Three postpartum antiretroviral regimens to prevent intrapartum HIV infection.
BACKGROUND
The safety and efficacy of adding antiretroviral drugs to standard zidovudine prophylaxis in infants of mothers with human immunodeficiency virus (HIV) infection who did not receive antenatal antiretroviral therapy (ART) because of late identification are unclear. We evaluated three ART regimens in such infants.


METHODS
Within 48 hours after their birth, we randomly assigned formula-fed infants born to women with a peripartum diagnosis of HIV type 1 (HIV-1) infection to one of three regimens: zidovudine for 6 weeks (zidovudine-alone group), zidovudine for 6 weeks plus three doses of nevirapine during the first 8 days of life (two-drug group), or zidovudine for 6 weeks plus nelfinavir and lamivudine for 2 weeks (three-drug group). The primary outcome was HIV-1 infection at 3 months in infants uninfected at birth.


RESULTS
A total of 1684 infants were enrolled in the Americas and South Africa (566 in the zidovudine-alone group, 562 in the two-drug group, and 556 in the three-drug group). The overall rate of in utero transmission of HIV-1 on the basis of Kaplan-Meier estimates was 5.7% (93 infants), with no significant differences among the groups. Intrapartum transmission occurred in 24 infants in the zidovudine-alone group (4.8%; 95% confidence interval [CI], 3.2 to 7.1), as compared with 11 infants in the two-drug group (2.2%; 95% CI, 1.2 to 3.9; P=0.046) and 12 in the three-drug group (2.4%; 95% CI, 1.4 to 4.3; P=0.046). The overall transmission rate was 8.5% (140 infants), with an increased rate in the zidovudine-alone group (P=0.03 for the comparisons with the two- and three-drug groups). On multivariate analysis, zidovudine monotherapy, a higher maternal viral load, and maternal use of illegal substances were significantly associated with transmission. The rate of neutropenia was significantly increased in the three-drug group (P<0.001 for both comparisons with the other groups).


CONCLUSIONS
In neonates whose mothers did not receive ART during pregnancy, prophylaxis with a two- or three-drug ART regimen is superior to zidovudine alone for the prevention of intrapartum HIV transmission; the two-drug regimen has less toxicity than the three-drug regimen. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development [NICHD] and others; ClinicalTrials.gov number, NCT00099359.).
Division of Infectious Diseases, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. knielsen@mednet.ucla.edu
Karin
K
Nielsen-Saines
D Heather
DH
Watts
Valdilea G
VG
Veloso
Yvonne J
YJ
Bryson
Esau C
EC
Joao
Jose Henrique
JH
Pilotto
Glenda
G
Gray
Gerhard
G
Theron
Breno
B
Santos
Rosana
R
Fonseca
Regis
R
Kreitchmann
Jorge
J
Pinto
Marisa M
MM
Mussi-Pinhata
Mariana
M
Ceriotto
Daisy
D
Machado
James
J
Bethel
Marisa G
MG
Morgado
Ruth
R
Dickover
Margaret
M
Camarca
Mark
M
Mirochnick
George
G
Siberry
Beatriz
B
Grinsztejn
Ronaldo I
RI
Moreira
Francisco I
FI
Bastos
Jiahong
J
Xu
Jack
J
Moye
Lynne M
LM
Mofenson
D044966:Anti-Retroviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D015658:HIV Infections / Q000401:mortality / Q000517:prevention & control* / Q000635:transmission; D015497:HIV-1; D006801:Humans; D041943:Infant Formula; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D053208:Kaplan-Meier Estimate; D019259:Lamivudine / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D019888:Nelfinavir / Q000009:adverse effects / Q000627:therapeutic use*; D019829:Nevirapine / Q000009:adverse effects / Q000627:therapeutic use*; D049590:Postpartum Period; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious; D015215:Zidovudine / Q000009:adverse effects / Q000627:therapeutic use*
D044966:Anti-Retroviral Agents; D019259:Lamivudine; D015215:Zidovudine; D019829:Nevirapine; D019888:Nelfinavir