| |
Cause-Specific Mortality in HIV-Positive Patients Who Survived Ten Years after Starting Antiretroviral Therapy
|
| |
| |
Download the PDF here
• The most frequent cause of death was non-AIDS non-liver cancer (41 deaths [25% of those classified]) followed by AIDS (35 [19%]), cardiovascular (22 [12%]) and liver-related (18 [10%]).
We studied factors that are prognostic for mortality in a large patient cohort who started combination ART without previous exposure to antiretroviral drugs and were treated for a decade.
Viral replication, lower CD4 count, prior AIDS, and transmission via injecting drug use continue to predict higher all-cause and AIDS-related mortality in patients treated with combination antiretroviral therapy for over a decade. Deaths from AIDS and non-AIDS infection are less frequent than deaths from other non-AIDS causes.
Summary
Among HIV positive patients who started combination ART 1996-1999 without prior exposure to antiretroviral drugs and survived for at least ten years, the majority were virally suppressed and had CD4 counts > 500 cells/μL. Nonetheless lower CD4 count and lack of HIV-1 viral suppression at ten years after starting ART, and AIDS before or during the first decade of ART, were strong predictors of death during the second decade of ART. Low CD4 count at ART start was no longer associated with increased mortality beyond ten years after accounting for CD4 count measured at ten years after starting ART. Compared with patients from other risk groups, those who reported IDU as route of HIV transmission experienced higher mortality from ten years after ART start.
The most frequently occurring causes of death were non-AIDS-defining malignancy, followed by AIDS, cardiovascular, and liver-related causes. Older age was strongly associated with cardiovascular mortality and with non-AIDS non-liver malignancies, IDU with non-AIDS infection and liver-related mortality, and low CD4 count and detectable viral replication at ten years after starting ART with AIDS mortality.
The five-year mortality risk was <5% in 60% of patients and was strongly age-related: fewer than 30% of patients aged over 60 had five-year mortality risk less than 10%.
Abstract
Objectives
To estimate mortality rates and prognostic factors in HIV-positive patients who started combination antiretroviral therapy between 1996-1999 and survived for more than ten years.
Methods
We used data from 18 European and North American HIV cohort studies contributing to the Antiretroviral Therapy Cohort Collaboration. We followed up patients from ten years after start of combination antiretroviral therapy. We estimated overall and cause-specific mortality rate ratios for age, sex, transmission through injection drug use, AIDS, CD4 count and HIV-1 RNA.
Results
During 50,593 person years 656/13,011 (5%) patients died. Older age, male sex, injecting drug use transmission, AIDS, and low CD4 count and detectable viral replication ten years after starting combination antiretroviral therapy were associated with higher subsequent mortality. CD4 count at ART start did not predict mortality in models adjusted for patient characteristics ten years after start of antiretroviral therapy.
• The most frequent causes of death (among 340 classified) were non-AIDS cancer, AIDS, cardiovascular, and liver-related disease.
• Older age was strongly associated with cardiovascular mortality, injecting drug use transmission with non-AIDS infection and liver-related mortality
• low CD4 and detectable viral replication ten years after starting antiretroviral therapy with AIDS mortality.
• Five-year mortality risk was <5% in 60% of all patients, and in 30% of those aged over 60 years.
Conclusions
Viral replication, lower CD4 count, prior AIDS, and transmission via injecting drug use continue to predict higher all-cause and AIDS-related mortality in patients treated with combination antiretroviral therapy for over a decade. Deaths from AIDS and non-AIDS infection are less frequent than deaths from other non-AIDS causes.
Mortality from ten years after start of ART
Mortality was substantially higher in patients aged 60-69 and >70 years from ten years after starting ART (adjusted HR 4.29 [95% CI 3.06-6.02] and 8.59 [5.82-12.7] respectively compared with age 16-39 (Table 3)). Mortality was also substantially higher in patients with CD4 count <100 cells/μL from ten years after ART start (adjusted HR 6.17 [4.46-8.53] compared with >750 cells/μL). Mortality rates were similar in patients with CD4 count 500-749 and >750 cells/μL. Mortality was higher in IDU compared with non-IDU (adjusted HR 2.58 [2.04-3.26]). Viral load >1000 copies/mL at ten years and an AIDS diagnosis in the first ten years
after starting ART were associated with higher subsequent mortality (adjusted HR 1.74 [1.40-2.15] and 1.68 [1.37-2.06] respectively). There was no difference in subsequent mortality between the patients on PI- (adjusted HR 1.17 [0.95-1.43] compared with NNRTI-) and NNRTI-based regimens at 10 years after ART start.
Lower CD4 count at ART start was weakly associated with higher mortality from ten years (Table 4). This was attenuated by adjustment for CD4 count at ten years after starting ART and other covariates, with a suggestion of lower subsequent mortality for patients with very low CD4 count at ART start after adjustment for ten year CD4 count [HR = 0.62 (0.46-0.83) for CD4 <50 vs. 350 cells/μL].
Results were similar to those in the main analysis when LTFU was considered a competing risk to death in the sensitivity analysis.
|
|
| |
| |
|
|
|
