Clinical deterioration during antituberculosis treatment in Africa: incidence, causes and risk factors.
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/microL [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/microL: RR = 1.4, 95% CI = 0.7-2.9; CD4+:200-350 cells/microL: RR = 2.0, 95% CI = 1.1-3.6; CD4+<200 cells/microL: 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/microL.


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/microL will likely reduce the high burden of clinical deterioration.
Pepper
Dominique J
DJ
Infectious Diseases Unit, GF Jooste Hospital, Cape Town, South Africa. dominiquepepper@gmail.com
Marais
Suzaan
S
Wilkinson
Robert J
RJ
Bhaijee
Feriyl
F
Maartens
Gary
G
McIlleron
Helen
H
De Azevedo
Virginia
V
Cox
Helen
H
McDermid
Cheryl
C
Sokhela
Simiso
S
Patel
Janisha
J
Meintjes
Graeme
G
D000349:Africa; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D000995:Antitubercular Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D015897:Comorbidity; D015658:HIV Infections / Q000150:complications / Q000401:mortality / Q000473:pathology* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D015994:Incidence; D011446:Prospective Studies; D012307:Risk Factors; D017211:Treatment Failure; D014376:Tuberculosis / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*
D019380:Anti-HIV Agents; D000995:Antitubercular Agents