John A Bartlett

Duke University, Durham, North Carolina, United States

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Publications (152)773.57 Total impact


  • No preview · Article · Dec 2016 · BMC Medical Education
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    ABSTRACT: Background. Due to the unintended potential misclassifications of the World Health Organization (WHO) immunological failure criteria in predicting virological failure, limited availability of treatment options, poor laboratory infrastructure and health care providers confidence in making switches, physicians delay switching patients to second-line antiretroviral therapy (ART). Evaluating whether timely switching and delayed switching is associated with the risk of opportunistic infections among patients with unrecognized treatment failure is critical to improve patient outcomes. Methods. A retrospective review of 637 adolescents and adults meeting WHO immunological failure criteria was conducted. Timely and delayed switching to second-line ART were defined when switching happens at<3 and≥3 months respectively after failure diagnosis is made. Cox proportional hazard marginal structural models were used to assess the effect of switching to second-line ART on the risk of developing opportunistic infections. Results. Of 637 patients meeting WHO immunological failure criteria, 396 (62.2%) switched to second-line ART. Of those switched, 230 (58.1%) were delayed. Switching to second-line ART reduced the risk of opportunistic infections (adjusted hazards ratio [AHR] 0.4, 95% CI 0.2 – 0.6). Compared to patients who received timely switch after failure diagnosis is made, those who delayed switching were more likely to develop opportunistic infections (AHR 2.2, 95% CI 1.1 – 4.3). Conclusion. Delayed switching to second-line ART after failure diagnosis may increase the risk of opportunistic infections. Serial immunological assessment for switching patients to second-line ART is critical to improve their outcomes.
    Preview · Article · Jan 2016 · Open Forum Infectious Diseases

  • No preview · Article · Oct 2015 · Cancer Epidemiology Biomarkers & Prevention
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    ABSTRACT: Background: Virologic failure in subtype C is characterized by high resistance to first-line antiretroviral (ARV) drugs, including efavirenz, nevirapine, and lamivudine, with nucleoside resistance including type 2 thymidine analog mutations, K65R, a T69del, and M184V. However, genotypic algorithms predicting resistance are mainly based on subtype B viruses and may under- or overestimate drug resistance in non-B subtypes. To explore potential treatment strategies after first-line failure, we compared genotypic and phenotypic susceptibility of subtype C human immunodeficiency virus 1 (HIV-1) following first-line ARV failure. Methods: AIDS Clinical Trials Group 5230 evaluated patients failing an initial nonnucleoside reverse-transcriptase inhibitor (NNRTI) regimen in Africa and Asia, comparing the genotypic drug resistance and phenotypic profile from the PhenoSense (Monogram). Site-directed mutagenesis studies of K65R and T69del assessed the phenotypic impact of these mutations. Results: Genotypic algorithms overestimated resistance to etravirine and rilpivirine, misclassifying 28% and 32%, respectively. Despite K65R with the T69del in 9 samples, tenofovir retained activity in >60%. Reversion of the K65R increased susceptibility to tenofovir and other nucleosides, while reversion of the T69del showed increased resistance to zidovudine, with little impact on other NRTI. Conclusions: Although genotype and phenotype were largely concordant for first-line drugs, estimates of genotypic resistance to etravirine and rilpivirine may misclassify subtype C isolates compared to phenotype.
    No preview · Article · Jul 2015 · The Journal of Infectious Diseases

