Extended-dose nevirapine to 6 weeks of age for infants to prevent HIV transmission via breastfeeding in Ethiopia, India, and Uganda: an analysis of three randomised controlled trials.
BACKGROUND
UNICEF/WHO recommends that infants born to HIV-infected mothers who do not have access to acceptable, feasible, affordable, sustainable, and safe replacement feeding should be exclusively breastfed for at least 6 months. The aim of three trials in Ethiopia, India, and Uganda was to assess whether daily nevirapine given to breastfed infants through 6 weeks of age can decrease HIV transmission via breastfeeding.


METHODS
HIV-infected women breastfeeding their infants were eligible for participation. Participants were randomly assigned to receive either single-dose nevirapine (nevirapine 200 mg to women in labour and nevirapine 2 mg/kg to newborns after birth) or 6 week extended-dose nevirapine (nevirapine 200 mg to women in labour and nevirapine 2 mg/kg to newborn babies after birth plus nevirapine 5 mg daily from days 8-42 for the infant). The randomisation sequences were generated by computer at a central data coordinating centre. The primary endpoint was HIV infection at 6 months of age in infants who were HIV PCR negative at birth. Analyses were by modified intention to treat, excluding infants with missing specimens and those with indeterminate or confirmed HIV infection at birth. These studies are registered with ClinicalTrials.gov, numbers NCT00074399, NCT00061321, and NCT00639938.


RESULTS
2024 liveborn infants randomised in the study had at least one specimen tested before 6 months of age (1047 infants in the single-dose group and 977 infants in the extended-dose group). The modified intention-to-treat population included 986 infants in the single-dose group and 901 in the extended-dose group. At 6 months, 87 children in the single-dose group and 62 in the extended-dose group were infected with HIV (relative risk 0.80, 95% CI 0.58-1.10; p=0.16). At 6 weeks of age, 54 children in the single-dose group and 25 in the extended-dose group were HIV positive (0.54, 0.34-0.85; p=0.009). 393 infants in the single-dose group and 346 in the extended-dose group experienced grade 3 or 4 serious adverse events during the study (p=0.54).


CONCLUSIONS
Although a 6-week regimen of daily nevirapine might be associated with a reduction in the risk of HIV transmission at 6 weeks of age, the lack of a significant reduction in the primary endpoint-risk of HIV transmission at 6 months-suggests that a longer course of daily infant nevirapine to prevent HIV transmission via breast milk might be more effective where access to affordable and safe replacement feeding is not yet available and where the risks of replacement feeding are high.


BACKGROUND
US National Institutes of Health; US National Institute of Allergy and Infectious Diseases; Fogarty International Center.
Bedri
Abubaker
A
Gudetta
Berhanu
B
Isehak
Abdulhamid
A
Kumbi
Solomon
S
Lulseged
Sileshi
S
Mengistu
Yohannes
Y
Bhore
Arvind V
AV
Bhosale
Ramesh
R
Varadhrajan
Venkat
V
Gupte
Nikhil
N
Sastry
Jayagowri
J
Suryavanshi
Nishi
N
Tripathy
Srikanth
S
Mmiro
Francis
F
Mubiru
Michael
M
Onyango
Carolyne
C
Taylor
Adrian
A
Musoke
Philippa
P
Nakabiito
Clemensia
C
Abashawl
Aida
A
Adamu
Rahel
R
Antelman
Gretchen
G
Bollinger
Robert C
RC
Bright
Patricia
P
Chaudhary
Mohammad A
MA
Coberly
Jacqueline
J
Guay
Laura
L
Fowler
Mary Glenn
MG
Gupta
Amita
A
Hassen
Elham
E
Jackson
J Brooks
JB
Moulton
Lawrence H
LH
Nayak
Uma
U
Omer
Saad B
SB
Propper
Lidia
L
Ram
Malathi
M
Rexroad
Vivian
V
Ruff
Andrea J
AJ
Shankar
Anita
A
Zwerski
Sheryl
S
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001942:Breast Feeding / Q000009:adverse effects*; D004334:Drug Administration Schedule; D005002:Ethiopia; D005260:Female; D015658:HIV Infections / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D007194:India; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D015337:Multicenter Studies as Topic; D019829:Nevirapine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011247:Pregnancy; D016032:Randomized Controlled Trials as Topic; D014454:Uganda
D019380:Anti-HIV Agents; D019829:Nevirapine