Article

Gray GE, Urban M, Chersich MF, et al. A randomized trial of two postexposure prophylaxis regimens to reduce mother-to-child HIV-1 transmission in infants of untreated mothers

Perinatal HIV Research Unit, University of the Witwatersrand, Johannesburg South Africa.
AIDS (Impact Factor: 6.56). 09/2005; 19(12):1289-97. DOI: 10.1097/01.aids.0000180100.42770.a7
Source: PubMed

ABSTRACT 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.

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    • "Mother–infant pairs were followed for 6 months and for mothers who chose to breastfeed, until one month after cessation of breastfeeding. The probability of infant HIV infection was 12.8% at 6 weeks and 16.3% at 12 weeks (Gray et al. 2005). Among the 1051 mother–child dyads originally enrolled in this study, 205 patients completed the first visit but then did not attend any follow-up visits, and an additional six patients were missing length and weight data. "
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    ABSTRACT: To evaluate growth parameters assessed by weight and length in HIV-infected and HIV-uninfected infants born to HIV-infected mothers in South Africa from birth to 6 months of age. We calculated z-scores for weight-for-age (WAZ), length-for-age (LAZ) and weight-for-length (WLZ) among a cohort of 840 mother-infant dyads. Multivariable Cox proportional hazards models with time-varying covariates were used to estimate the risk of falling <-2 z-scores for WAZ, LAZ, and WLZ as a function of infant and maternal characteristics. By 6 months after birth, a fifth of infants had WAZ <-2, 19% had an LAZ <-2, and 29% had a WLZ <-2. WLZ and WAZ were significantly lower in HIV-infected infants than in uninfected infants by 3 months of age and LAZ by 6 months of age (P<0.001). The risk of WAZ falling <-2 was associated with decreasing maternal CD4 cell count (adj. HR for CD4 cell count <200 cells/μl: 1.64; 95% CI: 1.10-2.43), premature birth (adj. HR: 2.82; 95% CI: 2.06-3.86) and formula feeding (adj. HR: 3.35; 95% CI: 1.64-6.85). The risk of LAZ falling <-2 was associated with increasingly lower maternal age (adj. HR for<20 years: 0.54; 95% CI: 0.31-0.96), lower maternal CD4 cell count (adj. HR for CD4 cell count <200 cells/μl: 1.72; 95% CI: 1.14-2.59), premature birth (adj. HR: 2.37; 95% CI: 1.70-3.30) and formula feeding (adj. HR: 4.22; 95% CI: 1.85-9.62). The risk of WLZ falling <-2 was significantly associated with infant HIV infection (adj. HR: 1.64; 95% CI: 1.16-2.32) and formula feeding (adj. HR: 1.78; 95% CI: 1.11-2.83). The risk of WAZ and LAZ falling <-2 was more than two times greater for HIV-infected infants than for uninfected infants with gastrointestinal infections. HIV-infected infants were more likely to be stunted and wasted than uninfected infants, which often occurred within 3 months after birth. Infants who were born to mothers with advanced HIV disease, formula-fed and co-infected with HIV and gastrointestinal infections were at greater risk for growth disturbances. Further interventions are needed to promptly initiate both HIV-infected mothers and infants on appropriate antiretroviral therapy and nutritional supplementation.
    Tropical Medicine & International Health 11/2010; 15(11):1364-74. DOI:10.1111/j.1365-3156.2010.02634.x · 2.30 Impact Factor
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    • "Although, return of mothers for PN-PMTCT has been reported between 30 and 63% in controlled MTCT trials (D'Adesky, 2001; Gray et al., 2005; Malonza, Richardson, Kreiss, Bwayo, & Stewart, 2003) there are limited data on the continuity of HIV/ AIDS care, for both the mothers and the exposed babies, beyond the peri-partum period in PMTCT program settings in SSA (Perez et al., 2004). We determined the level of adherence of mothers to the PN-PMTCT program and the factors associated with adherence to PN-PMTCT among the HIV-positive mothers who deliver at a public urban hospital in Uganda. "
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    ABSTRACT: Despite scale up of perinatal prevention of mother-to-child transmission (PMTCT) of HIV interventions, postnatal continuity of comprehensive HIV/AIDS care, for both the mother and baby, remains a challenge in developing countries. We determined adherence to the postnatal PMTCT program (PN-PMTCT) and the associated factors among mothers at a public urban hospital in Uganda. We interviewed HIV-positive postnatal mothers on discharge and we determined adherence to PN-PMTCT by the proportion of mothers that honored their return appointments by the end of eight weeks postpartum. We had focus group discussions to assess factors that influence adherence to PN-PMTCT. Of 289 mothers, only 110 (38%) adhered to PN-PMTCT. Previous attendance of a routine postnatal review and having access to a phone were significantly associated with adherence to PMTCT among mothers older than 25 years (odds ratio (OR) 3.6 (95% confidence interval (CI); 1.2-10.4)) and (OR 3.1 (95% CI; 1.3-7.1)), respectively. On the other hand, Christianity (OR 3.2 (95% CI; 1.1-9.0)) was significantly associated with adherence to PN-PMTCT among mothers below 25 years of age. Mothers' perceived benefits of the PN-PMTCT program, easy access to the program, and presence of social support from a spouse were important motivators for mothers to adhere to PN-PMTCT. Even with improved antenatal and intra-partum PMTCT services, only a third of the HIV-infected mothers adhered to the PN-PMTCT program. Mothers who previously attended a routine postnatal care were 3.6 fold more likely to adhere to PN-PMTCT. We recommend strategies to increase mothers' adherence to PN-PMTCT interventions in order to increase access to HIV/AIDS care for mothers and children in sub-Saharan Africa.
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    • "Cord-blood samples were collected into EDTA vacutainers by cordocentesis from infants born to 124 HIV-1-infected women enrolled as part of a post-exposure prophylaxis (PEP) trial conducted at Chris Hani Baragwanath Hospital in Soweto, South Africa (Gray et al., 2005). Women who had either received no prenatal care or who received prenatal care at community clinics where HIV testing and access to antiretroviral drugs were unavailable were eligible for this trial and were tested for HIV after delivery. "
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    ABSTRACT: The role of CC chemokines in protection against mother-to-child human immunodeficiency virus type 1 (HIV-1) transmission is not well understood. It was observed that mitogen-induced production of CCL3 and CCL4 by cord-blood mononuclear cells was increased among infants born to HIV-positive compared with HIV-negative mothers, and that a deficiency in production of CCL3 was associated with increased susceptibility to intrapartum HIV-1 infection. CCL3-L1 gene copy number was associated with CCL3 production and with vertical transmission. However, at equivalent CCL3-L1 gene copy numbers, infants who acquired HIV-1 infection relative to their exposed but uninfected counterparts had lower production of CCL3, suggesting that they may harbour some non-functional copies of this gene. Nucleotide changes that may influence CCL3 production were evident in the CCL3 and CCL3-L1 genes upstream of exon 2. Our findings suggest that infants who display a deficient-production phenotype of CCL3 are at increased risk of acquiring HIV-1, indicating that this chemokine in particular plays an essential role in protective immunity.
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