[e-drug] Breastfeeding or formula feeding plus zidovudine to infants

[e-drug@healthnet.org]

E-DRUG: Breastfeeding or formula feeding plus zidovudine to infants
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[Thanks  Kirsten for spotting this]

http://jama.ama-assn.org/cgi/content/abstract/296/7/794?etoc

Breastfeeding Plus Infant Zidovudine Prophylaxis for 6 Months vs Formula
Feeding Plus Infant Zidovudine for 1 Month to Reduce Mother-to-Child HIV
Transmission in Botswana A Randomized Trial: The Mashi Study

Ibou Thior, MD, MSc; Shahin Lockman, MD, MSc; Laura M. Smeaton, MSc;
Roger L. Shapiro, MD, MPH; Carolyn Wester, MD; S. Jody Heymann, MD, PhD;
Peter B. Gilbert, PhD; Lisa Stevens, MD; Trevor Peter, PhD, MPH; Soyeon
Kim, DSc; Erik van Widenfelt, BSc; Claire Moffat, MBChB, MPH; Patrick
Ndase, MBChB; Peter Arimi, MBChB; Poloko Kebaabetswe, PhD; Patson
Mazonde, MBChB; Joseph Makhema, MBChB; Kenneth McIntosh, MD; Vladimir
Novitsky, MD, PhD; Tun-Hou Lee, DSc; Richard Marlink, MD; Stephen
Lagakos, PhD; Max Essex, DVM, PhD; for the Mashi Study Team

JAMA. 2006;296:794-805.

Context. Postnatal transmission of human immunodeficiency virus-1 (HIV)
via breastfeeding reverses gains achieved by perinatal antiretroviral
interventions.

Objective. To compare the efficacy and safety of 2 infant feeding
strategies for the prevention of postnatal mother-to-child HIV
transmission.

Design, Setting, and Patients. A 2 x 2 factorial randomized clinical
trial with peripartum (single-dose nevirapine vs placebo) and postpartum
infant feeding (formula vs breastfeeding with infant zidovudine
prophylaxis) interventions. In Botswana between March 27, 2001, and
October 29, 2003, 1200 HIV-positive pregnant women were randomized from
4 district hospitals. Infants were evaluated at birth, monthly until age
7 months, at age 9 months, then every third month through age 18 months.

Intervention. All of the mothers received zidovudine 300 mg orally twice
daily from 34 weeks' gestation and during labor. Mothers and infants
were randomized to receive single-dose nevirapine or placebo. Infants
were randomized to 6 months of breastfeeding plus prophylactic infant
zidovudine (breastfed plus zidovudine), or formula feeding plus 1 month
of infant zidovudine (formula fed).

Main Outcome Measures. Primary efficacy (HIV infection by age 7 months
and HIV-free survival by age 18 months) and safety (occurrence of infant
adverse events by 7 months of age) end points were evaluated in 1179
infants.

Results. The 7-month HIV infection rates were 5.6% (32 infants in the
formula-fed group) vs 9.0% (51 infants in the breastfed plus zidovudine
group) (P = .04; 95% confidence interval for difference, -6.4% to
-0.4%). Cumulative mortality or HIV infection rates at 18 months were 80
infants (13.9%, formula fed) vs 86 infants (15.1% breastfed plus
zidovudine) (P = .60; 95% confidence interval for difference, -5.3% to
2.9%). Cumulative infant mortality at 7 months was significantly higher
for the formula-fed group than for the breastfed plus zidovudine group
(9.3% vs 4.9%; P = .003), but this difference diminished beyond month 7
such that the time-to-mortality distributions through age 18 months were
not significantly different (P = .21).

Conclusions. Breastfeeding with zidovudine prophylaxis was not as
effective as formula feeding in preventing postnatal HIV transmission,
but was associated with a lower mortality rate at 7 months. Both
strategies had comparable HIV-free survival at 18 months. These results
demonstrate the risk of formula feeding to infants in sub-Saharan
Africa, and the need for studies of alternative strategies.

Trial Registration  clinicaltrials.gov Identifier: NCT00197587


Author Affiliations: Department of Immunology and Infectious Diseases
(Drs Thior, Lockman, Shapiro, Wester, Stevens, and Peter; Mr van
Widenfelt; and Drs Makhema, Novitsky, Lee, Marlink, and Essex);
Department of Biostatistics (Ms Smeaton, Drs Kim and Lagakos); and
Department of Society, Human Development and Health (Dr Heymann),
Harvard School of Public Health, Boston, Mass; Botswana-Harvard School
of Public Health AIDS Initiative Partnership for HIV Research and
Education, Bontleng, Gaborone, Botswana (Drs Thior, Lockman, Shapiro,
Wester, Heymann, Stevens, Peter, and Kim; Mr. van Widenfelt; and Drs
Moffat, Ndase, Arimi, Makhema, Novitsky, Marlink, and Essex); Infectious
Disease Unit, Brigham and Women's Hospital, Boston, Mass (Dr Lockman);
Division of Infectious Diseases, Beth Israel Deaconess Medical Center,
Boston, Mass (Dr Shapiro); Department of Biostatistics, University of
Washington, and Fred Hutchinson Cancer Research Center, Seattle, Wash
(Dr Gilbert); Botswana Ministry of Health, Gaborone, Botswana (Drs
Kebaabetswe and Mazonde); and Division of Infectious Diseases,
Children's Hospital, Boston, Mass (Dr McIntosh).