The factors that control body composition in disease are uncertain. We planned to compare the rel... more The factors that control body composition in disease are uncertain. We planned to compare the relative influences of HIV infection, sex, race, and environment on body composition. We analyzed results of body composition studies performed by bioelectrical impedance analysis in 1415 adults from 2 cohorts: white and African American men and women from the United States, and African men and women (279 HIV-infected and 1136 control). The effects of sex and HIV infection on weight, body cell mass, and fat-free mass were analyzed by using both unadjusted and age-, weight-, and height-adjusted data. Control men weighed more and had more body cell mass and fat-free mass than did control women, although control women had more fat. The strongest correlates with body composition were height and weight, followed by sex. HIV infection, age, environment, and race. Control men and women weighed more and had more body cell mass, fat-free mass, and fat than did HIV-infected men. However, differences ...
Adherence to zidovudine (ZDV) prophylaxis among 78 pregnant HIV-infected women was measured with ... more Adherence to zidovudine (ZDV) prophylaxis among 78 pregnant HIV-infected women was measured with 2 physiologic markers. Long-term adherence was measured with blood assays for macrocytosis, a clinical indicator of ZDV use; 53 women (67.9%) were adherent. Short-term adherence was measured with urine assays for ZDV; 48 women (61.5%) were adherent. Comparison of urine assay and interview data indicated that 29%
Acknowledgments : Grant No. HRN-A-00-96-90010-00 from the U.S. Agency for International Developme... more Acknowledgments : Grant No. HRN-A-00-96-90010-00 from the U.S. Agency for International Development (USAID) provided financial support for the research reported in this paper. The authors thank Dr. William MacLeod for his comments,on earlier drafts of the paper.
Human milk oligosaccharides (HMOs) have multiple immunomodulatory functions that influence child ... more Human milk oligosaccharides (HMOs) have multiple immunomodulatory functions that influence child health. In this study we investigated whether HMO composition influences survival to 2 y of age in HIV-infected and HIV-exposed, uninfected (HEU) children during and after breastfeeding. In the context of an early weaning trial in 958 HIV-infected women in Lusaka, Zambia, we conducted a nested case-cohort analysis of mortality to 2 y of age among 103 HIV-infected and 143 HEU children. Breast-milk samples collected at 1 mo postpartum were analyzed for HMO content. Samples were selected to include mothers of all HIV-infected children detected by 6 wk of age, of whom 63 died at <2 y of age; mothers of all HEU children who died at <2 y of age (n = 66); and a random sample of 77 HEU survivors. Associations before and after weaning in HIV-infected and HEU infants separately were investigated by using Cox models. Among HEU children, higher maternal breast-milk concentrations of 2-linked fucosylated HMOs [2'-fucosyllactose and lacto-N-fucopentaose (LNFP) I] (HR: 0.33; 95% CI: 0.14, 0.74) as well as non-2-linked fucosylated HMOs (3-fucosyllactose and LNFP II/III; HR: 0.28; 95% CI: 0.13, 0.67) were significantly associated with reduced mortality during, but not after, breastfeeding after adjustment for confounders. Breastfeeding was protective against mortality only in HEU children with high concentrations of fucosylated HMOs. Among HIV-infected children, no consistent associations between HMOs and mortality were observed, but breastfeeding was protective against mortality. The oligosaccharide composition of breast milk may explain some of the benefits of breastfeeding in HEU children. HIV infection may modulate some of the consequences of HMOs on child survival.
Summary: α-Defensins have been observed to have anti-HIV activity but have not been investigated ... more Summary: α-Defensins have been observed to have anti-HIV activity but have not been investigated in relation to mother-to-child HIV transmission. We measured the concentration of α-defensins in breast milk of HIV-positive mothers and tested whether the concentrations were associated with HIV transmission. A nested case-control study of 32 HIV-positive women who transmitted HIV to their infants and 52 randomly selected
Background: Couple counseling has been promoted as a strategy to improve uptake of interventions ... more Background: Couple counseling has been promoted as a strategy to improve uptake of interventions to prevent mother-to-child HIV transmission (pMTCT) and to minimize adverse social outcomes associated with disclosure of HIV status.
