Lower risk of resistance after short-course HAART compared with zidovudine/single-dose nevirapine used for prevention of HIV-1 mother-to-child transmission.
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.
Lehman
Dara A
DA
Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.
Chung
Michael H
MH
Mabuka
Jennifer M
JM
John-Stewart
Grace C
GC
Kiarie
James
J
Kinuthia
John
J
Overbaugh
Julie
J
D019943:Amino Acid Substitution; D019380:Anti-HIV Agents / Q000008:administration & dosage; D023241:Antiretroviral Therapy, Highly Active; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D015751:Genes, pol; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy* / Q000635:transmission / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D007630:Kenya; D020125:Mutation, Missense; D019829:Nevirapine / Q000008:administration & dosage*; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy* / Q000821:virology; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage; D013997:Time Factors; D015215:Zidovudine / Q000008:administration & dosage*
D019380:Anti-HIV Agents; D017931:DNA Primers; D004279:DNA, Viral; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; D019829:Nevirapine