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A Retrospective Analysis of Long-Term Changes of Inflammatory Biomarkers in Individuals on Suppressive Three-Drug or Two-Drug Antiretroviral Regimens

36 Pages Posted: 21 Dec 2021

See all articles by Sergio Serrano-Villar

Sergio Serrano-Villar

Universidad de Alcalá, IRYCIS

María Rosa López-Huertas

Carlos III Institute of Health - National Centre for Microbiology

Daniel Jiménez

Universidad de Alcalá, IRYCIS

Carlos Galera

Hospital Universitario Virgen de la Arrixaca - HIV Unit

Javier Martínez-Sanz

Universidad de Alcalá - Department of Infectious Diseases

Elena Moreno

Universidad de Alcalá, IRYCIS

Alfonso Muriel

Universidad de Alcalá, IRYCIS - Biostatistics Unit

Felix Gutierrez

Hospital General Universitario de Elche

Carmen Busca

Hospital Universitario La Paz - HIV Unit

Joaquín Portilla

Hospital General Universitario de Alicante

Otilia Bisbal

Hospital Universitario Doce de Octubre - HIV Unit

José A. Iribarren

Hospital Universitario Donostia - HIV Unit

Francisco Tejerina

Hospital Universitario Gregorio Marañón - HIV Unit

Ignacio de los Santos

Hospital Universitario La Princesa - HIV Unit

Santiago Moreno

Universidad de Alcalá, IRYCIS; University of Alcala

More...

Abstract

Objectives: Because inflammation is associated with mortality and has been linked to HIV transcription in lymphoid tissues during ART, it is necessary to address the long-term effects of switching 3-drug (3DR) to 2-drug regimens (2DR) on inflammation.

Methods: Nested study in the Spanish AIDS Research Network. We selected PWH ART-naive initiating 3DR who achieved viral suppression in the first 48 weeks and either remained on 3DR or switched to 2DR (3TC+bPI; 3TC+DTG; DTG+RPV). We assessed the trajectories on inflammatory markers during ART using multivariate piecewise mixed models.

Results: We analyzed 619 plasma samples from 148 patients (3DR, N=90; 2DR, N=58), the median follow-up was 4.6 (IQR 3.2-6.2) years. There were no significant differences in baseline characteristics between groups. After adjusting for potential confounders, patients with 3DR experienced a slow decline of IL6, hs-CRP, sCD14, sCD163, and D-dimer over time. In contrast, compared to 3DR, switching to 2DR was associated with increases in IL-6 (p=0.001), hs-CRP (p=0.003), and D-dimer (p=0.001) after year 3 from virologic suppression. 2DR was associated with a higher risk of hs-CRP quartile increase (aOR 3.3, 95%CI 1.1-10) and D-dimer quartile increase (aOR 3.7, 95%CI 1.1-13). The adjusted biomarker trajectories did not reveal a distinct pattern according to the type of 2DR used (bPI vs DTG).

Conclusions: In this study in virally suppressed individuals, maintaining 3DR was associated with a more favorable long-term inflammatory profile than switching to 2DR. The potential clinical implications of these findings on the development of non-AIDS events deserve further investigation.

Funding Information: The HIV BioBank, integrated in the Spanish AIDS Research Network, is supported by Instituto de Salud Carlos III, Spanish Health Ministry (Grant nº proyectos RD06/0006/0035, RD12/0017/0037 and RD16/0025/0019) as part of the Plan Nacional R + D + I and co-financed by the European Development Regional Fund ‘‘A way to achieve Europe’’ (ERDF). The RIS Cohort (CoRIS) is funded by the Instituto de Salud Carlos III through the Red Temática de Investigación Cooperativa en SIDA (RIS C03/173, RD12/0017/0018 and RD16/0002/0006) as part of the Plan Nacional R+D+I and cofinanced by ISCIII-Subdirección General de Evaluacion and Fondo Europeo de Desarrollo Regional (FEDER)”. This work was supported by the Instituto de Salud Carlos III projects AC17/00019, PI18/00154, COV20/00349, and Gilead Sciences (Investigator Sponsored Research ISR-17-10192).

