Institute of Medicine supports 1997 AIDS study findings

HIVNET 012, a trial conducted in Uganda in 1997, found that nevirapine (Boehringer Ingelheim’s Viramune) is effective and safe in preventing HIV transmission from mother to unborn child during birth. However, previous evaluations of HIVNET 012 left lingering uncertainties about the trial’s results, suggesting the need for a definitive, objective review.

The Institute of Medicine (IOM)’s analysis of the design and methodology of the study determined that policy-makers and other scientists can rely on the resulting data and conclusions, despite some flaws in record keeping and procedural issues.

The IOM focused on the scientific validity of the study’s conclusions based on a close examination of how researchers from Johns Hopkins University and Uganda’s Makerere University conducted the trial. This independent review was requested and funded by the National Institutes of Health (NIH), which also funded the original trial in Uganda.

The Hopkins and Makerere researchers’ conclusion that nevirapine is effective is supported by data on rates of survival and HIV infection among newborns in the study, the committee determined, noting that the trial researchers accurately recorded that information in the database created for the study. No evidence was found that the trial researchers either failed to report or mistakenly reported the deaths of any of the infants.

Regarding the trial researchers’ findings on nevirapine’s safety, the committee’s review of source documents for a subset of 49 infants found that deaths, hospitalizations, and serious adverse events observed during clinic visits also were recorded accurately in the trial database. In some instances, however, not all serious adverse events that occurred simultaneously were reported, and some less-serious adverse events were underreported.

However, there was no evidence of a difference in the level of underreporting of adverse events among patients receiving nevirapine versus those receiving zidovudine, a second AIDS drug that also was studied in HIVNET 012. The trial investigators’ comparative findings on safety are valid, the committee said.

Questions in previous audits about whether any adverse events had been missed stemmed from the trial investigators’ use of a narrow but acceptable interpretation of what counted as “serious.”

Another concern about HIVNET 012 focused on whether cases of jaundice (hyperbilirubinemia) among infants in the study were underreported. While the study investigators reported only one infant with abnormal levels of bilirubin, a subsequent safety report issued by DAIDS initially stated that there were 63 cases of elevated bilirubin. DAIDS later retracted the safety report as incorrect. The IOM committee determined that the trial data confirm the original HIVNET 012 investigators’ findings.