Elective caesarean-section versus vaginal delivery in prevention of vertical HIV-1 transmission: a randomised clinical trial. Short-course oral zidovudine for prevention of mother-to-child transmission of HIV-1 in Abidjan, Côte d'Ivoire: a randomised trial. 6-month efficacy, tolerance, and acceptability of a short regimen of oral zidovudine to reduce vertical transmission of HIV in breastfed children in Côte d'Ivoire and Burkina Faso: a double-blind placebo-controlled multicentre trial. DITRAME Study Group. DIminution de la Transmission Mère-Enfant. Short-course zidovudine for perinatal HIV-1 transmission in Bangkok, Thailand: a randomised controlled trial. Bangkok Collaborative Perinatal HIV Transmission Study Group. Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: HIVNET 012 randomised trial.
Results from observational studies suggest that caesarean-section delivery may reduce the risk of mother-to-child transmission of HIV-1 infection in comparison with vaginal delivery. We carried out a randomised clinical trial to address this issue and to assess the extent of postdelivery complications.
                Eligible women were between 34 and 36 weeks of pregnancy, with a confirmed diagnosis of HIV-1 infection, and without an indication for caesarean-section delivery or a contraindication to this mode of delivery. Women were randomly assigned elective caesarean-section delivery at 38 weeks of pregnancy or vaginal delivery. An infant was classified as uninfected if he or she became negative for antibody to HIV-1 by age 18 months or was negative for virus by PCR or culture on at least two occasions, with no clinical, immunological, or viral evidence of infection. From 1993, to March, 1998, 436 women were randomised.
                We present the results of an analysis updated to November, 1998, with data on the infection status of 370 infants. Three (1.8%) of 170 infants born to women assigned caesarean-section delivery were infected, compared with 21 (10.5%) of 200 born to women assigned vaginal delivery (p<0.001). Seven (3.4%) of 203 infants of women who actually gave birth by caesarean section were infected compared with 15 (10.2%) of 167 born vaginally (p=0.009). There were few postpartum complications and no serious adverse events in either group.
                Our findings provide evidence that elective caesarean-section delivery significantly lowers the risk of mother-to-child transmission of HIV-1 infection without a significantly increased risk of complications for the mother. In Africa, the risk of mother-to-child transmission of HIV-1 infection is high. Short-course perinatal oral zidovudine might decrease the rate of transmission. We assessed the safety and efficacy of such a regimen among HIV-1-seropositive breastfeeding women in Abidjan, Côte d'Ivoire.
                From April, 1996, to February, 1998, all consenting, eligible HIV-1-seropositive pregnant women attending a public antenatal clinic in Abidjan were enrolled at 36 weeks' gestation and randomly assigned placebo or zidovudine (300 mg tablets), one tablet twice daily until the onset of labour, one tablet at onset of labour, and one tablet every 3 h until delivery. We used HIV-1-DNA PCR to test the infection status of babies at birth, 4 weeks, and 3 months. We stopped the study on Feb 18, 1998, when efficacy results were available from a study in Bangkok, Thailand, in which the same regimen was used in a non-breastfeeding population.
                280 women were enrolled (140 in each group). The median duration of the prenatal drug regimen was 27 days (range 1-80) and the median duration of labour was 7.5 h. Treatment was well tolerated with no withdrawals because of adverse events. All babies were breastfed. Among babies with known infection status at age 3 months, 30 (26.1%) of 115 babies in the placebo group and 19 (16.5%) of 115 in the zidovudine group were identified as HIV-1 infected. The estimated risk of HIV-1 transmission in the placebo and zidovudine groups were 21.7% and 12.2% (p=0.05) at 4 weeks, and 24.9% and 15.7% (p=0.07) at 3 months. Efficacy was 44% (95% CI -1 to 69) at age 4 weeks and 37% (-5 to 63) at 3 months.
                Short-course oral zidovudine was safe, well tolerated, and decreased mother-to-child transmission of HIV-1 at age 3 months. Substantial efforts will be needed to ensure successful widespread implementation of such a regimen. Zidovudine reduces the rate of vertical transmission of HIV in non-breastfed populations. We assessed the acceptability, tolerance, and 6-month efficacy of a short regimen of oral zidovudine in African populations practising breastfeeding.
                A randomised double-blind placebo-controlled trial was carried out in public clinics of Abidjan, Côte d'Ivoire, and Bobo-Dioulasso, Burkina Faso. Eligible participants were women aged 18 years or older, who had confirmed HIV-1 infection and pregnancy of 36-38 weeks duration, and who gave written informed consent. Exclusion criteria were severe anaemia, neutropenia, abnormal liver function, and sickle-cell disease. Women were randomly assigned zidovudine (n=214; 300 mg twice daily until labour, 600 mg at beginning of labour, and 300 mg twice daily for 7 days post partum) or matching placebo (n=217). The primary outcome was the diagnosis of HIV-1 infection in the infant on the basis of sequential DNA PCR tests at days 1-8, 45, 90, and 180. We compared the probability of infection at a given age in the two groups. Analyses were by intention to treat.
