Awewura Kwara

Alpert Medical School - Brown University, Providence, Rhode Island, United States

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Publications (39)93.59 Total impact

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    ABSTRACT: In Sub-Saharan Africa, increasing numbers of children with perinatally acquired HIV (PAHIV) are living into adolescence. These adolescents face numerous unique challenges such as parent illness/death and years of medication use. Optimizing care for these youth requires an understanding of the factors that contribute to physical health, psychological well-being, social relationships, and quality of life (QOL). This mixed methods study collected quantitative questionnaire data from 40 Ghanaian adolescents with PAHIV (50% female, 12-19 years old) who received care through an adolescent HIV clinic in Kumasi, Ghana. The study also presents results from qualitative interviews conducted with 20 adolescents. Results from quantitative analyses suggested that a significant number of participants were not virally suppressed (67%) and participants reported barriers to treatment adherence, limited social support, concerns about disclosure and HIV-related stigma, limited resources, and lower than expected QOL. Salient themes from the qualitative analyses included limited understanding of how HIV is transmitted, the interplay between food insecurity and treatment adherence and the need for developing safe relationships through which adolescents can discuss their illness without fear of accidental disclosure of their HIV status.
    No preview · Article · Dec 2015 · AIDS Care
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    ABSTRACT: Background The global burden of Hepatitis B virus (HBV) and HIV co-infection is enormous. The risk of developing cirrhosis and hepatocellular cancer is associated with HBV DNA levels. The main objective of the study was to determine proportion of Hepatitis B viremia in ART-naïve and ART-experienced co-infected Ghanaian patients and factors associated with HBV viremia after at least 36 weeks of lamivudine with or without tenofovir containing ART. Methods Hepatitis B and HIV co-infected patients who were ART-naïve or had received at least 9 months of lamivudine-containing ART were enrolled in a cross-sectional study at Korle-Bu Teaching Hospital. Demographic and clinical data were collected and samples obtained for Hepatitis B serology, liver function tests and HBV DNA. Factors associated with viremia were determined using univariate and multivariate logistic regression analysis. Results Of 3108 HIV-infected patients screened, 257 (8.3 %) were HBsAg-positive, of which 235 enrolled. Overall, 152 (64.7 %) were ART-experienced and 83 (35.3 %) were ART-naïve. Eighty-nine-percent of ART-naïve and 42.1 % of ART-experienced patients had HBV DNA > 20 IU/mL. In multivariate analysis of all patients, being ART-naïve (OR 10.1, 95 % CI 4.6 – 21.9) and elevated ALT (OR 3.7, 95 % CI 1.8 – 7.9) were associated with Hepatitis B viremia. In treatment experienced patients, elevated ALT (OR 4.8 CI 2.0 – 12.1) and male sex (OR 2.1, 95 % CI 1.0 – 4.2) were associated with Hepatitis B viremia. Conclusions Majority of ART-naïve (89 %) and 42 % of ART-experienced patients had detectable hepatitis B viremia > 20 IU/mL. An abnormal serum ALT was significantly associated with hepatitis B viremia in HBV and HIV co-infected patients irrespective of treatment status. Baseline and on-treatment ALT may be a useful non-invasive predictor of Hepatitis B viremia in resource-constrained countries in sub-Saharan Africa where infection is endemic and viral load tests are not widely available.
    Full-text · Article · Dec 2015 · BMC Infectious Diseases
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    ABSTRACT: Introduction: In resource-limited settings, men may face considerable barriers to accessing HIV care as early interventions tend to focus on antenatal care settings. Methods: We performed a retrospective chart review of all adult patients referred to Komfo Anokye Teaching Hospital HIV clinic in Kumasi, Ghana in 2011 to identify the differences in clinical and demographic variables by gender at presentation to care using two-sample t tests with adjusted variance and Wilcox rank sum tests for continuous variables and Pearson chi-squared tests for categorical variables. We also compared differences in clinical and demographic variables among men stratified by CD4 count at initiation of care in order to identify variables associated with later entry to care. Results: Demographically, men were more likely to be older (men age 42 vs. 37, p<0.01), have a greater number of dependent children (1.8 v. 1.5, p=0.04), to be living with or married to their partner (65.4% vs. 49.0%, p<0.01), and to have a higher level of education (tertiary education, 45.8% vs. 25.4%, p<0.01) than women. Clinically, men were more likely to have a lower CD4 count at entry to care (260 v. 311 cells/μL, p<0.01), to report clinical symptoms to the nurse during intake (p<0.01), and to have any history of alcohol use (p<0.01). Conclusion: Men in Ghana are accessing treatment at a later stage of their disease than women. Efforts to test and link men to care early should be intensified.
