TABLE 2.

Selected key trials affecting PMTCT policy over the past decade^a

Trial/site (reference)	Details						Results
	General	Antenatal	Intrapartum	Postpartum		Infant feeding
				Mother	Baby
ZDV ± NVP/Thailand (53)	n = 1,844 Thai women; double-blind RCT; 3 arms	All women on ZDV 300 mg BID beginning at 28 wk	All women on ZDV 300 mg every 3 h, plus: arm 1, NVP 200 mg × 1; arm 2, placebo; arm 3, NVP 200 mg × l	No ARVs	All infants received 2 mg/kg ZDV every 6 h × 1 wk, plus: arm 1, NVP 6 mg × 1 at 48-72 h; arm 2, placebo; arm 3, placebo	Formula	Placebo-placebo group stopped early; transmission rate 6.3%, compared to 1.1 % in NVP-NVP group and 2.8% in NVP-placebo group
Infant PEP, NVP vs NVP + ZDV (NVAZ trial)/Malawi (83)	n = 1,119 babies; randomized, phase 3, open-label trial	No ARVs	No NVP (women presenting late for delivery)	No ARVs	Arm 1, NVP 2 mg/kg × 1 immediately after birth; arm 2, NVP 2 mg/kg × 1 immediately after birth + ZDV 4 mg/kg BID × 1 wk	Breast	In babies HIV uninfected at birth, at 6-8 wk transmission was 7.7% in NVP + ZDV group and 12.1 % in NVP-only group (36% protective efficacy)
Infant PEP, NVP vs NVP + ZDV (NVAZ trial)/Malawi (84)	Infants born to 894 women; randomized, phase 3, open-label trial	No ARVs	NVP 200 mg × 1	No ARVs	Arm 1, NVP 2 mg/kg × 1 at 48-72 h; arm 2, NVP 2 mg/kg × 1 at 48-72 h + ZDV 4 mg/kg BID × 1 wk	Breast	In babies HIV uninfected at birth, at 6-8 wk transmission was 6.9% in NVP + ZDV group and 6.5% in NVP-only group (when mothers received intrapartum NVP, addition of short-course ZDV to NVP for infants did not decrease MTCT compared to NVP alone)
Infant PEP and NVP resistance/Malawi (NVAZ trial) (31)	95 infants infected with HIV; plasma collected at 6-8 wk of age; genotyping in 78 samples	No ARVs	Arm 1, NVP 200 mg × 1; arm 2, NVP 200 mg × 1; arm 3, no NVP; arm 4, no NVP	No ARVs	Arm 1, NVP 2 mg/kg × 1 immediately after birth; arm 2, NVP 2 mg/kg × 1 immediately after birth + ZDV 4 mg/kg BID × 1 wk; arm 3, NVP 2 mg/kg × 1 immediately after birth; arm 4, NVP 2 mg/kg × 1 immediately after birth + ZDV 4 mg/kg BID × 1 wk	Breast	Resistance in infants: arm 1, 87%; arm 2, 57%; arm 3, 74%; arm 4, 27% (NVP resistance lower with no maternal NVP); transmission rates comparable in all groups at 6-8 wk of life except arm 3 (no maternal NVP and infant single-dose NVP) (range, 14.1-16.3%)
Infant feeding and ZDV (Mashi study)/Botswana (88)	n = 1,200 HIV-infected pregnant women; RCT	All women on ZDV 300 mg BID from 34 wk	Arm 1, ZDV 300 mg every 3 h; arm 2, ZDV 300 mg every 3 h + NVP 200 mg × 1	No ARVs	Arm 1, NVP × 1 at birth plus ZDV × 6 mo; arm 2, NVP × 1 at birth plus ZDV × 1 mo	Arm 1, breast; arm 2, formula	Risk of infant transmission at 7 mo higher in breast-fed ZDV group than in formula-fed group (9% vs 5.6%); cumulative mortality at 7 mo was higher in formula-fed group than in breast-fed ZDV group (9.3% vs 4.9%); 18-mo HIV-free survival similar among two groups
Six-week extended-dose NVP for infants (SWEN study)/Ethiopia, India, Uganda (5)	Three coordinated but separate RCTs; combined analysis	No ARVs	All women received NVP 200 mg × 1	No ARVs	Arm 1, NVP 2 mg/kg × 1 at birth; arm 2, NVP 2 mg/kg × 1 at birth, followed by NVP 5 mg daily days 8-42	Breast	At 6 wk of age, for the infants on prolonged NVP, risk of HIV infection was 2.5% vs 5.3% in single-dose NVP infants (P = 0.009); at 6 mo, risk of postnatal transmission in the extended-NVP group was 6.9% vs 9% in the single-dose NVP group (P = 0.16); overall mortality at 6 mo was 3.6% in the single-dose group compared to 1.1% in the extended-dose group (P = 0.02)
Postexposure prophylaxis for infants (PEPI trial)/Malawi (52)	Open-label phase 3 RCT; n = 3,016 infants	No ARVs	NVP × 1 (unless late presenter)	No ARVs (referred for treatment if CD4 < 200)	Arm 1, NVP 2 mg/kg × 1 + ZDV 4 mg/kg BID × 1 wk (NVAZ trial); arm 2, ZDV 4 mg/kg BID × 7 days + NVP × 14 wk; arm 3, ZDV 4 mg/kg BID × 14 wks + NVP × 14 wk	Breast	At 9 mo, MTCT in NVAZ group was 10.0%, compared to 6.4% for extended-ZDV/NVP and 5.2% extended-NVP groups (40 and 51% reductions, respectively); no significant differences between two extended-prophylaxis groups
