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Kendall, Michelle

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Kendall

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Michelle

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Kendall, Michelle
Author's Publications: search.filters.isAuthorOfPublication.15627bd7-d0d6-476c-bb29-a04355de6e77

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    The Clinical Impact of Continuing to Prescribe Antiretroviral Therapy in Patients with Advanced AIDS Who Manifest No Virologic or Immunologic Benefit
    (Public Library of Science, 2013) Wohl, David A.; Kendall, Michelle; Feinberg, Judith; Alston-Smith, Beverly; Owens, Susan; Chafey, Suzette; Marco, Michael; Maxwell, Sharon; Benson, Constance; Keiser, Philip; van der Horst, Charles; Jacobson, Mark A.
    Introduction: Despite the efficacy and tolerability of modern antiretroviral therapy (ART), many patients with advanced AIDS prescribed these regimens do not achieve viral suppression or immune reconstitution as a result of poor adherence, drug resistance, or both. The clinical outcomes of continued ART prescription for such patients have not been well characterized. Methods: We examined the causes and predictors of all-cause mortality, AIDS-defining conditions, and serious non-AIDS-defining events among a cohort of participants in a clinical trial of pre-emptive therapy for CMV disease. We focused on participants who, despite ART had failed to achieve virologic suppression and substantive immune reconstitution. Results: 233 ART-receiving participants entered with a median baseline CD4+ T cell count of 30/mm3 and plasma HIV RNA of 5 log10 copies/mL. During a median 96 weeks of follow-up, 24.0% died (a mortality rate of 10.7/100 patient-years); 27.5% reported a new AIDS-defining condition, and 22.3% a new serious non-AIDS event. Of the deaths, 42.8% were due to an AIDS-defining condition, 44.6% were due to a non-AIDS-defining condition, and 12.5% were of unknown etiology. Decreased risk of mortality was associated with baseline CD4+ T cell count ≥25/mm3 and lower baseline HIV RNA. Conclusions: Among patients with advanced AIDS prescribed modern ART who achieve neither virologic suppression nor immune reconstitution, crude mortality percentages appear to be lower than reported in cohorts of patients studied a decade earlier. Also, in contrast to the era before modern ART became available, nearly half of the deaths in our modern-era study were caused by serious non-AIDS-defining events. Even among the most advanced AIDS patients who were not obtaining apparent immunologic and virologic benefit from ART, continued prescription of these medications appears to alter the natural history of AIDS—improving survival and shifting the causes of death from AIDS- to non-AIDS-defining conditions.
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    Predictors and outcomes of Mycobacterium tuberculosis bacteremia among patients with HIV and tuberculosis co-infection enrolled in the ACTG A5221 STRIDE study
    (BioMed Central, 2015) Crump, John A; Wu, Xingye; Kendall, Michelle; Ive, Prudence D; Kumwenda, Johnstone J; Grinsztejn, Beatriz; Jentsch, Ute; Swindells, Susan
    Background: We evaluated predictors and outcomes of Mycobacterium tuberculosis bacteremia among participants undergoing baseline mycobacterial blood culture in the ACTG A5221 STRIDE study, a randomized clinical trial comparing earlier with later ART among HIV-infected patients suspected of having tuberculosis with CD4-positive T-lymphocyte counts (CD4 counts) <250 cells/mm3. We conducted a secondary analysis comparing participants with respect to presence or absence of M. tuberculosis bacteremia. Methods: Participants with a baseline mycobacterial blood culture were compared with respect to the presence or absence of M. tuberculosis bacteremia. Baseline predictors of M. tuberculosis bacteremia were identified and participant outcomes were compared by mycobacteremia status. Results: Of 90 participants with baseline mycobacterial blood cultures, 29 (32.2%) were female, the median (IQR) age was 37 (31–45) years, CD4 count was 81 (33–131) cells/mm3, HIV-1 RNA level was 5.39 (4.96–5.83) log10 copies/mL, and 18 (20.0%) had blood cultures positive for M. tuberculosis. In multivariable analysis, lower CD4 count (OR 0.85 per 10-cell increase, p = 0.012), hemoglobin ≤8.5 g/dL (OR 5.8, p = 0.049), and confirmed tuberculosis (OR 17.4, p = 0.001) were associated with M. tuberculosis bacteremia. There were no significant differences in survival and AIDS-free survival, occurrence of tuberculosis immune reconstitution inflammatory syndrome (IRIS), or treatment interruption or discontinuation by M. tuberculosis bacteremia status. IRIS did not differ significantly between groups despite trends toward more virologic suppression and greater CD4 count increases at week 48 in the bacteremic group. Conclusions: Among HIV-infected tuberculosis suspects, lower CD4 count, hemoglobin ≤8.5 g/dL, and the presence of microbiologically confirmed pulmonary tuberculosis were associated with increased adjusted odds of mycobacteremia. No evidence of an association between M. tuberculosis bacteremia and the increased risk of IRIS was detected. Trial registration ClinicalTrials.gov: NCT00108862.
