Intermittent use of ART is associated with increased mortality

A recent Canadian study demonstrates that even after adjusting for other prognostic factors, intermittent use of antiretroviral therapy (ART) was associated with increased mortality.

Dr Robert S Hogg and colleagues at the British Columbia Centre for Excellence in HIV/AIDS, Vancouver, report in the 3 May issue of AIDS a study to characterise the impact of intermittent use of triple drug ART on survival. They carried out a population-based analysis of 1,282 ART-naïve patients in British Columbia who started triple combination therapy between August 1996 and December 1999.

Therapy use was estimated by dividing the number of months of medications by the number of months of follow-up. Intermittent therapy was defined as the participant having obtained less than 75% of their medication in the first 12 months. The researchers measured the cumulative all-cause mortality rates from the start of triple drug ART to 30 September 2000.

By that date 106 patients had died. Cumulative mortality was 3.9% at 12 months. In a multivariate model, each 100 cell decrease in baseline CD4+ T cell count and the intermittent use of ARV drugs were associated with increased mortality, with risk ratios of 1.31 (95% confidence interval [CI], 1.16-1.49; P< 0.001) and 2.90 (95% CI, 1.93-4.36; P < 0.001), respectively.

The researchers measured the intermittent use of therapy over the first year in order to control for downward drift, while other factors were measured at the end of the period.

After adjusting for all other factors, they found that those participants who used ARV drugs intermittently were 2.97 times (95% CI, 1.33-6.62; P = 0.008) more likely to die.

Dr Hogg and colleagues conclude: “Our study demonstrates that even after adjusting for other prognostic factors intermittent use of antiretroviral therapy was associated with increased mortality.”

Comment

Despite the title it should be emphasised that this study was less about “intermittent therapy” and more about poor adherence. This should not be confused with intermittent therapy in the sense of “structured treatment interruptions”. This study further emphasises that poor adherence in patients with low CD4 counts is associated with disease progression and death. In patients with high CD4 counts and well controlled HIV, however, planned treatment interruptions are a completely different issue.