  • No preview · Article · Apr 2015
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    ABSTRACT: Despite comparable screening rates for precancerous lesions, higher incidence and mortality related to cervical cancer in minority women persists. Recent evidence suggests that minority women with precancerous cervical lesions harbor a wider range of human papillomavirus (HPV) genotypes, many of these distinct from HPV16/18, those most commonly found in Caucasian women. The goal of the analysis was to determine if inflammatory cytokines and chemokines varied by HPV 16/18 versus other genotypes in cervical cancer tissues from Tanzanian women. HPV genotypes and concentrations of chemokines and cytokines were measured from homogenized fresh tumor tissue of thirty-one women with invasive cervical cancer (ICC). Risk factors for cervical cancer including age, parity, hormonal contraceptive use and cigarette smoking were obtained by questionnaire. Generalized linear models were used to evaluate differences between chemokines/cytokine levels in women infected with HPV16/18 and those infected with other HPV genotypes. After adjusting for age, parity and hormonal contraceptives, IL-17 was found significantly more frequently in invasive cervical cancer samples of women infected with HPV16/18 compared to women infected with other HPV genotypes (p = 0.033). In contrast, higher levels for granular macrophage colony-stimulating factor (p = 0.004), IL-10 (p = 0.037), and IL-15 (p = 0.041) were found in ICC tissues of women infected with genotypes other than HPV16/18 when compared to those of women infected with HPV16/18. While the small sample size limits inference, our data suggest that infection with different HPV genotypes is associated with distinct pro-inflammatory cytokine expression profiles; whether this explains some of the racial differences observed in cervical cancer is still unclear. Future studies are needed to confirm these findings.
    Full-text · Article · Mar 2015 · Infectious Agents and Cancer
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    Preview · Article · Feb 2015 · Annals of Global Health
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    Preview · Article · Feb 2015 · Annals of Global Health
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    ABSTRACT: Objective. ACTG A5230 evaluated lopinavir/ritonavir (LPV/r) monotherapy following virologic failure on first-line regimens in Africa and Asia. Methods. Eligible subjects had received first-line regimens for at least 6 months and had plasma HIV-1 RNA levels 1000-200,000copies/mL. All subjects received LPV/r 400/100mg twice daily. Virologic failure (VF) was defined as failure to suppress to <400 copies/mL by week 24, or confirmed rebound to >400 copies/mL at or after week 16 following confirmed suppression. Subjects with VF added emtricitabine 200mg/tenofovir 300mg (FTC/TDF) once daily. The probability of continued HIV-1 RNA <400 copies/mL on LPV/r-monotherapy through week 104 was estimated with a 95% confidence interval (CI); predictors of treatment success were evaluated with Cox proportional hazards models. Results. 123 subjects were enrolled. Four subjects died and 2 discontinued prematurely; 117 /123 (95%) completed 104 weeks. Through week 104, 49 subjects met the primary endpoint; 47 had VF, and 2 intensified treatment without VF. Of the 47 subjects with VF, 41 (33%) intensified treatment, and 39/41 subsequently achieved levels <400 copies/mL. The probability of continued suppression <400copies/mL over 104 weeks on LPV/r-monotherapy was 60% [95% CI 50%, 68%]; 80-85% maintained levels <400 copies/mL with FTC/TDF intensification as needed. Ultrasensitive assays on specimens with HIV-1 RNA level<400 copies/mL at weeks 24, 48 and 104 revealed that 61%, 62% and 65% were suppressed to <40 copies/mL, respectively. Conclusion. LPV/r monotherapy after first-line virologic failure with FTC/TDF intensification when needed provides durable suppression of HIV-1 RNA over 104 weeks.
    Full-text · Article · Feb 2015 · Clinical Infectious Diseases
  • Matthew P Rubach · Venance P Maro · John A Bartlett · John A Crump
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    ABSTRACT: We describe the laboratory-confirmed etiologies of illness among participants in a hospital-based febrile illness cohort study in northern Tanzania who retrospectively met Integrated Management of Adolescent and Adult Illness District Clinician Manual (IMAI) criteria for septic shock, severe respiratory distress without shock, and severe pneumonia, and compare these etiologies against commonly used antimicrobials, including IMAI recommendations for emergency antibacterials (ceftriaxone or ampicillin plus gentamicin) and IMAI first-line recommendations for severe pneumonia (ceftriaxone and a macrolide). Among 423 participants hospitalized with febrile illness, there were 25 septic shock, 37 severe respiratory distress without shock, and 109 severe pneumonia cases. Ceftriaxone had the highest potential use of all antimicrobials assessed, with responsive etiologies in 12 (48%) septic shock, 5 (14%) severe respiratory distress without shock, and 19 (17%) severe pneumonia illnesses. For each syndrome 17-27% of participants had etiologic diagnoses that would be non-responsive to ceftriaxone, but responsive to other available antimicrobial regimens including amphotericin for cryptococcosis and histoplasmosis; anti-tuberculosis therapy for bacteremic disseminated tuberculosis; or tetracycline therapy for rickettsioses and Q fever. We conclude that although empiric ceftriaxone is appropriate in our setting, etiologies not explicitly addressed in IMAI guidance for these syndromes, such as cryptococcosis, histoplasmosis, and tetracycline-responsive bacterial infections, were common.
