thirds of breastfeeding infants infected after birth, born to mothers on
antiretroviral therapy (ART), developed resistance to one or more
antiretroviral drugs according to Clement Zeh and colleagues in a secondary
analysis of the Kisumu Breastfeeding Study (KiBS) published in PLoS Medicine this month.
drug resistance appears to have developed as a result of exposure to
antiretrovirals in breast milk or exposure to antiretroviral prophylaxis
immediately after infection, not through transmission of drug-resistant virus
from the mother.
resistance mutations in HIV-infected infants developed between two weeks and
six months after birth increasing over time: from 30% by week six, to 63% by
week 14 and 67% by six months.
resistance was found among infants infected before two weeks of age or after
six months when the mothers stopped ART and stopped breastfeeding.
authors note this pattern suggests resistance was transmitted through exposure
to maternal ART through breast milk, not through mother-to-child transmission
(MTCT) of drug-resistant virus.
resource-poor settings MTCT continues to cause significant death and disease.
one-third of the estimated 450,000 children infected each year are infected
through breastfeeding. Safe alternatives are often not feasible for the
majority of women in such settings. The risks for infant death and disease
linked to not breastfeeding are greater than the risks associated with HIV
these settings breastfeeding is the norm. Proven strategies to reduce the risks
of MTCT through breast milk include giving mothers ART during the (recommended)
six-month breastfeeding period. What happens is that maternal viral load in
breast milk is reduced, and infants also get an indirect prophylaxis of ART
through breast milk.
have shown that antiretroviral drugs (including zidovudine, lamivudine,
nevirapine and efavirenz) when given to nursing mothers are present in breast
antiretroviral drugs in breast milk can also have a negative effect for infants
infected just before or during the breastfeeding period. Low levels of drug in
the infant can encourage the evolution of drug-resistant virus if infection
occurs despite prophylaxis.
authors assessed this risk in a secondary analysis of the KiBS trial findings
by looking at those infants who became HIV-infected during this time.
parent trial, a single-arm open label prevention of mother-to-child
transmission trial, looked at the safety and efficacy of giving zidovudine,
lamivudine, and either nevirapine or nelfinavir to HIV-infected women from 34
weeks of pregnancy through six months of breastfeeding.
women were enrolled between July 2003 and November 2006 and gave birth to 502
infants. By the end of two years 32 (6%) infants were HIV-infected of which 24
(75%) were infected within the first six months of life.
the 24, nine were exposed to mothers on a nelfinavir-based regimen and the
other 15 exposed to mothers on a nevirapine-based regimen throughout the
nine (100%) of those exposed to a nelfinavir-based regimen and seven (47%) of
those exposed to a nevirapine-based regimen developed drug resistance (95% CI:
most common mutations, M184V and K103N, conferred resistance to lamivudine and
infants were given single-dose nevirapine within 48 hours of birth.
samples from mothers and infants were taken at various stages and analysed for
of the eight (of the 24 HIV-infected children) who were HIV-positive by two
weeks of age had any signs of development of drug resistance. Similarly no
mutations were seen in the eight infants infected after the breastfeeding
period of six months.
the mothers of the 24 children the majority (84%) had no drug resistance
mutations. Only one mother-child pair had overlapping mutation patterns that
might imply the transmission of drug-resistant virus.
authors note that the timing of the development of drug resistance suggests
this happened either through single-dose nevirapine given to the infants or
indirectly through ART in breast milk. Findings from the SWEN study support
this suggestion. (Infants given nevirapine prophylaxis while their mothers were
on ART developed nucleoside reverse transcriptase inhibitor resistance in that
major limitation, the authors note, is that HIV drug resistance genotyping was
done on viral isolates from maternal plasma and not on breast milk isolates.
light of the increasing use of infant prophylaxis during breastfeeding, it is
likely that drug resistance will be seen more frequently.
authors suggest improved early infant diagnosis and treatment may help
alleviate the problem.
authors conclude that close monitoring for the development of resistance in
infants in PMTCT programmes who are exposed to ART through breast milk is
needed, so that treatment can be tailored accordingly.