Concerns that viral load blips during antiretroviral treatment for heavily treatment-experienced patients might carry a higher risk of treatment failure than in patients on their first combination may be allayed by a US study presented today, which found that blips as high as 500 copies/ml, or even 1,000 copies/ml do not necessarily signal viral rebound.
Researchers had previously been concerned that a viral blip above 50 copies or 200 copies would be more likely to signal the emergence of drug-resistant virus in patients with extensive drug resistance, and the subsequent failure of the regimen. However, an analysis of three studies (ACTG 398 and 359, salvage studies of amprenavir, abacavir, adefovir and efavirenz with or without a second protease inhibitor, and nelfinavir/saquinavir versus ritonavir/saquinavir plus adefovir or delavirdine or both) found no relationship between single blips above 50 copies and subsequent treatment failure (defined as two consecutive measurements above 50 copies). Even when the threshold was raised to 500 copies/ml, viral load blips still failed to predict rebound above 1,000 copies/ml after 38 weeks of follow up.
The authors of the study pointed out that the findings have implications for definitions of success or failure in future clinical trials.
"Defining virologic failure by the occurrence of 1 or more episodes of HIV RNA > 50 copies/mL, after initial suppression to
Average blip peaks at 165 copies - but may be higher/ml
Another study presented today, which looked at 123 patients followed over approximately two and half years, found that the mean level of viral load reached during a blip above 50 copies was 165 copies/ml, and half of patients experienced blips no higher than 110 copies/ml. The average interval of testing in this cohort was every 31 days, and 77% of the cohort was found to have at least one blip during the follow up period when tested at this high frequency. On average, one in ten viral load measurements found a blip, but a relatively small number of patients within the group accounted for the majority of the blips detected.
However, the research group which conducted this study argued that the peak of viral load during a blip may be much higher, and that it is characterised by a rapid early increase to a level between 500 and 1,000 copies/ml, followed by a slow second phase of decline below the limit of detection.
Blips did not become more frequent as the length of time on treatment increased, and the researchers suggested that the random pattern of viral load blips is more likely to reflect occasional changes in drug concentration driven by other factors such as dietary changes or concomitant medications, or intercurrent infections, rather than declining adherence or efficacy of treatment.
Di Mascio et al. Viral blip dynamics during HAART. Ninth Conference on Retroviruses and Opportunistic Infections, Seattle, abstract 94, 2002.
Havlir D et al. Are episodes of transient viremia ("blips" in HIV RNA) predictive of virologic failure in heavily treatment-experienced patients? Ninth Conference on Retroviruses and Opportunistic Infections, Seattle, abstract 93, 2002.