Research question
Exclusive breastfeeding is crucial to infant survival in developing countries, but carries a risk of mother to child transmission (MTCT) of HIV. The main aim of this WHO-coordinated study is to optimise the use of antiretroviral (ARV) drugs during the antepartum, intrapartum and postpartum periods to prevent MTCT of Human Immunodeficiency Virus Type 1 (HIV) and preserve the health of the mother in settings where the majority of HIV-positive women breastfeed.
Rationale
The use of HAART is central to PMTCT strategies in a westernized setting. However its use has never been demonstrated to prevent postnatal transmission as a consequence of breastfeeding.
Data source and methods
Kesho Bora is a randomised controlled multicentre trial conducted at 5 sub-Saharan sites (Bobo-Dioulasso, Nairobi, Mombasa, Durban, and the Africa Centre). Women with clinical HIV stages 1, 2 or 3, with CD4+ cell counts between 200 and 500 cells/mm3 with no contraindication received one of two different regimens for the prevention of MTCT of HIV:
1) A triple-ARV regimen (ZDV, 3TC and LPV/r) beginning as soon as possible after 28 weeks gestation, through delivery, until six months postpartum; or
2) A short-course regimen consisting of ZDV beginning as soon as possible after 28 weeks gestation until the onset of labour, plus one dose of ZDV and one dose of NVP at the onset of labour, and one week of zidovudine/lamivudine postpartum.
All infants born to women enrolled in either part of the study received one dose of NVP within 72 hours of birth and one week of zidovudine. All women enrolled in the RCT whose HIV disease progresses to WHO Clinical Stage 4 or whose CD4+ count falls below 200 cells/mm3 at any time until one year postpartum will be offered HAART (provided they have no contraindication). Women who have WHO Clinical Stage 3 disease, a CD4 count of < 350 cells/mm3 at the time of enrolment, and are randomized to the triple-ARV regimen will be continued on long-term HAART for their own health consistent with new WHO PMTCT guidelines.
Preliminary results (presented at IAS, 19-22 July 2009)
Of 882 women enrolled across all sites (101 at the Africa Centre), 413 received triple ARV prophylaxis and 411 received short course prophylaxis. At 12 months, the cumulative HIV infections or death amongst infants was 10.4 (7.7-13.9) in the triple therapy arm compared with 16.3 (12.9-20.5) in the short course arm (p=0.022). The reduction in infant infection was effect was particularly marked in women with a baseline CD4 of 200-350 receiving triple therapy compared with short course prophylaxis (6.1% versus 11.1% at 12 months, p=0.044) whilst no significant difference was seen in women with the higher baseline CD4 of 350-500 (4.9% versus 7.4%, p=0.33). Data is awaited during the follow up period to determine if prophylactic triple ARVs have any effect on maternal disease progression.
The trial will close on 31st May 2010.
Policy implications
The Kesho Bora preliminary results were instrumental in shaping recent WHO guidelines which were issued in November 2009 (Rapid Advice: Use of antiretroviral drugs for treating pregnant women and preventing HIV infection in infants). These advise the use of maternal HAART for all women with CD4 of less than 350 cells/mm3 or stage 3 or 4. In addition the prophylactic use of triple therapy from 14 weeks gestation until 1 week after the cessation of breastfeeding is provided as an option for women with a CD4 over 350 cells/mm3 with stage 1or 2. It is anticipated that South Africa will adopt the new maternal HAART guidelines from April 2010.