CBV + NVP to reduce NNRTI resistance/South Africa (60)	RCT, open label; n = 228 infants, 226 mothers	No ARVs	Arm 1, NVP 200 mg × 1; arm 2, NVP 200 mg × 1 + CBV every 12 h; arm 3, NVP 200 mg × 1 + CBV every 12 h	Arm 1, no ARVs; arm 2, CBV BID × 4 days; arm 3, CBV BID × 7 days	Arm 1, NVP 2 mg/kg × 1; arm 2, NVP 2 mg/kg × 1 + ZDV/lamivudine × 4 days; arm 3, NVP 2 mg/kg × 1 + ZDV/lamivudine × 7 days	Breast and formula	Arm 1 stopped early; overall MTCT rate was 9.2% in utero and 10.5% at 6 wk; NNRTI resistance in 7/9 infants in single-dose NVP group, 1/8 in 4-day dual-therapy group, and 0/7 in 7-day dual-therapy group
Tenofovir and emtricitabine to reduce viral resistance (TD2)/Zambia (20, 21)	n = 397 women; 355 infants at 6 weeks postpartum; open-label RCT	ZDV from 32 wk	Arm 1, NVP 200 mg × 1; arm 2, NVP 200 mg × 1 + 300 mg tenofovir/200 mg emtricitabine (Truvada) × 1		NVP 2 mg/kg × 1 + ZDV 4 mg/kg BID × 1 wk	Breast	Primary evaluation, among women with viral loads >2,000 copies/ml, 30% had NNRTI resistance mutations in the single-dose NVP group, compared to 14% in the Truvada group; secondary evaluation, Truvada was not significantly associated with decreased MTCT (at 6 wk, 1.6% infants infected from Truvada group compared to 2.8% in single-dose NVP group; P = 0.67)
NVP resistance following single-dose NVP in PMTCT (Mashi study)/Botswana (54)	n = 218 women; n = 47 HIV-infected infants (20 with HIV RNA at 24 mo); prospective observational cohort nested within RCT	ZDV from 32 wk	All women received ZDV, and in addition: arm 1, NVP 200 mg × 1; arm 2, placebo	NVP-based HAART for CD4 < 200 or AIDS-defining illness	Arm 1, NVP × 1 at 48-72 h; arm 2, placebo (subsequently modified based on external data to provide single-dose NVP to all infants)	Formula with 1 mo ZDV or breast with 6 mo ZDV	Of 60 women starting ART within 6 mo of delivery, 10/24 (41.7%) had virologic failure in single-dose NVP group compared to 0/36 in placebo group; of 158 women starting ART > 6 mo after delivery, failure rates did not differ, with 8% in single-dose NVP group and 12% in placebo group (P = 0.39); of 47 infected infants,12 died before ART and 5 died after ART; of 25 remaining, virologic failure was 9% vs 77% in placebo vs single-dose NVP groups, respectively, at both 6 mo and 12 mo
Effectiveness of NVP in successive pregnancies for PMTCT/South Africa, Cote d'lvoire (57)	Two prospective cohorts; n = 120 (S. Africa)	No ARVs	South Africa: NVP 200 mg × 1 on two occasions in subsequent pregnancies	No ARVs	NVP 2 mg/kg × 1 at 48-72 h	Arm 1, breast; arm 2, formula	Median delivery interval for two cohorts was 21 and 26 mo; effectiveness not reduced by prior exposure (South Africa, 11.1% MTCT rates for both pregnancies)
Zambia Exclusive Breastfeeding Study (ZEBS) with abrupt vs routine weaning (87)	n = 297 HIV-infected women	No ARVs	NVP 200 mg × 1	No ARVs	NVP 2 mg/kg × 1 at 48 h	Arm 1, exclusive breast-feeding with abrupt weaning (24 h) at 4 mo postpartum; arm 2, exclusive breast-feeding to 6 mo with introductory weaning foods thereafter	Of 71 breast milk samples analyzed, 21/31 in early-weaning group had detectable HIV RNA compared to 17/40 in women still breast-feeding (68% vs 42.5%)
MTCT during exclusive breast-feeding in first 6 mo of life/South Africa (25)	2,722 women (n = 1372 HIV infected)	No ARVs	NVP 200 mg × 1	No ARVs	NVP 2 mg/kg × 1 at 48 h	Exclusive breast-feeding	Median exclusive breast-feeding was 159 days; cumulative MTCT was 14.1% by 6 wk of age and 19.5% by 6 mo of age; MTCT also associated with maternal CD4 < 200 and birth wt < 2,500 g; for infants uninfected at 6 wk, MTCT was 1.1% after 1 mo and 4% after 5 mo’ infants with mixed feeding had almost 11 × increased MTCT than exclusively breast-fed infants

^aFor key prior studies, see reference 90. Abbreviations: ZDV, zidovudine; NVP, nevirapine; CBV, Combivir; NNRTI, nonnucleoside reverse transcriptase inhibitor; RCT, randomized controlled trial; BID, twice a day.