What is HIVNET 024?

Obstetric risk factors for HIV maternal-child transmission (MCT) include pre-term birth, prolonged rupture of the membranes, and both clinical and histologic chorioamnionitis.  Each of these risk factors for HIV MCT may operate through a common pathway in which HIV-infected maternal white cells enter the amniotic fluid following bacterial infections of the placental membranes and result in both “histologic chorioamnionitis” and perinatal HIV transmission.

HIVNET 024 is a randomized, double blinded, controlled phase III clinical trial of antibiotics to prevent chorioamnionitis-associated perinatal HIV transmission.  Using a simple 2-arm design, half the subjects will receive two courses of antibiotics, with the control subjects receiving two courses of a placebo. A total of 600 HIV-negative women will be enrolled to conceal the HIV status and avoid stigmatization of participating women at sites where this is deemed appropriate and necessary. Follow-up will continue until 12 months after the last woman delivers or until sufficient events accrue to provide adequate power for the primary endpoints.

Determination of whether the use of this regimen is 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 in the two cohorts, is of interest. Data from the HIV-positive and negative women will not be combined in the analysis.

• HIVNET 024 study summary
• HIVNET 024 SSP 16 December 2003 (PDF)
• HIVNET 024 v 5.0 Protocol (PDF)
• Summary of version changes (PDF)
• HIVNET 024 v 4.0 Protocol & successive docs (PDF)
• HIVNET 024 v 3.0 Protocol (PDF)
• HIVNET 024 v 2.0 Protocol (PDF)
• HIVNET 024 v 1.0 Protocol (PDF)

Protocol Status: Participants Off Study & Primary Analysis Complete

Study Summary

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 Regimen: 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.

SDMC Protocol Specialist: Lynda Marie Emel get info

Protocol Co-Chair: Taha Taha get info

Protocol Chair: Robert Goldenberg get info

CORE Protocol Specialist: Megan Valentine get info