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Persistent Replication of Human Immunodeficiency Virus Type 1 despite Treatment of Pulmonary Tuberculosis in Dually Infected Subjects

Case Western Reserve University, Department of Medicine,¹ University Hospitals of Cleveland,² Louis Stokes Department of Veterans Affairs Cleveland,³ Department of Molecular Biology, Lerner Research Institute,⁴ Department of Clinical Pathology,⁵ Cleveland Clinic Foundation, Cleveland, Ohio, and Makerere University, Kampala, Uganda⁶

Received 3 June 2005/ Returned for modification 13 July 2005/ Accepted 25 August 2005

Tuberculosis (TB) is the most common life-threatening infection in human immunodeficiency virus (HIV)-infected persons and frequently occurs before the onset of severe immunodeficiency. Development of TB is associated with increased HIV type 1 (HIV-1) viral load, a fall in CD4 lymphocyte counts, and increased mortality. The aim of this study was to examine how treatment of pulmonary TB affected HIV-1 activity in HIV-1/TB-coinfected subjects with CD4 cell counts of >100 cells/µl. HIV-1/TB-coinfected subjects were recruited in Kampala, Uganda, and were monitored over time. Based upon a significant (0.5 log₁₀ copies/ml) decrease in viral load by the end of treatment, two patient groups could be distinguished. Responders (n = 17) had more rapid resolution of anemia and pulmonary lesions on chest radiography during TB treatment. This group had a significant increase in viral load to levels not different from those at baseline 6 months after completion of TB treatment. HIV-1 viral load in nonresponders (n = 10) with TB treatment increased and at the 6 month follow-up was significantly higher than that at the time of diagnosis of TB. Compared to baseline levels, serum markers of macrophage activation including soluble CD14 decreased significantly by the end of TB treatment in responders but not in nonresponders. These data further define the impact of pulmonary TB on HIV-1 disease. HIV-1 replication during dual HIV-1/TB infection is not amenable to virologic control by treatment of TB alone. Concurrent institution of highly active antiretroviral treatment needs to be evaluated in patients dually infected with pulmonary TB and HIV-1.