Virologic Failure Experienced by 12% With Persistent, Low-Level Viral Load

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About 12% of HIV-infected people who have a persistently low but detectable viral load go on to experience virologic failure, according to study results (read abstract; view poster) presented at ICAAC 2012. These findings suggest that consistent viral load testing may help predict virologic failure. The study also sheds light on why some individuals experience low but detectable viral loads despite treatment.

Researchers from the Swiss Cohort Study analyzed patient data gathered from January 2000 to December 2010. They studied a case group consisting of 179 patients with persistent low-level viremia (LLV), defined as a viral load between 21 and 400 copies/mL, for at least three consecutive viral load tests, with at least eight weeks in between the first and last test. They also included a control group consisting of 5,389 patients, all of whom had a viral load below 20 copies/mL through at least 32 weeks without any regimen switches.

To find factors associated with LLV, they compared the two groups and found a number of key differences. Mean age was slightly higher in the case group (46 vs. 44), which was statistically significant (P = .03). A higher percentage of the case group had a nadir CD4 count below 200 (69.8% vs. 62.1%), which was also statistically significant (P = .01). Average treatment duration was slightly shorter in the case group (2.7 years vs. 3.1 years), which was statistically significant (P = .01). The case group also had a higher rate of suboptimal adherence (18.9% vs. 21.3%), but this was not statistically significant (P = .14).

Fewer case patients were taking NNRTI-based regimens (28.9% vs. 39.9%), which was used as a reference point in a multivariate analysis of treatment options. Taking a PI-based regimen raised the odds of persistent LLV by 85% (P = .03), while taking a regimen comprised of NRTIs increased the odds of LLV 837% (P < .001). Taking other drug-class combinations more than doubled the odds of LLV (P = .04).

While none of the control patients experienced virologic failure, the investigators went on to analyze 155 members of the case group (those with persistent LLV). About 12% experienced virologic failure within 48 weeks. When compared to the rest of the group, two predictors of virologic failure were noted, although neither was statistically significant: diabetes (P = .1) and suboptimal adherence (P = .06). Also worth noting is that 26 members of the case group had very low-level viremia, defined as a detectable viral load between 21 and 49 copies/mL, but none of these patients experienced virologic failure.

In terms of treatment adjustments, NATAP reported:

Among people with persistent low-level viremia, records showed that 115 (64% of 179) did not intensify their antiretroviral regimen and 51 (28%) did. People taking a nucleoside-only combination and those entering the cohort in 2009 or 2010 (when more new antiretrovirals rapidly became available) were more likely to intensify their regimen.
Among the 115 people who did not intensify their regimen, 12% had virologic failure within 24 weeks, compared with 9% in the intensification group, a nonsignificant difference (P = 0.. While 33% who did not intensify their regimen regained an undetectable viral load within 24 weeks, 63% who did intensify regained an undetectable load, a highly significant difference (P = 0.001).

Even with treatment intensification, the rate of virologic failure among those with LLV did not change, suggesting more research needs to be done to understand and prevent virologic failure.

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