Background. Conflicting results have been reported among studies of protease inhibitor (PI) use during pregnancy and preterm birth. Uncontrolled confounding by indication may explain some of the ...differences among studies. Methods. In total, 777 human immunodeficiency virus (HIV)–infected pregnant women in a prospective cohort who were not receiving antiretroviral (ARV) treatment at conception were studied. Births <37 weeks gestation were reviewed, and deliveries due to spontaneous labor and/or rupture of membranes were identified. Risk of preterm birth and low birth weight (<2500 g) were evaluated by using multivariable logistic regression. Results. Of the study population, 558 (72%) received combination ARV with PI during pregnancy, and a total of 130 preterm births were observed. In adjusted analyses, combination ARV with PI was not significantly associated with spontaneous preterm birth, compared to ARV without PI (odds ratio OR, 1.22; 95% confidence interval CI, 0.70–2.12). Sensitivity analyses that included women who received ARV prior to pregnancy also did not identify a significant association (OR, 1.34; 95% CI, 0.84–2.16). Low birth weight results were similar. Conclusions. No evidence of an association between use of combination ARV with PI during pregnancy and preterm birth was found. Our study supports current guidelines that promote consideration of combination ARV for all HIV-infected pregnant women.
Antiretrovirals (ARVs) are recommended for maternal health and to reduce HIV-1 mother-to-child transmission, but suboptimal adherence can counteract its benefits.
To describe antepartum and ...postpartum adherence to ARV regimens and factors associated with adherence.
We assessed adherence rates among subjects enrolled in Pediatric AIDS Clinical Trials Group Protocol 1,025 from August 2002 to July 2005 on tablet formulations with at least one self-report adherence assessment. Perfectly adherent subjects reported no missed doses 4 days before their study visit. Generalized estimating equations were used to compare antepartum with postpartum adherence rates and to identify factors associated with perfect adherence.
Of 519 eligible subjects, 334/445 (75%) reported perfect adherence during pregnancy. This rate significantly decreased 6, 24, and 48 weeks postpartum 185/284 (65%), 76/118 (64%), and 42/64 (66%), respectively (P < 0.01). Pregnant subjects with perfect adherence had lower viral loads. The odds of perfect adherence were significantly higher for women who initiated ARVs during pregnancy (P < 0.01), did not have AIDS (P = 0.02), never missed prenatal vitamins (P < 0.01), never used marijuana (P = 0.05), or felt happy all or most of the time (P < 0.01).
Perfect adherence to ARVs was better antepartum, but overall rates were low. Interventions to improve adherence during pregnancy are needed.
Objective The objective of the study was to review pregnancy and neonatal outcomes among perinatally infected pregnant patients at our institution. Study Design A retrospective review of maternal and ...neonatal records for all 10 perinatally infected adolescents between 1997 and 2007 was performed. Demographics, CD4 and viral load, antiretroviral treatment, medical comorbidities, pregnancy outcomes, and neonatal human immunodeficiency virus (HIV) status were abstracted. Results The median age at first pregnancy was 18.5 years and 70% were African American. The most common comorbidities were hematologic abnormalities (70%) and cervical dysplasia/sexually transmitted infections (STIs) (80%). Initial median CD4 and viral load were 317 cells/mm3 and 8780 copies/mL, respectively. The median gestational age at delivery was 38 weeks. The most common obstetrical complications were preeclampsia (23%) and premature rupture of membranes/preterm delivery (31%). The cesarean delivery (CD) rate was 62%, with HIV as the indication in 75%. All infants were born alive; 1 was HIV infected. Conclusion Despite high rates of STIs, CD, preterm delivery, and hypertensive disorders, perinatal outcomes were favorable.