    No preview · Article · Oct 2015 · Pan African Medical Journal
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    ABSTRACT: Despite the success of prevention of mother-to-child transmission programs, transition to care in the postpartum period is vulnerable to being lost to care. The authors performed a 2-year retrospective study of postpartum HIV-infected patients at Komfo Anokye Teaching Hospital in Kumasi, Ghana. The outcome was classified as optimal follow-up, suboptimal follow-up, and loss to follow-up (LTFU). Univariate and multivariate analyses were used to identify factors associated with optimal retention. Follow-up was optimal in 66%, suboptimal in 16%, and LTFU in 18% of patients. The rate of LTFU was 22% among women diagnosed at pregnancy and 13% among those with known HIV diagnosis (P = .078). Adherence counseling (odds ratio [OR] 5.0, confidence interval [CI] 1.6-15.7; P = .006) and family planning (FP; OR 2.3, CI 1.0-5.3; P = .041) were predictive of optimal follow-up. At 1 year, only two-thirds of postpartum women remained in care. Investigating barriers to adherence counseling and FP may impact engagement in care among HIV-infected women. © The Author(s) 2015.
    No preview · Article · Aug 2015 · Journal of the International Association of Providers of AIDS Care
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    ABSTRACT: Background: Pharmacokinetic data on the first-line antituberculosis drugs using the World Health Organization (WHO) revised dosages for children are limited. We investigated the pharmacokinetics of these drugs in children who were mostly treated with revised dosages. Methods: Children with tuberculosis on first-line therapy for at least 4 weeks had blood samples collected at predose, 1, 2, 4, and 8 hours postdose. Drug concentrations were determined by validated liquid chromatography mass spectrometry methods, and pharmacokinetic parameters were calculated using noncompartmental analysis. Factors associated with plasma peak concentration (Cmax) and the area under the time-concentration curve 0-8 hours (AUC0-8h) of each drug was examined using univariate and multivariate analysis. Results: Of the 62 children, 32 (51.6%) were male, 29 (46.8%) were younger than 5 years old, and 28 (45.2%) had human immunodeficiency virus (HIV) coinfection. Three patients had undetectable pyrazinamide and ethambutol concentrations. The median (interquartile range) AUC0-8h for isoniazid was 17.7 (10.2-23.4) µg·h mL(-1), rifampin was 26.0 (15.3-36.1) µg·h mL(-1), pyrazinamide was 144.6 (111.5-201.2) µg·h mL(-1), and ethambutol was 6.7 (3.8-10.4) µg·h mL(-1). Of the children who received recommended weight-band dosages, 44/51 (86.3%), 46/56 (82.1%), 27/56 (48.2%), and 21/51 (41.2%) achieved target Cmax for isoniazid, pyrazinamide, ethambutol, and rifampin, respectively. In multivariate analysis, age, sex, HIV coinfection status, and drug dosage in milligrams per kilogram were associated with the drugs' plasma drug Cmax or AUC0-8h. Conclusions: The revised dosages appeared to be adequate for isoniazid and pyrazinamide, but not for rifampin or ethambutol in this population. Higher dosages of rifampin and ethambutol than currently recommended may be required in most children.
