Background:  Both short-course zidovudine (ZDV) and a 2-dose regimen of oral intrapartum/newborn nevirapine (NVP) significantly reduce perinatal HIV-1 transmission. We studied the safety, tolerance, development of resistance, and transmission rates of combining these regimens. 

Methods:  HIV-infected pregnant antiretroviral-naive women received antenatal ZDV 300 mg twice daily from 34 to 36 weeks’ gestation until labor, oral ZDV 300 mg every 3 hours and oral NVP 200 mg once during active labor following hospital admission. Infants received NVP 2 mg/kg orally once between 48 and 72 hours of life, plus ZDV syrup 2 mg/kg x 4 weeks. All women had CD4 cell counts (FACScan 2 color) done at delivery and viral load (Roche Amplicor Monitor v. 1.5) at baseline, at or around the time of delivery, and 1 month postpartum, and resistance testing at 1 month postpartum (Visible Genetics Tru-Gene HIV). Infant samples for PCR and resistance (Roche Amplicor HIV-DNA PCR v. 1.0) were collected at 1 to 3 days, and 1, 2, and 4 months of age. Infants with >1 positive result were classified as HIV-infected.

Results: From February 2001 through January 2003, 271 eligible women were offered enrollment, 228 consented and 220 delivered; follow-up study visits were completed in June 2003. Maternal median CD4 cell count and viral load at delivery was 378 cells/mL and 3214 copies/mL; viral load was below 400 copies/mL in 18% of women. Of the 32%  of women who delivered via Cesarean section, 56% were elective. Of 220 women, 219 (99%) received some ZDV prior to delivery and 208 (95%) received NVP during labor. All 223 infants (3 sets of twins) received NVP and, of 223, 212 (95%) had at least 2 weeks of ZDV postnatally. Eight maternal adverse events >grade 3 were reported; and 37 infant adverse events >grade 3 were reported from 30 infants, anemia being the most common. Perinatal transmission occurred in 10 infants (Kaplan Meier estimate 4.6%, 95% CI 2.5 - 8.5%); 5 had PCR-positive birth specimens. Of the 220 women, 204 (93%) visited at 1 month postpartum, and 190 (93%) had specimens tested successfully for ARV resistance; of these, 33 (17%) and 3 (2%) had NVP and ZDV resistance mutations, respectively. Of 10 infected infants, 2 (20%) exhibited NVP resistance in their 2-month sample.

Conclusions: ZDV/NVP was well tolerated by mothers and infants in this study. Use of this simple combination regimen should be considered given the excellent safety profile and transmission rate data.

Keywords: Perinatal HIV transmission; Antiretroviral; Thailand