Predictors and outcomes of Mycobacterium tuberculosis bacteremia among patients with HIV and tuberculosis co-infection enrolled in the ACTG A5221 STRIDE study

John A Crump, Xingye Wu, Michelle A Kendall, Prudence D Ive, Johnstone J Kumwenda, Beatriz Grinsztejn, Ute Jentsch, Susan Swindells, John A Crump, Xingye Wu, Michelle A Kendall, Prudence D Ive, Johnstone J Kumwenda, Beatriz Grinsztejn, Ute Jentsch, Susan Swindells

Abstract

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/mm(3). 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/mm(3), 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 .

Figures

Figure 1
Figure 1
Time-to-first new AIDS-defining illness or death among participants with and without mycobacteremia, ACTG A5221 STRIDE study.

References

    1. Iseman MD. A clinician’s guide to tuberculosis. 1. Philadelphia: Lippincott Williams & Wilkins; 2000. Extrapulmonary tuberculosis in adults; pp. 145–97.
    1. Crump JA, Ramadhani HO, Morrissey AB, Saganda W, Mwako MS, Yang L-Y, et al. Bacteremic disseminated tuberculosis in sub-saharan Africa: a prospective cohort study. Clin Infect Dis. 2012;55:242–50. doi: 10.1093/cid/cis409.
    1. McDonald LC, Archibald LK, Rheanpumikankit S, Tansuphaswadikul S, Eampokalap B, Nwanyanawu O, et al. Unrecognised Mycobacterium tuberculosis bacteraemia among hospital inpatients in less developed countries. Lancet. 1999;354:1159–63. doi: 10.1016/S0140-6736(98)12325-5.
    1. Shao HJ, Crump JA, Ramadhani HO, Uiso LO, Ole-Nguyaine S, Moon AM, et al. Early versus delayed fixed dose combination abacavir/lamivudine/zidovudine in patients with HIV and tuberculosis in Tanzania. AIDS Res Hum Retroviruses. 2009;25:1277–85. doi: 10.1089/aid.2009.0100.
    1. Abdool Karim SS, Naidoo K, Grobler A, Padayatchi N, Baxter C, Gray AL, et al. Integration of antiretroviral therapy with tuberculosis treatment. N Engl J Med. 2011;365:1492–501. doi: 10.1056/NEJMoa1014181.
    1. Abdool Karim SS, Naidoo K, Grobler A, Padayatchi N, Baxter C, Gray A, et al. Timing of initiation of antiretroviral drugs during tuberculosis therapy. N Eng J Med. 2010;362:697–706. doi: 10.1056/NEJMoa0905848.
    1. Havlir DV, Kendall MA, Ive P, Kumwenda J, Swindells S, Qasba SS, et al. Timing of antiretroviral therapy for HIV-1 infection and tuberculosis. N Engl J Med. 2011;365:1482–91. doi: 10.1056/NEJMoa1013607.
    1. Luetkemeyer AF, Kendall MA, Nyirenda M, Wu X, Ive P, Benson CA, Andersen JW, Swindells S, Sanne IM, Havlir DV, Kumwenda J. Adult AIDS Clinical Trials Group A5221 Study Team. Tuberculosis immune reconstitution inflammatory syndrome in A5221 STRIDE: timing, severity, and implications for HIV-TB programs. J Acquir Immune Defic Syndr. 2014;65:423–8. doi: 10.1097/QAI.0000000000000030.
    1. Burman W, Weis S, Vernon A, Khan A, Benator D, Jones B, et al. Frequency, severity and duration of immune reconstitution events in HIV-related tuberculosis. Int J Tuberc Lung Dis. 2007;11:1282–9.
    1. Meintjes G, Lawn SD, Scano F, Maartens G, French MA, Worodria W, et al. Tuberculosis-associated immune reconstitution inflammatory syndrome: case definitions for use in resource-limited settings. Lancet Infect Dis. 2008;8:516–23. doi: 10.1016/S1473-3099(08)70184-1.
    1. Archibald LK, den Dulk MO, Pallangyo KJ, Reller LB. Fatal Mycobacterium tuberculosis bloodstream infections in febrile hospitalized adults in Dar es Salaam, Tanzania. Clin Infect Dis. 1998;26:290–6. doi: 10.1086/516297.
    1. Crump JA, Ramadhani HO, Morrissey AB, Saganda W, Mwako MS, Yang L-Y, et al. Invasive bacterial and fungal infections among hospitalized HIV-infected and HIV-uninfected adults and adolescents in northern Tanzania. Clin Infect Dis. 2011;52:341–8. doi: 10.1093/cid/ciq103.
    1. Crump JA, Tyrer MJ, Lloyd-Owen SJ, Han L-Y, Lipman MC, Johnson MA. Miliary tuberculosis with paradoxical expansion of intracranial tuberculomas complicating human immunodeficiency virus infection in a patient receiving highly active antiretroviral therapy. Clin Infect Dis. 1998;26:1008–9. doi: 10.1086/517636.

Source: PubMed

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