                Women were enrolled between September, 1995, and February, 1998, when enrolment to the placebo group was stopped. Analysis was based on 421 women and 400 lifeborn infants. Baseline demographic, clinical, and laboratory characteristics were similar in the two groups. The Kaplan-Meier probability of HIV infection in the infant at 6 months was 18.0% in the zidovudine group (n=192) and 27.5% in the placebo group (n=197; relative efficacy 0.38 [95% CI 0.05-0.60]; p=0.027). Adjustment for centre, period of recruitment, mode of delivery, maternal CD4-cell count, duration of labour, prolonged rupture of membranes, and duration of breastfeeding did not change the treatment effect. The proportions of women taking more than 80% of the planned maximum dose were 75% before delivery, 81% during labour, and 83% post partum, without statistical difference between the groups. No major adverse biological or clinical event was reported in excess among women and children of the zidovudine group.
                A short course of oral zidovudine given during the peripartum period is well accepted and well tolerated, and provides a 38% reduction in early vertical transmission of HIV-1 infection despite breastfeeding. Many developing countries have not implemented the AIDS Clinical Trials Group 076 zidovudine regimen for prevention of perinatal HIV-1 transmission because of its complexity and cost. We investigated the safety and efficacy of short-course oral zidovudine administered during late pregnancy and labour.
                In a randomised, double-blind, placebo-controlled trial, HIV-1-infected pregnant women at two Bangkok hospitals were randomly assigned placebo or one zidovudine 300 mg tablet twice daily from 36 weeks' gestation and every 3 h from onset of labour until delivery. Mothers were given infant formula and asked not to breastfeed. The main endpoint was babies' HIV-1-infection status, tested with HIV-1-DNA PCR at birth, 2 months, and 6 months. We measured maternal plasma viral concentrations by RNA PCR.
                Between May, 1996, and December, 1997, 397 women were randomised; 393 gave birth to 395 live-born babies. Median duration of antenatal treatment was 25 days, and median number of doses during labour was three. 99% of women took at least 90% of scheduled antenatal doses. Adverse events were similar in the study groups. Of 392 babies with at least one PCR test, 55 tested positive: 18 in the zidovudine group and 37 in the placebo group. The estimated transmission risks were 9.4% (95% CI 5.2-13.5) on zidovudine and 18.9% (13.2-24.2) on placebo (p=0.006; efficacy 50.1% [15.4-70.6]). Between enrolment and delivery, women in the zidovudine group had a mean decrease in viral load of 0.56 log. About 80% of the treatment effect was explained by lowered maternal viral concentrations at delivery.
                A short course of twice-daily oral zidovudine was safe and well tolerated and, in the absence of breastfeeding, can lessen the risk for mother-to-child HIV-1 transmission by half. This regimen could prevent many HIV-1 infections during late pregnancy and labour in less-developed countries unable to implement the full 076 regimen. The AIDS Clinical Trials Group protocol 076 zidovudine prophylaxis regimen for HIV-1-infected pregnant women and their babies has been associated with a significant decrease in vertical HIV-1 transmission in non-breastfeeding women in developed countries. We compared the safety and efficacy of short-course nevirapine or zidovudine during labour and the first week of life.
                From November, 1997, to April, 1999, we enrolled 626 HIV-1-infected pregnant women at Mulago Hospital in Kampala, Uganda. We randomly assigned mothers nevirapine 200 mg orally at onset of labour and 2 mg/kg to babies within 72 h of birth, or zidovudine 600 mg orally to the mother at onset of labour and 300 mg every 3 h until delivery, and 4 mg/kg orally twice daily to babies for 7 days after birth. We tested babies for HIV-1 infection at birth, 6-8 weeks, and 14-16 weeks by HIV-1 RNA PCR. We assessed HIV-1 transmission and HIV-1-free survival with Kaplan-Meier analysis.
                Nearly all babies (98.8%) were breastfed, and 95.6% were still breastfeeding at age 14-16 weeks. The estimated risks of HIV-1 transmission in the zidovudine and nevirapine groups were: 10.4% and 8.2% at birth (p=0.354); 21.3% and 11.9% by age 6-8 weeks (p=0.0027); and 25.1% and 13.1% by age 14-16 weeks (p=0.0006). The efficacy of nevirapine compared with zidovudine was 47% (95% CI 20-64) up to age 14-16 weeks. The two regimens were well tolerated and adverse events were similar in the two groups.
                Nevirapine lowered the risk of HIV-1 transmission during the first 14-16 weeks of life by nearly 50% in a breastfeeding population. This simple and inexpensive regimen could decrease mother-to-child HIV-1 transmission in less-developed countries.
Zidovudine, nevirapine and delivery by elective caesarean section appear to be very effective in decreasing the risk of mother-to-child transmission of HIV infection.