    Full-text · Article · May 2015
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    ABSTRACT: IntroductionUnderstanding sex differences in willingness to test and testing experience could aid the design of focus interventions to enhance uptake and engagement with care, treatment and support services. This study determined differences in perceived risk of acquiring HIV, willingness to test and HIV testing experience in an urban fishing community.MethodsA cross-sectional community survey was conducted in 2013 among men and women in two fishing communities (Chorkor and James Town) in Accra. In all, 554 subjects (¿18 years) were involved, 264 in Chorkor and 290 in James Town. Data on demographic characteristics, perceived risk for HIV and willingness to test for HIV and testing experience were collected with a structured questionnaire. Descriptive statistics and Chi square test were used for the analysis at 95% significant level, using SPSS version 21.ResultsOf 554 subjects, 329 (59.4%) were females, and median age was 32 years. Overall, only 91(40.4%) men and 118(35.9%) women perceived themselves to be at risk of acquiring HIV. A significant proportion of women were willing to test for HIV compared to men (86.3% vs. 80.0%, P¿=¿0.048). Women were more likely to have ever tested for HIV compared to men (42.2 % vs. 28.6%, P¿=¿0.001) and more women had tested within 12 months prior to survey than men (49.6% vs. 40.6%, P¿=¿0.230). Of the number who had tested for HIV infection, a higher proportion of men tested voluntarily 42(65.6%), while a higher proportion of women tested as part of healthcare service received 96(69.1%); (P =0.001; indicating women vs. men).Conclusion Sex differences in risk perception and willingness to test need more focused public education and behaviour change communication strategies to achieve high coverage. Community-based strategies could improve HIV testing among men whilst more access to testing in health settings should be available to women in these communities.
    Full-text · Article · Nov 2014 · International Journal for Equity in Health
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    ABSTRACT: Efavirenz is commonly used to treat patients coinfected with human immunodeficiency virus and tuberculosis. Previous clinical studies have observed paradoxically elevated efavirenz plasma concentrations in patients with the CYP2B6*6/*6 genotype (but not the CYP2B6*1/*1 genotype) during coadministration with the commonly used four-drug antituberculosis therapy. This study sought to elucidate the mechanism underlying this genotype-dependent drug-drug interaction. In vitro studies were conducted to determine whether one or more of the antituberculosis drugs (rifampin, isoniazid, pyrazinamide, or ethambutol) potently inhibit efavirenz 8-hydroxylation by CYP2B6 or efavirenz 7-hydroxylation by CYP2A6, the main mechanisms of efavirenz clearance. Time- and concentration-dependent kinetics of inhibition by the antituberculosis drugs were determined using genotyped human liver microsomes (HLMs) and recombinant CYP2A6, CYP2B6.1, and CYP2B6.6 enzymes. Although none of the antituberculosis drugs evaluated at up to 10 times clinical plasma concentrations were found to inhibit efavirenz 8-hydroxylation by HLMs, both rifampin (apparent inhibition constant [Ki] = 368 μM) and pyrazinamide (Ki = 637 μM) showed relatively weak inhibition of efavirenz 7-hydroxylation. Importantly, isoniazid demonstrated potent time-dependent inhibition of efavirenz 7-hydroxylation in both HLMs (inhibitor concentration required for half-maximal inactivation [KI] = 30 μM; maximal rate constant of inactivation [kinact] = 0.023 min−1) and recombinant CYP2A6 (KI = 15 μM; kinact = 0.024 min−1) and also formed a metabolite intermediate complex consistent with mechanism-based inhibition. Selective inhibition of the CYP2B6.6 allozyme could not be demonstrated for any of the antituberculosis drugs using either recombinant enzymes or CYP2B6*6 genotype HLMs. In conclusion, the results of this study identify isoniazid as the most likely perpetrator of this clinically important drug-drug interaction through mechanism-based inactivation of CYP2A6.
    Full-text · Article · May 2014 · Antimicrobial Agents and Chemotherapy
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    ABSTRACT: Efavirenz is widely prescribed for HIV-1 infection, and CYP2B6 polymorphisms 516G→T and 983T→C define efavirenz slow metabolizer genotypes. To identify genetic predictors of higher plasma efavirenz concentrations beyond these two common functional alleles, we characterized associations with mid-dosing interval efavirenz concentrations in 84 HIV-infected adults, all carrying two copies of these major loss-of-function CYP2B6 alleles. Study participants had been randomized to efavirenz-containing regimens in prospective clinical trials and had available plasma efavirenz assay data. Analyses focused on secondary metabolism pathway polymorphisms CYP2A6 -48T→G (rs28399433), UGT2B7 735A→G (rs28365062) and UGT2B7 802T→C (rs7439366). Exploratory analyses also considered 196 polymorphisms and 8 copy number variants in 41 drug metabolism/transport genes. Mid-dosing interval efavirenz concentrations at steady-state were obtained ≥8 h but <19 h post-dose. Linear regression was used to test for associations between polymorphisms and log-transformed efavirenz concentrations. Increased efavirenz concentrations were associated with CYP2A6 -48T→G in all subjects (P = 3.8 × 10(-4)) and in Black subjects (P = 0.027) and White subjects (P = 0.0011) analysed separately; and with UGT2B7 735 G/G homozygosity in all subjects (P = 0.006) and in Black subjects (P = 0.046) and White subjects (P = 0.062) analysed separately. In a multivariable model, CYP2A6 -48T→G and UGT2B7 735 G/G homozygosity remained significant (P < 0.05 for each). No additional polymorphisms or copy number variants were significantly associated with efavirenz concentrations. Among individuals with a CYP2B6 slow metabolizer genotype, CYP2A6 and possibly UGT2B7 polymorphisms contribute to even higher efavirenz concentrations.
