Comments by Global Strategies for HIV Prevention on Nevirapine Resistance

The Resistance Issue

The issue of resistance to nevirapine and its impact on subsequent use in HIV-infected women has been debated. Several important facts need to be considered.

1. Nevirapine resistance occurs even with single-dose nevirapine given to mothers. This resistance is transient and there is no evidence that it prevents the effectiveness of nevirapine in subsequent pregnancies. Health care workers have known about nevirapine resistance for over five years and have taken this into consideration in making recommendations for PMTCT.

2. All drugs used to treat HIV infection result in resistance. HIV rapidly mutates and resistance is inevitable. The use of combination antiretroviral drugs, which controls viral replication, reduces but does not eliminate the possibility of resistance. It is not logical to withhold nevirapine to save the life of an infant based on theoretical concerns regarding subsequent responses to therapy. Resistance can develop whether nevirapine is used for PMTCT or for treatment of HIV infection.
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3. WHO, UNAIDS and other international and national health organizations recommend combination drug therapy to treat HIV-infected adults who meet certain criteria for initiation of treatment. Several low-cost regimens include nevirapine as recommended therapy in resource poor countries. Resistance to nevirapine can occur with any of the recommended regimens for treatment of HIV-infected individuals.

4. The "threat of resistance" arguments are backwards. The greatest threat for the development of widespread nevirapine resistance is not from its use as single-dose nevirapine for PMTCT in several hundreds of thousands of pregnant women. Rather widespread nevirapine resistance is more likely to result from its use with combination drugs to treat millions of HIV-infected individuals worldwide and could jeopardize its use for PMTCT.

5. Withholding nevirapine, on the theoretical basis of blunting a subsequent response if used in combination therapy to treat HIV infection, would result in HIV infection and subsequent death of hundreds of thousands of infants for whom no other options are available. In contrast, over 17 antiretroviral drugs are available which can be used in various combinations to treat HIV infection if resistance occurs. In most resource poor countries the only option for preventing HIV-infected babies is single-dose nevirapine.

Conclusion

So what is behind the recent publication of information that has been known for over 4 years by the FDA, the international AIDS community, WHO, UNAIDS and the scientific community? Basically, the media report deceptively presents itself as new information.

Importantly, however, the clinical research and scientific community have gone far beyond the 1999 HIVNET 012 report and have conducted multiple additional studies to confirm both the effectiveness and safety of nevirapine used either as a single dose for PMTCT or in combination with other antiretroviral drugs. Many of these studies are completed and confirm the safety and effectiveness of single-dose nevirapine and its much greater effectiveness when used with other antiretroviral agents to reduce HIV transmission by over 90%. The media report fails to acknowledge these advances.

It is absolutely essential that PMTCT programs move forward quickly to save the lives of infants from fatal HIV infection. Once an opportunity is missed to prevent HIV infection, one cannot go back and eradicate an already established and ultimately fatal infection. We all want to treat with the best combination antiretroviral drugs available to prevent as many infections of babies as possible. We also want to optimally treat the mother's HIV infection.

But as we move toward that goal, single-dose nevirapine may be the only option for resource poor countries until more effective therapy becomes available.

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