Dutch researchers this week confirmed the Thai findings reported last year, showing that women exposed to a single dose of nevirapine (Viramune)may still have detectable levels of the drug in their blood more than two weeks later. The authors of the study, published in the August 1st edition of the Journal of Acquired Immune Deficiency Syndromes, say that short three to five day courses of antiretroviral treatment after delivery may not be sufficient to prevent all mothers from developing nevirapine resistance.
Nevirapine causes drug resistance when it is given as a single drug because HIV needs only one mutation to become highly resistant to the drug. Levels of nevirapine below 3mg/L are likely to give rise to drug resistance.
Last year the Thai and US researchers reported that subtherapeutic levels of nevirapine may persist for much longer than previously assumed in some women. Almost half of the participants in a pharmacokinetic substudy in Thailand had detectable nevirapine levels 14 days after delivery (Cressey 2005).
In the Dutch study reported this week, researchers at Nijmegen University recruited 44 HIV-negative Dutch women, administered a single 200mg dose of nevirapine and then carried out blood and saliva sampling twice a week for 21 days.
Using a liquid chromatography assay with a lower detection limit of 0.15mg/L, they found that seven of 44 women still had detectable nevirapine levels on day 21 of the study, and that the median time to the first undetectable nevirapine sample in plasma was 17 days (range 10-21 days). The time to an undetectable level was slightly shorter in saliva samples (14 days).
The authors note that recent studies that have attempted to `cover the tail` of nevirapine by giving either zidovudine (AZT, Retrovir) or zidovudine plus lamivudine (AZT/3TC, Combivir) for three to five days may be underestimating the amount of time for which coverage will be needed.
“This may not be sufficient to prevent the development of all nevirapine mutations. Indeed, nevirapine resistance was not fully absent in the intervention arm.”
However they warn that increasing the duration of coverage with other drugs may increase the risk that resistance to those drugs might develop instead.
Cressey TR et al. Persistence of nevirapine exposure during the postpartum period after intrapartum single-dose nevirapine in addition to zidovudine prophylaxis for the prevention of mother-to-child transmission of HIV-1. J Acquir Immune Defic Syndr 38(3): 283-288, 2005.