Study
Location(s)
Mode of Infant Feeding
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Antiretroviral (ARV) Drugs
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Antepartum and Intrapartum
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Postpartum
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Mother-to-Child Transmission (MTCT) Rate and Efficacy
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PACTG 076
United States, France34
Formula feeding |
ZDV vs. placebo |
Long (from 14 weeks)
IV IP
|
Long (6 weeks), infant only |
- MTCT at 18 months was 8.3% in ZDV arm vs. 25.5% in placebo arm (68% efficacy).
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CDC short-course ZDV trial
Thailand11
Formula feeding |
ZDV vs. placebo |
Short (from 36 weeks)
Oral IP
|
None |
- MTCT at 6 months was 9.4% in ZDV arm vs. 18.9% in placebo arm (50% efficacy).
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DITRAME (ANRS 049a) trial
Ivory Coast, Burkina Faso10,35
Breastfeeding |
ZDV vs. placebo |
Short (from 36 weeks)
Oral IP
|
Short (1 week), mother only |
- MTCT was 18.0% in ZDV arm vs. 27.5% in placebo arm at 6 months (38% efficacy) and 21.5% vs. 30.6% at 15 months (30% efficacy).
- MTCT was 22.5% in ZDV arm vs. 30.2% in placebo arm in pooled analysis at 24 months (26% efficacy).
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CDC short-course ZDV trial
Ivory Coast9,10
Breastfeeding |
ZDV vs. placebo |
Short (from 36 weeks)
Oral IP
|
None |
- MTCT was 16.5% in ZDV arm vs. 26.1% in placebo arm at 3 months (37% efficacy).
- MTCT was 22.5% in ZDV arm vs. 30.2% in placebo arm in pooled analysis at 24 months (26% efficacy).
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PETRA trial
South Africa, Tanzania, and Uganda4
Breastfeeding and formula feeding |
AP/IP/PP ZDV + 3TC vs. IP/PP ZDV + 3TC vs. IP-only ZDV + 3TC vs. placebo |
Short (from 36 weeks)
Oral IP
|
Short (1 week), mother and infant |
- MTCT was 5.7% at 6 weeks for AP/IP/PP ZDV + 3TC, 8.9% for IP/PP ZDV + 3TC, 14.2% for IP-only ZDV + 3TC, and 15.3% for placebo (efficacy compared with placebo: 63%, 42%, and 0%, respectively).
- MTCT was 14.9% at 18 months for AP/IP/PP ZDV + 3TC, 18.1% for IP/PP ZDV + 3TC, 20.0% for IP-only ZDV + 3TC, and 22.2% for placebo (efficacy compared with placebo: 34%, 18%, and 0%, respectively).
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HIVNET 012 trial Uganda3
Breastfeeding |
sdNVP vs. ZDV |
No AP ARV
Oral IP: sdNVP vs. oral ZDV
|
sdNVP within 72 hours of birth, infant only vs. ZDV (1 week), infant only |
- MTCT was 11.8% in NVP arm vs. 20.0% in ZDV arm at 6–8 weeks (42% efficacy); 15.7% in NVP arm vs. 25.8% in ZDV arm at 18 months (41% efficacy).
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SAINT trial
South Africa5
Breastfeeding and formula feeding |
sdNVP vs. ZDV + 3TC |
No AP ARV
Oral IP: sdNVP vs. ZDV + 3TC
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sdNVP within 48 hours of birth, mother and infant vs. ZDV + 3TC (1 week), mother and infant |
- MTCT was 12.3% in sdNVP arm vs. 9.3% in ZDV + 3TC arm at 8 weeks (difference not statistically significant, P = 0.11).
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Perinatal HIV Prevention Trial (PHPT-1)
Thailand12
Formula feeding |
Four ZDV regimens with different durations of AP and infant PP administration, no placebo |
Long (from 28 weeks), short (from 36 weeks)
Oral IP
|
Long (6 weeks), short (3 days), infant only |
- Short-short arm stopped at interim analysis (10.5%). MTCT was 6.5% in long-long arm vs. 4.7% in long-short arm and 8.6% in short-long arm at 6 months (no statistical difference). In utero transmission was significantly higher with short vs. long maternal therapy regimens (5.1% vs. 1.6%).
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PACTG 316 trial Bahamas, Belgium, Brazil, France, Germany, Italy, Spain, Sweden, Switzerland, United Kingdom, United States21
Formula feeding |
sdNVP vs. placebo among women already receiving ZDV alone (23%) or ZDV + other ARV drugs (77% combination therapy) |
Nonstudy ARV regimen
Oral IP: placebo vs. sdNVP + IV ZDV
|
Placebo vs. sdNVP within 72 hours of birth + nonstudy ARV drugs (ZDV), infant only |
- 77% of women received dual- or triple-combination ARV regimens during pregnancy.