    No preview · Article · Nov 2014 · The American journal of tropical medicine and hygiene
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    ABSTRACT: Abnormal skin findings are identified in over 90% of human immunodeficiency virus (HIV)-infected persons globally. A prospective cohort study of HIV-infected patients with skin complaints commencing antiretroviral therapy (ART) in northern Tanzania was undertaken. Consecutive HIV-infected subjects presenting with skin complaints, who met criteria for ART initiation, were recruited at a Tanzanian Regional Dermatology Training Center. A single dermatologist evaluated all subjects; baseline skin biopsies were performed, and CD4+ cell counts and plasma HIV RNA levels were measured. All subjects received a fixed-dose combination of stavudine, lamivudine, and nevirapine. A total of 100 subjects were enrolled; 86 subjects completed six months of follow-up. Median baseline CD4+ cell counts and plasma HIV RNA levels were 120 cells/μl and 5.2 log10 copies/ml. The most common dermatologic condition was papular pruritic eruption (47%). The median baseline score on the Burn Scale was 38%. After six months, 10 subjects had achieved the complete resolution of skin abnormalities. In those without complete resolution, the median Burn Scale score improved to 7%. Five patients developed new eruptions by month 3, which in two cases were attributed to drug reactions. In the 86 subjects remaining on ART after six months, the median CD4+ cell count had increased to 474 cells/μl, and plasma HIV RNA levels were <400 copies/ml in 85 (99%) subjects. Patients with HIV infection with skin complaints experienced marked clinical improvements following ART initiation.
    No preview · Article · Sep 2014 · International journal of dermatology
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    ABSTRACT: The Kilimanjaro Christian Medical University (KCMU) College and the Medical Education Partnership Initiative (MEPI) are addressing the crisis in Tanzanian health care manpower by modernizing the college's medical education with new tools and techniques. With a $10 million MEPI grant and the participation of its partner, Duke University, KCMU is harnessing the power of information technology (IT) to upgrade tools for students and faculty. Initiatives in eLearning have included bringing fiber-optic connectivity to the campus, offering campus-wide wireless access, opening student and faculty computer laboratories, and providing computer tablets to all incoming medical students. Beyond IT, the college is also offering wet laboratory instruction for hands-on diagnostic skills, team-based learning, and clinical skills workshops. In addition, modern teaching tools and techniques address the challenges posed by increasing numbers of students. To provide incentives for instructors, a performance-based compensation plan and teaching awards have been established. Also for faculty, IT tools and training have been made available, and a medical education course management system is now being widely employed. Student and faculty responses have been favorable, and the rapid uptake of these interventions by students, faculty, and the college's administration suggests that the KCMU College MEPI approach has addressed unmet needs. This enabling environment has transformed the culture of learning and teaching at KCMU College, where a path to sustainability is now being pursued.
    No preview · Article · Aug 2014 · Academic medicine: journal of the Association of American Medical Colleges
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    Dorothy E Dow · John A Bartlett
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    ABSTRACT: The integrase strand transfer inhibitors (INSTIs) are the newest antiretroviral class in the HIV treatment armamentarium. Dolutegravir (DTG) is the only second-generation INSTI with FDA approval (2013). It has potential advantages in comparison to first-generation INSTI’s, including unboosted daily dosing, limited cross resistance with raltegravir and elvitegravir, and a high barrier to resistance. Clinical trials have evaluated DTG as a 50-mg daily dose in both treatment-naïve and treatment-experienced, INSTI-naïve participants. In those treatment-naïve participants with baseline viral load
    Full-text · Article · Jun 2014
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    Preview · Article · Jun 2014 · Annals of Global Health
