Table 1.
Summary of randomised controlled trials, by publication date, that evaluated the effects of antiretroviral drugs to reduce mother-to-child transmission of HIV-1 (see text).
| Trial name; journal and year published | Study site and sample size | Intervention and comparison | Transmission rate Relative Risk Reduction (RRR)/efficacy (95% CI) | Infant mortality Relative Risk (RR) (95% CI) | Still birthRelative Risk (RR) (95% CI) |
| PACTG 076; NEJM 1994 | USA & France 60 centres 409 women | ZDV v placebo in mothers and infants No breast feeding MotherZDV antepartum orally 100 mg 5 times daily starting at 14–34 weeks' gestation ZDV intrapartum iv 2 mg/kg over 1 hour then 1 mg/kg/h until delivery InfantZDV orally 2 mg/kg every 6 hours for 6 weeks | At 18 monthsZDV 8.3%Placebo 25.5% RRR66% (35–97) | At 18 monthsRR 1.33 (0.30–5.87) | At 18 monthsRR 0.33 (0.01–8.11) |
| Thai-CDC; Lancet 1999 | Thailand 2 hospitals 393 women | ZDV v placebo in mothers No breast feeding MotherZDV antepartum orally 300 mg twice daily from 36 weeks' gestationZDV intrapartum orally 300 mg every 3 hours until delivery InfantNo ART | At 6 monthsZDV 9% Placebo 19% RRR50% (15–70) | In the first 4–8 weeks of life RR 0.50 (0.05–5.50) | RR 3.02 (0.12–73.57) |
| DITRAME Study 1; Lancet 1999; | Ivory Coast 1 clinic 280 women | ZDV v placebo in mothers Breast feeding MotherZDV antepartum orally 300 mg twice daily from 36 weeks' gestationZDV intrapartum orally 300 mg every 3 hours until delivery Infant No ART | At 4–8 weeks ZDV 12.2% Placebo 21.7%RRR/efficacy 44% (9–79) At 3–4 months ZDV 15.7% Placebo 24.9%RRR37% (4–70) | In the first week of lifeRR 0.13 (0.02–0.99)In the first 3 to 4 months of lifeRR 0.15 (0.05–0.49) | RR3.50 (0.74–16.55) |
| DITRAME Study 2 Lancet 1999 | Ivory Coast & Burkina FasoMultiple clinics 421 women | ZDV v placebo in mothers Breast feedingMotherZDV antepartum orally 300 mg twice daily from 36–38 weeks' gestation ZDV intrapartum orally single dose 600 mg at onset of labour ZDV postpartum orally 300 mg twice daily for 7 days Infant No ART | At 3–4 months RRR34.00 (6.56–61.44)At 6 months RRR 35% (10–60) At 12 monthsRRR34 (9–60)At 18 months RRR 30 (3–57) | In the first week of lifeRR 2.03 (0.51–8.0)In the first 4–8 weeksRR1.77 (0.53–5.97)In the first 3–4 months RR 0.74 (0.3–1.58)In the first 6 monthsRR0.62 (0.35–1.09) In the first 12 monthsRR 0.75 (0.48–1.17) In the first 18 monthsRR 0.80 (0.53–1.21) | RR 0.14 (0.02–1.17) |
| HIVNET 012 Lancet 1999 (6-month follow-up)Lancet 2003 (18-month follow-up) | Uganda 1 hospital 626 women | NVP v ZDV in mothers and infants Breast feeding NVPMotherNVP orally 200 mg at onset of labourInfantNVP orally 2 mg/kg within 72 hours of deliveryZDVMother ZDV orally 600 mg at onset of labour; 300 mg every 3 hours until deliveryInfant ZDV orally 4 mg/kg twice daily for 1 week | At 4-8 weeks ZDV 21.3% NVP 11.9% At 3–4 months ZDV 25.1% NVP 13.1%RRR39% (12–66) At 18 months ZDV 25.8% NVP 13.5%RRR39% (14–64) | In the first week of lifeRR 2.50 (0.49–12.79)At 4–8 weeksRR 2.50 (0.79–7.89) At 18 months RR 1.24 (0.81–1.89) | RR 2.00 (0.18–21.94) |
