Causes and determinants of mortality in HIV-infected adults with tuberculosis: an analysis from the CAMELIA ANRS 1295-CIPRA KH001 randomized trial.
BACKGROUND
Shortening the interval between antituberculosis treatment onset and initiation of antiretroviral therapy (ART) reduces mortality in severely immunocompromised human immunodeficiency virus (HIV)-infected patients with tuberculosis. A better understanding of causes and determinants of death may lead to new strategies to further enhance survival.


METHODS
We assessed mortality rates, causes of death, and factors of mortality in Cambodian HIV-infected adults with CD4 count ≤200 cells/µL and tuberculosis, randomized to initiate ART either 2 weeks (early ART) or 8 weeks (late ART) after tuberculosis treatment onset in the CAMELIA clinical trial.


RESULTS
Six hundred sixty-one patients enrolled contributed to 1366.1 person-years of follow-up; 149 (22.5%) died. There were 8.3 deaths per 100 person-years (95% confidence interval [CI], 6.4-10.7) in the early-ART group and 13.8 deaths per 100 person-years (95% CI, 11.2-16.9) in the late-ART group (P = .002). Tuberculosis was the primary cause of death (28%), followed by other HIV-associated conditions (19%). Factors independently associated with mortality in the first 26 weeks were the age, body mass index, hemoglobin, interrupted or ineffective tuberculosis treatment before identification of drug resistance, disseminated tuberculosis, and nontuberculous mycobacterial disease. After 50 weeks in the trial, the most frequent causes of death were non-HIV related or tuberculosis related, including drug toxicity; factors associated with mortality were late ART, loss to follow-up, and absence of cotrimoxazole prophylaxis.


CONCLUSIONS
Despite ART introduction, mortality remained high, with tuberculosis as the leading cause of death. Reducing tuberculosis-related mortality remains a challenge in resource-limited settings and requires innovative strategies. Clinical Trials Registration. NCT00226434.
Cambodian Health Committee Epidemiology and Public Health Unit, Institut Pasteur du Cambodge, Phnom Penh, Cambodia.
Olivier
O
Marcy
Cambodian Health Committee ANRS, Ho Cho Minh City, Vietnam.
Didier
D
Laureillard
Emerging Diseases Epidemiology Unit, Institut Pasteur, Paris, France.
Yoann
Y
Madec
Cambodian Health Committee Calmette Hospital, Phnom Penh, Cambodia.
Sarin
S
Chan
Assistance Publique-Hôpitaux de Paris, Hôpital Tenon, Paris, France.
Charles
C
Mayaud
Epidemiology and Public Health Unit, Institut Pasteur du Cambodge, Phnom Penh, Cambodia.
Laurence
L
Borand
Khmer Soviet Friendship Hospital, Phnom Penh.
Narom
N
Prak
Donkeo Provincial Hospital, Takeo Médecins Sans Frontières, Phnom Penh.
Chindamony
C
Kim
Cambodian Health Committee Svay Rieng Provincial Hospital, Svay Rieng.
Kim Khemarin
KK
Lak
Calmette Hospital, Phnom Penh, Cambodia.
Chanroeurn
C
Hak
Cambodian Health Committee Médecins Sans Frontières, Phnom Penh Siem Reap Provincial Hospital, Siem Reap, Cambodia.
Bunnet
B
Dim
Cambodian Health Committee.
Thim
T
Sok
Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Le Kremlin-Bicêtre, France.
Jean-François
JF
Delfraissy
Cambodian Health Committee Program in Cellular and Molecular Medicine, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts.
Anne E
AE
Goldfeld
Université de Nantes, INSERM UMR 1087 CNRS UMR 6291, Institut du Thorax, CHU de Nantes, France.
François-Xavier
FX
Blanc
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D000890:Anti-Infective Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D000995:Antitubercular Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy / Q000401:mortality*; D006801:Humans; D016867:Immunocompromised Host; D008297:Male; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use; D014376:Tuberculosis / Q000150:complications / Q000188:drug therapy / Q000401:mortality*
D019380:Anti-HIV Agents; D000890:Anti-Infective Agents; D000995:Antitubercular Agents; D015662:Trimethoprim, Sulfamethoxazole Drug Combination
HIV; adult; cause of death; mortality; tuberculosis