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    ABSTRACT: Background In low- and middle-income countries, the association between delay to treatment and prognosis for Kaposi’s sarcoma (KS) patients is yet to be studied. Methods This is a prospective study of HIV-infected adults with histologically-confirmed KS treated at the Uganda Cancer Institute (UCI). Standardized interviews were conducted in English or Luganda. Medical records were abstracted for KS stage at admission to UCI. Multivariable logistic regression assessed relationships between diagnostic delay and stage at diagnosis. Results Of 161 patients (90% response rate), 69% were men, and the mean age was 34.0 years (SD 7.7). 26% had been seen in an HIV clinic within 3 months, 72% were on antiretroviral therapy, and 26% had visited a traditional healer prior to diagnosis. 45% delayed seeking care at UCI for ≥3 months from symptom onset. Among those who delayed, 36% waited 6 months, and 25% waited 12 months. Common reasons for delay were lack of pain (48%), no money (32%), and distance to UCI (8%). In adjusted analysis patients who experienced diagnostic delay were more likely than those who did not delay to have poor-risk KS stage (OR 3.41, p = 0.002, 95% CI: 1.46-7.45). In adjusted analyses visiting a traditional healer was the only variable associated with greater likelihood of delay (OR 2.69, p = 0.020, 95% CI: 1.17-6.17). Conclusions Diagnostic delay was associated with poor-risk stage at diagnosis, and visiting a traditional healer was associated with higher odds of delay. The relationship between traditional and Western medicine presents a critical intervention point to improve KS-related outcomes in Uganda.
    Full-text · Article · May 2014 · Infectious Agents and Cancer
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    ABSTRACT: Background: The development of drug resistance to nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) has been associated with baseline human immunodeficiency virus (HIV)-1 RNA level (VL), CD4 cell counts (CD4), subtype, and treatment failure duration. This study describes drug resistance and levels of susceptibility after first-line virologic failure in individuals from Thailand, South Africa, India, Malawi, Tanzania. Methods: CD4 and VL were captured at AIDs Clinical Trial Group (ACTG) A5230 study entry, a study of lopinavir/ritonavir (LPV/r) monotherapy after first-line virologic failure on an NNRTI regimen. HIV drug-resistance mutation associations with subtype, site, study entry VL, and CD4 were evaluated using Fisher exact and Kruskall-Wallis tests. Results: Of the 207 individuals who were screened for A5230, sequence data were available for 148 individuals. Subtypes observed: subtype C (n = 97, 66%) AE (n = 27, 18%), A1 (n = 12, 8%), and D (n = 10, 7%). Of the 148 individuals, 93% (n = 138) and 96% (n = 142) had at least 1 reverse transcriptase (RT) mutation associated with NRTI and NNRTI resistance, respectively. The number of NRTI mutations was significantly associated with a higher study screening VL and lower study screening CD4 (P < .001). Differences in drug-resistance patterns in both NRTI and NNRTI were observed by site. Conclusions: The degree of NNRTI and NRTI resistance after first-line virologic failure was associated with higher VL at study entry. Thirty-two percent of individuals remained fully susceptible to etravirine and rilpivirine, protease inhibitor resistance was rare. Some level of susceptibility to NRTI remained; however, VL monitoring and earlier virologic failure detection may result in lower NRTI resistance.
    Full-text · Article · May 2014 · Clinical Infectious Diseases
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    ABSTRACT: Routine tuberculosis culture remains unavailable in many high-burden areas, including Tanzania. This study sought to determine the impact of providing mycobacterial culture results over standard of care [unconcentrated acid-fast (AFB) smears] on management of persons with suspected tuberculosis. Adults and children with suspected tuberculosis were randomized to standard (direct AFB smear only) or intensified (concentrated AFB smear and tuberculosis culture) diagnostics and followed for 8 weeks. The primary endpoint was appropriate treatment (i.e. antituberculosis therapy for those with tuberculosis, no antituberculous therapy for those without tuberculosis). Seventy participants were randomized to standard (n = 37, 52.9%) or intensive (n = 33, 47.1%) diagnostics. At 8 weeks, 100% (n = 22) of participants in follow up randomized to intensive diagnostics were receiving appropriate care, vs. 22 (88.0%) of 25 participants randomized to standard diagnostics (p = 0.14). Overall, 18 (25.7%) participants died; antituberculosis therapy was associated with lower mortality (9% who received antiuberculosis treatment died vs. 26% who did not, p = 0.04). Under field conditions in a high burden setting, the impact of intensified diagnostics was blunted by high early mortality. Enhanced availability of rapid diagnostics must be linked to earlier access to care for outcomes to improve.
    Full-text · Article · Feb 2014 · BMC Infectious Diseases
