Browsing by Author "Semba, Richard D."
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Item Associations of Chemokine Receptor Polymorphisms With HIV-1 Mother-to-Child Transmission in Sub-Saharan Africa: Possible Modulation of Genetic Effects by Antiretrovirals(Journal of acquired immune deficiency syndromes, 1999) Singh, Kumud K.; Hughes, Michael D.; Chen, Jie; Phiri, Kelesitse; Rousseau, Christine; Kuhn, Louise; Coutsoudis, Anna; Jackson, J. Brooks; Guay, Laura A.; Musoke, Philippa; Mmiro, Francis; Semba, Richard D.; Spector, Stephen A.Background—HIV-1 mother-to-child transmission (MTCT) remains an important route of infection in sub-Saharan Africa. Methods—Genetic variants in CCR5 promoter, CCR2, CX3CR1, and Stromal cell-derived factor-1 (SDF-1) genes were determined in 980 infants from sub-Saharan Africa using real-time polymerase chain reaction to determine association with MTCT. Results—In antiretroviral-naive mother–infant pairs (n = 637), CCR5 promoter polymorphisms at positions 59029: A allele vs. G/G [odds ratio (OR): 1.61, 95% confidence interval (CI): 1.04 to 2.48; P = 0.032] and 59356: T allele vs. C/C (OR: 0.63, 95% CI: 0.41 to 0.96; P = 0.033) and CCR2-180: G allele vs. A/A (OR: 3.32, 95% CI: 1.13 to 9.73; P = 0.029) were associated with risk of MTCT. Treatment of HIV-1–infected mothers and infants with single-dose nevirapine or perinatal zidovudine altered but did not eliminate the association of genetic variants with MTCT. Conclusions—CCR5 promoter, CCR2, and CX3CR1 polymorphisms were associated with risk of MTCT likely through their role as an HIV-1 coreceptor or by modulating the early immune response. genetics may continue to alter MTCT when short-course interventions that only partially suppress virus are used. These findings will need to be confirmed in validation cohorts with a large number of infected infants.Item Associations of Chemokine Receptor Polymorphisms With HIV-1 Mother-to-Child Transmission in Sub-Saharan Africa: Possible Modulation of Genetic Effects by Antiretrovirals(Journal of acquired immune deficiency syndromes, 2008) Singh, Kumud K.; Hughes, Michael D.; Chen, Jie; Phiri, Kelesitse; Rousseau, Christine; Kuhn, Louise; Coutsoudis, Anna; Jackson, J. Brooks; Guay, Laura A.; Musoke, Philippa; Mmiro, Francis; Semba, Richard D.; Spector, Stephen A.HIV-1 mother-to-child transmission (MTCT) remains an important route of infection in sub-Saharan Africa.Genetic variants in CCR5 promoter, CCR2, CX3CR1, and Stromal cell-derived factor-1 (SDF-1) genes were determined in 980 infants from sub-Saharan Africa using real-time polymerase chain reaction to determine association with MTCT.In antiretroviral-naive mother–infant pairs (n = 637), CCR5 promoter polymorphisms at positions 59029: A allele vs. G/G [odds ratio (OR): 1.61, 95% confidence interval (CI): 1.04 to 2.48; P = 0.032] and 59356: T allele vs. C/C (OR: 0.63, 95% CI: 0.41 to 0.96; P = 0.033) and CCR2-180: G allele vs. A/A (OR: 3.32, 95% CI: 1.13 to 9.73; P = 0.029) were associated with risk of MTCT. Treatment of HIV-1–infected mothers and infants with single-dose nevirapine or perinatal zidovudine altered but did not eliminate the association of genetic variants with MTCT.CCR5 promoter, CCR2, and CX3CR1 polymorphisms were associated with risk of MTCT likely through their role as an HIV-1 coreceptor or by modulating the early immune response. Host genetics may continue to alter MTCT when short-course interventions that only partially suppress virus are used. These findings will need to be confirmed in validation cohorts with a large number of infected infants.Item Effect Of Periodic Vitamin A Supplementation On Mortality And Morbidity Of Human Immunodeficiency Virus–Infected Children In Uganda: A Controlled Clinical Trial(Nutrition, 2005) Semba, Richard D.; Ndugwa, Christopher; Perry, Robert T.; Clark, Tamara D.; Jackson, J. Brooks; Melikian, George; Tielsch, James; Mmiro, Francis; F.R.C.O.G.We investigated whether vitamin A supplementation would decrease mortality and morbidity rates in children infected with the human immunodeficiency virus (HIV).We conducted a randomized, double-blind, placebo-controlled clinical trial at Mulago Hospital, a large hospital that serves the urban and semiurban populations of Kampala, Uganda. One hundred eighty-one HIV-infected children were enrolled at 6 mo and randomized to receive vitamin A supplementation, 60 mg retinol equivalent, or placebo every 3 mo from ages 15 to 36 mo. Morbidity was assessed through a 7-d morbidity history every 3 mo, and vital events were measured. Children received daily trimethoprim-sulfamethoxazole prophylactic therapy.After age 15 mo, children were followed for a median of 17.8 mo (interquartile range = 11.1 to 21.0 mo). The trial was stopped when there was a new policy to implement a program of mass supplementation of vitamin A in the country. Mortality rates among 87 children in the vitamin A group and 94 children in the control group were 20.6% and 32.9%, respectively, yielding a relative risk of 0.54 (95% confidence interval, 0.30 to 0.98; P = 0.044) after adjusting for baseline weight-for-height Z score. Children who received vitamin A had lower modified point prevalences of persistent cough (odds ratio, 0.47; 95% confidence interval, 0.23 to 0.96; P = 0.038) and chronic diarrhea (odds ratio, 0.48; 95% confidence interval, 0.19 to 1.18; P = 0.11) and a shorter duration of ear discharge (P = 0.03). Vitamin A supplementation had no significant effect on modified point prevalences of fever, ear discharge, bloody stools, or hospitalizations.Vitamin A supplementation decreases mortality rate in HIV-infected children and should be considered in the care for these children in developing countries.Item Human Nutrition and Metabolism Severity of Human Immunodeficiency Virus Infection Is Associated with Decreased Phase Angle, Fat Mass and Body Cell Mass in Adults with Pulmonary Tuberculosis Infection in Uganda(Journal of Nutrition, 2001) Shah, Snehal; Whalen, Christopher; Kotler, Donald P.; Mayanja, Harriet; Namale, Alice; Melikian, George; Mugerwa, Roy; Semba, Richard D.Although coinfection with tuberculosis and human immunodeficiency virus (HIV) is emerging as a major problem in many developing countries, nutritional status has not been well characterized in adults with tuberculosis and HIV infection. We compared nutritional status between 261 HIV-positive and 278 HIV-negative adults with pulmonary tuberculosis in Kampala, Uganda, using anthropometry and bioelectrical impedance analysis. Among 163 HIV-positive and 199 HIV-negative men, intracellular water–to–extracellular water (ICW:ECW) ratio was 1.48 6 0.26 and 1.59 6 0.48 (P 5 0.006) and phase angle was 5.42 6 1.05 and 5.76 6 1.30 (P 5 0.009), respectively. Among 98 HIV-positive and 79 HIV-negative women, ICW:ECW was 1.19 6 0.16 and 1.23 6 0.15 (P 5 0.11) and phase angle was 5.35 6 1.27 and 5.43 6 0.93 (P 5 0.61), respectively. There were no significant differences in BMI, body cell mass, fat mass or fat-free mass between HIV-positive and HIV-negative adults. Among HIV-positive subjects, BMI, ICW:ECW, body cell mass, fat mass and phase angle were significantly lower among those with CD41 lymphocytes # 200 cells/ m L compared with those who had .200 cells/ m L. In sub- Saharan Africa, coinfection with pulmonary tuberculosis and HIV is associated with smaller body cell mass and intracellular water, but not fat-free mass, and by large differences in ICW:ECW and phase angleItem Iron Deficiency Anemia Is Highly Prevalent among Human Immunodeficiency Virus–Infected and Uninfected Infants in Uganda(The Journal of nutrition, 2002) Totin, Dana; Ndugwa, Christopher; Mmiro, Francis; Perry, Robert T.; Jackson, J. Brooks; Semba, Richard D.Although anemia is a common finding among human immunodeficiency (HIV)-infected infants in sub-Saharan Africa, the factors contributing to the pathogenesis of anemia have not been well characterized. We sought to characterize the relative contribution of iron deficiency and chronic disease to the anemia among infants. Hemoglobin, ferritin, erythropoietin, tumor necrosis factor-α (TNF-α), neopterin, CD4+ lymphocyte count and plasma HIV load were measured in 165 HIV-infected and 39 uninfected 9-mo-old infants seen in an outpatient pediatric clinic in Kampala, Uganda. Among HIV-infected and uninfected infants, the prevalence of anemia (hemoglobin < 110 g/L) was 90.9 and 76.9%, respectively (P = 0.015), and the prevalence of iron deficiency anemia (hemoglobin < 110 g/L and ferritin < 12 μg/L) was 44.3 and 45.4%, respectively (P = 0.92). The relatively higher prevalence of anemia among HIV-infected infants was attributed to the anemia of chronic disease. Among infants with and without iron deficiency, the fitted regression line was log10 plasma erythropoietin = 2.86 − 0.016 · hemoglobin, and log10 plasma erythropoietin = 4.11 − 0.028 · hemoglobin, respectively, with a difference in the slope of the regression lines between log10 erythropoietin and hemoglobin among infants with and without iron deficiency (P = 0.049). Infants in Uganda have an extremely high prevalence of anemia, and nearly half of the anemia is due to iron deficiency. The erythropoietin response to anemia appears to be upregulated among infants with iron deficiency.