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.
BACKGROUND
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.


METHODS
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.


METHODS
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).


METHODS
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.


BACKGROUND
clinicaltrials.gov Identifier: NCT00197587.
Thior
Ibou
I
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Mass 02115, USA.
Lockman
Shahin
S
Smeaton
Laura M
LM
Shapiro
Roger L
RL
Wester
Carolyn
C
Heymann
S Jody
SJ
Gilbert
Peter B
PB
Stevens
Lisa
L
Peter
Trevor
T
Kim
Soyeon
S
van Widenfelt
Erik
E
Moffat
Claire
C
Ndase
Patrick
P
Arimi
Peter
P
Kebaabetswe
Poloko
P
Mazonde
Patson
P
Makhema
Joseph
J
McIntosh
Kenneth
K
Novitsky
Vladimir
V
Lee
Tun-Hou
TH
Marlink
Richard
R
Lagakos
Stephen
S
Essex
Max
M
D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D001902:Botswana; D001942:Breast Feeding; D018572:Disease-Free Survival; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000401:mortality / Q000517:prevention & control* / Q000635:transmission*; D015497:HIV-1; D006801:Humans; D007223:Infant; D041943:Infant Formula; D007226:Infant Mortality; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D019829:Nevirapine / Q000627:therapeutic use; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy / Q000517:prevention & control*; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D015215:Zidovudine / Q000627:therapeutic use*
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; D019829:Nevirapine