| PHPT-1; N Engl J Med 2000; | Thailand 27 sites 1437 women | Various durations of ZDV v each other in mothers and infants No breast feeding MotherZDV long-long (LL)ZDV antepartum orally 300 mg twice daily starting at 28 weeks' gestationZDV intrapartum orally 300 mg every 3 hours until delivery InfantZDV orally 2 mg/kg every 6 hours for 6 weeks ZDV long-short (LS)MotherZDV from 28 weeks antepartumInfant No ZDV ZDV short-long (SL)MotherZDV from 36 weeks antepartum InfantZDV for 6 weeks ZDV short-short (SS) Mother ZDV from 36 weeks antepartumInfantZDV for 3 days to infant | At 6 months LL 6.5% LS 4.7% SL 8.6% SS 10.5% RRRLL v SL+24% (–21 to +69)RRRLS v SL 45% (2–88)SS discontinued at first interim analysis | LL v SLAt 6 monthsRR 0.82 (0.24 –2.82) LS v SL At 6 monthsRR 1.38 (0.44–4.31) | LL v SL RR 0.55 (0.23–1.33) LS v SL RR0.33 (0.11–1.01) |
| Limpongsanurak J Med Assoc Thai 2001 | Thailand 3 hospitals 182 women | ZDV v placebo in mothersNo breast feeding MotherZDVZDV 250 mg orally twice daily from 38 weeks anetpartum ZDV iv 2 mg/kg during first hour of labour, then 1 mg/kg until delivery Infant No treatment Placebo MotherPlacebo capsules and 5% iv dextrose during labourInfantNo treatment | At 6 monthsZDV 14.9% Placebo 16.3%RRR+9% (–26 to +44) | NR | RR 3.07 (0.13–74.28) |
| PETRA A, B, & C Lancet 2002 | South Africa, Uganda, Tanzania 5 sites 1797 women | ZDV + 3TC v placebo in mothers and infantsBreast feeding and no breast feeding Petra A MotherZDV antepartum orally 300 mg + 3TC 150 mg twice daily from 36 weeks' gestationZDV intrapartum orally 300 mg every 3 hours until delivery + 3TC 150 mg twice dailyZDV 300 mg + 3TC 150 mg orally twice daily postpartum for 1 week InfantZDV 4 mg/kg + 3TC 2 mg/kg orally twice daily for 1 week Petra B MotherZDV 600 mg orally intrapartum at onset of labour, then 300 mg every 3 hours + 3TC 150 mg twice daily until deliveryZDV 300 mg + 3TC 150 mg twice daily post partum for 1 week InfantZDV 4 mg/kg + 3TC 2 mg/kg orally twice daily for 1 week Petra C MotherZDV 600 mg orally intrapartum at onset of labour then 300 mg every 3 hours until delivery InfantNo treatment | At 4–8 weeks Petra A 7.0% Petra B 11.6% Petra C 17.5% Placebo 18.1%RRR Petra A v placebo63% (41–85)RRR Petra B v placebo42% (13–71)RRR Petra C v placebo+7% (–32 to +46)At 18 months RRR Petra A v placebo33 (–12 to +78; absolute numbers not reported)RRR Petra B v placebo18% (–27 to +63)RRR Petra C v placebo10% (–41 to +61)With prolonged breast feeding, transmission rates for all groups combined were 80% | In the first 4–8 weeks Petra A v placeboRR 0.35 (0.11–1.14) Petra B v placeboRR 0.71 (0.28–1.81)Petra C v placeboRR 0.98 (0.41–2.34) In the first 18 monthsPetra A v placeboRR 0.76 (0.50–1.14) Petra B v placebo RR 1.05 (0.73–1.51)Petra C v placebo RR 0.96(0.66–1.39) | Petra A v placeboRR 0.40 (0.07–2.15)Petra B v placeboRR 1.19 (0.34–4.20)Petra C v placeboRR 0.80 (0.20–3.18) |