- Trial stopped early because of very low MTCT in both arms: 1.4% in sdNVP arm vs. 1.6% in placebo arm (53% of MTCT was in utero).
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Perinatal HIV Prevention Trial (PHPT-2)
Thailand19
Formula feeding |
ZDV alone vs. ZDV + maternal and infant sdNVP vs. ZDV + maternal sdNVP |
ZDV from 28 weeks
Oral IP: ZDV alone or ZDV + sdNVP
|
ZDV for 1 week with or without sdNVP, infant only |
- ZDV-alone arm was stopped because of higher MTCT than the NVP-NVP arm (6.3% vs. 1.1%). In arms in which the mother received sdNVP, MTCT rate did not differ significantly between the infant receiving or not receiving sdNVP (2.0% vs. 2.8%).
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DITRAME Plus (ANRS 1201.0) trial
Ivory Coast14
Breastfeeding and formula feeding |
Open label, ZDV + sdNVP |
ZDV from 36 weeks
Oral IP: ZDV plus sdNVP
|
sdNVP + ZDV for 1 week, infant only |
- MTCT was 6.5% (95% CI, 3.9%–9.1%) at 6 weeks; MTCT for historical control group receiving short ZDV (98% breastfed) was 12.8%.
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DITRAME Plus (ANRS 1201.1) trial
Ivory Coast14
Breastfeeding and formula feeding |
Open label, ZDV + 3TC + sdNVP |
ZDV + 3TC from 32 weeks (stopped at 3 days PP)
Oral IP: ZDV + 3TC + sdNVP
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sdNVP + ZDV for 1 week, infant only |
MTCT was 4.7% (95% CI, 2.4%–7.0%) at 6 weeks; MTCT for historical control group receiving short ZDV (98% breastfed) was 12.8%.
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NVAZ trial
Malawi6
Breastfeeding |
Neonatal sdNVP vs. sdNVP + ZDV |
No AP or IP ARV (latecomers) |
sdNVP with or without ZDV for 1 week, infant only |
- MTCT was 15.3% in sdNVP + ZDV arm and 20.9% in sdNVP-only arm at 6–8 weeks. MTCT rate at 6–8 weeks among infants who were HIV uninfected at birth was 7.7% and 12.1%, respectively (36% efficacy).
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Postnatal NVP + ZDV trial
Malawi7
Breastfeeding |
Neonatal sdNVP vs. sdNVP + ZDV |
No AP ARV
Oral IP: sdNVP
|
sdNVP with or without ZDV for 1 week, infant only |
- MTCT was 16.3% in NVP + ZDV arm and 14.1% in sdNVP-only arm at 6–8 weeks (difference not statistically significant). MTCT rate at 6–8 weeks among infants who were HIV uninfected at birth was 6.5% and 16.9%, respectively.
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Post-exposure Infant Prophylaxis
South Africa8
Breastfeeding and formula feeding |
Neonatal sdNVP vs.
ZDV for 6 weeks |
No AP or IP ARV |
sdNVP vs. ZDV for 6 weeks |
- For formula-fed infants only, MTCT was 14.3% in sdNVP arm vs. 14.1% in ZDV arm at 6 weeks (not significant, P = 0.30). For breastfed infants only, MTCT was 12.2% in sdNVP arm and 19.6% in ZDV arm (P = 0.03).
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Mashi
Botswana20,36
Breastfeeding and formula feeding |
Initial: short-course ZDV with/without maternal and infant sdNVP and with/without breastfeeding
Revised: short-course ZDV + infant sdNVP with/without maternal sdNVP and with/without breastfeeding; women with CD4 T-lymphocyte (CD4-cell) counts <200 cells/mm3 receive combination therapy
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1st randomization
ZDV from 34 weeks
Oral IP: ZDV + either sdNVP vs. placebo
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2nd randomization
Breastfeeding + ZDV (infant) 6 months + sdNVP, infant only
vs.
Formula feeding + ZDV (infant) 4 weeks + sdNVP, infant only |
- Initial design: In formula-feeding arm, MTCT at 1 month was 2.4% in maternal and infant sdNVP arm and 8.3% in placebo arm (P = 0.05). In breastfeeding + infant ZDV arm, MTCT at 1 month was 8.4% in sdNVP arm and 4.1% in placebo arm (difference not statistically significant).
- Revised design: MTCT at 1 month was 4.3% in maternal + infant sdNVP arm and 3.7% in maternal placebo + infant sdNVP arm (no significant difference; no interaction with mode of infant feeding).
- MTCT at 7 months was 9.1% in breastfeeding + ZDV arm and 5.6% in formula-feeding arm; mortality at 7 months was 4.9% in breastfeeding + ZDV arm vs. 9.3% in formula-feeding arm; HIV-free survival at 18 months was 15.6% breastfeeding + ZDV arm versus 14.2% formula-feeding arm.
