This past week a controversy arose when it was reported in the media that testing of the drug nevirapine at Uganda's Mulago Hospital failed to meet international standards and that pregnant women who take the drug once to inhibit passing HIV to their babies may develop resistance to it that can limit drug therapies to combat the deadly disease. News articles were rife with headlines such as AIDS Drug Concerns Threaten S. Africa Program and Many Now Worry AIDS Drug Will Be Halted. 

In response, the National Institute of Allergy and Infectious Diseases issued this statement, The HIVNET 012 Study and the Safety and Effectiveness of Nevirapine in Preventing Mother-to-Infant Transmission of HIV and also a Questions and Answers fact sheet: Questions and Answers: The HIVNET 012 Study and the Safety and Effectiveness of Nevirapine in Preventing Mother-to-Infant transmission of HIV. The following response to this controversy was written exclusively for The Pop Reporter by Dr. Ronald Gray, Robertson Professor of Reproductive Epidemiology, Johns Hopkins University, Bloomberg School of Public Health. Dr. Gray has published extensively in population and family health sciences and has a particular interest in the HIV epidemic in Africa.

Nevirapine and Prevention of Mother-to-child HIV Transmission in Africa: What Are the Facts?

From a public health perspective it is important to note that the FDA review and disapproval, as well as multiple subsequent audits and reviews, did not question the efficacy of the drug for preventing pediatric HIV infection, nor did they demonstrate safety concerns.

The plot then thickened. It was known that the HIV virus rapidly mutates, and that resistant virus was a problem with NVP, especially if the drug was used alone (monotherapy). Such resistance was observed in the blood of both mothers and children in the 012 trial, but it appeared to fade over about one year. Nevertheless, there was concern that the resistant virus would remain in the lymph glands and would re-emerge if NVP was subsequently used for HAART therapy. This concern appears warranted, because a 2004 Thai study showed that women who had received NVP had a poorer response to subsequent HAART regimens containing NVP.

This conjunction of events, non-FDA approval and criticism of the trial and the problem of NVP, has generated a perfect storm of media attention. It is further exacerbated by claims that NIH did not communicate the information on NVP resistance when plans were being made for the Presidential Emergency Program for AIDS Relief (PEPFAR), which is the main US effort to provide drugs (including NVP) to the developing world. This accusation of withholding information on resistance is a canard, because the problem of NVP resistance was well documented and widely known.

In all the media hype, accusation and counteraccusation, release of documents under the Freedom of Information Act, personal attacks and acrimony, there seems to be little concern for preventing pediatric HIV infection. We have a dilemma of massive proportions: Millions of mothers are infected with HIV, particularly in Africa. The only affordable, simple and effective preventive measure available is the single-dose NVP regimen. Taking this drug will select resistant virus and likely compromise the response to later HAART therapy for the mother and child, if such therapy contains nevirapine or related drugs (called NNRTIs). Should we ban NVP because of an administratively imperfect trial and double the number of HIV infected infants? Should we withhold NVP to avoid drug resistance, so that these mothers and children will respond better to HAART at some time in the future when they become immunodeficient? Does the FDA's concerns about imperfect documentation of side effects in an efficacy trial outweigh the risk of infant HIV infection and death?

I think we need to get our priorities straight. NVP is an imperfect drug, it has toxicities, it has resistance problems, but it is the only regimen that can be used at time of delivery. Other regimens (e.g., short-course AZT) taken for the last weeks of pregnancy should be provided to women where possible, but since 80% or more of births in Africa occur at home without medical supervision, this is not a feasible option for most women. We need research, particularly on combination therapy during labor and
delivery, but, while waiting for this research, we only have NVP to fall back on.

The media do children a grave disservice by promoting disinformation without considering the public health benefits. This disinformation could lead governments (such as South Africa) or donors to restrict access to this valuable drug, and infected children would pay the price for such misguided policy.