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Multicenter Study
. 2023 Jan 6;76(1):25-31.
doi: 10.1093/cid/ciac762.

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

Olof Elvstam  1   2 , Kasper Malmborn  1 , Sixten Elén  1 , Gaetano Marrone  3 , Federico García  4 , Maurizio Zazzi  5 , Anders Sönnerborg  6   7 , Michael Böhm  8 , Carole Seguin-Devaux  9 , Per Björkman  1   10
Affiliations
Multicenter Study

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

Olof Elvstam et al. Clin Infect Dis. .

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 multicenter European cohort.

Methods: People with HIV-1 who started ART in 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 1424 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 subanalyses 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 1 DRM.

Conclusions: Both blips and LLV during ART are associated with increased risk of subsequent VF.

Keywords: HIV-1; low-level viremia; treatment failure; viral blips.

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Conflict of interest statement

Potential conflicts of interest. O. E. reports grant to his institution from Pfizer and honoraria as speaker from Gilead Sciences, outside the submitted work. M. Z. reports research grants from MSD, Theratechnologies, and ViiV healthcare, consulting fees for advisory boards from MSD, Gilead Sciences, Theratechnologies, and ViiV healthcare, support for attending meetings from Gilead Sciences and Theratechnologies, and receipt for drug in in vitro studies from Theratechnologies, outside the submitted work. A. S. reports grants from Gilead Sciences and GSK/ViiV, consulting fees from Immune System Regulation AB, honoraria as speaker from GSK/ViiV, MSD, and Astra Zeneca, participation on a Data Safety Monitoring Board or Advisory Board from Astra Zeneca, Gilead Sciences, and GSK/ViiV, outside the submitted work. C. S. D. reports grant from the Ministry of Health of Luxembourg. P. B. reports grant to his institution from the Swedish Heart-Lung Foundation and from Gilead Sciences, honoraria as speaker and participation in an Advisory Board from Gilead Sciences, outside the submitted work. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
Exclusion Flowchart of Study Participants. Abbreviations: ART, antiretroviral therapy; RT, reverse transcriptase; VL, viral load.
See this image and copyright information in PMC

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