Report 3 -  4th International Workshop on HIV Drug Resistance and Treatment Strategies
Written by Jules Levin
Sitges, Spain, June 12-16 2000

Intermittent Viral Load Blips and Viral Load Rebound

Diane Havlir delivered an oral presentation  on intermittent viral load blips (HIV RNA 50-200) and if they are predictive of virologic rebound (>200 copies/ml) in patients receiving initial combination therapy.

She defined intermittent viremia, for this study, as HIV RNA >50 copies/ml with a subsequent measure <50 copies/ml after confirming virologic suppression (<50 copies/ml) with 24 weeks of therapy with indinavir, AZT and 3TC. Virologic rebound is 2 consecutive HIV RNA >200 copies/ml. (ACTG 343 maintenance failures were excluded). The median duration of therapy of the patients in the study they used for this analysis (ACTG 343) was 84 weeks. In ACTG 343 they found:

Predictors Of Intermittent Viremia (>50 c/ml)

Baseline HIV RNA and maintenace therapy were predictors of blips. Baseline resistance at 215 position and time to <200 c/ml HIV RNA were borderline significant in predicting blips.

They used a modified Roche PCR viral load test with a low detection limit of 2.5 copies/ml. They found that median viral load was higher in subjects with intermittent viremia (23 copies/ml) compared to those without intermittent viremia (P<0.001). Only 8% of RNA measures in patients with intermittent viremia were <2.5 copies/ml compared to 52% of patients without intermittent viremia (P=0.013).

Havlir concluded that in this study population in 343 intermittent blips did not lead to viral rebound within the time frame they looked at (84 weeks): 9/96 (9.3%) of patients with intermittent viremia had viral rebound; 20/145 (13.8%) with viral suppression had viral rebound. Baseline HIV RNA was the only predictor of virologic failure in the model they used.

They also looked patients in the Merck 035 study in which patients received indinavir+AZT/3TC. Again they found those with intermittent blips had higher median RNA (7.3 copies/ml) than those with suppressed viremia (2.5 copies/ml). But individuals with suppressed viremia also had blips, its just that they were blips were <50 copies/ml. In this patient group with a median duration of 4.5 years of observation 0/6 patients with intermittent viremia had viral rebound, and 0/7 patients with viral suppression had viral rebound.

Intermittent viremia (>2.5 copies/ml) was present in all patients treated for as long as 5 years. One resistant researcher I spoke with at this meeting found resistant virus when he observed blips. This resistant virus was not present before therapy. He and I think it's intuitive that given enough time viral rebound will occur if there are blips. Havlir's study extends to 5 years in small numbers of individuals.  

Why do patients have persistent intermittent viremia? Havlir said it could be ongoing infection, latently infected cells, and sanctuaries.