Nearly two-thirds of adults starting antiretroviral therapy (ART) changed their regimen in a six-year analysis of a Polish cohort. People over 50 years old changed their first-line regimen less often than younger people, and worse adherence in younger people largely explained the age-based difference.
Despite continuing improvements in the convenience and tolerability of antiretrovirals, first-line regimen modifications remain frequent in observational studies. Researchers working with the Polish Observational Cohort of HIV/AIDS Patients (POLCA) Study Group noted that ART changes differ by age but that reasons for these differences remain poorly studied. Because older patients make up a growing proportion of people with HIV, the POLCA investigators analyzed age-based factors in first-line regimen changes in three age groups.
POLCA is an observational cohort of initially antiretroviral-naive adults seen at a large HIV outpatient clinic in Warsaw, which follows European AIDS Clinical Society guidelines. All study participants started ART and follow-up continued until February 28, 2013, or the first ART regimen modification, defined as any change in the anchor drug of a regimen -- a protease inhibitor (PI), non-nucleoside reverse transcriptase inhibitor (NNRTI), integrase inhibitor or fusion inhibitor. Simplifying a regimen to combination antiretrovirals did not count as a modification. The researchers divided cohort members into three groups according to age at the first visit: under 30, 30 to 50, and over 50 years.
The analysis included 2,027 patients, 689 in the youngest group, 1,202 in the middle age group and 136 in the oldest group. While 72.4% of participants started a PI, 26.1% started an NNRTI and 1.5% started another regimen. Women made up a significantly higher proportion of the youngest group (26.3% versus 14.1% in the middle group and 11.0% in the oldest group, P < .0001). Men who have sex with men made up 38.9% of the youngest group, 24.9% of the middle group and 35.3% of the oldest group (P < .0001).
The oldest group had the lowest nadir CD4+ count (median 166 cells/mm3 versus 244 cells/mm3 in the youngest group and 173 cells/mm3 in the middle group, P < .0001). Entering care with a CD4+ count below 350 cells/mm3 proved significantly more frequent in the oldest patients than in the youngest and middle groups (64.0% versus 42.5% versus 55.0%, P < .0001). The oldest cohort members also had a significantly lower latest CD4+ count than the youngest group (median 488 versus 504 cells/mm3, P = .012).
Median time on the first antiretroviral regimen measured 4.4 years. Through a median follow-up of 5.8 years, 1268 people (62.5%) modified their first regimen. Kaplan-Meier analysis determined that the oldest age group stayed with its first ART regimen significantly longer than the two younger groups (P < .001). The most frequent reasons for regimen modifications were nonadherence (30.8%) and treatment-related toxicity (29.6%). Nonadherence proved a more frequent reason for modification in the younger groups (28.0% in the youngest and 34.0% in the middle group) than in the oldest group (15.7%) (P < .001). Rates of toxicity as a cause of modification were similar across the three age groups. Treatment failure as a cause of modification tended to be most frequent in the oldest group (10.8% versus 4.8% in the youngest group and 6.5% in the middle group, P = .09).
In the oldest group, Cox proportional hazard analysis determined that starting with a PI regimen more than doubled chances of ART modification (hazard ratio [HR] 2.17, 95% confidence interval [CI] 1.18 to 4.0, P = .01). Entering care with a CD4+ count below 350 cells/mm3 more than halved chances of treatment modification (HR 0.45, 95% CI 0.23 to 0.90, P = .02).
In the middle age group, Cox modeling determined that men had a 50% higher risk of treatment modification (HR 1.50, 95% CI 1.03 to 2.18, P = .034), and infection while injecting drugs lowered the risk about 40% (HR 0.59, 95% CI 0.40 to 0.87, P = .007). In this age group, every 100-cell higher nadir CD4+ count raised the chances of treatment modification 44% (HR 1.44, 95% CI 1.32 to 1.57, P < .001). Starting ART with an integrase inhibitor or a fusion inhibitor also boosted ART modification risk in the middle age group, but the low proportion of people starting treatment with these antiretroviral classes makes these findings hard to interpret.
In the youngest age group, Cox modeling identified only one independent predictor of treatment modification: Every 100-cell higher nadir CD4+ count lowered chances about 10% (HR 0.89, 95% CI 0.81 to 0.98, P = .017).
The POLCA investigators concluded that, although rates of first ART modification proved similar in the three age groups studied, the reasons for changing a first regimen differed from group to group.
Mark Mascolini writes about HIV infection.
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