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Background:
ZDV starting at 28 weeks' gestation decreases in utero transmission to 1-2%,
yet 4-5% intrapartum transmission still occurs. Adding NVP to ZDV during
labor and in neonates may further reduce intrapartum transmission.
Methods:
Eligibility : ZDV prophylaxis as soon as possible after 28 wks'
gestation (>2 wks), labor oral loading dose and 1 wk for infants (6 wks if
mother <4 wks); formula feeding. 3-arms 1) NVP+ZDV mother/ NVP+ZDV infant;
2) NVP+ZDV mother/placebo+ZDV infant; 3) placebo+ZDV mother/placebo+ZDV
infant (Reference).
Dosing: NVP mother 200 mg po at onset of labor, NVP infant 6 mg po48-72
hours after birth.
Endpoint : HIV-infected infants (2 PCR+ on 2 samples); vs uninfected
(2 PCR after 1 month). After the first interim analysis based on 629
outcomes, the ZDV alone arm was discontinued as HIV transmission was higher
than in the NVP+ZDV mother/NVP+ZDV infant arm (P<=0.00036).
Results:
As of March 5, 2003, 1833 women (ARV naive: 99%) have been enrolled and 1726
have delivered. Median baseline CD4+: 370/mm ³ (18%<200); log viral load:
3.94; Delay between study treatment intake and delivery: 6.7 hours (13%<2
hrs; 26%<3 hrs); non-elective C-sections: 21%. Infants: Median delay from
birth to study treatment intake: 48.5 hrs (98%<72 hrs). The second interim
analysis in February 2003 did not raise safety concerns and confirmed the
first analysis results. Enrolment was stopped on March 1, 2003 as the
planned sample size for non-inferiority comparison of NVP+ZDV mother/placebo+ZDV
infant with NVP+ZDV mother/ NVP+ZDV infant (delta 2.5%, power 80%) had been
reached.
Conclusions:
While adding
NVP during labour and in the neonate to oral ZDV prophylaxis significantly
decreases HIV transmission, the need for the infant NVP dose still needs to
be established. |