Adherence to antiretroviral therapy (ART) in pregnancy is crucial to optimize its efficacy and minimize mother-to-child transmission. Our objective was to examine adherence patterns to ART and health ...behaviors during and after pregnancy among HIV-positive women enrolled in A5084, a prospective, observational, multisite study. Between 2002-2005, HIV-infected women between 20 and 34 weeks'gestation completed at least 1 self-reported adherence questionnaire antepartum (AP), and were followed through 12 weeks' postpartum (PP). Questionnaires also addressed tobacco, alcohol, and illicit drugs use. Adherence was defined as reporting not having missed any doses for more than 3 months. Exact McNemar's tests were used for paired binary data and exact logistic regression was used for predictors of nonadherence. We report on 149 women (55% black, 26% Hispanic, 32% less than 25 years, 9% with AIDS, 100% on ART). PP, 31 (21%) women stopped ART and 18 (12%) withdrew from the study. AP, 57% reported adherence to ART and PP, 45% (p = 0.03, n = 87). AP, 11% reported ongoing alcohol use and 23% tobacco use compared to 37% and 30% PP (p < 0.0001, n = 103; p = 0.07, n = 99, respectively). Although 39% ever used marijuana (n = 116) and 25% used illicit drugs (n = 107), few participants reported use during the study. In multivariate analyses, those who had ever used illicit drugs had 5.95 times higher odds (p = 0.002) and those who missed prenatal vitamins had 4.84 times higher odds (p = 0.001) of ART nonadherence. Women reporting a history of illicit drug use and/or having missed prenatal vitamins should be targeted for programs to enhance adherence to ART during pregnancy.
Background. Conflicting results have been reported among studies of protease inhibitor (PI) use during pregnancy and preterm birth. Uncontrolled confounding by indication may explain some of the ...differences among studies. Methods. In total, 777 human immunodeficiency virus (HIV)-infected pregnant women in a prospective cohort who were not receiving antiretroviral (ARV) treatment at conception were studied. Births <37 weeks gestation were reviewed, and deliveries due to spontaneous labor and/or rupture of membranes were identified. Risk of preterm birth and low birth weight (<2500 g) were evaluated by using multivariable logistic regression. Results. Of the study population, 558 (72%) received combination ARV with PI during pregnancy, and a total of 130 preterm births were observed. In adjusted analyses, combination ARV with PI was not significantly associated with spontaneous preterm birth, compared to ARV without PI (odds ratio OR, 1.22; 95% confidence interval CI, 0.70–2.12). Sensitivity analyses that included women who received ARV prior to pregnancy also did not identify a significant association (OR, 1.34; 95% CI, 0.84–2.16). Low birth weight results were similar. Conclusions. No evidence of an association between use of combination ARV with PI during pregnancy and preterm birth was found. Our study supports current guidelines that promote consideration of combination ARV for all HIV-infected pregnant women.
Systemic and intracellular pharmacokinetics of zidovudine were determined for 28 human immunodeficiency virus type 1—infected pregnant women and their newborn infants. Plasma zidovudine and ...intracellular zidovudine monophosphate and triphosphate concentrations were determined in serial maternal samples and cord blood at delivery. Higher levels of cord blood zidovudine were associated with lower maternal zidovudine clearance and longer infusion times. Median levels of zidovudine monophosphate and triphosphate in maternal (1556 and 67 fmol/106 cells) and cord (1464 and 70 fmol/106 cells) blood were similar but highly variable. Intersubject pharmacokinetic variability for zidovudine is substantial, but intravenous therapy provides plasma concentrations and intracellular zidovudine triphosphate levels consistent with high antiviral activity. The substantial amount of intracellular zidovudine triphosphate in cord blood provides an explanation for the clinical success of zidovudine in reducing vertical transmission. Studies of simpler oral regimens of zidovudine can now be evaluated regarding the ability to achieve these pharmacologic end points associated with highly effective parenteral therapy.
