Nevirapine Used for Prevention of HIV

Lower Risk of Resistance After Short-Course HAART Compared With Zidovudine/Single-Dose Nevirapine Used for Prevention of HIV-1 Mother-to-Child Transmission.

Antiretroviral resistance after short-course regimens used to prevent mother-to-child transmission has consequences for later treatment. Directly comparing the prevalence of resistance after short-course regimens of highly active antiretroviral therapy and zidovudine plus single-dose nevirapine (ZDV/sdNVP) will provide critical information when assessing the relative merits of these antiretroviral interventions. In a clinical trial in Kenya, pregnant women were randomized to receive either ZDV/sdNVP or a short-course of highly active antiretroviral therapy through 6 months of breastfeeding. Plasma samples were collected 3-12 months after treatment cessation, and resistance to reverse transcriptase inhibitors was assessed using both a sequencing assay and highly sensitive allele-specific polymerase chain reaction assays. No mutations associated with resistance were detectable by sequencing in either the ZDV/sdNVP or highly active antiretroviral therapy arms at 3 months posttreatment, indicating that resistant viruses were not present in >20% of virus. Using allele-specific polymerase chain reaction assays for K103N and Y181C, the authors detected low levels of resistant virus in 75% of women treated with ZDV/sdNVP and only 18% of women treated with highly active antiretroviral therapy (P =0.007). Y181C was more prevalent than K103N at 3 months and showed little evidence of decay by 12 months. The study finding provides evidence that compared with ZDV/sdNVP, HAART reduces but does not eliminate nevirapine resistance.

This small Kenyan trial is the first study to compare directly the prevalence of HIV resistance after short-course antiretroviral treatment with standard prophylactic regimens. Of 58 women initially randomised, 40 women had plasma samples for analysis by sequencing assay and highly sensitive polymerase chain reaction. One study arm received zidovudine twice daily for 6 weeks before delivery, single-dose nevirapine during labour, and for the babies, single dose nevirapine. The women in the other study arm received twice-daily zidovudine, nevirapine, and 3TC for 6 weeks before and 6 months after delivery. The big difference seen in the levels of resistant virus 3 months or more after ceasing to take drugs may well be due to the fact that in the first arm, nevirapine was not accompanied by any other antiretroviral drug during labour. Antiretroviral treatment for 6 months did not eliminate nevirapine resistance, suggesting that after nevirapine is stopped, treatment cessation strategies should include temporarily continuing zidovudine and 3TC to prevent single drug pressure caused by nevirapine’s longer half-life