A multicenter randomized controlled trial of nevirapine versus a combination of zidovudine and lamivudine to reduce intrapartum and early postpartum mother-to-child transmission of human immunodeficiency virus type 1. A randomized trial of two postexposure prophylaxis regimens to reduce mother-to-child HIV-1 transmission in infants of untreated mothers. Extended antiretroviral prophylaxis to reduce breast-milk HIV-1 transmission. Short-course oral zidovudine for prevention of mother-to-child transmission of HIV-1 in Abidjan, Côte d'Ivoire: a randomised trial. Antiretroviral regimens in pregnancy and breast-feeding in Botswana. Breast milk HIV-1 suppression and decreased transmission: a randomized trial comparing HIVNET 012 nevirapine versus short-course zidovudine. 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. A randomized control trial of an Ultra-Short zidovudine regimen in the prevention of perinatal HIV transmission in rural Zimbabwe. Development of nevirapine resistance in infants is reduced by use of infant-only single-dose nevirapine plus zidovudine postexposure prophylaxis for the prevention of mother-to-child transmission of HIV-1.
To determine the efficacy and safety of 2 inexpensive and easily deliverable antiretroviral (ARV) regimens for the prevention of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) type 1 during labor and delivery, HIV-infected pregnant women were screened at 11 maternity health institutions in South Africa and were enrolled in an open-label short course ARV regimen of either nevirapine (Nvp) or multiple-dose zidovudine and lamivudine (Zdv/3TC). The overall estimated HIV-1 infection rates in 1307 infants by 8 weeks were 12.3% (95% confidence interval [CI], 9.7-15.0) for Nvp and 9.3% (95% CI, 7.0-11.6) for Zdv/3TC (P=.11). Excluding infections detected within 72 h (intrauterine), new HIV-1 infections were detected in 5.7% (95% CI, 3.7-7.8) and 3.6% (95% CI, 2.0-5.3) of infants in the Nvp and Zdv/3TC groups, respectively, in the 8 weeks after birth. There were no drug-related maternal or pediatric serious adverse events. Common complications were obstetrical for mothers (Nvp group, 24.3%; Zdv/3TC group, 26.3%) and respiratory for infants (Nvp group, 16.1%; Zdv/3TC group, 17.0%). This study further confirms the efficacy and safety of short-course ARV regimens in reducing MTCT rates in developing countries. Single-dose nevirapine (NVP) prophylaxis to mother and infant is widely used in resource-constrained settings for preventing mother-to-child transmission (MTCT) of HIV-1. Where women do not access antenatal care or HIV testing, postexposure prophylaxis to the infant may be an important preventative strategy.
                This multicentre, randomized, open-label clinical trial (October 2000 to September 2002) in South Africa compared single-dose NVP with 6 weeks of zidovudine (ZDV), commenced within 24 h of delivery among 1051 infants whose mothers had no prior antiretroviral therapy. HIV-1 infection rates were ascertained at birth, and at 6 and 12 weeks of age. Kaplan-Meier survival methods were used to estimate HIV-1 infection rates in an intention-to-treat analysis.
                Overall, 6 week and 12 week MTCT probability was 12.8% [95% confidence interval (CI),10.5-15.0] and 16.3% (95% CI,13.4-19.2), respectively. At 12 weeks, among infants who were not infected at birth, 24 (7.9%) infections occurred in the NVP arm and 41 (13.1%) in the ZDV arm (log rank P = 0.06). Using multivariate analysis, factors associated with infection following birth were ZDV use [odds ratio (OR), 1.8; 95% CI,1.1-3.2; P = 0.032), maternal CD4 cell count < 500 x 10(6) cells/l (OR, 2.5; 95% CI,1.3-5.0; P = 0.007), maternal viral load > 50 000 copies/ml (OR, 3.6; 95% CI,2.0-6.2; P < 0.0001) and breastfeeding (OR, 2.2; 95% CI,1.3-3.8; P = 0.006).
                A single-dose of NVP given to infants offers protection against HIV-1 infection and should be a strategy used in infants of mothers with untreated HIV infection. Effective strategies are urgently needed to reduce mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) through breast-feeding in resource-limited settings.
