Laura Freimanis

Maternal antiretroviral drugs during pregnancy and infant low birth weight and preterm birth

Objective:To determine the relationship between maternal antiretroviral regimens during pregnancy and adverse infant outcomes [low birth weight (LBW) and preterm birth]. The a priori hypothesis was that protease inhibitor (PI)-containing regimens are associated with an increased risk of LBW and preterm birth. Design:Prospective cohort study of HIV-1-infected women and their infants (NISDI Perinatal Study). Methods:Data were analysed from 681 women receiving at least one antiretroviral drug [in order of increasing complexity: one or two nucleoside reverse transcriptase inhibitors (1–2 NRTI), two NRTI plus one non-nucleoside reverse transcriptase inhibitor (NNRTI) (HAART/NNRTI), or two NRTI plus one PI (HAART/PI)] for at least 28 days during pregnancy, and who delivered live born, singleton infants with known birth weight and gestational age by 1 March 2005. Multivariable logistic regression modeling was used to assess the relationship of maternal ART with LBW and with preterm birth, adjusting for covariates. Results:The incidence of LBW and preterm birth, respectively, was 9.6% and 7.4% (1–2 NRTI), 7.4% and 5.8% (HAART/NNRTI), and 16.7% and 10.6% (HAART/PI). There was no statistically significant increased risk of LBW [adjusted odds ratio (AOR), 1.5; 95% confidence interval (95% CI), 0.7–3.2] or preterm birth (AOR, 1.1; 95% CI, 0.5–2.8) among women who received HAART/PI compared with women receiving 1–2 NRTI. Conclusions:Among a population of HIV-1-infected women in Latin America and the Caribbean, maternal receipt of PI-containing ART regimens during pregnancy was not associated with a statistically significant increase in risk of LBW or preterm birth.

Infectious Disease Morbidity Among Young HIV-1–Exposed But Uninfected Infants in Latin American and Caribbean Countries: The National Institute of Child Health and Human Development International Site Development Initiative Perinatal Study

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.

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.

Clinical characteristics and outcomes of influenza and other influenza-like illnesses in Mexico City

Summary Background Influenza-like illnesses (ILI) are estimated to cause millions of deaths annually. Despite this disease burden, the etiologic causes of ILI are poorly described for many geographical regions. Methods Beginning in April 2010, we conducted an observational cohort study at five hospitals in Mexico City, enrolling subjects who met the criteria for ILI. Evaluations were conducted at enrollment and on day 28, with the collection of clinical data and a nasopharyngeal swab (or nasal aspirate in children). Swabs were tested by multiplex PCR for 15 viral pathogens and real-time PCR for influenza. Results During the first year, 1065 subjects were enrolled in this study, 55% of whom were hospitalized; 24% of all subjects were children. One or more pathogens were detected by PCR in 64% of subjects, most commonly rhinovirus (25% of all isolates) and influenza (24% of isolates). Six percent of subjects died, and of those, 54% had no pathogen identified. Rhinovirus was the most common pathogen among those who died, although it did not have the highest case fatality rate. Conclusions Multiple respiratory viruses beyond influenza are associated with significant morbidity and mortality among adults and children in Mexico City. Detection of these agents could be useful for the adjustment of antibiotic treatment in severe cases.

Excess respiratory viral infections and low antibody responses among HIV-exposed, uninfected infants

Objective: HIV-exposed uninfected (HEUs) infants have frequent severe infection, hospitalization, and death. We performed a serologic investigation to determine the role of common childhood respiratory pathogens in the excess incidence of infections in HEUs. Design: Prospective cohort study of mother–infant pairs. Methods: Among 247 HEUs and 88 HIV-unexposed uninfected (HUU) infant–mother pairs, we measured maternal antibodies to respiratory syncytial virus (RSV) and pneumococcus (PNC 1, 5, 6B, 14); infant antibodies to RSV, influenza A (flu), parainfluenza viruses (1, 2, 3), and PNC 1, 5, 6B, and 14 were measured at 0 and 6 months, and antitetanus antibodies at 6 months. Results: HIV-infected mothers had higher RSV and lower PNC antibody concentrations at delivery than uninfected mothers. Transplacental transfer of maternal antibodies, particularly for RSV, was lower in HEUs compared with HUUs. At birth, HEUs had higher concentrations of anti-RSV antibodies than HUUs, but lower antibodies to the other respiratory agents. At 6 months, HEUs had significantly higher proportions of seroconversions and higher antibody concentrations against parainfluenza viruses 1, 2, and 3. There were no significant differences in seroconversions to flu and RSV, but antibody concentrations to RSV were six-fold lower in HEUs versus HUUs at 6 months. Antibody responses to at least two doses of tetanus vaccine were also six-fold lower in HEUs compared with HUUs. Conclusion: Six-month-old HEUs had a higher incidence of respiratory viral infections than HUUs. In addition to the low passive protection from maternal antibodies, low antibody responses of HEUs may contribute to increased morbidity and mortality.

Low vitamin D status among pregnant Latin American and Caribbean women with HIV Infection

To evaluate the prevalence and predictors of low vitamin D status among pregnant women with HIV infection.