Risk Factors for Short-Term Virologic Outcomes Among HIV-Infected Patients Undergoing Regimen Switch of Combination Antiretroviral Therapy

Abstract

We investigated risk factors for unfavorable virologic responses among HIV-infected patients who recently switched antiretroviral regimens. We identified HIV-infected patients who switched antiretroviral regimens (defined as adding ≥2 new medications) between 2001 and 2008 at Kaiser Permanente California. Virological response, measured after 6 months on the new regimen, was classified as (1) maximal viral suppression (HIV RNA <75/ml), (2) low-level viremia (LLV; 75-5000/ml), or (3) advanced virologic failure (>5000/ml). Potential risk factors examined included (1) HIV disease factors, e.g., prior AIDS, CD4 cell count; (2) history of antiretroviral use, e.g., therapy classes of the newly switched regimen, medication adherence, and virologic failure at previous regimens; and (3) novel patient-level factors including comorbidities and healthcare utilization. Adjusted odds ratios (aOR) for LLV and advanced virologic failure were obtained from multivariable nominal logistic regression models. A total of 3447 patients were included; 2608 (76%) achieved maximal viral suppression, 420 (12%) had LLV, and 419 (12%) developed advanced virologic failure. Factors positively associated with LLV and advanced virologic failure included number of regimens prior to switch [aOR(per regimen)=1.38 (1.17-1.62) and 1.77 (1.50-2.08), respectively], nucleotide reverse transcriptase inhibitor-only regimens (vs. protease inhibitor-based) [aOR=2.78 (1.28-6.04) and 5.10 (2.38-10.90), respectively], and virologic failure at previous regimens [aOR=3.15 (2.17-4.57) and 4.71 (2.84-7.81), respectively]. Older age, higher CD4 cell count, and medication adherence were protective for unfavorable virologic outcomes. Antiretroviral regimen-level factors and immunodeficiency were significantly associated with virologic failure after a recent therapy switch and should be considered when making treatment change decisions.