Integration of antiretroviral treatment within antenatal care in Gauteng Province, South Africa. 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. Antiretroviral treatment and prevention of peripartum and postnatal HIV transmission in West Africa: evaluation of a two-tiered approach.
Antenatal clinics are a key entry point into HIV treatment and care, together with interventions to reduce mother-to-child transmission (MTCT). Further evaluation is needed of interventions linking antenatal with antiretroviral (ARV) treatment services and effectiveness of triple-ARV regimens for reducing MTCT in resource-constrained settings.
                Data were gathered from HIV-infected women attending antenatal care from June 2004 to July 2005 at Coronation Women and Children Hospital, South Africa. After a patient record review, interventions were implemented to strengthen service linkages and integrate ARV treatment within antenatal care. Laboratory investigations were streamlined, including CD4 cell count testing at the first antenatal visit. MTCT risk for women initiating ARV treatment is compared with that of women-infant pairs receiving single-dose nevirapine (sd-NVP).
                In total, 164 pregnant women initiated ARV treatment and 863 received sd-NVP. After changes to service delivery, time-to-treatment initiation was reduced from a median of 56 days to 37 days (P = 0.041). The risk of MTCT for women receiving ARV treatment (5 [4.3%] of 116 women) was lower than for those given sd-NVP (74 [10.7%] of 692 women; P = 0.032).
                Strengthening linkages and integrating key components of ARV treatment within antenatal care reduces time-to-treatment initiation. In this setting, among women with a high MTCT risk, triple-ARV regimens are effective in reducing HIV infection in infants. 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. Highly active antiretroviral treatment (HAART) has only been recently recommended for HIV-infected pregnant women requiring treatment for their own health in resource-limited settings. However, there are few documented experiences from African countries. We evaluated the short-term (4 wk) and long-term (12 mo) effectiveness of a two-tiered strategy of prevention of mother-to-child transmission of HIV (PMTCT) in Africa: women meeting the eligibility criteria of the World Health Organization (WHO) received HAART, and women with less advanced HIV disease received short-course antiretroviral (scARV) PMTCT regimens.
                The MTCT-Plus Initiative is a multi-country, family-centred HIV care and treatment program for pregnant and postpartum women and their families. Pregnant women enrolled in Abidjan, Côte d'Ivoire received either HAART for their own health or short-course antiretroviral (scARV) PMTCT regimens according to their clinical and immunological status. Plasma HIV-RNA viral load (VL) was measured to diagnose peripartum infection when infants were 4 wk of age, and HIV final status was documented either by rapid antibody testing when infants were aged > or = 12 mo or by plasma VL earlier. The Kaplan-Meier method was used to estimate the rate of HIV transmission and HIV-free survival. Between August 2003 and June 2005, 107 women began HAART at a median of 30 wk of gestation, 102 of them with zidovudine (ZDV), lamivudine (3TC), and nevirapine (NVP) and they continued treatment postpartum; 143 other women received scARV for PMTCT, 103 of them with sc(ZDV+3TC) with single-dose NVP during labour. Most (75%) of the infants were breast-fed for a median of 5 mo. Overall, the rate of peripartum HIV transmission was 2.2% (95% confidence interval [CI] 0.3%-4.2%) and the cumulative rate at 12 mo was 5.7% (95% CI 2.5%-9.0%). The overall probability of infant death or infection with HIV was 4.3% (95% CI 1.7%-7.0%) at age week 4 wk and 11.7% (95% CI 7.5%-15.9%) at 12 mo.
                This two-tiered strategy appears to be safe and highly effective for short- and long-term PMTCT in resource-constrained settings. These results indicate a further benefit of access to HAART for pregnant women who need treatment for their own health.
ECS is an efficacious intervention for the prevention of MTCT among HIV-1-infected women not taking ARVs or taking only zidovudine. The risk of PPM with ECS is higher than that associated with vaginal delivery, yet lower than with NECS. Among HIV-1-infected women, more advanced maternal HIV-1 disease stage and concomitant medical conditions (e.g., diabetes) are independent risk factors for PPM. The risk of MTCT of HIV-1 according to mode of delivery among HIV-1-infected women with low viral loads (low either because the woman's HIV-1 disease is not advanced, or because her HIV-1 disease is well-controlled with ARVs) is unclear. Therefore, an important issue to be addressed in one or more large studies (individual studies or an individual patient data meta-analysis combining data from more than one study) is assessment of the effectiveness of ECS for prevention of MTCT of HIV-1 among HIV-1-infected women with undetectable viral loads (with or without receipt of highly active ARV therapy (HAART)).