The distribution and stability of human immunodeficiency virus type 1 (HIV-1) in breast milk (BM)... more The distribution and stability of human immunodeficiency virus type 1 (HIV-1) in breast milk (BM) components remain largely unknown. Inhibitory effects, if any, of BM on HIV RNA and DNA PCR amplification are poorly understood. We have addressed these issues by using virus-spiked BM samples from HIV-negative women. BM samples from HIV-negative women were spiked with HIV-1 virions or cells containing a single integrated copy of HIV DNA (8E5/LAV). After incubation under different experimental conditions, viral RNA was detected by the Roche Amplicor UltraSensitive assay in whole-milk, skim milk, and lipid fractions. We found excellent correlation between HIV-1 input copy and recovery in whole milk (r ؍ 0.965, P < 0.0001), skim milk (r ؍ 0.972, P < 0.0001), and the lipid fraction (r ؍ 0.905, P < 0.001). PCR inhibition was observed in less than 10% of the spiked samples. Similar levels of inhibition were noted in BM samples collected from HIV-infected women. HIV proviral DNA was detected in BM samples using real-time PCR (linear correlation between the threshold cycle versus log DNA copy number, >0.982). The effects of incubation duration and temperature and repeated freeze-thaw cycles on HIV RNA recovery were analyzed. HIV RNA levels were remarkably stable in whole milk after three freeze-thaw cycles and for up to 30 h at room temperature. Our findings improve the understanding of the dynamics of HIV detection in BM and the conditions for BM sample collection, storage, and processing.
The effect of abrupt weaning, advocated as a safe transition from exclusive breastfeeding in HIV-... more The effect of abrupt weaning, advocated as a safe transition from exclusive breastfeeding in HIV-exposed children, on the quantity of HIV viral load in breast milk (BMVL) is not known.
Background: We previously reported no benefit of early weaning for HIV-free survival of children ... more Background: We previously reported no benefit of early weaning for HIV-free survival of children born to HIV-infected mothers in intent-to-treat analyses. Since early weaning was poorly accepted, we conducted a secondary analysis to investigate whether beneficial effects may have been hidden.
Background: Breast milk transmission of HIV-1 remains a major route of pediatric infection. Defin... more Background: Breast milk transmission of HIV-1 remains a major route of pediatric infection. Defining the characteristics of viral variants to which breastfeeding infants are exposed is important for understanding the genetic bottleneck that occurs in the majority of mother-to-child transmissions. The blood-milk epithelial barrier markedly restricts the quantity of HIV-1 in breast milk, even in the absence of antiretroviral drugs. The basis of this restriction and the genetic relationship between breast milk and blood variants are not well established.
In a cluster randomized trial, Kojo Yeboah-Antwi and colleagues find that integrated management o... more In a cluster randomized trial, Kojo Yeboah-Antwi and colleagues find that integrated management of malaria and pneumonia in children under five by community health workers is both feasible and effective.
In March 2012, The Elizabeth Glaser Pediatric AIDS Foundation trained maternal and child health w... more In March 2012, The Elizabeth Glaser Pediatric AIDS Foundation trained maternal and child health workers in Southern Province of Zambia to use a new rapid syphilis test (RST) during routine antenatal care. A recent study by Bonawitz et al. (2014) evaluated the impact of this roll out in Kalomo District. This paper estimates the costs and cost-effectiveness from the provider's perspective under the actual conditions observed during the first year of the RST roll out. Information on materials used and costs were extracted from program records. A decision-analytic model was used to evaluate the costs (2012 USD) and cost-effectiveness. Basic parameters needed for the model were based on the results from the evaluation study. During the evaluation study, 62% of patients received a RST, and 2.8% of patients tested were positive (and 10.4% of these were treated). Even with very high RST sensitivity and specificity (98%), true prevalence of active syphilis would be substantially less (es...
Severe pneumonia in children under 5 years of age continues to be an important clinical entity wi... more Severe pneumonia in children under 5 years of age continues to be an important clinical entity with treatment failure rates as high as 20%. Where severe pneumonias are common, predictive tools for treatment failure like chest radiography and pulse oximetry are not available or affordable. Thus, there is a need for development of simple, accurate and inexpensive clinical tools for prediction of treatment failure. Using clinical, chest radiographic and pulse oximetry data from 1702 children recruited in the Amoxicillin Penicillin Pneumonia International Study (APPIS) trial we developed and validated a simple clinical tool. For development, a randomly derived development sample (n = 889) was used. The tool which was based on the results of multivariate logistic regression models was validated on a separate sample of 813 children. The derived clinical tool in its final form contained three clinical predictors: age of child, excess age-specific respiratory rate at baseline and at 24 hr of hospitalization. This tool had a 70% and 66% predictive accuracy in the development and validation samples, respectively. The tool is presented as an easy-to-use nomogram. It is possible to predict the likelihood of treatment failure in children with severe pneumonia based on clinical features that are simple and inexpensive to measure.
