HIV-1 Disease Progression During Highly Active Antiretroviral Therapy: An Application Using Population-Level Data in British Columbia: 1996―2011

• Published in: Journal of acquired immune deficiency syndromes (1999) Vol. 63; no. 5; pp. 653 - 659
• Main Authors: NOSYK, Bohdan, JEONG MIN, LIMA, Viviane D, YIP, Benita, HOGG, Robert S, MONTANER, Julio S. G
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 15-08-2013; Lippincott Williams & Wilkins Ovid Technologies
• Subjects: Adult; AIDS/HIV; Anti-HIV Agents - therapeutic use; Antiretroviral drugs; Antiretroviral Therapy, Highly Active - methods; Biological and medical sciences; British Columbia; CD4 Lymphocyte Count; Clinical outcomes; Cohort Studies; Disease Progression; Drug therapy; Female; Fundamental and applied biological sciences. Psychology; HIV; HIV Infections - drug therapy; HIV Infections - pathology; HIV-1 - isolation & purification; Human immunodeficiency virus; Human viral diseases; Humans; Indexing in process; Infectious diseases; Male; Medical sciences; Microbiology; Miscellaneous; Models, Statistical; Plasma - virology; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral Load; Virology; Canada; British Columbia; North America; America; British Columbia Canada; Disease development; Immunopathology; HIV-1 virus; acquired immune deficiency syndromes; Retroviridae; AIDS; Lentivirus; Immune deficiency; Infection; Virus; CD4; transition probabilities; Viral disease; multi-state Markov models; Antiviral; Models; Human immunodeficiency virus
• ISSN: 1525-4135; 1944-7884
• DOI: 10.1097/QAI.0b013e3182976891

Accurately estimating rates of disease progression is of central importance in developing mathematical models used to project outcomes and guide resource allocation decisions. Our objective was to specify a multivariate regression model to estimate changes in disease progression among individuals on highly active antiretroviral treatment in British Columbia, Canada, 1996-2011.
We used population-level data on disease progression and antiretroviral treatment utilization from the BC HIV Drug Treatment Program. Disease progression was captured using longitudinal CD4 and plasma viral load testing data, linked with data on antiretroviral treatment. The study outcome was categorized into (CD4 count ≥ 500, 500-350, 350-200, <200 cells/mm, and mortality). A 5-state continuous-time Markov model was used to estimate covariate-specific probabilities of CD4 progression, focusing on temporal changes during the study period.
A total of 210,083 CD4 measurements among 7421 individuals with HIV/AIDS were included in the study. Results of the multivariate model suggested that current highly active antiretroviral treatment at baseline, lower baseline CD4 (<200 cells/mm), and extended durations of elevated plasma viral load were each associated with accelerated progression. Immunological improvement was accelerated significantly from 2004 onward, with 23% and 46% increases in the probability of CD4 improvement from the fourth CD4 stratum (CD4 < 200) in 2004-2008 and 2008-2011, respectively.
Our results demonstrate the impact of innovations in antiretroviral treatment and treatment delivery at the population level. These results can be used to estimate a transition probability matrix flexible to changes in the observed mix of clients in different clinical stages and treatment regimens over time.