| PACTG 316; JAMA 2002 | United States, Europe, Brazil, Bahamas Multiple sites 1270 women | NVP v placebo in mothers receiving standard ART at discretion of treating physician and NVP in infantsNo breast feeding Mother NVP 200 mg orally intrapartum at onset of labourInfant NVP 2 mg/kg orally within 72 hours | At 4–8 weeks Standard ART 1.6% ART+NVP 1.4%RRR13% (–83 to +109) Study stopped early | At 4–8 weeks At 4-8 wekks RR RR 0.60 ( 0.14–2.50) | RR 2.99 (0.12–73.33) |
| SAINT; J Infect Dis 2003 | South Africa 11 sites 1317 women | ZDV + 3TC v NVP in mothers and infants Breast feeding and no breast feeding (approximately 45% breast fed at delivery; 30% at 8 weeks)ZDVMother ZDV 600 mg orally intrapartum at onset of labour, then 300 mg every 3 hours + 3TC 150 mg twice daily until delivery ZDV 300 mg + 3TC 150 mg twice daily post partum for 1 week InfantZDV 4 mg/kg + 3TC 2 mg/kg orally twice daily for 1 week NVP MotherNVP 200 mg orally intrapartum at onset of labourInfant NVP 6 mg orally within 48 hrs | At 4–8 weeks NVP 12.3% ZDV+ 3TC 9.3%RRR24% (–5 to +53) Increased HIV transmission risk in breastfeeding group Odds ratio (OR) 7 (2–25) | At 4 to 8 weeks RR 1.01 (0.54–1.89) | NR |
| Kiarie 2003; AIDS 2003 | Kenya1 hospital 188 women | THAI CDC ZDV regimen in mothers v HIVNET 012 NVP regimen in mothers and infants No breast feeding | At 4–8 weeksTHAI CDC ZVD 9% HIVNET 012 NVP 22%RRR58% (–5–120) | At 4–8 weeksRR0.99 ( 0.21–4.72) | RR 1.48 ( 0.25–8.58) |
| NVAZ; Lancet 2003 | Malawi6 clinics 1119 women | NVP v NVP + ZDV in infantsBreast feeding InfantNVP 2 mg/kg stat oral dose postpartum NVP + ZDV NVP as above + ZDV 4 mg/kg twice daily for 1 week | At 4–8 weeksNVP 20.9% NVP + ZDV 15.3%RRR37% (4–70) | At 4–8 weeks RR1.26 (0.60–2.67) | NR |
| Thistle 2004; Centr Afr J Med 2004 | Zimbabwe 1 hospital 222 women | Different regimens of ZDV v each other Breast feeding Mother ZDV antepartum 300 mg twice daily from 36 weeks' gestation ZDV intrapartum 300 mg every 3 hours during labourInfant PlaceboMother Placebo antepartum 300 mg twice daily from 36 weeks' gestation ZDV intrapartum 300 mg every 3 hours during labourInfant ZDV 2mg/kg twice daily for 3 days | At 4–8 weeks ZDV 18.9% Placebo 15.7%RRR17% (–42 to 76) At 6 months 8% (43 to +59) At 18 months 9% (–34 to +52) | At 4–8 weeksZDV v placebo RR 1.00 (0.21–4.85) At 3–4 monthsRR 1.75 (0.53–5.81) At 6 months RR2.00 (0.71–5.66) At 12 monthsRR2.00 (0.71–5.66) | None in either group |
| Taha 2004; JAMA 2004 | Malawi6 clinics 894 women | ZDV + NVP v NVP alone in infants Breast feeding MotherNVP 200 mg at onset of labour to all mothersInfantZDV + NVP ZDV 4 mg/kg orally twice daily for 1 week + NVP 2 mg/kg within 72 hours of delivery NVP alone NVP 2 mg/kg within 72 hours of delivery | At 4–8 weeks NVP 14.1% NVP + ZDV 16.3%RRR13% (–16 to +42) | RR 1.74 ( 0.51–5.91) | NR |
| PHPT-2; N Engl J Med 2004 | Thailand 37 sites 1844 women | NVP v placebo in 4 different regimens to mothers and infants No breast feeding All mothers received oral ZDV 300 mg twice daily from 28 weeks' gestation and 300 mg every 3 hours once in labourAll infants received oral ZDV 2 mg/kg every 6 hours for 1 weekNVP-PLMotherNVP 200 mg orally at onset of labourInfant placebo NVP-NVPMother NVP 200 mg orally at onset of labourInfant NVP 6 mg orally within 72 hours of birthPL-PLMotherplaceboInfantplacebo | At 6 months NVP-PL 2.8% NVP-NVP 1.9% Placebo-Placebo 6.5% RRRNVP-NVP v NVP-PL29% (–26 to +84) Placebo arm discontinued at first interim analysis | At 6 months NVP-NVP v NVP-PLRR0.20 (0.04–0.91) | NVP-NVP v NVP-PLRR 0.25 (0.05–1.17)Placebo-Placebo arm discontinued at first interim analysis |
