Early treatment outcomes and HIV status of patients with extensively drug-resistant tuberculosis in South Africa: a retrospective cohort study.
BACKGROUND
Data from Kwazulu Natal, South Africa, suggest that almost all patients with extensively drug-resistant (XDR) tuberculosis are HIV-positive, with a fatal outcome. Since, there are few data for the treatment-related outcomes of XDR tuberculosis in settings with a high HIV prevalence, we investigated the associations of these diseases in such settings to formulate recommendations for control programmes.


METHODS
In a retrospective cohort study, we analysed the case records of patients (>16 years old) with XDR tuberculosis (culture-proven at diagnosis) between August, 2002, and February, 2008, at four designated provincial treatment facilities in South Africa. We used Cox proportional hazards regression models to assess risk factors associated with the outcomes-mortality and culture conversion.


RESULTS
195 of 227 patients were analysed. 21 died before initiation of any treatment, and 174 patients (82 with HIV infection) were treated. 62 (36%) of these patients died during follow-up. The number of deaths was not significantly different in patients with or without HIV infection: 34 (41%) of 82 versus 28 (30%) of 92 (p=0.13). Treatment with moxifloxacin (hazard ratio 0.11, 95% CI 0.01-0.82; p=0.03), previous culture-proven multidrug-resistant tuberculosis (5.21, 1.93-14.1; p=0.001), and number of drugs used in a regimen (0.59, 0.45-0.78, p<0.0001) were independent predictors of death. Fewer deaths occurred in patients with HIV infection given highly active antiretroviral therapy than in those who were not (0.38, 0.18-0.80; p=0.01). 33 (19%) of 174 patients showed culture conversion, of which 23 (70%) converted within 6 months of initiation of treatment.


CONCLUSIONS
In South Africa, patients with XDR tuberculosis, a substantial proportion of whom are not infected with HIV, have poor management outcomes. Nevertheless, survival in patients with HIV infection is better than previously reported. The priorities for the country are still prevention of XDR tuberculosis, and early detection and management of multidrug-resistant and XDR tuberculosis through strengthened programmes and laboratory capacity.


BACKGROUND
South African Medical Research Council, European Union Framework 7 program, and European Developing Countries Clinical Trials Partnership.
Dheda
Keertan
K
Lung Infection and Immunity Unit, Division of Pulmonology and University of Cape Town Lung Institute, Department of Medicine, Cape Town, South Africa. keertan.dheda@uct.ac.za
Shean
Karen
K
Zumla
Alimuddin
A
Badri
Motasim
M
Streicher
Elizabeth M
EM
Page-Shipp
Liesl
L
Willcox
Paul
P
John
Melanie-Anne
MA
Reubenson
Gary
G
Govindasamy
Darshini
D
Wong
Michelle
M
Padanilam
Xavier
X
Dziwiecki
Alicia
A
van Helden
Paul D
PD
Siwendu
Sweetness
S
Jarand
Julie
J
Menezes
Colin N
CN
Burns
Avril
A
Victor
Thomas
T
Warren
Robin
R
Grobusch
Martin P
MP
van der Walt
Martie
M
Kvasnovsky
Charlotte
C
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy*; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D000995:Antitubercular Agents / Q000009:adverse effects / Q000627:therapeutic use*; D054908:Extensively Drug-Resistant Tuberculosis / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D013019:South Africa; D015996:Survival Rate; D016896:Treatment Outcome; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy
D000995:Antitubercular Agents