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    ABSTRACT: Mother to child transmission (MTCT) of HIV-1 remains an important problem in sub-Saharan Africa where most new pediatric HIV-1 infections occur. Early infant diagnosis of HIV-1 using dried blood spot (DBS) PCR among exposed infants provides an opportunity to assess current MTCT rates. We conducted a retrospective data analysis on mother-infant pairs from all PMTCT programs in three regions of northern Tanzania to determine MTCT rates from 2008-2010. Records of 3,016 mother-infant pairs were assessed to determine early transmission among HIV-exposed infants in the first 75 days of life. Of 2,266 evaluable infants in our cohort, 143 had a positive DBS PCR result at ≤75 days of life, for an overall transmission rate of 6.3%. Transmission decreased substantially over the period of study as more effective regimens became available. Transmission rates were tightly correlated to maternal regimen: 14.9% (9.5, 20.3) of infants became infected when women received no therapy; 8.8% (6.9, 10.7) and 3.6% (2.4, 4.8) became infected when women received single-dose nevirapine (sdNVP) or combination prophylaxis, respectively; the lowest MTCT rates occurred when women were on HAART, with 2.1% transmission (0.3, 3.9). Treatment regimens changed dramatically over the study period, with an increase in combination prophylaxis and a decrease in the use of sdNVP. Uptake of DBS PCR more than tripled over the period of study for the three regions surveyed. Our study demonstrates significant reductions in MTCT of HIV-1 in three regions of Tanzania coincident with increased use of more effective PMTCT interventions. The changes we demonstrate for the period of 2008-2010 occurred prior to major changes in WHO PMTCT guidelines.
    Full-text · Article · Feb 2014 · PLoS ONE
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    ABSTRACT: Background: Contemporary teaching in sub-Saharan African medical schools is largely through didactic and problem-based approaches. These schools face challenges from burgeoning student numbers, severe faculty shortages, faculty without instruction in teaching methods and severe infrastructure inadequacies. Team-based learning (TBL) is a pedagogy which may be attractive because it spares faculty time. TBL was piloted in a module on ectoparasites at the Kilimanjaro Christian Medical University College (KCMU Co.). Methods: TBL orientation began six weeks before starting the module. Students were issued background readings and individual and group readiness assessment tests, followed by module application, discussion and evaluation. At completion, student perceptions of TBL were assessed using a 5-point Likert scale evaluating six domains, with a score of 5 being most favourable. Strength of consensus measures (sCns) was applied. Final examination scores were compiled for 2011 (didactic) and 2012 (TBL). Results: About 158 students participated in the module. The mean student scores across the six domains ranged from 4.2 to 4.5, with a high degree of consensus (range 85-90%). The final examination scores improved between 2011 and 2012. Conclusions: KCMU Co. student perceptions of TBL were very positive, and final exam grades improved. These observations suggest future promise for TBL applications at KCMU Co. and potentially other schools.
    Full-text · Article · Feb 2014 · Medical Teacher
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    ABSTRACT: The projected cancer burden in Africa demands a comprehensive surveillance strategy. Kilimanjaro Christian Medical Centre (KCMC) is developing a population-based cancer registry, and understanding stakeholders' perceptions of factors impacting cancer registration sustainability is critical to its long-term success. We conducted 11 semi-structured qualitative interviews with clinicians and administrators. Interviews were double-coded and evaluated for predetermined and emerging themes. Nearly half (45%) of participants discussed change commitment, stating that the cancer registry would benefit KCMC and that they were committed to it. However, change efficacy was low - participants were not confident in their shared ability to sustain the registry. Most participants (73%) discussed the importance of resource availability and administration support. Several themes emerged across interviews: (i) lack of cancer registry awareness, (ii) ambiguity about its purpose, (iii) the importance of training, (iv) the importance of outcome data, and (v) the importance of international partners. These findings may facilitate cancer registry development and sustainability in similar settings.
    No preview · Article · Jan 2014 · World health & population

Publication Stats

4k Citations
773.57 Total Impact Points

Institutions

  • 1991-2015
    • Duke University
      • • Department of Medicine
      • • Department of Surgery
      Durham, North Carolina, United States
  • 1988-2015
    • Duke University Medical Center
      • • Department of Medicine
      • • Division of Infectious Diseases
      • • Department of Surgery
      Durham, North Carolina, United States
  • 2014
    • The Children's Hospital of Philadelphia
      Filadelfia, Pennsylvania, United States
  • 2007
    • Kilimanjaro Christian Medical Centre
      Moschi, Kilimanjaro, Tanzania