    Full-text · Article · Apr 2014 · Journal of Antimicrobial Chemotherapy
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    ABSTRACT: To identify factors associated with variability in rifampin plasma pharmacokinetics and explore the relationship between rifampin pharmacokinetics and change in efavirenz plasma pharmacokinetics with rifampin coadministration. In this randomized, cross-over study, 12 healthy volunteers received either efavirenz 600 mg/day or efavirenz 600 mg with rifampin 600 mg/day for 8 days. After a washout period of at least 2 weeks, subjects crossed over to the alternate 8-day regimen. Samples were obtained for pharmacokinetic assessment on day 8 of each study cycle. Drugs concentrations were determined by a validated high-performance liquid chromatography. Pharmacokinetic parameters were calculated using noncompartmental analysis. Multivariate analysis was used to examine factors associated with rifampin pharmacokinetics. Spearman correlation analysis was used to investigate relationship between rifampin pharmacokinetics and change in efavirenz plasma pharmacokinetics with rifampin coadministration. Of 11 evaluable subjects, the median interquartile range, rifampin peak concentration (Cmax) , area under the concentration-time curve (AUC0-24 hour ), and weight-normalized clearance were 8.9 (7.3-13.8) μg/ml, 48.8 (29.6-67.4) μg·h/ml, and 0.19 (0.11-0.29) L/h/kg, respectively. Solute carrier organic anion transporter family member 1B1 (SLCO1B1) c.388A→G and SLCO1B1 c.463C→A polymorphisms jointly had significant effect on rifampin Cmax (R(2) = 0.75). Male sex and SLCO1B1 c.463C→A polymorphism together influenced rifampin AUC0-24 hour (R(2) = 0.52) and weight-normalized clearance (R(2) = 0.65). All four volunteers with rifampin Cmax less than 8 μg/ml (lower end of the normal range) had c.463CA genotype. Rifampin Cmax and AUC0-24 hour had no significant relationship with the efavirenz AUC0-24 hour ratio or weight-normalized clearance ratio in the presence versus absence of rifampin (p>0.05). Men with the SLCO1B1c.463CA genotype are at increased risk of lower rifampin plasma exposure. However, plasma rifampin concentrations did not correlate with the extent of induction of efavirenz clearance by rifampin during coadministration.
    No preview · Article · Mar 2014 · Pharmacotherapy

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  • No preview · Article · Jan 2014 · Advances in Infectious Diseases
  • A K Wilhelm · G Paci · M Lartey · A Kwara
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    ABSTRACT: Loss-to-follow-up (LTFU) during highly active antiretroviral therapy (HAART) may lead to treatment failure and increased mortality among HIV-infected patients. We investigated LTFU rate among HIV-infected patients at Korle-Bu Teaching Hospital (KBTH), and sought to identify sub-groups at-risk for treatment default in order to improve outcomes among high-risk patients. We conducted a cross-sectional retrospective chart review of 290 HIV-infected patients who initiated HAART at KBTH between January 1, 2008, and June 31, 2008. Patients were classified as LTFU if they did not return for regularly scheduled care within the study period. Chi-square and t-tests were used to compare demographic and clinical characteristics of patients continuing treatment and those who defaulted. Of the 290 patients who initiated HAART, 41 (14%) defaulted, and 7 (2%) died during the 18-month study period. The mean age was 38.7 ± 9.4 years and 184 (64%) were female. The mean baseline CD4 cell count was 183 ± 144 cells/µl. Age, gender, educational level, marital status, presence of opportunistic infection, body mass index, baseline CD4 cell count, WHO disease stage 3 or 4, HAART initiation while pregnant, incidence of poor adherence, and time to initiating HAART after clinic enrollment were not associated with treatment default (P> 0.05). A majority of patients initiating HAART in an urban Ghanaian clinic remained in care through one-year of follow-up. Patients who defaulted therapy were indistinguishable demographically and clinically from those who remained in care. Standardized pre-treatment adherence counseling sessions may have influenced the favorable outcomes.
