CROI 2010: Even Low-level, Short-term Detectable Viral Load Raises the Risk of Virological Treatment Failure and Death

People with HIV who have persistent episodes of low-level viremia are more likely to experience sustained virological rebound and have a higher risk of death than individuals who maintain consistently undetectable viral load (< 50 copies/mL) or experience only transient "blips," according to a poster presented at the 17th Conference on Retroviruses & Opportunistic Infections (CROI 2010) last month in San Francisco.

Mark Hull and colleagues with the Canadian Observational Cohort Collaborationevaluated the effect of ongoing viremia (detectable virus in the blood) on risk of virological rebound and mortality among HIV positive people on combination antiretroviral therapy (ART).

The analysis included 1674 HIV patients; most (84%) were men and the median age was 41 years. All participants had 2 consecutive plasma viral load measurements < 400 copies/mL at least 30 days apart, followed by at least 6 subsequent measurements over 24 months (the classification period), which the researchers used to categorize them into 4 groups:

• Fully suppressed: maintained plasma viral load < 50 copies/mL throughout the classification period;
• Transient viremia: achieved plasma viral load < 50 copies/mL and remained below this level for more than 75% of the classification period, but had infrequent low-level viremia (50-1000 copies/mL) less than 25% of the time.
• Short-term persisting viremia: maintained plasma viral load < 50 copies/mL for 25%-75% of the classification period, with the remainder spent with > 50 copies/mL.
• Long-term persisting viremia: maintained plasma viral load < 50 copies/mL for only 25% or less of the classification period but had detectable viremia most of the time.

After the initial classification period, participants were followed to determine time to virological rebound, defined as 2 consecutive plasma viral load measurements > 1000 copies/mL, and time to death. From the time of initial viral suppression, the median follow-up time for virological rebound (1674 patients) was 36 months and the median follow-up time for mortality outcomes (1430 patients) was 51 months.

Results

• Compared with the fully suppressed group, the transient viremia group had a similar risk of sustained virological rebound (hazard ratio [HR] 1.12, where 1.0 indicates equal risk).
• The short-term persisting viremia group was about 6 times more likely to experience virological rebound than the fully suppressed group (HR 6.05).
• The long-term persisting viremia group had more than a 20-fold higher risk than the fully suppressed group (HR 20.46).
• People in the short-term persisting viremia group who mostly had low-level viral load (majority of measurements < 200 copies/mL) were still more likely to experience virological rebound (HR 4.95) and death (HR 4.25) than people in the transient viremia group with the same viral load levels.

"Those patients experiencing persisting viremia (short-term and long-term) were more likely to experience subsequent viral rebound," the investigators concluded. "Patients with only short-term low-level viremia remained at higher risk of virological rebound and increased mortality compared to those with full suppression or only transient low-level viremia."

Given these findings, they advised, "Sustained virological suppression remains an important target for ART therapy."

Montreal Chest Institute, McGill University Health Ctr, Quebec, Canada; University of Toronto, Ontario, Canada; British Columbia Ctr for Excellence in HIV/AIDS, Vancouver, BC, Canada; Clin Med l’Actuel, Montreal, Quebec, Canada.

3/26/10

Reference

M Hull, M Loutfy, W Zhang, and others (Canadian Observational Cohort Collaboration). Persistent Low-level Viremia Is Associated with Increased Risk of Virologic Failure and Mortality. 17th Conference on Retroviruses & Opportunistic Infections (CROI 2010). San Francisco. February 16-19, 2010. Abstract 504.