To evaluate the effects of antiretroviral treatment (ART) for mother-to-child transmission of HIV and infant/maternal characteristics on total lymphocytes (TLC) and lymphocyte subsets in uninfected ...children of HIV-1-infected mothers.
The European Collaborative Study followed 1663 uninfected children from birth until at least 8 years of age using a standard protocol.
Smoothers (running medians) illustrated patterns of immune markers over age by ART exposure and race. Associations between lymphocyte parameters and maternal/infant characteristics were quantified in linear regression analyses using z-scores obtained after modelling log10-transformed TLC, CD4 and CD8 cell counts using the LMS method. Cox proportional hazard models assessed time to TLC, CD4 and CD8 cell counts below the defined cut-off. Covariates included prematurity, gender, race, drug withdrawal and ART exposure.
Overall, black children had lower TLC, CD4 and CD8 cell counts than white children, and an increased risk of TLC, CD4 and CD8 cell counts below the cut-off. ART exposure was associated with TLC levels (but not with TLC below the cut-off for lymphopenia), with reduced CD4 cell counts in the first year of life, and with reduced CD8 cell counts until at least 8 years of age. Duration and intensity of ART exposure was associated with TLC levels.
The effect of ART exposure in fetal and early life on TLC and CD8 cell counts was prolonged until at least 8 years. These results add to the growing list of adverse effects associated with ART used as prevention of mother-to-child transmission of HIV.
Antiretroviral drugs (ARV) as prophylaxis to prevent mother-to-child transmission of HIV results in decreased haematological parameters during and shortly after exposure, with recent data suggesting ...a more prolonged inhibition of haematopoiesis until at least 18 months.
Data on 156 HIV-infected and 1533 uninfected children in the European Collaborative Study followed from birth until at least 8 years of age.
Smoothers and splines were used to elucidate patterns over age; linear mixed effects allowed for repeated measurements. Covariates included the child's HIV-1 infection status, prematurity, gender, race, drug withdrawal symptoms at birth and ARV exposure; effects on neutrophil count were quantified in regression analyses using z-scores (SD from mean) of neutrophil counts obtained after modelling untransformed values using the LMS method. For HIV-infected children, progression to AIDS and ARV therapy were also included.
After approximately 4 months of age, neutrophil counts were consistently and substantially lower in HIV-infected children than in uninfected children; in both groups, black children had significantly lower counts than white children across the whole age range. In uninfected children, male gender and ARV exposure were associated with reduced neutrophil count until at least 8 years of age. In HIV-infected children, advanced disease and ARV treatment were significantly associated with neutrophil count.
A considerably longer effect of exposure to ARV was shown in uninfected children than previously thought and significant associations were shown between race and gender and neutrophil count, as previously observed for lymphocyte counts. The clinical relevance of these reduced levels of neutrophils requires further investigation.
BackgroundConsiderable uncertainty remains as to whether early initiation of antiretroviral therapy (ART) in children with vertically acquired human immunodeficiency virus (HIV) infection increases ...the benefit in terms of immunological response MethodsThe association between immunological outcome and early initiation of and/or more-potent ART was investigated, using age-standardized z scores for CD4 cell counts (hereafter, “CD4 z scores”), in 131 HIV-infected children enrolled in the European Collaborative Study, a birth cohort study ResultsMedian age at initiation of the most-potent ART was 4 years (range, 0.1–15.5 years). Initiation of treatment after 5 months of age resulted in nonsignificantly lower CD4 z scores 6 months after initiation. Time to a 20% increase in CD4 z score was associated with age at initiation of the most-potent ART (adjusted hazard ratios AHRs, 0.37 P<.01 and 0.43 P=.05 for 5 months–5 years of age and >5 years of age, respectively, compared with <5 months of age), ethnicity (AHR, 0.48 P=.01, for black vs. white), and highly active ART (HAART) with or without prior ART (AHRs, 3.16 P<.01 and 3.95 P<.001, vs. mono or dual ART, respectively). The risk of subsequent deterioration of CD4 z score was similar for children who initiated ART in different age groups (χ2=0.824; P=.82) ConclusionsWe confirm the effectiveness of HAART with respect to the recovery of CD4 cell count and suggest a benefit of initiating ART before the age of 5 months. Age at initiation of the most-potent ART was not associated with the likelihood of sustaining the recovery of CD4 cell count
To estimate RNA viral load patterns over age in vertically infected children that account for between- and within-individual variation, treatment and assay cut-off detection level. To investigate ...possible sex-based differences.