Background. Pregnancy outcomes of perinatally human immunodeficiency virus–infected women (PHIV) are poorly defined. Methods. We compared preterm delivery and birth weight (BW) outcomes (low BW LBW, ...<2500 g), small-for-gestational-age SGA, and BW z scores BWZ) in HIV-exposed uninfected infants of PHIV vs nonperinatally HIV-infected (NPHIV) pregnant women in the Pediatric HIV/AIDS Cohort Study Surveillance Monitoring of ART Toxicities or International Maternal Pediatric Adolescent AIDS Clinical Trials P1025 studies. Mixed effects models and log binomial models were used to assess the association of maternal PHIV status with infant outcomes. Age-stratified analyses were performed. Results. From 1998 to 2013, 2270 HIV-infected pregnant women delivered 2692 newborns (270 born to PHIV and 2422 to NPHIV women). PHIV women were younger, (mean age 21 vs 25 years, P < .01) and more likely to have a pregnancy CD4 count <200 cells/mm3 (19% vs 11%, P = .01). No associations between maternal PHIV status and preterm delivery, SGA, or LBW were observed. After adjustment, BWZ was 0.12 lower in infants of PHIV vs NPHIV women (adjusted mean, −0.45 vs −0.33; P = .04). Among women aged 23–30 years (n = 1770), maternal PHIV was associated with LBW (aRR = 1.74; 95% confidence interval, 1.18, 2.58; P < .01). Conclusion. The overall lack of association between maternal PHIV status and preterm delivery or infant BW outcomes is reassuring. The higher rates of LBW observed in PHIV women aged 23–30 years warrants further mechanism-based investigations as this is a rapidly growing and aging population worldwide. Clinical Trials Registration. PHACS SMARTT study, NCT01310023. Clinical Trials Registration. IMPAACT 1025, NCT00028145.
To evaluate the effect of protease inhibitors on lipid and lactate levels and gastrointestinal symptoms in pregnancy.
Acquired Immunodeficiency Syndrome (AIDS) Clinical Trials Group (ACTG) A5084 was ...an observational cohort study of human immunodeficiency virus (HIV)-infected pregnant women. Women recruited between 20 and 34 weeks of gestation were required to be on a stable, highly active antiretroviral therapy (HAART) regimen, stratified by protease inhibitor compared with no protease inhibitor regimens. Interval history was assessed, and lipid and lactate levels were drawn every 8 weeks during pregnancy and 12 weeks postpartum, with levels closest to delivery and postpartum used for analysis. Statistical comparisons used Kruskal-Wallis and Fisher exact tests.
One-hundred fifty-eight women were evaluated. Total cholesterol levels (median 230 mg/dL, interquartile range 197, 259, compared with 212 179, 246 mg/dL, P=.042) and triglycerides (median 224 mg/dL, interquartile range 187, 288, compared with 185 142, 230 mg/dL, P<.001 were elevated in the protease inhibitor group during pregnancy and remained higher in this group after delivery (total cholesterol 185 163, 224 mg/dl compared with 171 140, 190 mg/dL, P<.004; triglycerides 122 87, 175 mg/dL compared with 89 66, 150 mg/dL, P=.02). No difference was seen in lactate levels or rates of gastrointestinal symptoms between groups. Obstetric outcomes were similar between the two groups. A higher number of low birth weight infants were born to women in the highest twentieth percentile of triglycerides compared with the lowest across medication groups.
Cholesterol and triglycerides were higher in protease inhibitor-treated women in pregnancy. Lactate and gastrointestinal symptoms were not different. A higher number of low birth weight infants were noted in women with high triglycerides, but other elevated lipid levels did not affect pregnancy outcomes.
ClinicalTrials.gov, www.clinicaltrials.gov, NCT00017797
II.
Didanosine (ddI) pharmacokinetics in antepartum and postpartum human immunodeficiency virus (HIV)—infected women and their neonates were studied. HIV-infected pregnant women received an intravenous ...(iv) ddI infusion (1.6 mg/kg/h) or an oral dose (200 mg bid or 125 mg bid) at 31 weeks antepartum and 6 weeks postpartum. Blood samples were obtained regularly up to 6 or 8 h after drug administration. The same oral dose of ddI (bid) was administered until labor began. Then, ddI was infused iv until delivery. An oral pharmacokinetic study (60 mg/m2) was conducted in infants at day 1 and at week 6 after birth. Plasma concentrations of ddI were measured by radioimmunoassay. After iv ddI administration, only the maternal plasma clearance was found to be significantly increased antepartum (1028 ±231 mL/min) versus postpartum (707 ± 213 mL/min). No pharmacokinetic parameters after oral administration were significantly affected by pregnancy. The pharmacokinetics of ddI in the neonates were highly variable. We conclude that the oral ddI dose need not be adjusted during pregnancy.
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