Key resistance mutation fades in the long-term in most women who receive single-dose nevirapine

Resistance to nevirapine falls to very low levels over time in women who received a single dose of the drug to prevent mother-to-child transmission of HIV, according to research in the March 1^st edition of The Journal of Infectious Diseases.

Single-dose nevirapine has been shown to be safe, inexpensive and effective for the prevention of HIV-1 mother-to-child transmission. However exposure to single-dose nevirapine is associated with the development of nevirapine-related resistance. The most common type of mutation detected is theK103N mutation.

K103N-containing virus can persist at low levels for years in the absence of antiretroviral therapy exposure in patients who are infected with resistant strains and in patients who discontinue a non-nucleoside reverse transcriptase inhibitor-containing regimen.

Investigators analysed the persistence of K103N resistance in a five-year follow-up of the HIVNET 012 study.

A total of 144 of the 306 antiretroviral therapy-naive Ugandan women who received single-dose nevirapine on HIVNET 012 were included in the investigators' analysis. They had annual study visits two to five years after the original nevirapine exposure.

The investigators found that 60 (42%) had K103N detected at the six-to-eight week visit (≥0.5% K103N). K103N was undetectable in a total of 100 women by two years, 127 by three years and 139 by four and five years. The remaining women either had K103N detected or had no sample available for testing.

The estimated cumulative rates of fading for all 144 women at two, three, four and five years by use of his model were 88%, 92%, 99% and 99% respectively. In examining predictors of fading among all 144 women, subtype (D>A), higher baseline viral load, and lower baseline CD4 count were significant predictors for longer time to fading of K103N.

Available studies suggest that nevirapine-resistant virus that emerges after single-dose nevirapine exposure are unlikely to compromise subsequent treatment with women with non-nucleoside reverse transcriptase -containing regimens, provided that there is sufficient time to allow for fading of nevirapine resistant strains. This report demonstrates that HIV-1 variants with K103N can persist at very low levels for years in some women following single-dose nevirapine exposure.

Data in this report suggest that the rate of fading on nevirapine-resistant strains may vary from one geographical region to another, depending on which subtypes are prevalent.

The investigators conclude, “our findings demonstrate fading of nevirapine resistance to very low levels after single dose nevirapine exposure, and recent clinical studies suggest that the response to non-nucleoside reverse transcriptase containing ART is not compromised by prior single dose nevirapine exposure if treatment initiation occurs at a time distant from the exposure. These observations support continued use of single dose nevirapine as an important option for prevention of mother-to-child transmission in settings where more complex regimens are not available.”