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: 5.55). 09/2005; 19(12):1289-97. DOI: 10.1097/01.aids.0000180100.42770.a7
Source: PubMed


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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    • "Our data reinforce the findings of several previous studies suggesting that latently HIV-1 infected cells are an important source of mother to child-transmission [9,14,15,20,45]. The ability of short-course antiretroviral regimens to reduce the breast milk transmission could be explained by effects of treatment on infectious virions [46-51]. In contrast, ART may prove to be poorly efficient at controlling cell-associated viral transmission since: (i) cell-associated HIV-1 RNA levels in breast milk are only modestly affected by ART [20], and (ii) we detected HIV-1-AgSCs and cell-associated HIV-1 RNA in women with undetectable HIV-1 plasma viral load. "
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    ABSTRACT: Transmission of human immunodeficiency virus type 1 (HIV-1) through breast-feeding may involve both cell-free and cell-associated virus. This latter viral reservoir remains, however, to be fully explored. CD4+ T cell-associated virus production in breast milk was therefore investigated. The ex vivo spontaneous production of HIV-1 antigen and HIV-1 RNA by CD4+ T cells was measured in paired blood and breast milk samples from 15 HIV-1 infected women treated or not with antiretroviral drugs. Spontaneous antigen secreting cells (HIV-1-AgSCs) from breast milk and blood were enumerated by an ELISpot assay, and cell-associated HIV-1 RNA was quantified by real-time PCR in supernatants of CD4+ T cells cultured for 18 hours without addition of polyclonal activators. Among the CD4+ T cells present in breast milk, memory cells expressing high levels of cell-surface activation markers were predominant. Spontaneous HIV-1-AgSCs were detected and enumerated in the breast milk of all 15 women, with a median number of 13.0 and 9.5 HIV-1- AgSCs/106 CD4+ T cells in aviremic (n = 7) and viremic (n = 8) women, respectively. Cell- associated HIV-1 RNA was detected in cell-free supernatants from 4/7 aviremic and 5/8 viremic individuals at median levels of 190 and 245 copies/ml, respectively. Activated CD4+ T cells producing HIV-1 are detected in the breast milk of untreated individuals as well as those receiving highly active antiretroviral therapy. This finding strongly suggests that HIV-1 replication occurs in latently infected CD4+ T cells that, upon spontaneous activation, revert to productively infected cells. These cells might be responsible for a residual breast milk transmission despite maternal highly active antiretroviral therapy.
    Full-text · Article · May 2011 · Retrovirology
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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.
    Preview · Article · Nov 2010 · Tropical Medicine & International Health
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    • "Active research in this area produced continued refinements in prophylactic antiretroviral drug regimens. Studies in Malawi and South Africa demonstrated how post-partum prophylaxis could be effective for the large number of infants whose mothers had not accessed optimal antenatal care [5,6]. A pivotal study in Thailand was particularly useful in demonstrating the improved outcomes with combination zidovudine and nevirapine prophylaxis [7]. "
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    ABSTRACT: Clinical and epidemiologic research has identified increasingly effective interventions to reduce mother to child HIV transmission in resource-limited settings These scientific breakthroughs have been implemented in some programmes, although much remains to be done to improve coverage and quality of these programmes. But prevention of HIV transmission is not enough. It is necessary also to consider ways to improve maternal health and protect child survival. A win-win approach is to ensure that all pregnant and lactating women with CD4 counts of <350 cells/mm3 have access to antiretroviral therapy. On its own, this approach will substantially improve maternal health and markedly reduce mother to child HIV transmission during pregnancy and delivery and through breastfeeding. This approach can be combined with additional interventions for women with higher CD4 counts, either extended prophylaxis to infants or extended regimens of antiretroviral drugs to women, to reduce transmission even further. Attempts to encourage women to abstain from all breastfeeding or to shorten the optimal duration of breastfeeding have led to increases in mortality among both uninfected and infected children. A better approach is to support breastfeeding while strengthening programmes to provide antiretroviral therapy for pregnant and lactating women who need it and offering antiretroviral drug interventions through the duration of breastfeeding. This will lead to reduced HIV transmission and will protect the health of women without compromising the health and well-being of infants and young children.
    Full-text · Article · Dec 2009 · Journal of the International AIDS Society
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