Persistence of genotypic resistance to nelfinavir among women exposed to prophylactic antiretroviral therapy during pregnancy.

We assessed the development of drug resistance in women exposed to antiretroviral therapy (ART) for prevention of mother-to-child transmission (PMTCT) after 24 weeks postpartum in a prospective cohort of HIV-1-infected women. HIV-1-infected women, who received prophylactic ART during pregnancy, had genotypic resistance testing performed at the start (T1) of and 24 weeks after ART interruption (T2). The women had CD4 counts >250 cells/ml and no AIDS defining conditions. Of the 30 eligible women, the median age was 27 years [25-75% interquartile range (IQR): 21-32] and the median gestational age of ART initiation was 22 weeks (IQR: 19-27): 19 (63.3%) received zidovudine (ZDV) plus lamivudine (3TC) plus nelfinavir (NFV). At entry, most women (96.7%) were asymptomatic (CDC93 A1/A2), with a median CD4 count of 446 (IQR: 353-686) and median viral load (VL) of 8560 copies/ml (IQR: 3,252-19,515). No HIV-1 vertical transmission was observed. HIV subtype B was the most prevalent (70%). The development of new mutations associated with ART resistance was analyzed at T2. NFV resistance was observed in 4 out of 17 (23.5%) patients exposed to this drug: two major mutations D30N (1/17) and L90M (1/17) and minor mutations (N88S, 2/17). Mutations on positions 44, 69, and 118 (1/28) were present on reverse transcriptase (RT) analysis. No new nonnucleoside reverse transcriptase inhibitor (NNRTI)-associated mutation was observed. In this cohort, ART regimens were very efficient at blocking HIV vertical transmission. However, the high rate of NFV-resistant mutations observed in the postpartum period indicates the need for discussion of ART choices during pregnancy and the potential impact on future therapeutic options for these women. Women previously exposed to ART for PMTCT who will start HIV treatment should have genotypic resistance testing performed.

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.

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

Evaluation of hematological, virologic and anthropometric parameters as progression markers in HIV-1 infected children / Avaliação dos parâmetros hematológicos, virológicos e antropométricos como marcadores de progressão em crianças infectadas pelo HIV-1

OBJETIVO: Analisar a utilidade da contagem total de linfócitos, contagem global de leucócitos, hemoglobina, estado nutricional, contagem de linfócitos T CD4+ e carga viral como marcadores de progressão da doença e/ou óbito em crianças infectadas pelo HIV. MÉTODOS: Estudo de coorte retrospectiva em população de crianças infectadas pelo HIV, assintomáticas ou com sintomas leves e/ou moderados e virgens de tratamento antirretroviral. Os eventos de interesse foram: progressão para categoria clínica C (de acordo com a classificação dos Centers for Disease Control and Prevention - CDC, de 1994) ou óbito. Valores da contagem global de leucócitos, contagem total de linfócitos, hemoglobina, escore z peso/idade, contagem de linfócitos T CD4+ e carga viral plasmática obtidos à admissão foram considerados na análise do risco de ocorrência dos eventos de interesse. A população foi estratificada em faixas etárias: <12, > 12 e < 36, > 36 e < 60 meses. RESULTADOS: Cento e vinte pacientes, admitidos entre 1997 e 2003, preencheram os critérios para inclusão deste estudo. A mediana global do tempo de acompanhamento foi de 7,4 meses (intervalo interquartil 25-75% = 3,8-21,1). Em análise multivariada, apenas a contagem de linfócitos T CD4+, segundo as categorias da Organização Mundial da Saúde, e o escore z peso/idade ≤ -2 foram preditores do risco de progressão da doença em crianças maiores de 12 meses de idade. Em menores de 12 meses, nenhuma das variáveis analisadas esteve associada ao risco de progressão. CONCLUSÃO: Evidencia-se a importância do estado nutricional na avaliação do risco de progressão da doença em crianças maiores de 12 meses de idade infectadas pelo HIV.

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, > 12 to < 36, > 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.