Extending the use of daily infant nevirapine to six months reduced the risk of
breastfeeding mother-to-child transmission by a significant 76% in
HIV-positive mothers with CD4 cell counts over 350 and not yet
eligible for antiretroviral treatment Yvonne Maldonado reported on
behalf of the HPTN 046 study at the Eighteenth
Conference on Retroviruses and Opportunistic Infections (CROI)
in Boston last week.
the risk for infant death was similar in both the nevirapine and
placebo arms, approximately two-thirds of all deaths happened after
six months of age when most infants had stopped breastfeeding.
Cessation of breastfeeding was not controlled for in the study.
study findings showed that daily infant nevirapine (extended-dose
nevirapine) given to breastfeeding infants for six (SWEN) or 14 weeks
(PEPI-Malawi) or six months (BAN) was more effective in reducing
mother-to-child transmission (MTCT) compared to single-dose
the analysis presented Dr Maldonado reported on the incremental
protective benefits of extended-dose nevirapine to six months
directly compared to six weeks.
resource-poor settings, MTCT continues to cause significant death and
disease. Approximately 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
prophylaxis has proven effective in reducing MTCT. While maternal antiretroviral therapy (ART)
is also effective in reducing MTCT many women, even if eligible (at
CD4 cell counts below 350 cells/mm3),
are not able to access treatment in resource-poor settings where
coverage is severely limited. Those who do access ART often do so
late in pregnancy. Viral suppression can take several weeks. So it is
critical to look at the role of infant prophylaxis in reducing MTCT
associated with breastfeeding.
046 was a randomised, placebo-cotrolled, double-blind trial
undertaken in South Africa, Tanzania, Uganda and Zimbabwe.
multi-site study began in March 2007 with enrolment completed in
January 2010. For the first six weeks of life all infants received
A total of 1522
breastfeeding, uninfected infants born to 1505 mothers were
randomised at six weeks of age to get extended nevirapine (759
infants/752 mothers) or placebo (763 infants/753 mothers) for six
the time of randomisation, 29% of mothers were on ART for their own
health in each arm (221 in the extended-dose nevirapine and 219 in
the placebo). Median maternal CD4 cell counts were 560 cells/mm3
and 528 cells/mm3 in
the extended-dose and placebo arms, respectively. At six months the
percentages of mothers on ART increased slightly to 31% and 32% in
the nevirapine and placebo arms, respectively.
of infants were reported to be exclusively breastfeeding at three
months; between six and nine months over 90% of all infants stopped
breastfeeding. There was no significant difference between the arms.
nevirapine given for six months, compared to six weeks, where the
mother was on ART at the time of randomisation, resulted in a 55%
reduction in the infection rate (1.1% in the extended-dose nevirapine
arm and 2.4% in the placebo arm).
those mothers not on ART for their own health (CD4 cell counts over
350) the six-month infection rate was 2.4% (1.4% in the extended-dose
arm and 3.4% in the placebo arm, p = 0.027).
treatment stopped at six months the rates of MTCT between 6 and 12
months were similar in both arms.
were no significant differences in adverse or serious events between
Maldonado concluded that the benefits of extending the daily dose of
nevirapine in breastfeeding infants of mothers with CD4 cell counts
over 350 cells/mm3 and not on ART was significant in reducing MTCT.
results, she added “support the benefits and safety of extended
infant nevirapine for women who do not yet require ART for their own
health [or cannot access it], a group of women relatively unprotected
at this time.”