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

Author:

Elvstam Olof12ORCID,Malmborn Kasper1,Elén Sixten1,Marrone Gaetano3,García Federico4,Zazzi Maurizio5,Sönnerborg Anders67,Böhm Michael8,Seguin-Devaux Carole9,Björkman Per110

Affiliation:

1. Department of Translational Medicine, Lund University , Malmö , Sweden

2. Department of Infectious Diseases, Växjö Central Hospital , Växjö , Sweden

3. Department of Infectious Diseases and Clinical Virology, Karolinska University Hospital , Stockholm , Sweden

4. Servicio de Microbiología, Hospital Clinico Universitario San Cecilio, Instituto de Investigacíon Ibs. Granada, Ciber de Enfermedades Infecciosas, CIBERINFEC , Granada , Spain

5. Department of Medical Biotechnologies, University of Siena , Siena , Italy

6. Division of Infectious Diseases, Department of Medicine Huddinge, Karolinska Institutet , Stockholm , Sweden

7. Department of Infecious Diseases, Karolinska University Hospital , Stockholm , Sweden

8. Institute of Virology, Faculty of Medicine and University Hospital of Cologne, University of Cologne , Cologne , Germany

9. Department of Infection and Immunity, Luxembourg Institute of Health , Esch sur Alzette , Luxembourg

10. Department of Infectious Diseases, Skåne University Hospital , Malmö , Sweden

Abstract

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.

Funder

Department of Research and Development, Region Kronoberg, Växjö

Swedish State

ALF agreement

Region Skåne

Skåne University Hospital

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Microbiology (medical)

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