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SWEN
Uganda, Ethiopia, India23
Breastfeeding |
sdNVP vs. NVP for 6 weeks |
No AP ARV
Oral IP: sdNVP |
Infant sdNVP vs. NVP for 6 weeks |
- Postnatal infection in infants uninfected at birth:
- MTCT at 6 weeks was 5.3% in sdNVP arm vs. 2.5% in extended NVP arm (risk ratio 0.54, P = 0.009).
- MTCT at 6 months was 9.0% in sdNVP arm vs. 6.9% in extended NVP arm (risk ratio 0.80, P = 0.16).
- HIV-free survival was significantly lower in extended NVP arm at both 6 weeks and 6 months of age.
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PEPI-Malawi Trial
Malawi 22
Breastfeeding |
sdNVP + ZDV for 1 week (control) vs. two extended infant regimens (NVP or NVP/ZDV) for 14 weeks |
No AP ARV
Oral IP: sdNVP (if mother presents in time)
|
Infant sdNVP + ZDV for 1 week (control) vs. control + NVP for 14 weeks vs. control + NVP/ZDV for 14 weeks |
- Postnatal infection in infants uninfected at birth:
- MTCT at age 6 weeks was 5.1% in control vs. 1.7% in extended NVP (67% efficacy) and 1.6% in extended NVP/ZDV arms (69% efficacy).
- MTCT at age 9 months was 10.6% in control vs. 5.2% in extended NVP (51% efficacy) and 6.4% in extended NVP/ZDV arms (40% efficacy).
- No significant difference in MTCT between the extended prophylaxis arms; however, more hematologic toxicity with NVP/ZDV.
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MITRA
Tanzania25
Breastfeeding |
Infant 3TC for 6 months (observational) |
ZDV/3TC from 36 weeks through labor |
Maternal ZDV/3TC for 1 week; infant 3TC for 6 months |
- MTCT at age 6 months was 4.9% (postnatal MTCT between ages 6 weeks and 6 months was 1.2%).
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Kisumu Breastfeeding Study (KiBS)
Kenya27
Breastfeeding |
Maternal triple-drug prophylaxis
(observational) |
ZDV/3TC/NVP (NFV if CD4-cell count >250 cells/mm3) from 34 weeks through labor |
Maternal ZDV/3TC/NVP (NFV if CD4-cell count >250 cells/mm3) for 6 months; infant sdNVP |
- MTCT at age 6 months was 5.0% (postnatal MTCT between ages 7 days and 6 months was 2.6%).
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MITRA-PLUS
Tanzania24
Breastfeeding |
Maternal triple-drug prophylaxis (observational) |
ZDV/3TC/NVP (NFV if CD4-cell count >200 cells/mm3) from 34 weeks through labor |
Maternal ZDV/3TC/NVP (NFV if CD4-cell count >200 cells/mm3) for 6 months; infant ZDV/3TC for 1 week |
- MTCT at age 6 months was 5.0% (postnatal MTCT between ages 6 weeks and 6 months was 0.9%), not significantly different from 6 months infant prophylaxis in MITRA.
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Kesho Bora
Multi-African16
Breastfeeding primarily |
Antepartum ZDV/sdNVP with no postnatal prophylaxis vs. maternal triple-drug prophylaxis in women with CD4-cell counts of 200–500 cells/mm3 |
Arm 1: ZDV/3TC/LPV/r
Arm 2:
ZDV + sdNVP
From 28 weeks through labor
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Arm 1: Maternal ZDV/3TC/LPV/r for 6 months; infant sdNVP + ZDV for 1 week
Arm 2: Maternal ZDV/3TC for 1 week (no further postnatal prophylaxis); infant sdNVP + ZDV for 1 week (no further postnatal prophylaxis)
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- MTCT at birth was 1.8% with maternal triple-drug prophylaxis Arm 1 and 2.5% with ZDV/sdNVP Arm 2, not significantly different. In women with CD4-cell counts 350–500 cells/mm3, MTCT at birth was 1.7% in both arms.
- MTCT at age 12 months was 5.4% with maternal triple-drug prophylaxis Arm 1 and 9.5% with ZDV/sdNVP (with no further postnatal prophylaxis after 1 week) Arm 2 (P = 0.029).
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Mma Bana
Botswana1
Breastfeeding |
Maternal triple-drug prophylaxis (compares 2 regimens) in women with CD4-cell counts >200 cells/mm3 |
Arm 1: ZDV/3TC/ABC
Arm 2: ZDV/3TC/LPV/r
From 26 weeks through labor
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Arm 1: Maternal ZDV/3TC/ABC for 6 months; infant sdNVP + ZDV for 4 weeks
Arm 2: Maternal ZDV/3TC/LPV/r for 6 months; infant sdNVP + ZDV for 4 weeks
|
- MTCT at age 6 months overall was 1.3%: 2.1% in ZDV/3TC/ABC Arm 1 and 0.4% in ZDV/3TC/LPV/r Arm 2 (P = 0.53).
