Years ago in medical school during the Infectious Diseases course, I would sit for hours memorizing the different HIV antiretroviral medications and combinations. This included memorizing the variation of treatments appropriate for pregnant women, for in the US it was still estimated that annually, 100-200 infants were infected with HIV perinatally – during pregnancy, labor and delivery, or breastfeeding. Soon after, I learned of the HIV epidemic and perinatal transmission on a global scale – and the numbers were startling.
It is estimated that there are over 16 million HIV infected women of reproductive age in the world and over 2 million children who are primarily infected by mother-to-child transmission (MTCT) of HIV. In many resource-limited countries, if HIV medications are even available, the cost of is often prohibitive. One of the simplest and most accessible interventions has been single-dose nevirapine, which has drastically reduced peripartum HIV transmission. With this progress, however, new challenges have arisen.
Two recent New England Journal of Medicine articles take a closer look at the effects of single-dose nevirapine (sdNVP) on the response to subsequent antiretroviral therapy in both mothers with HIV and their children. At nine sites in six countries in Africa, Palumbo et al. investigate the optimal antiretroviral regimen for HIV infected children previously exposed to sdNVP, while Lockman et al. investigate the optimal regimens in 241 HIV-infected mothers who have been exposed to sdNVP.
NEJM deputy editor and infectious disease specialist Lindsey Baden commented on why this is a critical issue: “In resource-limited settings, single-dose nevirapine is a practical, affordable, and accessible therapy to help prevent HIV mother to child transmission. These articles provide tremendous insight on how to upscale this intervention safely with consideration of its long term effects.”
After a single-dose, nevirapine remains in the body at clinically significant levels for days, potentially influencing development of HIV mutations that may cause resistance to future nevirapine-based therapies in both the mother and the child. Palumbo et al. found that in children previously exposed to sdNVP perinatally, there was a higher rate of failed treatment with subsequent HIV nevirapine-based therapy as opposed to lopinavir/ritonavir-based therapy (39.6% vs. 21.7%). Similarly, Lockman et al. showed that mothers who had been exposed to sdNVP also had a higher rate of failed treatment with subsequent nevirapine-based HIV therapy compared to lopinavir/ritonavir-based therapy (26% vs. 8%).
In an editorial, Dr. Marc Lallemant, research associate in the Department of Immunology and Infectious Diseases and senior scientist at the Institut de Recherche pour le Développement, highlights the important questions raised in interpreting these studies. How does the timing of subsequent HIV therapy and the method of HIV bulk sequencing affect the results of these studies? Lallemant also notes that despite a preference for highly active antiretroviral therapy, in resource limited settings, sdNVP will likely remain an important cornerstone in prevention of mother-to-child transmission of HIV. This leads to important concerns. Do the effects noted in these studies persist in the long term? Are there implementable strategies that can screen or closely monitor who would be responsive nevirapine-based therapy in order to preserve the safe use of sdNVP? Continued exploration of both sides of this coin will be necessary to develop an optimal regimen, both safe and accessible, for the millions HIV infected mothers and children in resource-limited settings.