death. Values of total leukocyte count, total lymphocyte count, hemoglobin, weight-for-age z score, CD4+ T-lymphocyte count and plasma viral load obtained at admission were considered in the risk analysis of events of interest. The population was stratified into age groups: 12 to 36 to < 60 months. RESULTS: One hundred and twenty patients, admitted between 1997 and 2003, met the inclusion criteria for the present study. The total median of follow-up duration was 7.4 months (25-75% interquartile range = 3.8-21.1). In the multivariate analysis, only CD4+ T-lymphocytes count, according to the categories of the World Health Organization, and weight-for-age z score ≤ -2 were predictors of risk for disease progression in children older than 12 months. In children younger than 12 months, none of the variables was associated with risk of progression. CONCLUSION: Nutritional status is an important aspect in the assessment of risk of disease progression in HIV-infected children older than 12 months.

Stroke-like encephalopathy following high-dose intravenous methotrexate in an adolescent with osteosarcoma: a case report

Methotrexate (MTX) is an important cytostatic drug in cancer chemotherapy and the most widely used antimetabolite in childhood cancers. It is effective in the treatment of acute lymphoblastic leukemia (ALL), non-Hodgkin lymphoma, histiocytosis and osteosarcoma. Although its mechanism of action is not fully understood, it had been postulated as a cell cycle specific folate that inhibits dihydrofolate reductase achieving elevated levels of homocysteine and excitatory amino acid neurotransmitter metabolites. High dose MTX (HDMTX) is commonly used in the treatment of osteosarcoma.1 It can cause acute, subacute and chronic neurological complications. Stroke-like encephalopathy is a sub-acute MTX neurotoxicity and a rare syndrome that manifests with an abrupt onset of focal neurological deficits.2 It can cause hemiparesis, slurred speech, confusion,

Vertical Transmission of HIV-1 in the Metropolitan Area of Belo Horizonte, Brazil: 2006–2014

OBJECTIVE  To revise HIV-1 vertical transmission (VT) rates in the metropolitan area of Belo Horizonte, Brazil, from January of 2006 to December of 2014. METHODS  Descriptive study of a prospective cohort of HIV-1-infected pregnant women and their children, monitored by the Maternal and Child HIV/Aids Research Group of Research Group at Faculty of Medicine of Universidade Federal de Minas Gerais, Brazil. RESULTS  The VT general rate was 1.9% (13/673; confidence interval [CI] 95%: 1.0-3.3). The extensive use of combined highly active antiretroviral therapy (HAART) (89.7%; 583/650) strongly impacted the reduction of VT during this period. Maternal viral load (VL) higher than 1,000 copies/mL showed significant association with VT (OR:6.6; CI 95%:1.3-33.3). Maternal breastfeeding was described in 10 cases in this cohort (1.5%; CI 95%: 0.7-2.7), but it was not associated with VT. CONCLUSION  The present cohort data were coherent with the low VT rate described in other global populations, and it was considerably lower in comparison to the results of the same cohort during the period of 1998-2005, when the VT rate was 6.2%. These data confirm the efficiency of the National Guidelines, and emphasize the importance of adopting the international recommended procedures for prevention of mother-to-child transmission (MTCT) of HIV.