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BAN
Malawi26,37
Breastfeeding |
Postpartum maternal triple-drug prophylaxis vs. infant NVP in women with CD4-cell counts ≥250 cells/mm3 |
No AP drugs
IP regimens:
Arm 1 (control): ZDV/3TC + sdNVP
Arm 2: ZDV/3TC + sdNVP
Arm 3: ZDV/3TC + sdNVP
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Arm 1 (control): Maternal ZDV/3TC for 1 week; infant sdNVP + ZDV/3TC for 1 week
Arm 2: Control as above, then maternal ZDV/3TC/LPV/r for 6 months
Arm 3: Control as above, then infant NVP for 6 months
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- Postnatal infection in infants uninfected at age 2 weeks:
- MTCT at age 28 weeks was 5.7% in control Arm 1; 2.9% in maternal triple-drug prophylaxis Arm 2 (P = 0.009 vs. control); 1.7% in infant NVP Arm 3 (P <0.001 vs. control).
- MTCT at age 48 weeks was 7.0% in control Arm 1; 4% in maternal triple-drug prophylaxis Arm 2 (P = 0.0273 vs. control); 4% in infant NVP Arm 3 (P = 0.0027 vs. control).
- No significant difference between maternal triple-drug prophylaxis Arm 2 and infant NVP Arm 3 (P = 0.12 at 28 weeks and P = 0.426 at 48 weeks).
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HPTN 046
South Africa, Tanzania, Uganda, Zimbabwe33
Breastfeeding |
Postpartum prophylaxis of breast milk transmission of HIV with 6 weeks vs. 6 months of infant NVP |
AP drugs allowed if required for maternal health |
All infants received daily NVP from birth through age 6 weeks.
Arm 1: Daily infant NVP from 6 weeks through 6 months of age
Arm 2: Daily infant placebo from 6 weeks through age 6 months of age
|
- In infants uninfected at age 6 weeks, the 6-month infant HIV infection rate was 1.1% (0.3%–1.8%) in the extended NVP Arm 1 and 2.4% (1.3%–3.6%) in the placebo Arm 2 (P = 0.048).
- At infant randomization at age 6 weeks, 29% of mothers in each arm were receiving a triple-drug ARV regimen for treatment of HIV.
- For mothers receiving triple-drug ARV regimens at the time of randomization, in infants uninfected at age 6 weeks, the 6-month infant HIV infection rate was 0.2% and not statistically different between extended NVP Arm 1 (0.5%) and placebo Arm 2 (0%).
- For mothers with CD4- cell counts >350 cells/mm3 who were not receiving triple-drug ARV regimens, in infants uninfected at age 6 weeks, the 6-month infant HIV infection rate was 0.7% (0%–1.5%) in the extended NVP Arm 1 and 2.8% (1.3%–4.4%) in the placebo Arm 2 (P = 0.014).
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NICHD-HPTN 040/PACTG 1043 trial Argentina, Brazil, South Africa, United States18
Formula feeding |
Infant prophylaxis with 6 weeks ZDV vs. 6 weeks infant ZDV plus three doses of NVP in first week of life vs. 6 weeks infant ZDV plus 2 weeks of 3TC/NFV |
No AP drugs
If mother presented early enough, IV ZDV during labor through delivery
|
Arm 1 (control): Infant ZDV for 6 weeks
Arm 2: Control as above plus NVP with first dose within 48 hours of birth, second dose
48 hours later, and third dose 96 hours after the second dose
Arm 3: Control as above, plus 3TC and NFV from birth through 2 weeks of age
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- IP HIV transmission among infants with negative HIV test at birth: 4.8% (3.2%–7.1%) ZDV (Arm 1) vs. 2.2% (1.2%–3.9%) in ZDV plus NVP (Arm 2) (P = 0.046 compared with Arm 1) vs. 2.4% (1.4%–4.3%) in ZDV plus 3TC/NFV (Arm 3) (P = 0.046 compared with Arm 1).
- Overall HIV transmission rates, including in uteroinfection: 11.0% (8.7%–14.0%) ZDV (Arm 1) vs. 7.1% (5.2%–9.6%) in ZDV plus NVP (Arm 2) (P = 0.035 compared with Arm 1) vs. 7.4% (5.4%–9.9%) in ZDV plus 3TC/NFV (Arm 3) (P = 0.035 compared with Arm 1).
- Grade 3 or 4 neutropenia more frequent in ZDV/3TC/NFV Arm 3, 70 infants, compared with ZDV alone Arm 1, 33 infants, or ZDV/NVP Arm 2, 32 infants (P <0.001).
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