Risk factors of preterm delivery in HIV infected pregnant women receiving zidovudine for the prevention of perinatal HIV

Aim: Several studies have shown that preterm delivery, a primary cause of perinatal mortality and morbidity, is more frequent in HIV‐positive women. This study aimed to determine factors associated with prematurity in HIV‐infected women and identify risks for which specific interventions could be targeted. Methods: Data were prospectively collected in a clinical trial assessing the efficacy of different zidovudine prophylaxis durations for the prevention of perinatal HIV transmission in Thailand. Characteristics associated with prematurity – delivery before 37 weeks – were assessed using univariate and multivariate logistic regression and were subsequently used to identify subgroups of women at risk. Results: Among 979 women, independent prematurity risk factors were: viral load 4.5 log copies/mL; hemoglobin >11.5 g/dL; weight gain <0.25 kg/week; and body mass index <20 kg/m2. These factors allowed us to define four subgroups with an expected probability of prematurity increasing from 3% to 30%. The two subgroups with the highest expected probability of prematurity were considered to be ‘at risk’ as opposed to the two lowest (odds ratio = 2.6, 95% confidence interval: 1.7–4.0) and the sensitivity and specificity of the prediction were 51% and 71%, respectively. Conclusion: In this study, four risk factors of preterm delivery were identified allowing the identification of subgroups at increasing risk of prematurity. Adequate nutrition and the provision of highly active antiretroviral therapy during pregnancy as recommended by the World Health Organization for the prevention of perinatal transmission for immunocompromised women in resource‐constrained countries may reduce the risk of premature delivery

Efficacy and safety of 1-month postpartum zidovudine-didanosine to prevent HIV-resistance mutations after intrapartum single-dose nevirapine.

BACKGROUND: Intrapartum single-dose nevirapine plus third trimester maternal and infant zidovudine are essential components of programs to prevent mother-to-child transmission of human immunodeficiency virus (HIV) in resource-limited settings. The persistence of nevirapine in the plasma for 3 weeks postpartum risks selection of resistance mutations to nonnucleoside reverse-transcriptase inhibitors (NNRTIs). We hypothesized that a 1-month zidovudine-didanosine course initiated at the same time as single-dose nevirapine (sdNVP) would prevent the selection of nevirapine-resistance mutations. METHODS: HIV-infected pregnant women in the PHPT-4 cohort with CD4 cell counts >250 cells/mm3 received antepartum zidovudine from the third trimester until delivery, sdNVP during labor, and a 1-month zidovudine-didanosine course after delivery. These women were matched on the basis of baseline HIV load, CD4 cell count, and duration of antepartum zidovudine to women who received sdNVP in the PHPT-2 trial (control subjects). Consensus sequencing and the more sensitive oligonucleotide ligation assay were performed on samples obtained on postpartum days 7-10, 37-45, and 120 (if the HIV load was >500 copies/mL) to detect K103N/Y181C/G190A mutations. RESULTS: The 222 PHPT-4 subjects did not differ from matched control subjects in baseline characteristics except for age. The combined group median CD4 cell count was 421 cells/mm3 (interquartile range [IQR], 322-549 cells/mm3), the median HIV load was 3.45 log10 copies/mL (IQR, 2.79-4.00 log10 copies/mL), and the median duration of zidovudine prophylaxis was 10.4 weeks (IQR, 9.1-11.4 weeks). Using consensus sequencing, major NNRTI resistance mutations were detected after delivery in 0% of PHPT-4 subjects and 10.4% of PHPT-2 controls. The oligonucleotide ligation assay detected resistance in 1.8% of PHPT-4 subjects and 18.9% of controls. Major NNRTI resistance mutations were detected by either method in 1.8% of PHPT-4 subjects and 20.7% of controls (P < .001). CONCLUSIONS: A 1-month postpartum course of zidovudine plus didanosine prevented the selection of the vast majority of NNRTI resistance mutations