Therapy for Mother or Infant Reduces HIV Transmission during Breast-feeding
Treating HIV positive
mothers with a combination
antiretroviral regimen or giving infants nevirapine
for 28 days after birth both reduced the risk of mother-to-child
HIV transmission during breast-feeding, according to
findings from the BAN Study reported in the June
17, 2010 New England Journal of Medicine.
But the Mma Bana Study, described in the same issue,
found that women with HIV should start antiretroviral
therapy (ART) during pregnancy to have the greatest
effect in reducing transmission risk.
high-income countries, HIV positive pregnant women are advised
to use a complete ART regimen regardless of CD4 cell count and
to not breast-feed their infants. In resource-limited countries,
pregnant women with higher CD4 cell counts still often receive
the ACTG 076 regimen of zidovudine
(AZT; Retrovir) during pregnancy and labor, and for the infant
for 6 months after birth. A single dose of nevirapine
(Viramune) may also be used, though this can promote drug
resistance in the mother.
Due to competing risks related to unclean water and inadequate
nutrition, the World Health Organization recommends that HIV positive
mothers should breast-feed exclusively for 6 months if replacement
feeding is not "acceptable, feasible, affordable, sustainable,
and safe." But the rate of HIV transmission during breast-feeding
reaches about 9% after 18 months.
Charles Chasela and fellow investigators with the BAN Study Group
evaluated whether antiretroviral treatment during breast-feeding
-- either for the mother or for the baby -- can help reduce the
likelihood of mother-to-child HIV transmission.
analysis included 2369 HIV positive mothers in Malawi with a CD4
count of at least 250 cells/mm3. Women with anemia or pre-existing
liver impairment, and those who had previously used antiretroviral
drugs during pregnancy, were excluded. All women received oral
single-dose nevirapine during labor followed by zidovudine/lamivudine
(Combivir) for both mothers from the onset or labor and babies
from birth, continuing for 7 days.
pairs were randomly allocated into 3 groups after the first week.
In the first group, mothers were treated for 28 weeks with zidovudine/lamivudine
plus nevirapine, which was replaced with nelfinavir
(Viracept) and then lopinavir/ritonavir
(Kaletra) for women recruited later (after studies showed
nevirapine could cause hypersensitivity reactions in women with
CD4 counts > 250 cells/mm3); infants received no therapy.
the second group, infants were treated with nevirapine monotherapy
for 28 weeks (increasing from 10 mg daily for the first 2 weeks
to 30 mg daily starting at week 19); mothers received no treatment.
In the control group, neither mothers nor infants received antiretroviral
drugs during breast-feeding but received nutritional supplements
(enrollment in this arm was halted early).
Mothers were counseled to breast-feed exclusively for 6 months,
then wean the baby rapidly between 24 and 28 weeks, since studies
have shown that mixed feeding of breast milk and alternative foods
increases HIV transmission risk.
The primary outcome was the number of infants who became infected
with HIV after 2 months of age, indicating that transmission occurred
during breast-feeding rather than during gestation or delivery.
5.0% of infants were found to be HIV infected at 2 weeks.
2 and 28 weeks, the risk of infection was higher in the control
group (5.7%) than in either the maternal treatment group (2.9%;
P = 0.009) or the infant treatment group (1.7%; P < 0.001).
an analysis that included all randomized infants regardless
of infection status at 2 weeks, the risk of HIV infection
at 28 weeks was 10.9%, 8.2%, and 6.0%, respectively.
the combined risk of infant HIV infection or death between
2 and 28 weeks was higher in the control group (7.0%) than
in the maternal treatment group (4.1%; P = 0.02) or the infant
treatment group (2.6%; P < 0.001).
all infants regardless of HIV status at 2 weeks, the risk
of infection or death was 12.3%, 9.6%, and 7.1%, respectively.
receiving combination therapy during breast-feeding were more
likely to develop neutropenia (6.2%) than women in the infant
treatment group (2.6%) or the control group (2.3%).
of infants treated with nevirapine for 28 weeks developed
Based on these findings, the investigators concluded, "The
use of either a maternal antiretroviral regimen or infant nevirapine
for 28 weeks was effective in reducing HIV-1 transmission during
protective efficacy against HIV-1 transmission from 2 to 28 weeks
was 74% for infant nevirapine and 53% for the maternal antiretroviral
regimen," they elaborated in their discussion. "Infants
also had significantly increased HIV-1-negative survival with
both interventions, with a trend toward increased benefit when
the drug regimen was administered directly to the infant."