                Women with HIV-1 infection who were breast-feeding infants were enrolled in a randomized, phase 3 trial in Blantyre, Malawi. At birth, the infants were randomly assigned to one of three regimens: single-dose nevirapine plus 1 week of zidovudine (control regimen) or the control regimen plus daily extended prophylaxis either with nevirapine (extended nevirapine) or with nevirapine plus zidovudine (extended dual prophylaxis) until the age of 14 weeks. Using Kaplan-Meier analyses, we assessed the risk of HIV-1 infection among infants who were HIV-1-negative on DNA polymerase-chain-reaction assay at birth.
                Among 3016 infants in the study, the control group had consistently higher rates of HIV-1 infection from the age of 6 weeks through 18 months. At 9 months, the estimated rate of HIV-1 infection (the primary end point) was 10.6% in the control group, as compared with 5.2% in the extended-nevirapine group (P<0.001) and 6.4% in the extended-dual-prophylaxis group (P=0.002). There were no significant differences between the two extended-prophylaxis groups. The frequency of breast-feeding did not differ significantly among the study groups. Infants receiving extended dual prophylaxis had a significant increase in the number of adverse events (primarily neutropenia) that were deemed to be possibly related to a study drug.
                Extended prophylaxis with nevirapine or with nevirapine and zidovudine for the first 14 weeks of life significantly reduced postnatal HIV-1 infection in 9-month-old infants. (ClinicalTrials.gov number, NCT00115648.)
                2008 Massachusetts Medical Society 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. The most effective highly active antiretroviral therapy (HAART) to prevent mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) in pregnancy and its efficacy during breast-feeding are unknown.
                We randomly assigned 560 HIV-1-infected pregnant women (CD4+ count, > or = 200 cells per cubic millimeter) to receive coformulated abacavir, zidovudine, and lamivudine (the nucleoside reverse-transcriptase inhibitor [NRTI] group) or lopinavir-ritonavir plus zidovudine-lamivudine (the protease-inhibitor group) from 26 to 34 weeks' gestation through planned weaning by 6 months post partum. A total of 170 women with CD4+ counts of less than 200 cells per cubic millimeter received nevirapine plus zidovudine-lamivudine (the observational group). Infants received single-dose nevirapine and 4 weeks of zidovudine.
                The rate of virologic suppression to less than 400 copies per milliliter was high and did not differ significantly among the three groups at delivery (96% in the NRTI group, 93% in the protease-inhibitor group, and 94% in the observational group) or throughout the breast-feeding period (92% in the NRTI group, 93% in the protease-inhibitor group, and 95% in the observational group). By 6 months of age, 8 of 709 live-born infants (1.1%) were infected (95% confidence interval [CI], 0.5 to 2.2): 6 were infected in utero (4 in the NRTI group, 1 in the protease-inhibitor group, and 1 in the observational group), and 2 were infected during the breast-feeding period (in the NRTI group). Treatment-limiting adverse events occurred in 2% of women in the NRTI group, 2% of women in the protease-inhibitor group, and 11% of women in the observational group.
                All regimens of HAART from pregnancy through 6 months post partum resulted in high rates of virologic suppression, with an overall rate of mother-to-child transmission of 1.1%. (ClinicalTrials.gov number, NCT00270296.)
                2010 Massachusetts Medical Society To compare the effect of perinatal regimens of short-course nevirapine (HIVNET 012) and zidovudine [Thai-Centers for Disease Control and Prevention (CDC) regimen] on breast milk viral shedding and perinatal transmission during the first 6 weeks postpartum in a randomized clinical trial.
                Randomized clinical trial.
                Pregnant HIV-1 seropositive women in Nairobi, Kenya who planned to breastfeed were randomized to HIVNET 012 or Thai-CDC regimens. Two to four breast milk samples were collected each week between delivery and 6 weeks postpartum. Breast milk HIV-1 RNA was quantified using the Gen-Probe TMA assay. Infants were tested for HIV-1 DNA at birth and 6 weeks.
