Stopping triple
antiretroviral drug treatment, begun in pregnancy and continued throughout the
breast feeding period, was not associated with faster disease progression eighteen
months after stopping treatment, researchers from the Kesho Bora study reported
at the International AIDS Conference in Vienna last month.
Disease progression, however,
was delayed notably in the first six to 12 months after stopping, in those who
got triple antiretroviral therapy (zidovudine + lamivudine +
lopinavir/ritonavir or AZT+3TC+LPV/r) compared to those who got the standard
short-course antiretroviral therapy (zidovudine through delivery plus single-dose
nevirapine).
Disease progression was also delayed 18 months after stopping treatment in the sub-set of women who entered the study with CD4 counts above 350.
However, the study also showed that women who entered the study with a CD4 count below 350 did not have a slower rate of disease progression during the 18 months after stopping prophylaxis if they had received three-drug antiretroviral therapy during the breastfeeding period.
26% of women with CD4 cell
counts under 350 at randomisation had progressed to stage 4 disease or CD4 cell
counts less than 200 cells/mm³ 18 months after having stopped triple antiretroviral
therapy compared to 9.5% of women with CD4 cell counts over 350 at entry.
The purpose of the Kesho Bora
study was to compare the effect of two different regimens on the risk of
transmission during breastfeeding, and the long-term effect of stopping
antiretroviral treatment in mothers who received a period of triple-drug
prophylaxis.
Led by the World Health
Organization (WHO) in partnership with the French National Agency for Research
on AIDS (ANRS), US Centers for Disease Control and Prevention (CDC) and Eunice Kennedy Shriver National
Institute of Child Health (NICH) of the National Institutes of Health it
resulted in the WHO revised rapid advice recommendations in November 2009
(finalised in July 2010) for the use of antiretrovirals for treating pregnant
women and preventing HIV infection in infants.
The Kesho Bora study,
conducted in Kenya, South Africa and Burkina Faso previously provided evidence
that a protease-inhibitor based antiretroviral regimen given to women with CD4
cell counts between 200 and 500 cells/mm³ during pregnancy, delivery and
breastfeeding reduced mother-to-child transmission rates by 42% compared to the
then recommended short-course therapy. Nor was there any evidence of increased
risk to the health of the mother or her infant.
HIV-infected pregnant women
with CD4 cell counts between 200 and 500 were randomised at 28-36 weeks
pregnancy to start antiretroviral therapy (AZT+3TC+LPV/r) to 26 weeks after
delivery or stopping of breastfeeding, if earlier) or short-course antiretroviral
therapy (zidovudine through delivery plus single-dose nevirapine).
This analysis of the study
looked at the impact of triple antiretroviral treatment on the mother’s long-term
health (AIDS-free survival) at 18 months following delivery, and 18 months
after discontinuing triple ART.
HIV disease progression to
stage 4 disease or a CD4 cell count below 200 cells/mm³ was monitored to 18-24
months following delivery. All women were included.
|
Rate of progression to CD4 <200
or WHO stage 4 HIV disease, by baseline CD4 count
|
|
All CD4 counts
|
CD4 < 350 at entry
|
CD4 >350 at entry
|
|
From delivery
|
From stopping prophylaxis
|
From delivery
|
From stopping prophylaxis
|
From delivery
|
From stopping prophylaxis
|
Short-ARV
|
19.6
|
19.6
|
32.4
|
32.4
|
24.1
|
24.1
|
Triple ARV
|
12.4
|
14.7
|
20.4
|
25.9
|
10.4
|
9.5
|
Statistically significant?
|
Yes, P=0.003
|
No;
p=0.159
|
Yes; p=0.002
|
No;
p=-0.107
|
Yes;
P=0.002
|
Yes
P=0.013
|
Weighing up the benefits and
risks of antiretroviral therapy the researchers concluded that triple
antiretroviral therapy provides significant benefits in reducing
mother-to-child transmission, is safe with no apparent adverse effects on the
health of the mother and her child, and has a short-term impact on disease
progression in women with baseline CD4 counts below 350.
They conclude that their
findings reinforce the WHO recommendations of treating women at CD4 cell counts
of 350 cells/mm³ and stress the importance of starting treatment early
in pregnant women or those who are planning to get pregnant.