Virologic Failure Following Low-level Viremia and Viral Blips During Antiretroviral Therapy: Results From a European Multicenter Cohort

Abstract

Background It is unclear whether low-level viremia (LLV), defined as repeatedly detectable viral load (VL) of <200 copies/mL, and/or transient viremic episodes (blips) during antiretroviral therapy (ART), predict future virologic failure. We investigated the association between LLV, blips, and virologic failure (VF) in a multi-center European cohort. Methods People with HIV-1 who started ART 2005 or later were identified from the EuResist Integrated Database. We analyzed the incidence of VF (≥200 copies/mL) depending on viremia exposure, starting 12 months after ART initiation (grouped as suppression [≤50 copies/mL], blips [isolated VL of 51–999 copies/mL], and LLV [repeated VLs of 51–199 copies/mL]) using Cox proportional hazard models adjusted for age, sex, injecting drug use, pre-ART VL, CD4 count, HIV-1 subtype, type of ART, and treatment experience. We queried the database for drug resistance mutations (DRM) related to episodes of LLV and VF and compared those with baseline resistance data. Results During 81,837 person-years of follow-up, we observed 1,424 events of VF in 22,523 participants. Both blips (adjusted subhazard ratio [aHR], 1.7; 95% confidence interval [CI], 1.3−2.2) and LLV (aHR, 2.2; 95% CI, 1.6−3.0) were associated with VF, compared with virologic suppression. These associations remained statistically significant in sub-analyses restricted to people with VL <200 copies/mL and those starting ART 2014 or later. Among people with LLV and genotype data available within 90 days following LLV, 49/140 (35%) had at least one DRM. Conclusions Both blips and LLV during ART are associated with increased risk of subsequent VF.

Viral and Host Mediators of Non-Suppressible HIV-1 Viremia

“…8,9 Previous studies supporting the presence of active viral replication have reported that ART resistance mutations can accumulate when viremia persists in the low but detectable range 10,11 and that NSV can increase the risk of virologic failure. 12 While these factors can cause persistent NSV, other evidence has showed that persistent NSV can be maintained for long periods without leading to high-level virologic failure or the development of new resistance mutations. [13][14][15][16][17][18] While suboptimal ART adherence or emerging drug resistance may play a role in a subset of individuals with NSV, alternative mechanisms seem to underlie NSV in other PWH.…”

Managing psoriasis in HIV‐positive patients in the era of biologics

“…Findings from recent studies 6 support the monitoring of parameters like viral load in the follow‐up of HIV‐positive patients since this enables the detection of the so‐called blips (transient viraemic episodes) and low‐level viremia that can appear during ART treatment and seem to be associated with increased risk of subsequent virologic failure.…”

Predictors of Post-switch Viremia in People With HIV on Injectable Cabotegravir/Rilpivirine

“…These can be classified as viral "blips," typically defined as transient detectable HIV viral loads that subsequently return below the lower limit of detection, or as persistent low-level viremia (pLLV) in which the viral load remains less than 200 cpm but presents as multiple consecutive (2 or more) detectable viral loads. 11 The frequency of viral blips and pLLV with oral ART varies significantly across studies, partly due to varying definitions and viral load cutoffs. Although the clinical impact of viral blips is less clear, pLLV has been associated with increased risk of virologic failure in several studies using orally administered ARV regimens.…”

“…Although the clinical impact of viral blips is less clear, pLLV has been associated with increased risk of virologic failure in several studies using orally administered ARV regimens. [11][12][13] The mechanism of pLLV continues to be elucidated with studies showing an association with adherence to oral ART. 14 However, other proposed mechanisms include clonal expansion of infected T cells and inadequate drug penetration into sanctuary sites.…”