[pronut-hiv] Aidsmap: Kesho Bora study:Maternal ART during pregnancy and BF prevents more infections than short-course prophylaxis

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Kesho Bora study: Maternal ART during pregnancy and breastfeeding
prevents more infections than short-course prophylaxis
 
Keith Alcorn, Friday, July 24, 2009
 
Antiretroviral treatment for mothers started during pregnancy and
continued throughout the breastfeeding period resulted in a
significantly lower rate of mother to child HIV transmission when
compared with the standard short-course regimen, investigators on the
Kesho Bora study reported this week at the Fifth International AIDS
Society conference in Cape Town. 

The Kesho Bora study, conducted in Kenya, South Africa and Burkina
Faso, found that antiretroviral treatment for the mother with a protease
inhibitor-based regimen was significantly more effective than short
course treatment in which the mother took AZT from week 28-36 of
pregnancy with AZT/3TC and single dose nevirapine at the onset of
labour, and AZT/3TC for one week, while the infant received single dose
nevirapine with one weeek of AZT/3TC, and was either formula fed or
breastfed with weaning at 6 months. 

The differing short-course regimens studied reflect variations in
practice as a result of previous clinical trial results. 

In the Kesho Bora study 824 pregnant women not currently eligible for
antiretroviral treatment for their own health, with CD4 counts between
200 and 500 cells/mm3, were randomised to one of two regimens. 

Women in the triple therapy group (n=413) received AZT/3TC and
lopinavir/ritonavir (Kaletra) from the third trimester of pregnancy
until six months postpartum, the point at which breastfeeding was
recommended to cease. 

Women in the short-course group received AZT (zidovudine) from week
28-36 of pregnancy until the onset of labour, when they received AZT/3TC
and single dose nevirapine. They continued to take AZT/3TC for one week
after delivery, an amendment introduced to the study in December 2007. 

All infants received single dose nevirapine within 72 hours of
delivery, and one week of AZT treatment was added from December 2007. 

Women were counselled on the risk of transmission through breastfeeding
and offered the choice of free formula for bottle feeding, or exclusive
breastfeeding with weaning over a two-week period commencing at five and
half months. During the study 76% and 78% of mothers in the two study
arms breastfed at some point, with around 45% in each arm breastfeeding
exclusively during the first three months after delivery. The average
duration of breastfeeding was 21 weeks. 

Study recruitment began in June 2005 and the study was fully recruited
by August 2008, with the result that the majority of births in the study
occurred in the period before the December 2007 protocol amendment. 

In the triple ART arm there were 402 live births, and infant HIV
infections as measured by real-time PCR were detected in 1.8% at birth,
3.3% at six weeks, 4.9% at six months and 5.5% at one year. The
reduction in the risk of transmission at one year was 42% when compared
to the short-course regimen. A log rank test at 12 months showed this
difference to be statistically significant (p=0.039). 

In comparison there were 411 live births in the short-course arm, and
infant HIV infections were detected in 2.2% at birth, 4.8% at six weeks,
8.5% at six months and 9.5% at one year. 

A difference in infant survival became apparent after six months: 6.3%
of infants born to mothers in the triple therapy arm had died after 12
months of follow-up, compared to 10% of infants in the short-course arm,
a reduction in risk of 37%. However a log rank test at 12 months did not
show this difference to be statistically significant (p=0.086). 

Subgroup analysis showed that the reduction in HIV infection rate
associated with the triple therapy regimen was statistically significant
only in the group of mothers with baseline CD4 counts between 200 and
350 cells/mm3. In the infants born to these mothers there was a
cumulative HIV infection rate of 5.5% by six months in the triple ART
group and 10.5% in the short-course group, rising to 6.1% and 11.1% at
12 months (p=0.044). 

A significant difference was not detected in infants born to mothers
with baseline CD4 counts between 350 and 500 cells/mm3, and there was no
significant difference in HIV infections according to regimen in the
infants of mothers who ever breastfed during the study) (5.9% vs 10.2%,
p=0.064). 

The study authors note that the biggest effect of triple ART was
detected between six week and six months after delivery, and in mothers
with CD4 counts between 200 and 350, reinforcing the view that if
earlier treatment is to be recommended in resource-limited settings,
this group should be a priority. The median CD4 count in this study
population was 335 cells/mm3. 

The authors also noted that a small number of postnatal transmissions
occurred after six months, the point at which breastfeeding was
recommended to stop, indicating the importance of continuing ART until
breastfeeding stops completely. 

Analyses of adherence and the long-term impact of treatment on maternal
health will take place, and full results of the study, with 12-month and
18-month follow-up on all participants, are expected in 2010. 

Reference 

Kesho Bora Study Group. Triple-antiretroviral prophylaxis during
pregnancy and breastfeeding compared to short-ARV prophylaxis to prevent
mother-to-child transmission of HIV-1: the Kesho Bora randomized
controlled clinical trial in five sites in Burkina Faso, Kenya and South
Africa. Fifth International AIDS Society Conference on HIV Treatment,
Pathogenesis and Prevention, Cape Town, abstract WeLBPeC01, 2009. 

Chigesa et al. Both maternal HAART and daily infant nevirapine are
effective in reducing HIV-1 transmission during breastfeeding in a
randomized trial in Malawi: 28 week results of the Breastfeeding,
Antiretroviral and Nutrition (BAN) Study. Fifth International AIDS
Society Conference on HIV Treatment, Pathogenesis and Prevention, Cape
Town, abstract WeLBC103, 2009.