Declaration of Interests: Outside the submitted work, S. S.-V. reports personal fees from ViiV Healthcare, Janssen Cilag, Gilead Sciences, and MSD as well as non-financial support from ViiV Healthcare and Gilead Sciences and research grants from MSD and Gilead Sciences. J.M.-S. non-financial support from ViiV Healthcare, non-financial support from Jannsen Cilag, non-financial support from Gilead Sciences, outside the submitted work. J.P. reports grants from Instituto de Salud Carlos III during the conduct of the study; grants and personal fees from Gilead Sciences, personal fees from Janssen Cilag, personal fees from ViiV Health Care, personal fees from MSD, outside the submitted work. S.M. reports grants, personal fees and non-financial support from ViiV Healthcare, personal fees and non-financial support from Janssen, grants, personal fees and non-financial support from MSD, grants, personal fees and non-financial support from Gilead, outside the submitted work.

Ethics Approval Statement: All patients participating in the study gave their informed consent and protocols were approved by institutional ethical committees

Keywords: HIV, antiretroviral therapy, inflammation, d-dimer, C reactive protein

Suggested Citation

Serrano-Villar, Sergio and López-Huertas, María Rosa and Jiménez, Daniel and Galera, Carlos and Martínez-Sanz, Javier and Moreno, Elena and Muriel, Alfonso and Gutierrez, Felix and Busca, Carmen and Portilla, Joaquín and Bisbal, Otilia and Iribarren, José A. and Tejerina, Francisco and de los Santos, Ignacio and Moreno, Santiago, A Retrospective Analysis of Long-Term Changes of Inflammatory Biomarkers in Individuals on Suppressive Three-Drug or Two-Drug Antiretroviral Regimens. Available at SSRN: https://ssrn.com/abstract=3976877 or http://dx.doi.org/10.2139/ssrn.3976877

Sergio Serrano-Villar (Contact Author)

Universidad de Alcalá, IRYCIS ( email )

María Rosa López-Huertas

Carlos III Institute of Health - National Centre for Microbiology ( email )

Monforte de Lemos 5
Madrid, Madrid 28029
Spain

Daniel Jiménez

Universidad de Alcalá, IRYCIS ( email )

Ctra. De Colmenar Viejo
Madrid, 28034
Spain

Carlos Galera

Hospital Universitario Virgen de la Arrixaca - HIV Unit ( email )

Murcia
Spain

Javier Martínez-Sanz

Universidad de Alcalá - Department of Infectious Diseases ( email )

Spain

Elena Moreno

Universidad de Alcalá, IRYCIS ( email )

Ctra. De Colmenar Viejo
Madrid, 28034
Spain

Alfonso Muriel

Universidad de Alcalá, IRYCIS - Biostatistics Unit ( email )

Madrid
Spain

Felix Gutierrez

Hospital General Universitario de Elche ( email )

Elche
Spain

Carmen Busca

Hospital Universitario La Paz - HIV Unit ( email )

Paseo de la Castellana, 261
Madrid, 28046
Spain

Joaquín Portilla

Hospital General Universitario de Alicante ( email )

Alicante
Spain

Otilia Bisbal

Hospital Universitario Doce de Octubre - HIV Unit ( email )

Madrid
Spain

José A. Iribarren

Hospital Universitario Donostia - HIV Unit ( email )

San Sebastian, 20014
Spain

Francisco Tejerina

Hospital Universitario Gregorio Marañón - HIV Unit ( email )

Calle del Dr. Esquerdo, 46
Madrid
Sudan

Ignacio De los Santos

Hospital Universitario La Princesa - HIV Unit ( email )

Madrid
Spain

Santiago Moreno

Universidad de Alcalá, IRYCIS ( email )

Ctra. De Colmenar Viejo
Madrid, 28034
Spain

University of Alcala ( email )

Plaza de la Victoria, 2.
Alcala de Henares, Madrid 28801
Spain

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