Does Development of Resistance Matter in Use of Single-dose Nevirapine (Viramune) for Prevention of Mother-to-child Transmission of HIV?

By Ronald Baker, PhD

Although there has been increased attention to the worldwide HIV pandemic, with more than 600,000 children infected every year, mother-to-child transmission of HIV continues to be a serious problem.

In developed countries, potent combination antiretroviral therapy (HAART) is available for the prevention of MTCT (PMTCT), but in resource-poor countries, access to antiretroviral therapy is limited and many women are not even aware of their HIV status. Even when HAART is available, only 10%-20% of women in Africa are expected to be eligible for it for their own health, according to the U.S. Department of Health and Human Services.

Therefore, 80%-90% of women will continue to receive simpler regimens for PMTCT, which may include single-dose nevirapine (Viramune) or combination treatment that includes single-dose nevirapine, wrote the authors of a study published in the September 2007 issue of the American Journal of Obstetrics & Gynecology.

The HIV Network for Prevention Trials (HIVNET) 012 trials showed that a single 200 mg dose of nevirapine administered to women during labor and a single 2 mg/kg dose of nevirapine to their infants within 72 hours of birth could reduce the risk of mother-to-child HIV transmission by nearly 50%, according to the study authors.

In addition, they wrote, “This is the simplest PMTCT regimen to implement; at least 7 clinical trials that included more than 4000 mother-infant pairs have documented its safety and efficacy. In addition single-dose nevirapine is also the least expensive regimen available for PMTCT.”

However, resistance to nevirapine has been detected in a considerable proportion of women after using single-dose nevirapine for prevention of mother-to-child HIV transmission. This has led to concerns about the efficacy of subsequent nevirapine-based treatment.

The authors of the current study reviewed the results of prior studies in Thailand, Botswana, and South Africa that have assessed treatment response after single-dose nevirapine. These studies did not find any significant difference in virological response for women who began treatment more than 6 months after single-dose nevirapine exposure.

The authors noted that 2 studies found worse response rates in women when treatment was initiated within 6 months of single-dose nevirapine exposure. Furthermore, 2 studies found no difference in mother-to-child HIV transmission rates during repeat pregnancies among who had used single-dose nevirapine for PMTCT during an earlier pregnancy.

Based on their review of these studies, the authors concluded, “These data support the use of single-dose nevirapine as 1 option for the prevention of mother-to-child human immunodeficiency virus-1 transmission in resource-limited settings, particularly in settings where more complex regimens are not yet available.”

However, they added that, “Further research in the optimization of perinatal prevention regimens is needed.”

Discussion

To address the concerns about nevirapine resistance, officials in some resource-limited countries have suggested changes in their guidelines that would include a recommendation for all pregnant HIV positive women to receive HAART, regardless of immunological criteria (CD4 cell count).

The study authors argue that although HAART should be offered “when indicated and feasible,” this should not preclude the use of routine PMTCT efforts. Despite its simplicity, the authors wrote, “implementation of PMTCT programs has been slow in resource-limited countries” and implementation of HAART programs “presents even greater challenges.”

The authors noted that the long-term use of nevirapine during pregnancy is associated with toxicity in some women, in particular those with higher CD4 cell counts. Further, they noted that efavirenz (Sustiva) should not be used in pregnant women “due to the drug’s teratogenic potential.” Use of protease inhibitors is limited by cost, the need for refrigeration in some cases, and the need for toxicity monitoring

“Importantly,” wrote the authors, “clinical trials have not shown any appreciable increase in the efficacy of HAART for PMTCT over combination prophylaxis regimens such as long-course AZT (zidovudine; Retrovir) plus single-dose nevirapine.”

In conclusion, the authors suggested that NNRTI-based HAART regimens “will continue to be regarded as first-line therapy for HIV patients in resource-limited settings” and that “single-dose nevirapine will continue as an option for PMTCT.”

Finally, they stated that exclusion of single-dose nevirapine as an option for PMTCT “would further reduce the effectiveness of existing PMTCT programs” and likely result in an increase in “the already staggering number of HIV-infected infants worldwide.”

10/12/07

Reference
M S McConnell, J Stringer, AP Kourtis, and others. Use of single-dose nevirapine for the prevention of mother-to-child transmission of HIV-1: does development of resistance matter? American Journal of Obstetrics & Gynecology 197(3S): S56-S63. September 2007.