Olivier Marcy1, Didier Laureillard2, Yoann Madec3, Sarin Chan4, Charles Mayaud5, Laurence Borand6, Narom Prak7, Chindamony Kim8, Kim Khemarin Lak9, Chanroeurn Hak10, Bunnet Dim11, Thim Sok12, Jean-François Delfraissy13, Anne E Goldfeld14, François-Xavier Blanc15. 1. Cambodian Health Committee Epidemiology and Public Health Unit, Institut Pasteur du Cambodge, Phnom Penh, Cambodia. 2. Cambodian Health Committee ANRS, Ho Cho Minh City, Vietnam. 3. Emerging Diseases Epidemiology Unit, Institut Pasteur, Paris, France. 4. Cambodian Health Committee Calmette Hospital, Phnom Penh, Cambodia. 5. Assistance Publique-Hôpitaux de Paris, Hôpital Tenon, Paris, France. 6. Epidemiology and Public Health Unit, Institut Pasteur du Cambodge, Phnom Penh, Cambodia. 7. Khmer Soviet Friendship Hospital, Phnom Penh. 8. Donkeo Provincial Hospital, Takeo Médecins Sans Frontières, Phnom Penh. 9. Cambodian Health Committee Svay Rieng Provincial Hospital, Svay Rieng. 10. Calmette Hospital, Phnom Penh, Cambodia. 11. Cambodian Health Committee Médecins Sans Frontières, Phnom Penh Siem Reap Provincial Hospital, Siem Reap, Cambodia. 12. Cambodian Health Committee. 13. Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Le Kremlin-Bicêtre, France. 14. Cambodian Health Committee Program in Cellular and Molecular Medicine, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts. 15. Université de Nantes, INSERM UMR 1087 CNRS UMR 6291, Institut du Thorax, CHU de Nantes, France.
Abstract
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.
RCT Entities:
BACKGROUND: Shortening the interval between antituberculosis treatment onset and initiation of antiretroviral therapy (ART) reduces mortality in severely immunocompromised human immunodeficiency virus (HIV)-infectedpatients 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.
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