    No preview · Article · Mar 2013 · West African journal of medicine
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    ABSTRACT: Compare the Plan B levonorgestrel (LNG) area under the concentration- time curve (AUC(12)) prior to and with efavirenz (EFV). Design. Prospective, open-label, single-arm, equivalence study. Healthy HIV-negative subjects underwent 12 hr intensive pharmacokinetic (PK) sampling following single dose LNG alone and after 14 days of EFV. Geometric means, Geometric Mean Ratios, and 90% confidence intervals (CI) are reported for PK Parameters. T-tests were utilized. Clinical parameters and liver function tests (LFTs) were assessed. 24 women enrolled and 21 completed the study. With EFV, LNG AUC(12) was reduced 56% (95% CI: 49%, 62%) from 42.9 to 17.8 ng∗hr/mL, and maximum concentration (C(max)) was reduced 41% (95% CI: 33%, 50%) from 8.4 to 4.6 ng/mL. LNG was well tolerated with no grade 3 or 4 treatment-related toxicities. EFV significantly reduced LNG exposures. Higher LNG doses may be required with EFV. These results reinforce the importance of effective contraception in women taking EFV.
    Full-text · Article · Feb 2012 · Infectious Diseases in Obstetrics and Gynecology
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    ABSTRACT: The objective of this study was to investigate risk factors associated with tuberculosis (TB) transmission that was caused by Mycobacterium tuberculosis strain MS0006 from 2004 to 2009 in Hinds County, Mississippi. DNA fingerprinting using spoligotyping, mycobacterial interspersed repetitive unit, and IS6110-based restriction fragment length polymorphism of culture-confirmed cases of TB was performed. Clinical and demographic factors associated with strain MS0006 were analyzed by univariate and multivariate analysis. Of the 144 cases of TB diagnosed during the study period, 117 were culture positive with fingerprints available. There were 48 different strains, of which 6 clustered strains were distributed among 74 patients. The MS0006 strain accounted for 46.2% of all culture-confirmed cases. Risk factors for having the MS0006 strain in a univariate analysis included homelessness, HIV co-infection, sputum smear negativity, tuberculin skin test negativity, and noninjectable drug use. Multivariate analysis identified homelessness (odds ratio 7.88, 95% confidence interval 2.90-21.35) and African American race (odds ratio 5.80, 95% confidence interval 1.37-24.55) as independent predictors of having TB caused by the MS0006 strain of M. tuberculosis. Our findings suggest that a majority of recently transmitted TB in the studied county was caused by the MS0006 strain. African American race and homelessness were significant risk factors for inclusion in the cluster. Molecular epidemiology techniques continue to provide in-depth analysis of disease transmission and play a vital role in effective contact tracing and interruption of ongoing transmission.
