Lower risk of resistance after short-course HAART compared with zidovudine/single-dose nevirapine used for prevention of HIV-1 mother-to-child transmission

Abstract

Background: 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 (HAART) and zidovudine plus single-dose nevirapine (ZDV/sdNVP) will provide critical information when assessing the relative merits of these antiretroviral interventions.

Methods: In a clinical trial in Kenya, pregnant women were randomized to receive either ZDV/sdNVP or a short-course of HAART 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.

Results: No mutations associated with resistance were detectable by sequencing in either the ZDV/sdNVP or HAART 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, we detected low levels of resistant virus in 75% of women treated with ZDV/sdNVP and only 18% of women treated with HAART (P = 0.007). Y181C was more prevalent than K103N at 3 months and showed little evidence of decay by 12 months.

Conclusions: Our finding provides evidence that compared with ZDV/sdNVP, HAART reduces but does not eliminate nevirapine resistance.

FIGURE 1

Background levels of K103N and Y181C allele-specific PCR assays. Results of allele-specific PCR on 48 replicates of wild-type RNA template. Total HIV copy number was quantified by real-time PCR, and an average of 379 copies (range: 76–779) of wild-type RNA was tested in each reaction. A, Results of K103N allele-specific PCR on wild-type template. The average background across all 45 samples is shown with a dashed line. The lower limit of 0.2%, defined by a <5% false-positive rate is shown with a dotted line. B, Results of Y181C allele-specific PCR on wild-type template. The average background across all 45 samples is shown with a dashed line. The lower limit of 2%, defined by a <5% false-positive rate is shown with a dotted line. C, The false-positive rates at different lower limits of detection are shown. (figure modeled after Palmer et al. AIDS. 2006;20:701–710).