Immunoadjuvant prednisolone therapy for HIV-associated tuberculosis: A phase 2 clinical trial in Uganda

Harriet Mayanja-Kizza, Edward Jones-Lopez, Alphonse Okwera, Robert S. Wallis, Jerrold J. Ellner, Roy D. Mugerwa, Christopher C. Whalen

Research output: Contribution to journalArticle

Abstract

Background. Human immunodeficiency virus (HIV)-infected patients with tuberculosis (TB) respond to effective antituberculous therapy, but their prognosis remains poor. Mounting evidence from clinical studies supports the concept of copathogenesis in which immune activation that is triggered by TB and mediated by cytokines stimulates viral replication and worsens HIV infection, especially when immune function is preserved. Methods. We performed a phase 2, randomized, double-blind, placebo-controlled clinical trial in Kampala, Uganda, to determine whether immunoadjuvant prednisolone therapy in HIV-infected patients with TB who have CD4+ T cell counts ≥200 cells/μL is safe and effective at increasing CD4+ T cell counts. Results. Short-term prednisolone therapy reduced levels of immune activation and tended to produce higher CD4+ T cell counts. Although prednisolone therapy was associated with a more rapid clearance of Mycobacterium tuberculosis from the sputum, it was also associated with a transient increase in HIV RNA levels, which receded when prednisolone therapy was discontinued. The intervention worsened underlying hypertension and caused fluid retention and hyperglycemia. Conclusion. The benefits of prednisolone therapy on immune activation and CD4+ T cell counts do not outweigh the risks of adverse events in HIV-infected patients with TB and preserved immune function.

Original languageEnglish (US)
Pages (from-to)856-865
Number of pages10
JournalJournal of Infectious Diseases
Volume191
Issue number6
DOIs
StatePublished - Mar 15 2005
Externally publishedYes

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Immunologic Adjuvants
Uganda
Prednisolone
Tuberculosis
Clinical Trials
HIV
CD4 Lymphocyte Count
T-Lymphocytes
Therapeutics
Controlled Clinical Trials
Virus Diseases
Sputum
Mycobacterium tuberculosis
Hyperglycemia
Placebos
RNA
Cytokines
Hypertension

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Immunology

Cite this

Mayanja-Kizza, H., Jones-Lopez, E., Okwera, A., Wallis, R. S., Ellner, J. J., Mugerwa, R. D., & Whalen, C. C. (2005). Immunoadjuvant prednisolone therapy for HIV-associated tuberculosis: A phase 2 clinical trial in Uganda. Journal of Infectious Diseases, 191(6), 856-865. https://doi.org/10.1086/427995

Immunoadjuvant prednisolone therapy for HIV-associated tuberculosis : A phase 2 clinical trial in Uganda. / Mayanja-Kizza, Harriet; Jones-Lopez, Edward; Okwera, Alphonse; Wallis, Robert S.; Ellner, Jerrold J.; Mugerwa, Roy D.; Whalen, Christopher C.

In: Journal of Infectious Diseases, Vol. 191, No. 6, 15.03.2005, p. 856-865.

Research output: Contribution to journalArticle

Mayanja-Kizza, H, Jones-Lopez, E, Okwera, A, Wallis, RS, Ellner, JJ, Mugerwa, RD & Whalen, CC 2005, 'Immunoadjuvant prednisolone therapy for HIV-associated tuberculosis: A phase 2 clinical trial in Uganda', Journal of Infectious Diseases, vol. 191, no. 6, pp. 856-865. https://doi.org/10.1086/427995
Mayanja-Kizza H, Jones-Lopez E, Okwera A, Wallis RS, Ellner JJ, Mugerwa RD et al. Immunoadjuvant prednisolone therapy for HIV-associated tuberculosis: A phase 2 clinical trial in Uganda. Journal of Infectious Diseases. 2005 Mar 15;191(6):856-865. https://doi.org/10.1086/427995
Mayanja-Kizza, Harriet ; Jones-Lopez, Edward ; Okwera, Alphonse ; Wallis, Robert S. ; Ellner, Jerrold J. ; Mugerwa, Roy D. ; Whalen, Christopher C. / Immunoadjuvant prednisolone therapy for HIV-associated tuberculosis : A phase 2 clinical trial in Uganda. In: Journal of Infectious Diseases. 2005 ; Vol. 191, No. 6. pp. 856-865.
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