A total of 118 infected children with 894 RNA viral load measurements enrolled in the European Collaborative Study were prospectively followed from birth for up to 15 years.
Fractional polynomial and mixed effects models with censored data to assess the non-linear pattern of viral load over age, allowing for repeated measures.
The RNA viral load peaked at approximately 3 months of age, and gradually declined thereafter. The sex by age interaction was significant (chi2 = 19.7, P < 0.001); viral load peaked higher for girls than boys, but after 4 years the RNA load was consistently 0.25-0.5 log10 lower for girls than boys. The effects of sex and treatment on viral load vary over age (chi2 = 6.31, P = 0.043). Sex differences in RNA viral load relating to measurement without treatment were more pronounced than those under treatment. Disease progression was more rapid for girls than for boys up to the age of 4 years, and less rapid thereafter; the overall difference was not statistically significant.
Differences in RNA viral load over age between untreated boys and girls may have implications for policies for the initiation of antiretroviral therapy, but do not seem to translate into differences in progression to serious disease. The findings would suggest underlying biological explanations, which need further investigation.
Background. There have been no clinical trials in resource-rich regions that have addressed the question of which highly active antiretroviral therapy (HAART) regimens are more effective for optimal ...viral response in antiretroviral-naive, human immunodeficiency virus (HIV)-infected pregnant women. Methods. Data on 240 HIV-1-infected women starting HAART during pregnancy who were enrolled in the prospective European Collaborative Study from 1997 through 2004 were analyzed. An interval-censored survival model was used to assess whether factors, including type of HAART regimen, race, region of birth, and baseline immunological and virological status, were associated with the duration of time necessary to suppress viral load below undetectable levels before delivery of a newborn. Results. Protease inhibitor-based HAART was initiated in 156 women (65%), 125 (80%) of whom received nelfinavir, and a nevirapine-based regimen was initiated in the remaining 84 women (35%). Undetectable viral loads were achieved by 73% of the women by the time of delivery. Relative hazards of time to achieving viral suppression were 1.54 (95% confidence interval, 1.05–2.26) for nevirapine-based HAART versus PI-based regimens and 1.90 (95% confidence interval, 1.16–3.12) for western African versus non-African women. The median duration of time from HAART initiation to achievement of an undetectable viral load was estimated to be 1.4 times greater in women receiving PI-based HAART, compared with women receiving nevirapine-based HAART. Baseline HIV RNA load was also a significant predictor of the rapidity of achieving viral suppression by delivery, but baseline immune status was not. Conclusions. In this study, nevirapine-based HAART (compared with PI mainly nelfinavir-based HAART), western African origin, and lower baseline viral load were associated with shorter time to achieving viral suppression.
Orti et al discuss the neurologic complications of Epstein-Barr virus (EBV) infection and 2 cases of acute EBV infection with predominant and serious neurologic complications in pediatric patients. ...The study shows that neurologic complications of EBV acute infectious mononucleosis are uncommon, but physicians should be aware of it when fever, seizures, ataxia, or hallucinations are present. The use of acyclovir at early stages of severe cases may help result in favorable outcomes although its efficacy is not well documented.
Objectives
The aim of the study was to examine temporal and geographical patterns of mode of delivery in the European Collaborative Study (ECS), identify factors associated with elective caesarean ...section (CS) delivery in the highly active antiretroviral therapy (HAART) era and explore associations between mode of delivery and mother‐to‐child transmission (MTCT).
Methods
The ECS is a cohort study in which HIV‐infected pregnant women are enrolled and their infants prospectively followed. Data on 5238 mother–child pairs (MCPs) enrolled in Western European ECS sites between 1985 and 2007 were analysed.
