Babies born to HIV-positive mothers and given the
antiretroviral drug nevirapine through the
first six weeks of life to prevent infection via
breast-feeding are at high risk for developing drug-
resistant HIV if they get infected anyway, a team of
researchers reports. But the investigators
highlight the proven superiority of the six-week regimen in
preventing mother-to-child HIV
transmission in breast-fed infants.
In a study led by researchers at Johns Hopkins
Children's Center, risks of drug resistance in
the first year of life were compared in Indian infants
getting a standard single dose of nevirapine at
birth and those on the six-week regimen.
"While extended nevirapine prophylaxis dramatically
reduces HIV transmission during the first
six weeks of life, our data show that if infection does
occur, it will most likely be with strains
resistant to nevirapine, making HIV much harder to treat
early with nevirapine," said senior
investigator Deborah Persaud, a pediatric HIV expert at
Johns Hopkins. "But until other interventions
become available, the extended nevirapine regimen remains a
reasonable way to prevent infections
Published in the Jan. 1 issue of Public Library of
Science One, or PLoSOne, the research report
emphasized that especially in the developing world, where
bottle feeding is not safe or is too
expensive or simply unavailable, the extended nevirapine
therapy remains one of the best ways to
reduce mother-to-child transmission of HIV through breast
Given the high risk of death from HIV in infancy, the
benefits of fewer infections still
outweigh the risk of increased resistance, the researchers
The findings also suggest that because of their higher
risk for acquiring resistant HIV strains,
infants given extended courses of nevirapine — should
they get infected — should receive treatment
with protease inhibitors, or PIs, which are effective
against nevirapine-resistant strains.
"In the developing world, testing for resistance is
not available or [is] too expensive, so if
extended nevirapine regimens become widespread, PIs should
be made available as a first line of
treatment early on for all infants who get infected despite
prophylaxis," Persaud said.
The new report comes on the heels of two separate
multicenter studies from Johns Hopkins and
other institutions, published in 2008, showing that a six-
or 14-week regimen with nevirapine slashed
the risk of HIV infection from breast-feeding by 46 percent
or 66 percent, respectively.
For the current study, investigators analyzed samples
from 74 Indian babies infected with HIV;
22 were infected before birth, 19 during birth or during
early breast-feeding (three to six weeks
after birth), and 33 during late breast-feeding (around six
months after birth). Of the 19 infants
infected through breast-feeding in the first six weeks of
life, four were given daily nevirapine for six
weeks, and 15 received a single dose at birth. All four
babies on extended nevirapine developed
resistant strains of the virus, while only four of the 15
given a single dose tested positive for
resistant strains after infection.
It is important to keep in mind that while the risk of
resistance is higher with extended
nevirapine regimens once infection occurs, the risk of
acquiring HIV with extended regimens is
dramatically reduced, the investigators say. Thus, in the
long run, extended nevirapine regimens do not
lead to more resistant cases than the single-dose regimens
because single-dose regimens also carry
some risk of resistance and are less effective in
preventing new infections.
Indeed, when researchers compared resistance among
infants infected during late breast-
feeding, the gap in resistance risk virtually disappeared.
Fifteen percent of the 13 infants given
extended nevirapine developed resistance and so did 15
percent of the 20 infants who received a
single dose of the drug.
When investigators used more sensitive assays to
detect nevirapine-resistant mutations that
are normally not detected by standard tests, the proportion
of infants with resistant strains who had
received single-dose nevirapine went up from 38 percent to
59 percent among the 29 infants who got
the single dose but remained unchanged in the group
receiving the six-week regimen, 92 percent of 12.
Likewise, the proportion of infants testing positive for
resistance went up in the group infected after
six weeks of age. In that group, 31 percent of 13 infants
on the extended regimen tested positive for
resistant strains, and 40 percent of 20 infants who got the
single dose had resistant strains.
However, researchers say, the clinical significance of
mutations that are not detected by standard
testing remains unclear.
The infants in this trial were infected with HIV
subtype C, but previous studies have shown
that the six-week regimen increases resistance in infants
who get infected with other HIV subtypes
Despite the risk of HIV transmission, breast-feeding
for at least six months is widely
encouraged by the World Health Organization and other
organizations as a proven factor in better
infant survival. In 2007 alone, 420,000 infants acquired
HIV in utero, during birth or during breast-
feeding, according to WHO estimates. HIV infection is
estimated to occur in one out of 10 breast-fed
infants, with many of the infections occurring in the first
six to 14 weeks of life.
The research was funded by the Elizabeth Glaser
Pediatric AIDS Foundation and the National
Institutes of Health.
Anita Moorthy of Johns Hopkins is the first author on
the study. Other Johns Hopkins
investigators on the study are Robert Bollinger, Amita
Gupta and Carrie Ziemniak. Investigators from
the Indian arm of the trial are from Byramjee Jeejeebhoy
Medical College, the National AIDS
Research Institute and the India SWEN Study Team.