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    Dysfunctional HDL and progression of atherosclerosis in HIV-1-infected and -uninfected adults
    (BioMed Central, 2013) Kelesidis, Theodoros; Yang, Otto O; Kendall, Michelle; Hodis, Howard N; Currier, Judith S
    Background: HDL function rather than absolute level may be a more accurate indicator for risk of developing atherosclerosis. Dysfunctional HDL has increased redox activity and reduced antioxidant properties, but it is unknown whether abnormal HDL function is associated with progression of atherosclerosis in HIV-1-infected subjects. Findings: We retrospectively measured serum HDL function in 91 subjects from a prospective 3-year study of carotid artery intima-media thickness (CIMT), which enrolled triads of risk factor-matched persons that were HIV-1-uninfected (n=36) or HIV-1+ with (n=29) or without (n=26) protease inhibitor (PI)-based therapy for ≥ 2 years. HDL function was assessed using a biochemical assay that measures the oxidation of dihydrorhodamine 123 (DHR oxidation rate, DOR), in which higher DOR readout corresponds to dysfunctional HDL phenotype. There were no significant associations between DOR and HIV-1 infection. In univariate analysis of 55 HIV-1-infected subjects, greater waist circumference and lower serum HDL were significantly associated with higher baseline levels of DOR (p=0.01). These subjects had significant increases in levels of DOR over time (3 years) that were associated with white race (p=0.03), higher nadir CD4 count (p<0.001), and lower baseline CIMT (p<0.001). Lower baseline HDL levels, but not function of HDL (p>0.1) (DOR), were significantly associated (p=0.02) with progression of CIMT. Conclusion: In a small matched cohort study of HIV-1-infected subjects who had a low cardiovascular risk profile, HDL function changed over time and was independently associated with anthropometric parameters of obesity but not with progression of CIMT.
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    Biomarkers Associated with Death After Initiating Treatment for Tuberculosis and HIV in Patients with Very Low CD4 Cells
    (2018) Sattler, Fred R.; Chelliah, Daniel; Wu, Xingye; Sanchez, Alejandro; Kendall, Michelle; Hogg, Evelyn; Lagat, David; Lalloo, Umesh; Veloso, Valdilea; Havlir, Diane V.; Landay, Alan
    Background: The risk of short-term death for treatment naive patients dually infected with Mycobacterium tuberculosis and HIV may be reduced by early anti-retroviral therapy. Of those dying, mechanisms responsible for fatal outcomes are unclear. We hypothesized that greater malnutrition and/or inflammation when initiating treatment are associated with an increased risk for death. Methods: We utilized a retrospective case-cohort design among participants of the ACTG A5221 study who had baseline CD4 < 50 cells/mm3. The case-cohort sample consisted of 51 randomly selected participants, whose stored plasma was tested for C-reactive protein, cytokines, chemokines, and nutritional markers. Cox proportional hazards models were used to assess the association of nutritional, inflammatory, and immunomodulatory markers for survival. Results: The case-cohort sample was similar to the 282 participants within the parent cohort with CD4 <50 cells/mm3. In the case cohort, 7 (14%) had BMI < 16.5 (kg/m2) and 17 (33%) had BMI 16.5-18.5(kg/m2). Risk of death was increased per 1 IQR width higher of log10 transformed level of C-reactive protein (adjusted hazard ratio (aHR) = 3.42 [95% CI = 1.33-8.80], P = 0.011), interferon gamma (aHR = 2.46 [CI = 1.02-5.90], P = 0.044), MCP-3 (3.67 [CI = 1.08-12.42], P = 0.037), and with IL-15 (aHR = 2.75 [CI = 1.08-6.98], P = 0.033) and IL-17 (aHR = 3.99 [CI = −1.06-15.07], P = 0.041). BMI, albumin, hemoglobin, and leptin levels were not associated with risk of death. Conclusions: Unlike patients only infected with M. tuberculosis for whom malnutrition and low BMI increase the risk of death, this relationship was not evident in our dually infected patients. Risk of death was associated with significant increases in markers of global inflammation along with soluble biomarkers of innate and adaptive immunity.