Nevirapine resistance after single dose prophylaxis.
Nevirapine (NVP) is a potent non-nucleoside inhibitor of HIV-1 reverse transcriptase. In 1999, the HIVNET 012 trial in Uganda demonstrated that a simple regimen of NVP prophylaxis can dramatically reduce the rate of HIV-1 mother-to-child transmission (MTCT). In the HIVNET 012 regimen, women received a single dose of NVP in labor, and infants received a single dose of NVP within 72 h of birth. The simplicity, efficacy, and low cost of the HIVNET 012 regimen are attractive for prevention of MTCT in resource-poor settings. Plans are underway to implement this regimen in several resource-poor countries. Single mutations in HIV-1 RT can cause high level NVP-resistance and are likely to exist in most HIV-1 infected patients at low levels prior to antiretroviral drug exposure. This favors emergence of NVP-resistant HIV-1 following NVP exposure. NVP-resistant HIV-1 has been shown to emerge in some women and infants following single dose NVP. Emergence of NVP-resistant HIV-1 in this setting is more common among women with high baseline viral loads and low baseline CD4 cell counts. The rate of NVP-resistance in women receiving single dose NVP prophylaxis may also be influenced by HIV-1 subtype. The NVP-resistant HIV-1 typically fades from detection in women and infants over time. We review studies examining the emergence and fading of NVP-resistant HIV-1 in women and infants who received single dose NVP prophylaxis, and discuss the potential clinical relevance of NVP-resistance in this setting.
Eshleman
Susan H
SH
Department of Pathology, Johns Hopkins Medical Institutions, Ross Bldg. 646, 720 Rutland Ave., Baltimore, MD 21205, USA. seshlem@jhmi.edu
Jackson
J Brooks
JB
D018791:CD4 Lymphocyte Count; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D015658:HIV Infections / Q000517:prevention & control* / Q000635:transmission; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D006801:Humans; D007223:Infant; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D009154:Mutation; D019829:Nevirapine / Q000627:therapeutic use*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D014454:Uganda; D019562:Viral Load
D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine