Author
Timothy K. Thomas
Other affiliations: Kenya Medical Research Institute
Bio: Timothy K. Thomas is an academic researcher from Centers for Disease Control and Prevention. The author has contributed to research in topics: Population & Medicine. The author has an hindex of 17, co-authored 30 publications receiving 901 citations. Previous affiliations of Timothy K. Thomas include Kenya Medical Research Institute.
Topics: Population, Medicine, Nevirapine, Breastfeeding, Breast feeding
Papers
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TL;DR: The Kisumu breastfeeding study (Kenya) was a single-arm trial that assessed the feasibility and safety of a triple-antiretroviral regimen to suppress maternal HIV load in late pregnancy.
Abstract: Background: Effective strategies are needed for the prevention of mother-to-child HIV transmission (PMTCT) in resourcelimited settings. The Kisumu Breastfeeding Study was a single-arm open label trial conducted between July 2003 and February 2009. The overall aim was to investigate whether a maternal triple-antiretroviral regimen that was designed to maximally suppress viral load in late pregnancy and the first 6 mo of lactation was a safe, well-tolerated, and effective PMTCT intervention. Methods and Findings: HIV-infected pregnant women took zidovudine, lamivudine, and either nevirapine or nelfinavir from 34–36 weeks’ gestation to 6 mo post partum. Infants received single-dose nevirapine at birth. Women were advised to breastfeed exclusively and wean rapidly just before 6 mo. Using Kaplan-Meier methods we estimated HIV-transmission and death rates from delivery to 24 mo. We compared HIV-transmission rates among subgroups defined by maternal risk factors, including baseline CD4 cell count and viral load. Among 487 live-born, singleton, or first-born infants, cumulative HIV-transmission rates at birth, 6 weeks, and 6, 12, and 24 mo were 2.5%, 4.2%, 5.0%, 5.7%, and 7.0%, respectively. The 24mo HIV-transmission rates stratified by baseline maternal CD4 cell count ,500 and $500 cells/mm 3 were 8.4% (95% confidence interval [CI] 5.8%–12.0%) and 4.1% (1.8%–8.8%), respectively (p=0.06); the corresponding rates stratified by baseline maternal viral load ,10,000 and $10,000 copies/ml were 3.0% (1.1%–7.8%) and 8.7% (6.1%–12.3%), respectively (p=0.01). None of the 12 maternal and 51 infant deaths (including two second-born infants) were attributed to antiretrovirals. The cumulative HIV-transmission or death rate at 24 mo was 15.7% (95% CI 12.7%–19.4%). Conclusions: This trial shows that a maternal triple-antiretroviral regimen from late pregnancy through 6 months of breastfeeding for PMTCT is safe and feasible in a resource-limited setting. These findings are consistent with those from other trials using maternal triple-antiretroviral regimens during breastfeeding in comparable settings. Trial registration: ClinicalTrials.gov NCT00146380 Please see later in the article for the Editors’ Summary.
161 citations
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TL;DR: Analysis of a substudy of the Kisumu breastfeeding trial reveals the emergence of HIV drug resistance in HIV-positive infants born to HIV-infected mothers treated with antiretroviral drugs.
Abstract: Background: Nevirapine and lamivudine given to mothers are transmitted to infants via breastfeeding in quantities sufficient to have biologic effects on the virus; this may lead to an increased risk of a breastfed infant’s development of resistance to maternal antiretrovirals. The Kisumu Breastfeeding Study (KiBS), a single-arm open-label prevention of motherto-child HIV transmission (PMTCT) trial, assessed the safety and efficacy of zidovudine, lamivudine, and either nevirapine or nelfinavir given to HIV-infected women from 34 wk gestation through 6 mo of breastfeeding. Here, we present findings from a KiBS trial secondary analysis that evaluated the emergence of maternal ARV-associated resistance among 32 HIVinfected breastfed infants. Methods and Findings: All infants in the cohort were tested for HIV infection using DNA PCR at multiple study visits during the 24 mo of the study, and plasma RNA viral load for all HIV-PCR–positive infants was evaluated retrospectively. Specimens from mothers and infants with viral load .1,000 copies/ml were tested for HIV drug resistance mutations. Overall, 32 infants were HIV infected by 24 mo of age, and of this group, 24 (75%) infants were HIV infected by 6 mo of age. Of the 24 infants infected by 6 mo, nine were born to mothers on a nelfinavir-based regimen, whereas the remaining 15 were born to mothers on a nevirapine-based regimen. All infants were also given single-dose nevirapine within 48 hours of birth. We detected genotypic resistance mutations in none of eight infants who were HIV-PCR positive by 2 wk of age (specimens from six infants were not amplifiable), for 30% (6/20) at 6 wk, 63% (14/22) positive at 14 wk, and 67% (16/24) at 6 mo post partum. Among the 16 infants with resistance mutations by 6 mo post partum, the common mutations were M184V and K103N, conferring resistance to lamivudine and nevirapine, respectively. Genotypic resistance was detected among 9/9 (100%) and 7/15 (47%) infected infants whose mothers were on nelfinavir and nevirapine, respectively. No mutations were detected among the eight infants infected after the breastfeeding period (age 6 mo). Conclusions: Emergence of HIV drug resistance mutations in HIV-infected infants occurred between 2 wk and 6 mo post partum, most likely because of exposure to maternal ARV drugs through breast milk. Our findings may impact the choice of regimen for ARV treatment of HIV-infected breastfeeding mothers and their infected infants. Trial Registration: ClinicalTrials.gov NCT00146380 Please see later in the article for the Editors’ Summary.
104 citations
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TL;DR: Lamivudine and nevirapine, but not zidovudine, are transferred to infants via breast milk in biologically significant concentrations, and the extent and effect of infant drug exposure via breasts must be well understood in order to evaluate the benefits and risks of maternal antiretroviral use during lactation.
Abstract: There are limited data describing the concentrations of zidovudine, lamivudine, and nevirapine in nursing infants as a result of transfer via breast milk. The Kisumu Breastfeeding Study is a phase IIb open-label trial of prenatal, intrapartum, and postpartum maternal treatment with zidovudine, lamivudine, and nevirapine from 34 weeks of gestation to 6 months postpartum. In a pharmacokinetic substudy, maternal plasma, breast milk, and infant dried blood spots were collected for drug assay on the day of delivery and at 2, 6, 14, and 24 weeks after delivery. Sixty-seven mother-infant pairs were enrolled. The median concentrations in breast milk of zidovudine, lamivudine, and nevirapine during the study period were 14 ng/ml, 1,214 ng/ml, and 4,546 ng/ml, respectively. Zidovudine was not detectable in any infant plasma samples obtained after the day of delivery, while the median concentrations in infant plasma samples from postpartum weeks 2, 6, and 14 were 67 ng/ml, 32 ng/ml, and 24 ng/ml for lamivudine and 987 ng/ml, 1,032 ng/ml, and 734 ng/ml for nevirapine, respectively. Therefore, lamivudine and nevirapine, but not zidovudine, are transferred to infants via breast milk in biologically significant concentrations. The extent and effect of infant drug exposure via breast milk must be well understood in order to evaluate the benefits and risks of maternal antiretroviral use during lactation.
102 citations
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TL;DR: Hematological and biochemistry reference values from African population differ from those derived from a North American population, showing the need to develop region-specific reference values.
Abstract: Background: There is need for locally-derived age-specific clinical laboratory reference ranges of healthy Africans in subSaharan Africa. Reference values from North American and European populations are being used for African subjects despite previous studies showing significant differences. Our aim was to establish clinical laboratory reference values for African adolescents and young adults that can be used in clinical trials and for patient management. Methods and Findings: A panel of 298, HIV-seronegative individuals aged 13–34 years was randomly selected from participants in two population-based cross-sectional surveys assessing HIV prevalence and other sexually transmitted infections in western Kenya. The adolescent (,18 years)-to-adults ($18 years) ratio and the male-to-female ratio was 1:1. Median and 95% reference ranges were calculated for immunohematological and biochemistry values. Compared with U.Sderived reference ranges, we detected lower hemoglobin (HB), hematocrit (HCT), red blood cells (RBC), mean corpuscular volume (MCV), neutrophil, glucose, and blood urea nitrogen values but elevated eosinophil and total bilirubin values. Significant gender variation was observed in hematological parameters in addition to T-bilirubin and creatinine indices in all age groups, AST in the younger and neutrophil, platelet and CD4 indices among the older age group. Age variation was also observed, mainly in hematological parameters among males. Applying U.S. NIH Division of AIDS (DAIDS) toxicity grading to our results, 40% of otherwise healthy study participants were classified as having an abnormal laboratory parameter (grade 1–4) which would exclude them from participating in clinical trials. Conclusion: Hematological and biochemistry reference values from African population differ from those derived from a North American population, showing the need to develop region-specific reference values. Our data also show variations in hematological indices between adolescent and adult males which should be considered when developing reference ranges. This study provides the first locally-derived clinical laboratory reference ranges for adolescents and young adults in western Kenya.
80 citations
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TL;DR: A significant gap exists between future FP intentions and current FP practices, and integration of individual and couple FP services into routine HIV care, treatment and support services is needed in order to avoid unintended pregnancies and to prevent mother-to-child HIV transmission.
Abstract: Background: Preventing unintended pregnancies among HIV-positive women through family planning (FP) reduces pregnancy-related morbidity and mortality, decreases the number of pediatric HIV infections, and has also proven to be a cost-effective way to prevent mother-to-child HIV transmission. A key element of a comprehensive HIV prevention agenda, aimed at avoiding unintended pregnancies, is recognizing the attitudes towards FP among HIV-positive women and their spouse or partner. In this study, we analyze FP attitudes among HIV-infected pregnant women enrolled in a PMTCT clinical trial in Western Kenya. Methods and Findings: Baseline data were collected on 522 HIV-positive pregnant women using structured questionnaires. Associations between demographic variables and the future intention to use FP were examined using Fisher’s exact tests and permutation tests. Most participants (87%) indicated that they intended to use FP. However, only 8% indicated condoms as a preferred FP method, and 59% of current pregnancies were unintended. Factors associated with positive intentions to use FP were: marital status (p=0.04), having talked to their spouse or partner about FP (p,0.001), perceived spouse or partner approval of FP (p,0.001), previous use of a FP method (p=0.006), attitude toward the current pregnancy (p=0.02), disclosure of a sexually transmitted infection (STI) diagnosis (p=0.03) and ethnic group (p=0.03). Conclusion: A significant gap exists between future FP intentions and current FP practices. Support and approval by the spouse or partner are key elements of FP intentions. Counseling services should be offered to both members of a couple to increase FP use, especially given the high number of unplanned pregnancies among HIV-positive women. Condoms should be promoted as part of a dual use method for HIV and STI prevention and for contraception. Integration of individual and couple FP services into routine HIV care, treatment and support services is needed in order to avoid unintended pregnancies and to prevent mother-to-child HIV transmission.
51 citations
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TL;DR: Male circumcision significantly reduces the risk of HIV acquisition in young men in Africa and should be integrated with other HIV preventive interventions and provided as expeditiously as possible.
1,692 citations
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TL;DR: Aasld Guidelines for Treatment of Chronic Hepatitis B Norah Terrault;Natalie Bzowej;Kyong-Mi Chang;Jessica Hwang;Maureen Jonas;Hassan Murad; Hepatology
1,596 citations
01 Jan 2016
TL;DR: The logistic regression a self learning text is universally compatible with any devices to read and is available in the book collection an online access to it is set as public so you can get it instantly.
Abstract: Thank you very much for downloading logistic regression a self learning text. As you may know, people have search hundreds times for their favorite books like this logistic regression a self learning text, but end up in malicious downloads. Rather than reading a good book with a cup of tea in the afternoon, instead they are facing with some infectious bugs inside their desktop computer. logistic regression a self learning text is available in our book collection an online access to it is set as public so you can get it instantly. Our digital library spans in multiple countries, allowing you to get the most less latency time to download any of our books like this one. Merely said, the logistic regression a self learning text is universally compatible with any devices to read.
999 citations
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TL;DR: Applied Regression Analysis Bibliography Update 2000–2001,” Communications in Statistics: Theory and Methods, 2051– 2075.
Abstract: Christensen, R. (2002), Plane Answers to Complex Questions: The Theory of Linear Models (3rd ed.), New York: Springer-Verlag. Crocker, D. C. (1980), Review of Linear Regression Analysis, by G. A. F. Seber, Technometrics, 22, 130. Datta, B. N. (1995), Numerical Linear Algebra and Applications, Paci c Grove, CA: Brooks/Cole. Draper, N. R. (2002), “Applied Regression Analysis Bibliography Update 2000–2001,” Communications in Statistics: Theory and Methods, 2051– 2075. Golub, G. H., and Van Loan, C. F. (1996), Matrix Computations (3rd ed.), Baltimore, MD: Johns Hopkins University Press. Graybill, F. A. (2000), Theory and Application of the Linear Model, Paci c Grove, CA: Brooks/Cole. Hocking, R. R. (2003), Methods and Applications of Linear Models: Regression and the Analysis of Variance (2nd ed.), New York: Wiley. Porat, B. (1993), Digital Processing of Random Signals, Englewood Cliffs, NJ: Prentice-Hall. Ravishanker, N., and Dey, D. K. (2002), A First Course in Linear Model Theory, Boca Raton, FL: Chapman and Hall/CRC. White, H. (1984), Asymptotic Theory for Econometricians, Orlando, FL: Academic Press.
862 citations
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TL;DR: The role of immune activation in the pathogenesis of non-AIDS clinical events (major causes of morbidity and mortality in people on antiretroviral therapy) is receiving increased recognition and breakthroughs in the prevention of HIV important to public health include male medical circumcision.
687 citations