Highly active antiretroviral therapy in a large urban clinic: Risk factorsfor virologic failure and adverse drug reactions

Background: In clinical trials, highly active antiretroviral therapy (HAART ) reduces plasma HIV-1 RNA levels to less than 500 copies/mL in 60% to 90% of patients with HIV-1 infection. The performance of such therapy outside o f the clinical trial setting is unclear. Objective: To determine factors associated with failure to suppress HIV-1 R NA levels and adverse drug reactions in a cohort of patients in whom protea se inhibitor-containing therapy was begun in a large urban clinic. Design: Retrospective cohort study. Setting: Johns Hopkins HIV Clinic in Baltimore, Maryland. Patients: 273 protease inhibitor-naive patients began taking a protease inh ibitor regimen containing at least one other antiretroviral drug to which t he patients had not previously been exposed. Measurements: Demographic variables, plasma HIV-1 RNA levels, CD4(+) lympho cyte counts, and adverse drug reactions. Results: Levels of HIV-1 RNA were undetectable in 42% of the cohort at 1 to 90 days, in 44% at 3 to 7 months, and in 37% at 7 to 14 months. Factors as sociated with failure to suppress viral load at two or more time points inc luded higher rates of missed clinic appointments, nonwhite ethnicity, age 4 0 years or younger, injection drug use, lower baseline CD4(+) lymphocyte co unt, and higher baseline viral load. In a multivariate model, only higher r ates of missed clinic appointments were independently associated with viral suppression at 1 year. Ritonavir was associated with adverse drug reaction s about twice as frequently as indinavir or nelfinavir, and women experienc ed significantly more adverse effects than men. Conclusions: Unselected patients in whom HAART is started in a clinic setti ng achieve viral suppression substantially less frequently than do patients in controlled clinical trials. Missed clinic visits were the most importan t risk factor for failure to suppress HIV-l RNA levels. Studies are needed to identify interventions that maximize the performance of HAART in inner-c ity clinics.