Impact of maternal and infant antiretroviral drug regimens on drug resistance in HIV-infected breastfeeding infants.
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Date
2013
Journal Title
Journal ISSN
Volume Title
Publisher
Pediatric Infectious Disease Journal
Abstract
Background: The HIV Prevention Trials Network (HPTN) 046 trial evaluated
the efficacy of extended infant nevirapine (NVP) administration for
prevention of HIV transmission through breastfeeding. Infants received
daily NVP up to 6 weeks of age. HIV-uninfected infants (the intent-to-treat
group) received daily NVP or placebo up to 6 months of age. We analyzed
emergence of NVP resistance in infants who acquired HIV infection despite
prophylaxis.
Methods: HIV genotyping was performed using the ViroSeq HIV Genotyping
System. Medians and proportions were used to summarize data.
Two-sided Fisher exact tests were used to evaluate associations between
categorical variables.
Results: NVP resistance was detected in 12 (92.3%) of 13 infants who
were HIV-infected by 6 weeks and in 7 (28%) of 25 infants who were HIVuninfected
at 6 weeks and HIV-infected at 6 months of age (6/8 = 75% in
the NVP arm, 1/17 = 5.9% in the placebo arm, P = 0.001). Among those 25
infants, 4 had mothers who initiated an antiretroviral treatment regimen by
6 months postpartum. In all 4 cases, the treatment regimen included a nonnucleoside
reverse transcriptase inhibitor (NVP or efavirenz). NVP resistance
was detected in all 4 of those infants by 6 months of age (4/4 = 100%).
In contrast, only 3 (14.2%) of the remaining 21 HIV-infected infants whose
mothers did not initiate antiretroviral treatment developed NVP resistance
(P = 0.003).
Conclusions: Extended NVP prophylaxis significantly increased the risk of
NVP resistance in infants who acquired HIV infection after 6 weeks of age.
Treatment of maternal HIV infection was also associated with emergence of
NVP resistance in HIV-infected, breastfed infants.
Description
The HPTN 046 trial evaluated the efficacy of extended infant nevirapine (NVP) administration for prevention of HIV transmission through breastfeeding. Infants received daily NVP to 6 weeks of age. HIV-uninfected infants (the intent-to-treat group) received daily NVP or placebo up to 6 months of age. We analyzed emergence of NVP resistance in infants who acquired HIV-infection despite prophylaxis.
Keywords
Nevirapine resistance., Prevention of mother-to-child transmission., Extended nevirapine., HIV.
Citation
Fogel, J.M.; Mwatha, A.; Richardson, P.; Brown, E.R.; Chipato, T.; Alexandre, M.; Moodley, D.; Elbireer, A.; Mirochnick, M.; George, K.; Mofenson, L.M.; Zwerski, S.; Coovadia, H.M.; Eshleman, S.H. 2013. Impact of maternal and infant antiretroviral drug regimens on drug resistance in HIV-infected breastfeeding infants. The Pediatric infectious disease journal 32(4), 164-169..