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Mycobacterium tuberculosis microbiologic and clinical treatment outcomes in a randomized controlled trial of immediate versus CD4+-initiated antiretroviral therapy in HIV-infected adults with a high CD4+ cell count
Global Health Sciences Literature Digest
Published September 29, 2010
Journal Article

Chamie G, Charlebois ED, Srikantish P, et al. Mycobacterium tuberculosis microbiologic and clinical treatment outcomes in a randomized controlled trial of immediate versus CD4+-initiated antiretroviral therapy in HIV-infected adults with a high CD4+ cell count. Clin Infect Dis. 2010; 51: 359-62.

In Context

In patients with HIV, tuberculosis (TB) is a serious opportunistic infection that accounts for a considerable portion of HIV-related mortality in sub-Saharan Africa. The World Health Organization (WHO) has recently recommended that all patients with clinical TB and HIV infection begin antiretroviral therapy (ART) regardless of CD4 cell count.(1) An earlier cohort study found that ART was associated with more rapid TB culture and smear conversion.(2) The investigators conducted a randomized controlled trial to assess this question.

Objective

To compare ART plus TB therapy with TB therapy alone for risk of TB treatment failure

Setting/Population

This trial was conducted in Kampala, Uganda. The study population was HIV-infected patients with pulmonary TB and >350 CD4 cells/µL.

Methods

This was a randomized controlled trial that included two arms: patients who received TB therapy alone (isoniazid, rifampicin, ethambutol and pyrazinamide for two months and then isoniazid and rifampicin for four months) and patients who received TB therapy and ART (abacavir, lamivudine and zidovudine) two to four weeks after starting TB therapy. Trial endpoints were sputum smears and Mycobacterium tuberculosis cultures at 1, 2, 5, 12 and 18 months and chest radiographs at 1, 6,12, and 18 months.

Results

One hundred nine patients were randomized to the intervention (TB+ART) arm and 114 to the control arm; they had similar baseline characteristics. There was no difference in time to negative sputum culture or smears; there was no TB treatment failure in either arm but three recurrences in the intervention arm and four in the control arm. Overall, 18% of participants from both arms had positive sputum smears at five months of follow-up despite negative culture results; all had been smear positive and none isoniazid resistant at baseline. In multivariate analysis, pulmonary cavities and pleural thickening by radiograph were associated with persistent smear positivity.

Conclusions

The investigators concluded that the addition of ART to TB therapy in patients with ≥350 CD4 cells/µL did not improve TB outcomes over TB therapy alone.

Study Quality

Using the Cochrane Handbook's bias-risk assessment tool, the study was unclear in terms of sequence generation and allocation concealment but had low risk of bias in terms of blinding for key outcomes, incomplete outcomes, and selective outcome reporting and other potential biases. Overall, there was low risk of bias leading to the results the authors found.

Programmatic Implications

The implication of this study is the current WHO guidelines to treat everyone with HIV infection and TB with ART have been called into question for patients with ≥350 CD4 cells/µL. Additional studies will be needed to confirm these results before guidelines are revised.

References

  1. World Health Organization. Antiretroviral therapy for HIV infection in adults and adolescents. Recommendation for a public health approach. 2010 revision. Geneva, Switzerland: World Health Organization, 2010.
  2. Nahid P, Gonzalez LC, Rudoy I, et al. Treatment outcomes of patients with HIV and tuberculosis. Am J Respir Crit Care Med. 2007;175:1199-1206.