Tuberculosis and other HIV diseases accounted for three quarters of the deaths in the first 26 weeks of the CAMELIA trial of early versus delayed antiretroviral therapy (ART) for people being treated for TB. An array of factors explained a higher risk of death.
CAMELIA randomized HIV-positive Cambodian adults being treated for TB to begin ART 2 weeks or 8 weeks after TB therapy began. All study participants had a CD4 count at or below 200 cells/µL. Early ART resulted in a 34% overall lower death rate in the trial. The new study determined causes of death and used Cox proportional hazard models to identify factors associated with death.
The analysis involved 661 people, 149 of whom (22.5%) died. Mortality was significantly lower in the early-ART group than in the later ART group (8.3 versus 13.8 deaths per 100 person-years, P = 0.002).
Causes of death in the first 26 weeks of the trial in the early and late ART groups were TB (27% and 46%), other HIV conditions (27% and 20%), either TB or HIV conditions (19% and 14%), drug toxicity (3% and 6%), other non-TB/HIV conditions (19% and 10%), and unknown causes (5% and 4%). Factors independently associated with death in the first 26 weeks were older age, lower body mass index, lower hemoglobin, disseminated tuberculosis, and nontuberculous mycobacterial disease.
Causes of death from week 26 to week 50 in the early and late ART groups were TB (0% and 15%), HIV conditions (33% and 15%), either TB or HIV conditions (33% and 15%), drug toxicity (11% and 23%), other non-TB/HIV conditions (1% and 15%), and unknown caues (1% and 15%). Factors independently associated with death in trial weeks 26 to 50 were late ART, loss to follow-up, and no cotrimoxazole prophylaxis.
Although early ART lowered mortality in CAMELIA, the authors observe that “mortality remained high during the first 6 months following tuberculosis diagnosis, and tuberculosis was the leading cause of these deaths.” Among people alive at trial week 50, subsequent mortality was twice higher in the late ART group than in the early ART group.
To improve long-term survival, the CAMELIA team proposes reconsidering the appropriate time to stop cotrimoxazole prophylaxis. “Optimized case management,” they advise, “should include early ART initiation and opportunistic infection prophylaxis, appropriate management of TB-IRIS and toxicities, and support of adherence to avoid treatment interruption, but also possibly intensification of tuberculosis initial treatment.”
Source: Olivier Marcy, Didier Laureillard, Yoann Madec, Sarin Chan, Charles Mayaud, Laurence Borand, Narom Prak, Chindamony Kim, Kim Khemarin Lak, Chanroeurn Hak, Bunnet Dim, Thim Sok, Jean-François Delfraissy, Anne E. Goldfeld, François-Xavier Blanc, for the CAMELIA (ANRS 1295-CIPRA KH001) Study Team. Causes and determinants of mortality in HIV-infected adults with tuberculosis: an analysis from the CAMELIA ANRS 1295-CIPRA KH001 randomized trial. Clinical Infectious Diseases. 2014; 59: 435-445.
Source: IAS