Results
The elective CS rate increased from 16% in 1985–1993 to 67% in 1999–2001, declining to 51% by 2005–2007. In 2002–2004, 10% of infants were delivered vaginally, increasing to 34% by 2005–2007. During the HAART era, women in Belgium, the United Kingdom and the Netherlands were less likely to deliver by elective CS than those in Italy and Spain adjusted odds ratio (AOR) 0.07; 95% confidence interval (CI) 0.04–0.12. The MTCT rate in 2005–2007 was 1%. Among MCPs with maternal HIV RNA<400 HIV‐1 RNA copies/mL (n=960), elective CS was associated with 80% decreased MTCT risk (AOR 0.20; 95% CI 0.05–0.65) adjusting for HAART and prematurity. Two infants born to 559 women with viral loads <50 copies/mL were infected, one of whom was delivered by elective CS (MTCT rate 0.4%; 95% CI 0.04–1.29).
Conclusions
Our findings suggest that elective CS prevents MTCT even at low maternal viral loads, but the study was insufficiently powered to enable a conclusion to be drawn as to whether this applies for viral loads <50 copies/mL. Diverging mode of delivery patterns in Europe reflect uncertainties regarding the risk–benefit balance of elective CS for women on successful HAART.
Concerns have been raised over possible adverse effects of prophylactic antiretroviral therapy (ART) on the fetus and newborn. We analyzed data relating to uninfected children enrolled in the ...European Collaborative Study and investigated the association between ART exposure, perinatal problems, and major adverse health events later in life. Median length of follow-up was 2.2 (0-15.9) years. Of the 2414 uninfected children, 687 (28%) were exposed to ART in all three periods (antenatal, intrapartum, and neonatal). Of the 1008 infants exposed to ART at any time, 906 (90%) were exposed antenatally, 840 (83%) neonatally, and 750 (74%) both antenatally and neonatally. ART exposure was not significantly associated with pattern or prevalence of congenital abnormalities or low birth weight. In multivariate analysis, prematurity was associated with exposure to combination therapy without a protease inhibitor (PI) (OR = 2.66; 95% CI: 1.52-4.67) and with a PI (OR = 4.14; 95% CI: 2.36-7.23). ART exposure was associated with anemia in early life ( <.001). There was no evidence of an association with clinical manifestations suggestive of mitochondrial abnormalities. The absence of serious adverse events in this large cohort of uninfected children exposed to prophylactic ART in the short to medium term is reassuring.
To assess the association between type and timing of initiation of antiretroviral therapy in pregnancy and duration of pregnancy.
Prospective study.
Data on 3920 mother-child pairs were examined ...(3015 mother-child pairs from the European Collaborative Study and 905 from the Swiss Mother + Child HIV Cohort Study). Factors examined included gestational age, antiretroviral therapy during pregnancy, maternal CD4 count, viral load, illicit drug use (IDU) and mode of delivery. Deliveries at less than 37 weeks were defined as premature.
The prematurity rate was 17% and median gestational age 39 weeks. Twenty-three per cent (896 of 3920) of women received antiretroviral therapy during pregnancy: 64% (573 of 896) zidovudine monotherapy, 24% (215) combination therapy without protease inhibitors (PI) and 12% (108) combination therapy with PI. In multivariate analysis, adjusted for maternal CD4 count and IDU, odds ratio (OR) of prematurity was 2.60 95% confidence interval (CI), 1.43-4.75 and 1.82 (95% CI, 1.13-2.92) for infants exposed to combination therapy with and without a PI, respectively, compared to no treatment. Exposure to monotherapy was not associated with prematurity, but severe immunosuppression and IDU in pregnancy were. Women on combination therapy from before pregnancy were twice as likely to deliver prematurely as those starting therapy in the third trimester (OR, 2.17; 95% CI, 1.03-4.58).
Pregnancy issues should be discussed when making decisions about initiation of combination antiretroviral therapy for HIV-infected women. Elective caesarean section to reduce vertical transmission at 36 weeks rather than 38 weeks may be advisable in women on combination therapy with PI.
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