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Studies Disagree on Danger in Detectable Viral Load Under 50 Copies
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19th Conference on Retroviruses and Opportunistic Infections, March 5-8, 2012, Seattle
Mark Mascolini
Three studies--two presented at the Conference on Retroviruses [1,2] and one published in Clinical Infectious Diseases [3]--disagreed on whether a detectable viral load under 50 copies posed a risk of confirmed virologic rebound. The studies differed in size and methods, but all three considered rebounds during 1 year of follow-up.
A 438-person French study found no evidence that a load between 20 and 50 copies threatened virologic failure through 1 year of follow-up compared with a load consistently below 20 copies [1]. Across the Channel a 1247-person British analysis found that a still-detectable load under 40 copies almost tripled the risk of rebound above 400 copies when compared with a completely undetectable load [3]. A single-center 1214-person study at Bergamo's Ospedali Riuniti found a significantly increased risk of virologic failure in people with a load detectable above the 3-copy mark [2].
Researchers in Paris focused on two sets of patients--group 1 consisting of 413 people with a viral load always below 20 copies and group 2 including 25 people with at least two viral loads between 20 and 50 copies [1]. The investigators measured viral loads at least three times through the 1 year after inclusion in the study with the COBAS AmpliPrep TaqMan HIV-1 assay. During that time, 267 of 413 people in group 1 (65%) and 11 of 25 in group 2 (44%) had viral loads consistently below 20 copies, a nearly significant difference (P = 0.053).
During the 1 year of follow-up, 7 of 413 people in group 1 (2%) and 4 of 25 in group 2 (16%) had at least two viral loads between 20 and 50 copies, a significant difference (P = 0.002). But the proportion of people with virologic failures--defined as two successive viral loads above 50 copies--did not differ significantly between group 1 and group 2 (4% versus 8%, P = 0.32). Median viral load at failure was 250 copies in group 1 and 88 in group 2.
The Italian study focused on 1214 people with a viral load below 50 copies while taking a stable antiretroviral combination [2]. Most study participants (71.5%) had a viral load below 3 copies, while the rest had a load between 3 and 50. During 1 year of follow-up, 43 people (3.6%) endured virologic failure, defined as a confirmed viral load above 50 copies. Thirty-one people (2.6%) had a confirmed load above 200 copies.
Risk of virologic failure after 4 months of follow-up was 0.4% in those who began the study with a load below 3 copies and 3.2% in those who began with 3 to 50 copies. People in the 3- to 50-copy group had a 7.5 times higher risk of virologic failure (odds ratio 7.52, 95% confidence interval 3.8 to 15.0, P < 0.0001). Resistance mutations that can alter the efficacy of current regimens evolved in 13 of 43 people with virologic failure (30.2%).
The British study involved 1247 people with a load below 50 copies followed for 1 year with the Abbott RealTime assay to gauge rates of rebound above 50 or 400 copies [3]. Confirmed rebound rates above 50 copies were 34.2% for people who started the study with 40 to 49 copies, 11.3% for those who started with a detectable load below 40 copies, and 4.0% for people who started with completely undetectable viremia. Respective rebound rates above 400 copies were 13.0%, 3.8%, and 1.2%. Rates of rebound-emergent resistant virus did not differ significantly between the three study groups.
Compared with a completely undetectable initial viral load, a starting load between 40 and 49 copies more than quadrupled the risk of a confirmed rebound above 50 copies (adjusted hazard ratio 4.67), while a detectable load below 40 copies almost doubled that risk (adjusted hazard ratio 1.97). Respective hazards for a rebound above 400 copies were 6.91 in the 40-to-49 group and 2.88 in the under-40 group.
The French investigators suggested that detectable low-level viremia "seems to be a transient and dynamic phenomenon with about 40% of patients shifting from low-level viremia status to complete viral load suppression" during the 1 year of follow-up.
But both the Italian and British investigators suggested their findings imply that the goal of antiretroviral therapy should be something below the current 50-copy threshold. The British team proposed that "treatment efficacy should be reviewed" for people with a detectable viral load below 50 copies on the RealTime assay they used.
None of these research teams reported whether the detected rebounds had clinical consequences, and none noted what proportion of people had to change regimens.
References
1. Charpentier C, Landman R, Laouenan C, et al. Virological outcome of patients displaying persistent low-level viremia comprised between 20 and 50 copies/mL. 19th Conference on Retroviruses and Opportunistic Infections. March 5-8, 2012. Seattle. Abstract 349.
2. Cologni G, Callegaro A, Bernardini C, et al. Low-level Viremia during HAART. 19th Conference on Retroviruses and Opportunistic Infections. March 5-8, 2012. Seattle. Abstract 348.
3. Doyle T, Smith C, Vitiello P, et al. Plasma HIV-1 RNA detection below 50 copies/mL and risk of virologic rebound in patients receiving highly active antiretroviral therapy. Clin Infect Dis. 2012;54:724-732. http://cid.oxfordjournals.org/content/54/5/724.full.
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