The cause of death among patients with HIV receiving antiretroviral therapy varied according to age, sex and transmission-risk group, researchers for the Antiretroviral Therapy Cohort Collaboration reported.
The time since starting ART also played a role: AIDS-related deaths decreased with time since starting ART, but the mortality related to non-AIDS malignancies increased.
“As patients become increasingly treatment-experienced, monitoring patterns of causes of death over longer durations of ART will be important for optimizing management of [people with HIV], many of whom develop comorbidities,” the researchers wrote in Clinical Infectious Diseases. “Understanding changes in cause-specific deaths with ART duration can help direct appropriate screening procedures, risk assessment and preventive treatment for [people with HIV].”
The study included data on patients enrolled in 16 cohorts in Europe and North America. The researchers evaluated the causes of death among the patients in the cohorts who died and coded the deaths accordingly. Patient characteristics, time from ART initiation to death, AIDS-defining conditions after ART and most recent CD4 count were included in the patient analysis.
Among the 65,121 patients in the cohorts, 4,237 died during 327,535 person-years of follow-up, for a mortality rate of 12.9 deaths per 1,000 person-years. The specific cause of death could be classified for 84.4% of the deaths: 1,496 died of AIDS, 461 died of a non-AIDS malignancy and 349 died of unnatural causes.
In the first 6 months of ART, the all-cause mortality rate was 24.3 per 1,000 person-years, which decreased to 10.2 per 1,000 person-years after 5 years of ART. The significant decrease is attributed to decreases in AIDS-related deaths: 13.2 per 1,000 person-years in the first 6 months of ART vs. 2.4 per 1,000 person-years after 5 years. However, the mortality due to non-AIDS malignancy increased from 1.1 per 1,000 person-years in the first 6 months of ART to 1.5 per 1,000 after 5 years.
Transmission of HIV by injection drug use was associated with higher rates of all causes of death compared with men who have sex with men during the first year of ART (HR=18.1; 95% CI, 6.2-52.7) and thereafter (HR=9.1; 95% CI, 5.8-14.2). Older age was associated with deaths from cardiovascular disease and non-AIDS malignancies. Lastly, CD4 count at baseline and at 12 months was associated with AIDS, non-AIDS infection and non-AIDS malignancy deaths.
“Continuing study of cause-specific mortality is required to clarify whether such mortality arises from effects of ART, prolonged exposure to the virus, consequences of restoration of CD4 counts after severe immunosuppression, or whether such mortality mainly reflects aging and non-HIV risk factors,” the researchers wrote. “Large studies would be required to compare age-standardized mortality rates and risk factors for HIV-positive and negative populations.”
Disclosure: See study for list of disclosures.