HIVNET 024
Phase III Trial of Antibiotics to Reduce Chorioamnionitis-Related Perinatal HIV Transmission
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What was HIVNET 024?
HIVNET 024 was a randomized, double blinded, controlled phase III clinical trial of antibiotics to prevent chorioamnionitis-associated perinatal HIV transmission.
Who participated in the study?
3,120 HIV-positive pregnant women 20-24 weeks gestation identified at antenatal clinics and their infants following birth. In addition, 450 HIV-negative women were also enrolled and treated indistinguishably from those who were HIV-positive.
What happened during the study?
Using a simple 2-arm design, half the subjects received two courses of antibiotics, with the control subjects receiving two courses of a placebo. A total of 600 HIV-negative women were enrolled to conceal the HIV status and avoid stigmatization of participating women at sites where this was deemed appropriate and necessary. Follow-up continued until 12 months after the last woman delivered or until sufficient events accrued to provide adequate power for the primary endpoints.
Results
Data regarding 1491 mother-infant pairs were analyzed. The overall I/EP HIV-1 transmission rate was 8.1% at 6 weeks. Almost all women (93%) ingested NVP within 24 h of delivery; 90% of infants were given NVP within 48 h after delivery. Variations in mother or infant dose timing did not influence transmission rates, even when the combined pattern of both was taken into account through multivariate analysis. In the subset of women ingesting NVP </= 2 h before delivery, early NVP administration to the infant (< 4 h after birth) was not associated with lower MTCT risk when compared with later administration (>/= 4 h). CONCLUSION: Variations in the timing of maternal and infant NVP doses (within reasonable proximity to delivery) do not appear to affect the risk of MTCT.
Why was this study important?
The study sought to determine whether the use of this regimen was associated with an improvement in birthweight, a reduction in pre-term birth, and a reduction in maternal chorioamnionitis in HIV-negative women, as well as whether adherence to the treatment regimen and tolerance of the antibiotics are similar among both two cohorts.
Protocol Status
Concluded
Study Purpose
To determine if low-cost antibiotic treatment given twice during pregnancy aimed at reducing chronic and acute chorioamnionitis will reduce perinatal HIV transmission.
Study Design
Randomized, double-blinded, controlled Phase III trial of antibiotics.
Study Population
Women 20-24 weeks gestation identified at antenatal clinics and their neonates following birth.
Study Size
3120 HIV-positive pregnant women. In order to prevent stigmatization and to investigate the impact of antibiotics on HIV-negative women in this setting, 450 additional HIV-negative women will be enrolled and treated indistinguishably from those who are HIV-positive.
Study Duration
Enrollment stopped early based on DSMB recommendation (Feb 03).
Follow up for: Mothers: from 20-24 weeks gestation to 12 months post-partum; Infants: Birth to 12 months of age.
Treatment Regime
At 20 - 24 weeks, women randomized to receive antibiotics will receive metronidazole 250 mg three times a day (TID) and erythromycin 250 mg TID orally for 7 days. Women randomized to the control group will receive identically appearing placebos. With the onset of contractions and/or premature rupture of membranes (PROM), study participants will initiate a second oral course of antibiotics consisting of metronidazole 250 mg and ampicillin 500 mg or placebo every 4 hours, continuing after delivery TID until the course is completed. All HIV-infected women and their neonates will be offered the HIVNET 012 nevirapine (NVP) regimen. If the mother accepts the nevirapine for herself and her baby, she will be given one oral dose of 200 mg NVP to be taken at onset of labor, and her baby will receive one oral dose of 2mg/kg NVP suspension at 72 hours post-birth or discharge, whichever occurs earlier. If the mother refuses nevirapine or is uninfected, she will receive a matched placebo at the 26-30 week visit to preserve participant confidentiality.
Primary Objectives
To determine if antibiotic treatment aimed at reducing chronic and acute chorioamnionitis will reduce HIV mother to child transmission (MCT).
Secondary Objectives
To determine if antibiotic treatment reduces preterm birth and maternal/infant morbidity and mortality.
To determine if antibiotic treatment reduces HIV MCT in women with BV or a positive FFN.
To determine if the reduction in HIV MCT potentially achieved by antibiotics is associated with a reduction in histologic chorioamnionitis, preterm birth, or vaginal viral load.
In HIV-negative women, to determine if the antibiotic regimen employed in this study is associated with an improvement in birthweight and other perinatal outcomes.
To determine the correlation between vaginal pH, the whiff test, a non-specific vaginal discharge and clue cells on a wet prep with a Gram stain diagnosis of BV, and to determine the sensitivity, specificity, positive and negative predictive values of these tests for diagnosing BV and predicting HIV MCT.