Public Release:  Reducing HIV risk of breastfeeding with 3-drug prophylaxis

Lancet

The risk of transmitting HIV to infants during breastfeeding can be halved with a triple-drug regimen taken by mothers. These findings indicate that prophylaxis* with a three-drug regimen can safely replace older regimens in Africa, concludes the Article published Online first in Lancet Infectious Diseases.

Breastfeeding is vital for child health and development in low-resource settings, but infants born to HIV-positive mothers can be infected through breastfeeding. So a team of researchers from the World Health Organization (WHO) and five study sites in Burkina Faso, Kenya, and South Africa conducted a randomized, controlled trial to investigate whether three antiretroviral (ARV) drugs taken together by women during pregnancy and breastfeeding are more effective than the standard regimen used to prevent mother-to-child HIV transmission in these countries.

The Kesho Bora Study (meaning "a better future" in Swahili) enrolled HIV-positive pregnant women with CD4 cell counts 200-500 cells/mm3.** 824 women were randomly assigned to take either triple antiretroviral prophylaxis in late pregnancy and during breastfeeding, or the standard recommended regimen at the time. All infants received recommended drugs at and after birth. The study was a collaboration between and funded by several national and international institutions.***

The prophylaxis given to mothers was one of a combination of zidovudine (AZT), lamivudine (3TC), and lopinavir boosted with ritonavir (LOP-r) twice daily started at 28-34 weeks of pregnancy to a maximum of 6.5 months of breastfeeding; or zidovudine (AZT) alone twice daily for a similar time period during pregnancy plus single-dose nevirapine (NVP) during labour.

The cumulative rate of HIV transmission at 12 months of age was 43% lower with the triple-drug regimen compared with the standard regimen (5.4% vs 9.5%, p=0.02). The cumulative rate of infant HIV infection at age 6 weeks was not significantly different between the groups, but the risk of transmission during breastfeeding was 53% lower in the triple-drug group (2.2% vs. 4.7%, p=0•049). The greatest reduction was among the infants of women with CD4 cell counts 200-350 cells/mm3. At 12 months of age, 10•2% of infants from mothers in the triple-drug group had been infected with HIV or died compared with 16•0% of infants from mothers taking the standard regimen (p=0.017).

The Kesho Bora investigators also report that the three-drug regimen and the standard regimen were equally safe - no differences were found in serious adverse events between the groups. The authors conclude that "triple-ARV prophylaxis during pregnancy and continued during breastfeeding is safe and reduces the risk of HIV-1 transmission to infants".

Starting ARV prophylaxis earlier in pregnancy is more effective to reduce infant HIV infection, so "women should be encouraged to plan pregnancies and attend antenatal care sufficiently early", to diagnose and assess maternal HIV infection and start ARVs, say the authors. "However, for programmes to ensure timely screening and staging, rapid access to antiretrovirals, and comprehensive but rapid counselling to ensure good adherence to treatment or prophylaxis will be a challenge."

WHO guidelines were strongly influenced by the preliminary results of the Kesho Bora study - the revised WHO guidelines now recommend long-term treatment for all women with CD4 cell counts below 350 cells/mm3 and ARV prophylaxis (either to the mother or to the child) for the whole period of breastfeeding if the mother is not already receiving ARV treatment for her own health.

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Dr Timothy Farley, Department of Reproductive Health and Research, World Health Organization, Geneva, Switzerland T) +41 22 791 33 10, +41 79 254 68 32 E) FarleyT@who.int

Dr Isabelle de Vincenzi, Department of Reproductive Health and Research, World Health Organization, Geneva, Switzerland T) +33 450 77 46 79

Notes to Editors:

*Drugs taken to prevent HIV infection are known as antiretroviral (ARV) prophylaxis.

** Women with CD4-cell counts 200-500 cells/mm3 only were included, which is a critical group with immune-system impairment. Women with CD4 cell counts below 200 cells/mm3 were not included in the randomized trial as they were all given ARV treatment for their own health.

*** Funding sources: Agence nationale de recherches sur le sida et les hépatites virales (France), Department for International Development (UK), European and Developing Countries Clinical Trials Partnership, Thrasher Research Fund, Belgian Directorate General for International Cooperation (Belgium), Centers for Disease Control and Prevention (USA), Eunice Kennedy Shriver National Institute of Child Health and Human Development (USA), and UNDP/UNFPA/World Bank/WHO Special Programme of Research, Development and Research Training in Human Reproduction.

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