"Health care providers and mothers can ultimately choose
the option that best suits their cultural, economic, and individual
needs, since there is now evidence for 2 effective options to
prevent the transmission of HIV-1 to infants from their mothers
during breast-feeding in resource-limited countries," they
study reported in the same issue also demonstrated the benefits
of treating mothers during breast-feeding, though here treatment
was started during pregnancy and did not include an extended infant
The Mma Bana study included 560 HIV positive pregnant women in
Botswana who had a CD4 cell count above 200 cells/mm3. Starting
at 26 to 34 weeks of pregnancy and continuing through infant weaning
at 6 months, they were randomly assigned to receive either zidovudine/lamivudine/abacavir
(Trizivir combination pill) or else lopinavir/ritonavir plus
zidovudine/lamivudine; in addition, 170 women with a CD4 cell
count < 200 cells/mm3 started zidovudine/lamivudine plus nevirapine.
All infants received single-dose nevirapine after delivery and
zidovudine for 4 weeks.
More than 95% of women in all study arms achieved undetectable
viral load. The overall rate of mother-to-child HIV transmission
was very low at 1.1% -- in fact, it was among the lowest ever
seen in randomized studies of ART during pregnancy and breast-feeding
in resource-limited settings -- and did not differ significantly
between the Trizivir (2.1%) and lopinavir/ritonavir (0.4%) arms.
While 6 transmissions occurred during pregnancy, 2 cases occurred
during breast-feeding in the Trizivir arm.
In an accompanying editorial, Lynne Mofenson from the Pediatric,
Adolescent and Maternal AIDS Branch of the Eunice Kennedy Shriver
National Institute of Child Health and Human Development summarized
the clinical implications of the 2 studies.
maximally reduce transmission, antiretroviral regimens must start
during pregnancy," she wrote. "In the BAN study, which
did not include an antepartum regimen, in utero transmission was
5.0% as compared with 0.9% in the Mma Bana Study."
the BAN control group, the risk of postnatal infection was highest
between 2 and 12 weeks of age," she continued. "During
this early high-risk period, the infant regimen reduced postnatal
transmission by 86.1% (from 3.6% in the control group to 0.5%),
while the maternal regimen reduced transmission by 52.8% (from
3.6% in the control group to 1.7%)...This early difference in
efficacy probably reflected the time required for the triple-drug
regimen to suppress the maternal viral load. Therefore, in women
presenting late or during labor, the use of nevirapine in infants
may be particularly critical to prevent early postnatal infection."
of North Carolina Project, Lilongwe, Malawi; University of North
Carolina, Chapel Hill, CD; Principia, Chapel Hill, NC; Centers
for Disease Control and Prevention, Atlanta, GA.
Chasela, MG Hudgens, DJ Jamieson, and others (BAN Study Group).
Maternal or Infant Antiretroviral Drugs to Reduce HIV-1 Transmission.
New England Journal of Medicine 362(24): 2271-2281 (Abstract).
June 17, 2010.
Shapiro, MD Hughes, A Ogwu, and others. Antiretroviral Regimens
in Pregnancy and Breast-Feeding in Botswana. New England Journal
of Medicine 362(24): 2282-2294 (Abstract).
June 17, 2010.
Mofenson. Protecting the Next Generation -- Eliminating Perinatal
HIV-1 Infection (Editorial). New England Journal of Medicine
362(24): 2316-2318. June 17, 2010.