This is an archive of the Treatment Action Campaign's public documents from
December 1998 until October 2008. I created this website because the TAC's
website appears unmaintained and people were concerned that it
was becoming increasingly hard to find important documents.
The menu items have been slightly edited and a new stylesheet applied to the site. But none of the documents have been edited, not even for minor errors. The text appears on this site as obtained from the Internet Archive.
The period covered by the archive encompassed the campaign for HIV medicines, the civil disobedience campaigns, the Competition Commission complaints, the 2008 xenophobic violence and the PMTCT, Khayelitsha health workers and Matthias Rath court cases.
HIVNET 012 trial has been validated by an independent analysis of the Institute of Medicine of the National Academies
Date: April 7, 2005
Contacts: Christine Stencel, Media Relations Officer
Megan Petty, Media Relations Assistant
Office of News and Public Information
202-334-2138; e-mail <email@example.com>
FOR IMMEDIATE RELEASE
Findings From Perinatal HIV Prevention Study in Uganda are Valid, New Review Says
WASHINGTON -- A Ugandan drug trial's findings that the AIDS medication
nevirapine is effective and safe in preventing HIV transmission from mother to
unborn child during birth were well-supported, according to a new, independent
analysis by the Institute of Medicine of the National Academies. The IOM's
analysis of the design and methodology of the 1997 drug study in Uganda, called
HIVNET 012, determined that policy-makers and other scientists can rely on the
resulting data and conclusions, despite some flaws in record keeping and
"The data from the HIVNET 012 study, which showed that nevirapine effectively
prevents many infants from contracting HIV from their infected mothers, are
sound and reliable," said James Ware, chair of the committee that wrote the
report, and professor of biostatistics, Harvard School of Public Health,
Boston. "None of the shortcomings that we discovered upon reviewing the data
and conducting our own original analysis of source documents indicates a need
to retract or discount the study's findings. Our confidence in the trial's data
and findings is based on several factors, including evidence that the study's
design was both scientifically sound and ethically implemented, that
participants adhered well to the treatment regimens, and that a high percentage
of participants remained in the study so that the effectiveness and safety of
the drug could be thoroughly assessed."
Previous evaluations of HIVNET 012 left lingering uncertainties about the
trial's results, suggesting the need for a definitive, objective review. 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, which also funded the original
trial in Uganda.
The committee did not evaluate the trial's oversight by the National Institutes
of Health. It also did not examine the impact of other recent studies of
potential toxicity or resistance buildup associated with the use of nevirapine
either in short- or long-term treatment of HIV-infected individuals.
Because of inconsistencies in and challenges to previous audits, the committee
undertook its own assessment of the accuracy and completeness of the trial's
reporting through a review of medical records and other primary source
documents for a subset of 49 infants involved in the trial. In addition, the
committee reviewed information provided by NIH, the original investigators,
previous audits of the trial, and other information brought to its attention.
The findings of the HIVNET 012 study previously underwent audits by Westat
Corp. and by NIH's Division of AIDS (DAIDS).
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 the 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." The Hopkins and Makerere
researchers used hospitalization as the principal -- but not sole --
determinant to classify clinical events as "serious" to take into account the
high prevalence of malaria, tuberculosis, and other concurrent health problems
in Uganda. The IOM report finds that the investigators' use of a narrow
interpretation was reasonable, but it means that other researchers may not be
able to generalize the study's total rate of adverse events to all settings.
Other settings -- such as countries with lower rates of endemic diseases -- may
have different thresholds for hospitalization and interpretations of what counts
Another concern about HIVNET 012 focused on whether cases of jaundice -- or
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, based on its own analysis, determined that the
DAIDS safety report initially used an incorrect upper limit of the normal range
for bilirubin levels in newborns. When the correct upper limit is applied, the
trial data confirm the original HIVNET 012 investigators' findings and the
subsequent DAIDS retraction.
Overall, the Hopkins and Makerere researchers conducted the trial ethically and
in accordance with U.S. and international standards for research and management
of patient care, the IOM report says. Although there were some problems with
full documentation of compliance with all the requirements for the trial, the
committee determined that the HIVNET 012 study was designed and implemented
with approval from the boards that oversaw the trial's design and protocols;
that the researchers enrolled women only after they gave free and informed
consent; and that fathers were involved in the consent process when they were
Blood tests that detected the presence of nevirapine in mothers and infants and
other data showed that trial participants received the right drug and there was
a high level of adherence to the treatment regimens, the committee found. It
also noted that trial investigators achieved high rates of retention and
follow-up among participants.
The committee found no reason that medical journals should revise or retract
articles that reported on the efficacy and safety of nevirapine for reducing
mother-to-child transmission of HIV based on the HIVNET 012 trial.
The Institute of Medicine is a private, nonprofit institution that provides
health policy advice under a congressional charter granted to the National
Academy of Sciences. A committee roster follows.
A pre-publication version of Review of the HIVNET 012 Perinatal HIV Prevention
Study is available from the National Academies Press; tel. 202-334-3313 or
1-800-624-6242 or on the Internet at http://www.nap.edu. Reporters may obtain a
pre-publication copy from the Office of News and Public Information (contacts
INSTITUTE OF MEDICINE
Board on Population Health and Public Health Practice
Committee on Reviewing the HIVNET 012 Clinical Trial
James H. Ware, Ph.D. (chair)
Dean for Academic Affairs, and
Frederick Mosteller Professor of Biostatistics
School of Public Health
R. Alta Charo, J.D.
Elizabeth S. Wilson Professor of Law and Bioethics
University of Wisconsin Law School and Medica1 School, and
University of Wisconsin Law School
Ezra C. Davidson Jr., M.D.
Associate Dean of Primary Care, and
Professor of Obstetrics and Gynecology
Charles R. Drew University of Medicine and Science
Wafaa El-Sadr, M.D., M.P.H., M.P.A.
Center for Infectious Diseases Epidemiologic Research, and
Professor of Clinical Medicine and Epidemiology
Mailman School of Public Health
New York City
Mark W. Kline, M.D.
Professor of Pediatrics;
Chief of Retrovirology;
Director, AIDS International Training and Research Program;
Director, Baylor-CDC Global AIDS Technical Assistance Project; and
Associate Director of General Clinical Research Center
Baylor College of Medicine
Stephen W. Lagakos, Ph.D.
Henry Pickering Walcott Professor of Biostatistics and Chair
Department of Biostatistics
School of Public Health
J. Richard Landis, Ph.D.
Professor of Biostatistics, and
Director, Division of Biostatistics
Department of Biostatistics and Epidemiology
School of Medicine
University of Pennsylvania
George W. Rutherford III, M.D.
Salvatore Pablo Lucia Professor of Preventive Medicine;
Professor-in-Residence of Epidemiology, Preventive Medicine, Pediatrics, and
Family and Community Medicine;
Head, Division of Preventive Medicine and Public Health; and
Interim Director of Institute for Global Health
University of California
Charles van der Horst, M.D.
Professor of Medicine and Associate Chief
Division of Infectious Diseases
School of Medicine
University of North Carolina
Chapel Hill, and
University of the Witwatersrand
Johannesburg, South Africa
Alicia R. Gable, M.P.H.
Rose Marie Martinez, Sc.D.
Director, Board on Population Health and Public Health Practice
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