    Full-text · Article · Dec 2011 · Southern medical journal
  • Brian Temple · Awewura Kwara · Thomas Dobbs · Mike Holcomb
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    ABSTRACT: Background: HIV infection increases the risk of tuberculosis (TB) reactivation. Previously, we found that HIV, African American race and homelessness were risk factors for recently transmitted TB disease in one urban county. With molecular epidemiology we investigate TB among HIV seropositive (HIV +) and negative (HIV -) individuals in the state. Methods: This retrospective cohort study analyzed clinical and molecular strain data from the Mississippi State Department of Health and CDC respectively. Culture positive pulmonary TB cases, 2004-2010 were reviewed. Chi-squared or fisher exact analysis were used to describe categorical variables and t-test for continuous variables. Results: There were 595 culture positive cases from 2004-2010; 72% were males, 65% African Americans (AA), and 7% Hispanic; 13% were homeless with 21%alcohol and 12% non IV drug usage. HIV testing was available for 95%. There were 59(10%) HIV + of which 48/59(81%) were males, 47/52(90%) AA, 23/59(39%) homeless, 12/59(20%) and 19/59(32%) admitted to alcohol or non-IV drug usage, 32/59 lived in one county. HIV + were significantly younger (45.1 years ±8.8) than HIV - (51.5 years ± 19) (P=0.01). HIV + were more likely to be AA, non-homeless (p<0.001) and have non-cavitary chest x-ray findings (P<0.005); There were 90 Mycobacterium tuberculosis strains; 58 occurred in TB clusters, and 89% were of EuroAmerican Lineage. The dominant clusters in both HIV+ and HIV - were MS0006 and MS0003 respectively. In a sub-analysis of MS0006 strain, AA were more likely to be HIV + (p=0.04)); no statistical difference was noted in other key demographic and clinical characteristics. Conclusion: There was a high degree of clustering within the state and HIV+ persons with the majority belonging to the MS0006 and MS0003 strains. HIV + were younger and non-homeless. African American race was a risk factor for HIV/TB co-infection (P<0.001) and belonging to the MS0006 TB cluster (p=0.004). Measures to interrupt TB transmission in African Americans and HIV co-infected populations are necessary to accelerate TB elimination.
    No preview · Conference Paper · Oct 2011
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    A Kwara · D Shah · L A Renner
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    ABSTRACT: The burden of paediatric HIV infection remains high in resource-poor settings. Information on morbidity leading to hospitalisation as well as outcome is limited. The objective of this study was to determine the reasons for hospital admissions of HIV-infected paediatric patients to a tertiary teaching hospital and the outcome of these admissions. Retrospective chart review of inpatient records of all HIV-infected children aged 0 to 13 years admitted to the paediatric unit at Korle-Bu Teaching Hospital from 30 June 2007 to 30 June 2008 was performed. Abstracted data included age, gender, weight, presenting conditions, diagnosis, duration of hospitalisation, antiretroviral treatment, and outcome. A total of 102 admissions occurred among 76 children. The mean age of the children was 4.5 ± 3.79 years and 42 (55%) were males. HIV diagnosis was made during hospitalisation in 23 (30%) of the 76 patients. Overall, 55 (64%) of the 76 patients had a weight for age less than second percentile and 67% were not on antiretroviral therapy at time of admission. Of the 102 admissions, the predominant diagnosis included pneumonia (40%), gastroenteritis (24%), pulmonary tuberculosis (22%), and/or malaria (19%). Death occurred in 12 of the 102 admissions. Age, gender, and admitting diagnosis were not associated with death. Failure to thrive and common prevalent infections were the predominant reasons for hospitalisation for paediatric HIV/AIDS patients in Accra. Hospitalisations with these conditions should prompt early HIV testing. Efforts should be intensified to prevent maternal to child transmission of HIV infection.
    Preview · Article · Sep 2011 · West African journal of medicine
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    ABSTRACT: Tuberculosis (TB) remains a major cause of mortality despite availability of effective chemotherapy. This study was performed to identify contributing factors for poor outcome during anti-tuberculosis treatment at a teaching hospital chest clinic. Medical records of registered patients treated for TB between 1 January and 31 December, 2009 were reviewed and abstracted for demographic, clinical and outcome data. Risk factors for mortality during therapy were assessed using bivariate and multivariate logistics approaches. Of 599 patients, 355 (58.9%) completed therapy and/or were cured, 192 (32.1%) died, and 39 (6.5%) defaulted. In multivariate analysis, independent risk factors for mortality included pulmonary cases for which sputum smear status was unknown (odds ratio [OR] 13.7; 95% confidence interval [CI] 6.0, 31.4), HIV coinfection (OR, 3.6; 95% CI 2.4, 5.4), disseminated TB (OR, 2.2; 95% CI 1.0, 4.9), TB meningitis (OR, 2.8; 95% CI 1.5, 5.3), not having a treatment supporter (OR, 2.0; 95% CI 1.3, 3.1), and low body weight (OR, 11.0; 95% CI 3.1, 38.6). Not having a treatment supporter (OR, 3.2; 95% CI 1.6, 6.6) and HIV coinfection (OR, 2.4; 95% CI 1.2, 5.2) were also independently associated with treatment default. Our findings suggest that enhanced measures to reduce mortality and default in TB patients with HIV coinfection, disseminated or meningeal disease and those who have no treatment supporters may help improve treatment outcomes in Ghana.
