Kesho Bora study reports on effects on maternal health of stopping triple ART after breastfeeding

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.

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.