Makerere University, Johns Hopkins University Research Collaboration Investigators - December 22, 2004

An Associated Press Release and subsequent report printed by the local media has revisited past questions raised regarding the conduct of the HIVNET 012 study and the safety of Nevirapine used for the Prevention of Mother To Child Transmission of HIV infection. HIVNET 012, sponsored by the U.S. National Institutes of Health (NIH) and implemented by the Makerere University - Johns Hopkins University Research Collaboration showed that 2 doses of nevirapine, one to the mother and one to her new born baby, substantially lowered the risk of HIV transmission from mother to the child. Results from this trial were initially released with preliminary data in 1999 and final data in 2003.

The Associated Press article raised concerns about deficiencies in reporting of adverse events that would question the safety of this short course of Nevirapine, implying that investigators hid drug related toxicities in the safety reporting. This is absolutely untrue. We reiterate that there were no deaths or serious adverse events that were definitely related to Nevirapine in the HIVNET 012 study. We acknowledge that the HIVNET 012 trial was not perfect in its implementation but all adverse events were documented in the study records. The majority of illnesses common in Ugandan children and were not related to the Nevirapine or AZT used in the study. These common childhood illnesses included pneumonia, malaria, diarrhea and malnutrition.

When issues related to the accuracy of the trial results were initially raised in 2002, extensive and exhaustive reviews of the HIVNET 012 study were completed by the NIH, which validated both the efficacy and safety of Nevirapine. In response to the current allegations made by a dismissed and disgruntled NIH employee, there is presently an independent review being conducted by the US Institute of Medicine to dispel any lingering doubts about the conduct and results of the HIVNET 012 study. According to Dr. Thomas Fleming, protocol statistician, "the investigators did an excellent job in conducting this important and timely study in difficult settings particularly when one recognizes limitations provided by the available infrastructure in a developing country".

Several other independent clinical trials in the US, Europe, South Africa and Thailand have examined the safety and efficacy of this Nevirapine regimen for Prevention of Mother to Child HIV Transmission. The multi-center PACTG 316, phase III clinical trial conducted in the USA, Europe, Brazil and the Bahamas and the South African Intra partum Nevirapine Trial (SAINT) conducted in South Africa to name a few. No clinical or laboratory toxicities related to Nevirapine were observed in any of these studies. In addition, the single dose Nevirapine regimen to prevent Mother To Child Transmission of HIV has been used in hundreds of thousands of women and their babies in many countries here in Africa, Asia, America etc. both in practice and clinical trials without any significant toxicity for mothers or babies. It is important to understand that there are no data demonstrating significant Nevirapine induced toxicities in women or infants receiving short course nevirapine for PMTCT. Studies have shown a low risk of toxicity with long term use of Nevirapine in combination with other antiretroviral drugs for HIV treatment. All antiretroviral drugs have toxicities associated with their chronic use, however the risk of the drug related toxicity is lower than the benefit of antiretroviral therapy for HIV treatment.

Information about the emergence of Nevirapine resistance in the short term prophylaxis for PMTCT was released several years ago, as soon as it was known. Efforts are ongoing to assess the effect of nevirapine prophylaxis on response to subsequent High Active Antiretroviral Therapy (HAART). However, in the absence of any known negative impact on clinical outcomes for future treatment, it would be premature to withdraw the only safe and effective regimen to prevent Mother To Child Transmission of HIV that is currently available and accessible, throughout Sub Saharan Africa and other portions of the developing world. Let us not be derailed in our efforts to prevent the children in resource poor settings from becoming infected with HIV as we continue to look for more effective PMTCT regimens.
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