OBJECTIVE.In settings with limited assessment tools, we sought to determine whether early clinica... more OBJECTIVE.In settings with limited assessment tools, we sought to determine whether early clinical signs and symptoms and blood oxygen saturation would predict amoxicillin treatment failure in children with severe pneumonia (as defined by the World Health Organization). METHODS.Data were from a previously reported, multinational trial of orally admin- istered amoxicillin versus injectable penicillin for the treatment of World Health Organization-defined
The factors that control body composition in disease are uncertain. We planned to compare the rel... more The factors that control body composition in disease are uncertain. We planned to compare the relative influences of HIV infection, sex, race, and environment on body composition. We analyzed results of body composition studies performed by bioelectrical impedance analysis in 1415 adults from 2 cohorts: white and African American men and women from the United States, and African men and women (279 HIV-infected and 1136 control). The effects of sex and HIV infection on weight, body cell mass, and fat-free mass were analyzed by using both unadjusted and age-, weight-, and height-adjusted data. Control men weighed more and had more body cell mass and fat-free mass than did control women, although control women had more fat. The strongest correlates with body composition were height and weight, followed by sex. HIV infection, age, environment, and race. Control men and women weighed more and had more body cell mass, fat-free mass, and fat than did HIV-infected men. However, differences ...
Adherence to zidovudine (ZDV) prophylaxis among 78 pregnant HIV-infected women was measured with ... more Adherence to zidovudine (ZDV) prophylaxis among 78 pregnant HIV-infected women was measured with 2 physiologic markers. Long-term adherence was measured with blood assays for macrocytosis, a clinical indicator of ZDV use; 53 women (67.9%) were adherent. Short-term adherence was measured with urine assays for ZDV; 48 women (61.5%) were adherent. Comparison of urine assay and interview data indicated that 29%
Acknowledgments : Grant No. HRN-A-00-96-90010-00 from the U.S. Agency for International Developme... more Acknowledgments : Grant No. HRN-A-00-96-90010-00 from the U.S. Agency for International Development (USAID) provided financial support for the research reported in this paper. The authors thank Dr. William MacLeod for his comments,on earlier drafts of the paper.
Human milk oligosaccharides (HMOs) have multiple immunomodulatory functions that influence child ... more Human milk oligosaccharides (HMOs) have multiple immunomodulatory functions that influence child health. In this study we investigated whether HMO composition influences survival to 2 y of age in HIV-infected and HIV-exposed, uninfected (HEU) children during and after breastfeeding. In the context of an early weaning trial in 958 HIV-infected women in Lusaka, Zambia, we conducted a nested case-cohort analysis of mortality to 2 y of age among 103 HIV-infected and 143 HEU children. Breast-milk samples collected at 1 mo postpartum were analyzed for HMO content. Samples were selected to include mothers of all HIV-infected children detected by 6 wk of age, of whom 63 died at &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;2 y of age; mothers of all HEU children who died at &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;2 y of age (n = 66); and a random sample of 77 HEU survivors. Associations before and after weaning in HIV-infected and HEU infants separately were investigated by using Cox models. Among HEU children, higher maternal breast-milk concentrations of 2-linked fucosylated HMOs [2&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;-fucosyllactose and lacto-N-fucopentaose (LNFP) I] (HR: 0.33; 95% CI: 0.14, 0.74) as well as non-2-linked fucosylated HMOs (3-fucosyllactose and LNFP II/III; HR: 0.28; 95% CI: 0.13, 0.67) were significantly associated with reduced mortality during, but not after, breastfeeding after adjustment for confounders. Breastfeeding was protective against mortality only in HEU children with high concentrations of fucosylated HMOs. Among HIV-infected children, no consistent associations between HMOs and mortality were observed, but breastfeeding was protective against mortality. The oligosaccharide composition of breast milk may explain some of the benefits of breastfeeding in HEU children. HIV infection may modulate some of the consequences of HMOs on child survival.
Summary: α-Defensins have been observed to have anti-HIV activity but have not been investigated ... more Summary: α-Defensins have been observed to have anti-HIV activity but have not been investigated in relation to mother-to-child HIV transmission. We measured the concentration of α-defensins in breast milk of HIV-positive mothers and tested whether the concentrations were associated with HIV transmission. A nested case-control study of 32 HIV-positive women who transmitted HIV to their infants and 52 randomly selected
Background: Couple counseling has been promoted as a strategy to improve uptake of interventions ... more Background: Couple counseling has been promoted as a strategy to improve uptake of interventions to prevent mother-to-child HIV transmission (pMTCT) and to minimize adverse social outcomes associated with disclosure of HIV status.