| Gray 2005 AIDS 2005 | South Africa 3 hospitals 1530 women | NVP v ZDV in infants Breast feeding InfantNVP 2 mg/kg orally postpartum ZDV 4 mg/kg orally twice daily for first 6 weeks | At 3–4 monthsNVP 7.9% ZDV 13.1%RRR40% (–1 to +81) This analysis excluded infants already infected at birth | At 4–8 weeksRR 1.15 (0.52–2.54) | NR |
| Bhoopat 2005 J Acquir Immune Defic Syndr 2005 | Thailand2 hospitals 50 women | Different regimens of ZDV v each other No breast feeding Long Mother ZDV antepartum orally 300 mg twice daily from 62–92 days prior to delivery ZDV intrapartum 300 mg orally every 3 hours until deliveryInfant No treatment Short MotherZDV as above but only from 14–35 days prior to delivery Infant No treatment | At 3–4 monthsZDV long 0% ZDV short 14.8%RRR100% (–294 to +494) | NR | NR |
| Gray 2006; J Acquir Immune Defic Syndr 2006 | South Africa 1 hospital 373 women | d4T alone v ddI alone v d4T + ddI v ZDV (4 arms) No breast feeding Motherd4T alone d4T 40 mg orally twice daily ante- and intrapartum (from 34–36 weeks' gestation). An additional dose was administered approx 1 hour before delivery ddl aloneddI 200 mg orally twice daily ZDVZDV 300 mg twice dailyInfant Same regimen as the mother continued for 6 weeks postpartum | At 6 months d4T 12.1% ddI 10.6% d4T + ddI 4.6% ZDV 5.6%d4T v ZDV RR R116% (–280 to +49)d4T plus ddI v ZDV RRR 89% (–248 to +70) | d4T v ZDVAt 6 monthsRR 2.97 (0.83–10.61)d4T plus ddI v ZDVRR 0.66 (0.11–3.86) | NR |
| Mashi Report 1; AIDS 2006; | Botswana 4 sites Report 1709 women | NVP v placebo during labour Breast feeding MotherNVP 300 mg 3-hourly during labour All mothersZDV 300 mg orally twice daily from 36 weeks' gestation + ZDV 300 mg during labourAll infants ZDV 4 mg/kg twice daily orally for 4 weeks + NVP single dose. | At 4 weeks15/345 [4.3%] with NVP v 13/353 [3.7%] with PLARR –0.6% (–2.4% to +3.8%) | At 4 weeks 7/345 [2%] with NVP v 13/353 [4%] with PL P = 0.26 | |
| Thistle 2007; Pediatrics 2007 | Zimbabwe 1 hospital 609 infants | ZDV v placebo in mothers and infants receiving nevirapine Breast feeding Mother ZDV antepartum 300 mg twice daily from 36 weeks′ gestation ZDV intrapartum 300 mg every 3 hoursInfant ZDV 2 mg/kg orally every 6 hours for 3 days All mothers nevirapine 200 mg and infants 2 mg/kg within 72 hours of delivery | HIV infection or death at 6 weeks NVP 23.6% ZDV+ NVP 21.8%ARR1.8% (–5 to +8) Study discontinued at first interim analysis because could not recruit sufficient numbers of participants to demonstrate the pre-specified difference of 5% in the primary outcome | Reported only as a combined outcome; see HIV infection | NR |
iv = intravenously; Ref = reference; ZDV = zidovudine; NVP = nevirapine; 3TC = lamivudine; d4T = stavudine; ddI = didanosie; ART = anti-retroviral therapy; NS = not significant. *efficacy as reported in the Cochrane review