Immunologic, Virologic, and Clinical Consequences of Episodes of Transient Viremia During Suppressive Combination Antiretroviral Therapy

Abstract

Episodes of low-level viremia are frequent and short lasting, and the low proportion of episodes with clinical events suggests that leaving therapy unchanged is a clinically acceptable strategy. In contrast, high-level viremia is associated with resistance and is often followed by therapy changes.

Significance and Clinical Management of Persistent Low-Level Viremia and Very-Low-Level Viremia in HIV-1-Infected Patients

“…A minority (6 to 9%) of patients with initial LLV progressed to higher degrees of viremia (4,5,(30)(31)(32). Thus, approximately 4% to 8% of the total population that achieved an initial pVL of Ͻ50 cpm in the studies subsequently developed persistent LLV of Ͻ500 cpm.…”

“…LLV is common during cART, although actual rates vary across studies (ranging from 18 to 34%) due to differences in study designs, population, and pVL assay used (4,5,(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41). Virtually all of these studies included viral blips, and only a few provided estimates of LLV persistence after viral suppression (4,5,30,32).…”

“…Regimens containing a nonnucleoside reverse transcriptase inhibitor (NNRTI) plus two NRTIs have been shown to suppress pVL to lower HIV-1 RNA copy numbers than those with ritonavir-boosted PI plus two NRTIs (32,42,43,48,51,60,61). Since rebound to Ͼ50 cpm is more likely in those with VLLV than those in whom no viremia was detected, as discussed above, it has been hypothesized that recipients of PI-based regimens will be more prone to viral rebound and, by extension, persistent LLV.…”

Point Mutations and Antiviral Drug Resistance

“…On the other hand, it has been found that the incidence of persistent low-level viremia is more frequent than high-level viremia when evaluating the virological response in subjects with HIV infection and HAART, reporting incidences of 29% and 6.7% for readings > 50 copies/mL and > 1,000 copies/mL, respectively (Van Sighem et al, 2008). Likewise, the UK-CHIC study reported that the cumulative risk for resistance mutation detection for two of the three primary classes of ARV therapy within a population increases in time, passing from 6% to 14% and 20% after a follow-up period of 2, 4, and 6 years for each period (Phillips et al, 2005).…”

Evaluation of the safety and pharmacokinetic profile of the broad spectrum antiviral lectin Griffithsin.

“…Despite durable suppression of viral replication, T-cell activation during times of illness or infection can cause bursts of HIV-1 replication activity in infected cells [94]. The clinical significance of these "blips" are currently not thought to be relevant [103]. However, it is possible that detectable viremia may be indicative of the acquisition of viral resistance [103].…”