                From March to October 2003, 76 women were enrolled and 795 breast milk samples were collected from 60 women who were randomized and followed after delivery. Between 3 and 21 days postpartum, nevirapine was associated with significantly greater suppression of breast milk log10 HIV-1 RNA: days 3 to 7 (1.98 versus 2.42, P = 0.1); days 8 to 14 (1.78 versus 2.48, P = 0.005); days 15 to 21 (1.90 versus 2.97, P = 0.003). At 6 weeks, the HIV-1 perinatal transmission rate was significantly lower among those who took nevirapine than zidovudine (6.8% versus 30.3%, P = 0.02).
                Compared to a peripartum zidovudine regimen, nevirapine was significantly more likely to decrease HIV-1 RNA in breast milk during the first week and through the third week postpartum following single-dose administration, and corresponded with decreased transmission risk at 6 weeks. Sustained breast milk HIV-1 suppression may contribute to the ability of nevirapine to decrease perinatal transmission of HIV-1. 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. To assess the practicality and effectiveness of an Ultra-Short zidovudine regimen for prevention of perinatal HIV transmission in rural Zimbabwe.
                Double-blinded placebo-controlled randomized clinical trial.
                The Salvation Army Howard Hospital, a district hospital in rural Zimbabwe.
                222 HIV positive pregnant women presenting for antenatal care prior to 36 weeks were randomized. Twenty nine women were lost to follow up.
                In the Thai regimen, mothers received zidovudine (300 mg po bid) from 36 weeks gestation until labour, and zidovudine (300 mg po q3h) during labour, and the neonates received a placebo. In the Ultra-Short regimen, the mothers received a placebo from 36 weeks to labour, then zidovudine (300 mg po q3h) in labour. The neonates received zidovudine (2 mg/kg po qid) for the first three days of life.
                Infant HIV RNA status at six weeks of life.
                Results were available for 90 infants from the Thai group and 89 infants from the Ultra-Short group. Infant HIV seroconversion rates at six weeks of life were 18.9% (95%CI 10.8 to 27.0) with the Thai regimen, and 15.7% [95% Confidence Interval (CI) 8.1 to 23.4] with the Ultra-Short regimen. The upper bound of seroconversion in the Ultra-Short group was lower than the 25% seroconversion boundary that was specified to show equivalence.
                Although the Ultra-Short regimen has equivalent efficacy to the Thai regimen, it also has many practical advantages. Ultra-Short is thus a preferable protocol. We analyzed the development of nevirapine (NVP) resistance in human immunodeficiency virus type 1 (HIV-1)-infected Malawian infants who received regimens containing single-dose NVP (SD-NVP) for the prevention of mother-to-child transmission (MTCT) of HIV-1. All infants received SD-NVP, and some randomly received zidovudine (ZDV) as well. Mothers did or did not receive SD-NVP on the basis of when they arrived at the hospital for delivery. In infants 6-8 weeks of age, NVP resistance was less frequent when infants had received SD-NVP plus ZDV and mothers had not received SD-NVP than when infants had received SD-NVP alone and mothers had received SD-NVP (4/15 [27%] vs. 20/23 [87%]; P < .001). The risk of MTCT of HIV-1 was comparable with these regimens. Infant-only prophylaxis also eliminates the development of NVP resistance in mothers.
A regimen combining triple antiretrovirals is most effective for preventing transmission of HIV from mothers to babies. The risk of adverse events to both mother and baby appears low in the short-term but the optimal antiretroviral combination and the optimal time to initiate this to maximise prevention efficacy without compromising the health of either mother or baby remains unclear.
Short courses of antiretroviral drugs are also effective for reducing mother-to-child transmission of HIV and are not associated with any safety concerns in the short-term. ZDV given to mothers during the antenatal period, followed by ZDV+3TC intrapartum and postpartum for one week, and sd-NVP given to infants within 72 hours of delivery and ZDV for one week, may be most effective when considering short antiretroviral courses. Where HIV-infected women present late for delivery, post-exposure prophylaxis with a single dose of NVP immediately after birth plus ZDV for the first 6 weeks after birth is beneficial. The long term implications of the emergence of resistant mutations following the use of these regimens, especially those containing Nevirapine, require further study.