The therapeutic implications of timely linkage and early retention in HIV care

Following HIV diagnosis, linkage to outpatient treatment, antiretroviral initiation, and longitudinal retention in care represent the foundation for successful treatment. While prior studies have evaluated these processes in isolation, a systematic evaluation of successive steps in the same cohort of patients has not yet been performed. To ensure optimal long-term outcomes, a better understanding of the interplay of these processes is needed. Therefore, a retrospective cohort study of patients initiating outpatient care at the University of Alabama at Birmingham 1917 HIV=AIDS Clinic between January 2000 and December 2005 was undertaken. Multivariable models determined factors associated with: late diagnosis=linkage to care (initial CD4 \u3c 350 cells=mm3), timely antiretroviral initiation, and retention across the first two years of care. Delayed linkage was observed in two-thirds of the overall sample (n = 567) and was associated with older age (odds ratio [OR] = 1.31 per 10 years; 95%confidence interval [CI] = 1.06-1.62) and African American race (OR = 2.45; 95% CI = 1.60-3.74). Attending all clinic visits (hazard ratio [HR] = 6.45; 95% CI = 4.47-9.31) and lower initial CD4 counts led to earlier antiretroviral initiation. Worse retention in the first 2 years was associated with younger age (OR = 0.68 per 10 years;95% CI = 0.56-0.83), higher baseline CD4 count, and substance abuse (OR = 1.78; 95% CI = 1.16-2.73). Interventions to improve timely HIV diagnosis and linkage to care should focus on older patients and African Americans while efforts to improve retention should address younger patients, those with higher baseline CD4 counts, and substance abuse. Missed clinic visits represent an important obstacle to the timely initiation of antiretroviral therapy. These data inform development of interventions to improve linkage and retention in HIV care, an emerging area of growing importance

Increased regimen durability in the era of once-daily fixed-dose combination antiretroviral therapy

INTRODUCTION: Data on initial antiretroviral regimen longevity predates the arrival of newer nucleoside reverse transcriptase inhibitor backbones and once-daily regimens. Modern regimens are thought to possess greater tolerability and convenience. We hypothesized this would translate into greater durability. METHODS: Retrospective study of antiretroviral-naive patients starting treatment at the University of Alabama at Birmingham 1917 HIV/AIDS Clinic 1 January 2000-31 July 2007. Two periods of antiretroviral initiation were identified, prior and after August 2004 (arrival of once-daily fixed-dose regimens). Kaplan-Meier survival analyses of regimen durability by time period and regimen characteristics were performed. Staged Cox proportional hazards models evaluated the roles of dosing complexity and composition in explaining differences in regimen durability between study periods. RESULTS: Overall 542 patients started antiretroviral drugs (n = 309, January 2000-July 2004; n = 233, August 2004-July 2007). Median durability was 263 days longer in after August 2004 regimens. Regimens started before August 2004 had increased hazards for discontinuation relative to after August 2004 regimens [hazard ratio (HR) = 1.44; 95% confidence interval (CI) = 1.03-2.02]. Time period of initiation lost statistical significance when the model included dosing frequency (HR = 1.92 for at least twice daily vs. daily; 95% CI = 1.29-2.88). As regimen composition variables were added, time period and dosing frequency lost significance. Increased hazards of discontinuation were observed with didanosine or stavudine relative to abacavir or tenofovir use (HR = 1.92; 95% CI = 1.29-2.88) and all third drugs compared with non-nucleoside reverse transcriptase inhibitor-based regimens (triple-nucleoside reverse transcriptase inhibitor HR = 1.76; 95% CI = 1.14-2.73; unboosted-protease inhibitor HR = 1.58; 95% CI = 1.02-2.46; boosted-protease inhibitor HR = 1.57; 95% CI = 1.02-2.41). Affective mental health disorders increased the hazard of discontinuation in all models. CONCLUSION: Durability of contemporary once-daily fixed-dose antiretroviral regimens has significantly eclipsed the duration of earlier antiretroviral drug options. Our results indicate this is due to both more convenient dosing and improved tolerability of modern antiretroviral regimens