Women given a single dose of nevirapine to stop them passing on HIV to their babies run the risk of developing resistance to the drug even when it is added to stable background antiretroviral therapy, according to a study published in the 15 July 2002 edition of the Journal of Infectious Diseases.
The US study found that 14 of 95 (15%) women who were given a single dose of nevirapine during labour developed resistance mutations to the drug, even if they were receiving a multi-drug HAART combination. Worringly, investigators noted that the emergence of nevirapine resistance mutations was not related to CD4 count or viral load, and were not influenced by the type of HAART regimen prescribed before or during pregnancy. Resistance mutations were detected at a range of CD4 counts (including above 400) and viral load levels (including women with viral load below 1,000 copies).
These new data have emerged from a sub-study of PACTG 316, which compared the effect of adding single dose nevirapine or placebo to background therapy in HIV-positive pregnant women at the time of delivery, with a further dose given to the infant. Whilst this nevirapine regimen has been found effective in reducing mother-to-baby transmission in resource-poor settings, PACTG 316 was unable to detect any beneficial effect of adding nevirapine, most likely because the transmission rate in well-resourced settings is already very low.
The sub-study assessed the presence of resistance mutations in blood samples taken from study participants at a clinic visit scheduled six weeks after delivery. The tests used are unable to detect mutants which form less than 20-25% of the sample. This suggests that the detected prevalence of 15% may be an under-estimate of the true frequency of nevirapine resistance. Because drug resistant mutants are 'archived', women who have developed resistance to nevirapine as a result of exposure to this single dose are very unlikely to derive any benefit from future use of the drug, or from another NNRTI, efavirenz.
In areas of the world where it is possible to treat pregnant women with HAART, the investigators suggest that single dose nevirapine therapy presents risks, telling Reuters Health that “for women who are on standard antiretroviral therapy, there is no demonstrable benefit to adding the single dose of nevirapine for mother or baby.”
Cunningham CK et al. Development of resistance mutations in women receiving standard antiretroviral therapy who received intrapartum nevirapine to prevent perinatal human immunodeficiency virus type 1 transmission: A substudy of pediatric AIDS clinical trials group protocol 316. Journal of Infectious Diseases, 186:181-188, 2002