The determination of tryptophan degradation and neopterin production in PBMC reflects various pro- and anti-inflammatory cascades that are of relevance also in patients. It constitutes a robust and reliable approach to screen anti-inflammatory or immunosuppressive drugs and may improve throughput, speed and cost-effectiveness in drug discovery.
ObjectiveThe aim of the study was to assess the risk of adverse pregnancy outcomes after antenatal antiretroviral therapy in a well-defined prospective cohort of nontransmitting HIV-infected women.
MethodsProspective monitoring of 183 mother-child pairs from 13 centres in Germany and Austria, delivering between 1995 and 2001, was carried out. Following German-Austrian guidelines recommending an elective Caesarean section (CS) at 36 weeks, prematurity was defined as o36 weeks' gestation for these analyses.
ResultsOf 183 mother-child pairs, 42% were exposed to antenatal monotherapy and 17% to dual therapy. Of the 75 women exposed to highly active antiretroviral therapy (HAART), 21 (28%) received protease inhibitor (PI)-based HAART and the remaining 54 received nonnucleoside reverse transcriptase inhibitor-based HAART. In multivariable analysis (176 pregnancies), PI-based HAART exposure during pregnancy was associated with an increased risk of premature delivery [adjusted odds ratio 3.40; 95% confidence interval (CI) 1.13-10.2; P 5 0.029, compared with monotherapy]. Congenital abnormalities affected 3.3% infants. Perinatally, 18.9% of children (34 of 179) had respiratory problems requiring interventions, which were associated with prematurity but not with type of treatment exposure. From adjusted regression analysis, the mean birth weight z-score for children exposed to HAART with PI ( 1 0.46; 95% CI 0.01-0.92; P 5 0.047) or dual therapy ( 1 0.43; 95% CI 0.03-0.82; P 5 0.034) was slightly but significantly higher than that for those exposed to monotherapy; head circumference was appropriate for gestational age and there were no significant differences between treatment groups.
ConclusionsUse of antenatal PI-based HAART initiated before or during pregnancy was associated with a significantly increased risk of premature delivery at o36 weeks' gestation. The overall crude prematurity rate was 34% (63 of 183; 95% CI 28-42).Keywords: congenital abnormalities, HAART, HIV, pregnancy, prematurity There is a consistent body of evidence from European studies showing an increased risk of premature delivery with antenatal combination antiretroviral therapy (ART) and highly active antiretroviral therapy (HAART), especially with regimens containing a protease inhibitor (PI) [5,[7][8][9][10]. Although most studies based in the USA have not found such an association [11][12][13], a more recent, singlecentre study from Florida reported results consistent with those from Europe [14]. Concerns have also been raised over the possible teratogenic effects related to ART exposure in early pregnancy when organogenesis is occurring, although recent reports indicating a low prevalence of congenital malformations in infants with ART exposure have been reassuring [15,16].We assessed the risk of adverse pregnancy outcomes, namely neonatal and perinatal morbidity, prematurity and birth defects, associated with the use of antenatal ART in a well-defined bi-national cohort of nontransmitting HIVinfected pregnant women and their children.
MethodsP...
Viral load in vertically infected children, measured by reverse transcriptase-polymerase chain reaction, falls very gradually over time, descending from very high titers at the end of the first year, and reaching values seen in horizontally infected adults at approximately 5 years of age.
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