TY - JOUR
T1 - Virologic Failure Following Low-level Viremia and Viral Blips During Antiretroviral Therapy
T2 - Results From a European Multicenter Cohort
AU - Elvstam, Olof
AU - Malmborn, Kasper
AU - Elén, Sixten
AU - Marrone, Gaetano
AU - García, Federico
AU - Zazzi, Maurizio
AU - Sönnerborg, Anders
AU - Böhm, Michael
AU - Seguin-Devaux, Carole
AU - Björkman, Per
N1 - Funding Information:
Financial support. This work was supported by the Department of Research and Development, Region Kronoberg, Växjö (0825-011 8298 to O. E.), the Swedish State under the agreement between the Swedish government and the county councils, the ALF agreement (ALFSUS-40103 to P. B.), Region Skåne (REG 821541 to P. B.), Skåne University Hospital donation funds (20200907 to P. B.). The funders had no impact on the study design, data collection, decision to publish, or preparation of the manuscript.
Funding Information:
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.
Publisher Copyright:
© 2022 The Author(s).
PY - 2023/1/6
Y1 - 2023/1/6
N2 - 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.
AB - 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.
KW - HIV-1
KW - low-level viremia
KW - treatment failure
KW - viral blips
UR - http://www.scopus.com/inward/record.url?scp=85147275209&partnerID=8YFLogxK
UR - https://pubmed.ncbi.nlm.nih.gov/36100984
U2 - 10.1093/cid/ciac762
DO - 10.1093/cid/ciac762
M3 - Article
C2 - 36100984
SN - 1058-4838
VL - 76
SP - 25
EP - 31
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 1
ER -