    Full-text · Article · Sep 2011 · Transactions of the Royal Society of Tropical Medicine and Hygiene
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    ABSTRACT: Efavirenz-based antiretroviral regimen is preferred during rifampin-containing tuberculosis therapy. However, current pharmacokinetic data are insufficient to guide optimized concurrent dosing. This study aimed to better characterize the effects of rifampin on efavirenz pharmacokinetics. Subjects were randomized to receive 600 mg efavirenz/day or 600 mg efavirenz with 600 mg rifampin/day for 8 days, with plasma samples collected for pharmacokinetic analysis over 24 h on day 8. Treatments were then crossed over after at least a 2-week washout period, and procedures were repeated. Efavirenz concentrations were determined by high-performance liquid chromatography (HPLC), and pharmacokinetic parameters were estimated by noncompartmental analysis. Efavirenz pharmacokinetic differences between treatment periods were evaluated by paired t test. The coefficients of variation in efavirenz plasma AUC0-24 (area under the concentration-time curve from 0 to 24 h) were 50% and 56% in the absence and presence of rifampin, respectively. Of the 11 evaluable subjects (6 white, 5 black; 6 women, 5 men), the geometric mean AUC0-24 ratio on/off rifampin (90% confidence interval) was 0.82 (0.72, 0.92), with individual AUC0-24 ratios varying from 0.55 to 1.18. Five subjects had a 24-hour efavirenz concentration (C24) of <1,000 ng/ml on rifampin. They were more likely to have received a lower dose in milligrams/kilogram of body weight and to have lower efavirenz AUC0-24 values in the basal state. Although rifampin resulted in a modest reduction in efavirenz plasma exposure in subjects as a whole, there was high variability in responses between subjects, suggesting that efavirenz dose adjustment with rifampin may need to be individualized. Body weight and genetic factors will be important covariates in dosing algorithms.
    Preview · Article · Jul 2011 · Antimicrobial Agents and Chemotherapy

  • No preview · Conference Paper · May 2011
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    ABSTRACT: While foreign-born persons constitute only 11% of the population in the state of Rhode Island, they account for more than 65% of incident tuberculosis (TB) annually. We investigated the molecular-epidemiological differences between foreign-born and U.S.-born TB patients to estimate the degree of recent transmission and identify predictors of clustering. A total of 288 isolates collected from culture-confirmed TB cases in Rhode Island between 1995 and 2004 were fingerprinted by spoligotyping and 12-locus mycobacterial interspersed repetitive units. Of the 288 fingerprinted isolates, 109 (37.8%) belonged to 36 genetic clusters. Our findings demonstrate that U.S.-born patients, Hispanics, Asian/Pacific islanders, and uninsured patients were significantly more likely to be clustered. Recent transmission among the foreign-born population was restricted and occurred mostly locally, within populations originating from the same region. Nevertheless, TB transmission between the foreign-born and U.S.-born population should not be neglected, since 80% of the mixed clusters of foreign- and U.S.-born persons arose from a foreign-born source case. We conclude that timely access to routine screening and treatment for latent TB infection for immigrants is vital for disease elimination in Rhode Island.
    Full-text · Article · Mar 2011 · Journal of clinical microbiology

Publication Stats

615 Citations
93.59 Total Impact Points

Institutions

  • 2009-2015
    • Alpert Medical School - Brown University
      • Department of Medicine
      Providence, Rhode Island, United States
  • 2004-2014
    • Brown University
      • • Alpert Medical School
      • • Division of Infectious Diseases
      Providence, Rhode Island, United States
  • 2005-2011
    • Providence Hospital
      Mobile, Alabama, United States
  • 2003
    • Centers for Disease Control and Prevention
      • National Center for Emerging and Zoonotic Infectious Diseases
      Атланта, Michigan, United States