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Open Access Highly Accessed Research article

Clinical deterioration during antituberculosis treatment in Africa: Incidence, causes and risk factors

Dominique J Pepper123*, Suzaan Marais123, Robert J Wilkinson12345, Feriyl Bhaijee6, Gary Maartens7, Helen McIlleron7, Virginia De Azevedo8, Helen Cox9, Cheryl McDermid10, Simiso Sokhela8, Janisha Patel2 and Graeme Meintjes123

Author Affiliations

1 Infectious Diseases Unit, GF Jooste Hospital, Cape Town, South Africa

2 Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, South Africa

3 Department of Medicine, University of Cape Town, South Africa

4 Division of Medicine, Imperial College of London, London, UK

5 MRC National Institute for Medical Research, Mill Hill, London, NW7 1AA, UK

6 Groote Schuur Hospital, Cape Town, South Africa

7 Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, South Africa

8 Khayelitsha Site B Tuberculosis Clinic, City Health, Cape Town, South Africa

9 Macfarlane Burnet Institute for Medical Research and Public Health, Australia

10 MedecinsSans Frontieres, Cape Town, South Africa

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BMC Infectious Diseases 2010, 10:83  doi:10.1186/1471-2334-10-83

Published: 30 March 2010

Abstract

Background

HIV-1 and Mycobacterium tuberculosis cause substantial morbidity and mortality. Despite the availability of antiretroviral and antituberculosis treatment in Africa, clinical deterioration during antituberculosis treatment remains a frequent reason for hospital admission. We therefore determined the incidence, causes and risk factors for clinical deterioration.

Methods

Prospective cohort study of 292 adults who initiated antituberculosis treatment during a 3-month period. We evaluated those with clinical deterioration over the following 24 weeks of treatment.

Results

Seventy-one percent (209/292) of patients were HIV-1 infected (median CD4+: 129 cells/μL [IQR:62-277]). At tuberculosis diagnosis, 23% (34/145) of HIV-1 infected patients qualifying for antiretroviral treatment (ART) were receiving ART; 6 months later, 75% (109/145) had received ART. Within 24 weeks of initiating antituberculosis treatment, 40% (117/292) of patients experienced clinical deterioration due to co-morbid illness (n = 70), tuberculosis related illness (n = 47), non AIDS-defining HIV-1 related infection (n = 25) and AIDS-defining illness (n = 21). Using HIV-1 uninfected patients as the referent group, HIV-1 infected patients had an increasing risk of clinical deterioration as CD4+ counts decreased [CD4+>350 cells/μL: RR = 1.4, 95% CI = 0.7-2.9; CD4+:200-350 cells/μL: RR = 2.0, 95% CI = 1.1-3.6; CD4+<200 cells/μL: RR = 3.0, 95% CI = 1.9-4.7]. During follow-up, 26% (30/117) of patients with clinical deterioration required hospital admission and 15% (17/117) died. Fifteen deaths were in HIV-1 infected patients with a CD4+<200 cells/μL.

Conclusions

In multivariate analysis, HIV-1 infection and a low CD4+ count at tuberculosis diagnosis were significant risk factors for clinical deterioration and death. The initiation of ART at a CD4+ count of <350 cells/μL will likely reduce the high burden of clinical deterioration.