Swiss Study Records High Prevalence of Toxic Effects From Antiretroviral Treatment

Potent antiretroviral therapy, defined as a "combination that includes at least three agents -- a protease inhibitor, a non-nucleoside reverse transcriptase inhibitor or a nucleoside analogue reverse transcriptase inhibitor," is associated with a "high prevalence" of toxic side effects, according to an analysis from the Swiss HIV Cohort Study published in the Oct. 20 issue of the Lancet. The researchers conducted structured interviews with 1,160 patients attending seven outpatient clinics over a four-week period in August 1999 and September 1999. They also analyzed participants' blood samples for adverse levels of substances such as creatinine, bilirubin, glucose and cholesterol. The researchers then used a multiple logistic regression model to investigate the associations between the recorded abnormalities and the treatment combinations.

Findings
Forty-seven percent of patients reported adverse clinical events, while 27% experienced adverse laboratory results "probably or definitely attributed to antiretroviral treatment." Nine percent of the clinical events and 16% of the laboratory results were identified as "serious or severe." Sixty percent of study patients received single PI treatment (use of one PI and no NNRTI), while 15% were on PI-sparing treatment (no use of PIs and one NNRTI or triple use of NRTIs) or dual-PI treatment (use of two PIs and no NNRTI), and 10% were receiving three-class antiretroviral treatment (use of a PI, an NNRTI and an NRTI). The following is a summary of findings:

• Single PI treatment and PI-sparing treatment were associated with similar levels of adverse events.
• When compared to single-PI treatment, dual-PI treatment was associated with a greater risk of fever and diarrhea and increased concentrations of cholesterol, triglyceride and alkaline phosphatase.
• When compared with single-PI treatment, three-class antiretroviral treatment was associated with a higher prevalence of diarrhea and increased concentrations of cholesterol, triglyceride, alkaline phosphatase and lactate.
• Use of PI-sparing treatment was associated with a higher risk of vomiting and mood and sleep disorders and higher concentrations of amylase, bilirubin and urate but was also associated with a decreased risk of diarrhea.

A New Resource For Clinicians
The researchers state that they recorded associated adverse effects of specific antiretroviral drugs and drug combinations because, although some information on such side effects had been collected anecdotally and in some clinical trials, there was no "up-to-date or comprehensive" resource. "Various antiretroviral treatment regimens have comparable efficacy in controlling HIV-1 infection, therefore toxic effects, as well as the pill number, pill size, cost, previous medication history or drug interactions will drive the choice of treatment, in particular when patients suffer from co-morbidity, or from previous treatment-induced adverse side effects," the authors state. Such adverse effects have an influence on adherence, which in turn influences viral resistance, which may lead to the cessation of treatment, they note. Such postmarketing surveys of adverse effects are "essential for development of treatment guidelines," they conclude, adding that the "tolerability" of antiretroviral treatments needs to be improved (Fellay et al., Lancet, 10/20).