The distribution and stability of human immunodeficiency virus type 1 (HIV-1) in breast milk (BM)... more The distribution and stability of human immunodeficiency virus type 1 (HIV-1) in breast milk (BM) components remain largely unknown. Inhibitory effects, if any, of BM on HIV RNA and DNA PCR amplification are poorly understood. We have addressed these issues by using virus-spiked BM samples from HIV-negative women. BM samples from HIV-negative women were spiked with HIV-1 virions or cells containing a single integrated copy of HIV DNA (8E5/LAV). After incubation under different experimental conditions, viral RNA was detected by the Roche Amplicor UltraSensitive assay in whole-milk, skim milk, and lipid fractions. We found excellent correlation between HIV-1 input copy and recovery in whole milk (r ؍ 0.965, P < 0.0001), skim milk (r ؍ 0.972, P < 0.0001), and the lipid fraction (r ؍ 0.905, P < 0.001). PCR inhibition was observed in less than 10% of the spiked samples. Similar levels of inhibition were noted in BM samples collected from HIV-infected women. HIV proviral DNA was detected in BM samples using real-time PCR (linear correlation between the threshold cycle versus log DNA copy number, >0.982). The effects of incubation duration and temperature and repeated freeze-thaw cycles on HIV RNA recovery were analyzed. HIV RNA levels were remarkably stable in whole milk after three freeze-thaw cycles and for up to 30 h at room temperature. Our findings improve the understanding of the dynamics of HIV detection in BM and the conditions for BM sample collection, storage, and processing.
The effect of abrupt weaning, advocated as a safe transition from exclusive breastfeeding in HIV-... more The effect of abrupt weaning, advocated as a safe transition from exclusive breastfeeding in HIV-exposed children, on the quantity of HIV viral load in breast milk (BMVL) is not known.
Background: We previously reported no benefit of early weaning for HIV-free survival of children ... more Background: We previously reported no benefit of early weaning for HIV-free survival of children born to HIV-infected mothers in intent-to-treat analyses. Since early weaning was poorly accepted, we conducted a secondary analysis to investigate whether beneficial effects may have been hidden.
Background: Breast milk transmission of HIV-1 remains a major route of pediatric infection. Defin... more Background: Breast milk transmission of HIV-1 remains a major route of pediatric infection. Defining the characteristics of viral variants to which breastfeeding infants are exposed is important for understanding the genetic bottleneck that occurs in the majority of mother-to-child transmissions. The blood-milk epithelial barrier markedly restricts the quantity of HIV-1 in breast milk, even in the absence of antiretroviral drugs. The basis of this restriction and the genetic relationship between breast milk and blood variants are not well established.
In a cluster randomized trial, Kojo Yeboah-Antwi and colleagues find that integrated management o... more In a cluster randomized trial, Kojo Yeboah-Antwi and colleagues find that integrated management of malaria and pneumonia in children under five by community health workers is both feasible and effective.
In March 2012, The Elizabeth Glaser Pediatric AIDS Foundation trained maternal and child health w... more In March 2012, The Elizabeth Glaser Pediatric AIDS Foundation trained maternal and child health workers in Southern Province of Zambia to use a new rapid syphilis test (RST) during routine antenatal care. A recent study by Bonawitz et al. (2014) evaluated the impact of this roll out in Kalomo District. This paper estimates the costs and cost-effectiveness from the provider's perspective under the actual conditions observed during the first year of the RST roll out. Information on materials used and costs were extracted from program records. A decision-analytic model was used to evaluate the costs (2012 USD) and cost-effectiveness. Basic parameters needed for the model were based on the results from the evaluation study. During the evaluation study, 62% of patients received a RST, and 2.8% of patients tested were positive (and 10.4% of these were treated). Even with very high RST sensitivity and specificity (98%), true prevalence of active syphilis would be substantially less (es...
Severe pneumonia in children under 5 years of age continues to be an important clinical entity wi... more Severe pneumonia in children under 5 years of age continues to be an important clinical entity with treatment failure rates as high as 20%. Where severe pneumonias are common, predictive tools for treatment failure like chest radiography and pulse oximetry are not available or affordable. Thus, there is a need for development of simple, accurate and inexpensive clinical tools for prediction of treatment failure. Using clinical, chest radiographic and pulse oximetry data from 1702 children recruited in the Amoxicillin Penicillin Pneumonia International Study (APPIS) trial we developed and validated a simple clinical tool. For development, a randomly derived development sample (n = 889) was used. The tool which was based on the results of multivariate logistic regression models was validated on a separate sample of 813 children. The derived clinical tool in its final form contained three clinical predictors: age of child, excess age-specific respiratory rate at baseline and at 24 hr of hospitalization. This tool had a 70% and 66% predictive accuracy in the development and validation samples, respectively. The tool is presented as an easy-to-use nomogram. It is possible to predict the likelihood of treatment failure in children with severe pneumonia based on clinical features that are simple and inexpensive to measure.
OBJECTIVE.In settings with limited assessment tools, we sought to determine whether early clinica... more OBJECTIVE.In settings with limited assessment tools, we sought to determine whether early clinical signs and symptoms and blood oxygen saturation would predict amoxicillin treatment failure in children with severe pneumonia (as defined by the World Health Organization). METHODS.Data were from a previously reported, multinational trial of orally admin- istered amoxicillin versus injectable penicillin for the treatment of World Health Organization-defined
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