Clinical outcomes and risk factors for immune recovery and all‐cause mortality in Latin Americans living with HIV with virological success: a retrospective cohort study

Author:

Castillo‐Rozas Gabriel12,Tu Shengxin3,Luz Paula Mendes4ORCID,Mejia Fernando5ORCID,Sierra‐Madero Juan6ORCID,Rouzier Vanessa7ORCID,Shepherd Bryan E.3ORCID,Cortes Claudia P.28910ORCID

Affiliation:

1. Laboratory of Molecular and Cellular Virology Institute of Biomedical Sciences Faculty of Medicine University of Chile Santiago Chile

2. HIV/AIDS Workgroup, Faculty of Medicine University of Chile Santiago Chile

3. Department of Biostatistics Vanderbilt University Medical Center Nashville Tennessee USA

4. Evandro Chagas National Institute of Infectious Diseases Oswaldo Cruz Foundation Rio de Janeiro Brazil

5. Instituto de Medicina Tropical Alexander von Humboldt Universidad Peruana Cayetano Heredia Lima Perú

6. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán Ciudad de México México

7. Groupe Haitien d'Etudes du Sarcome de Kaposi et des Infections Opportunistes Port‐au‐Prince Haiti

8. Department of Internal Medicine Faculty of Medicine University of Chile Santiago Chile

9. Hospital Clínico San Borja Arriarán & Fundación Arriarán Santiago Chile

10. Millenium Institute on Immunology and Immunotherapy Santiago Chile

Abstract

AbstractIntroductionImmune reconstitution following antiretroviral therapy (ART) initiation is crucial to prevent AIDS and non‐AIDS‐related comorbidities. Patients with suppressed viraemia who fail to restore cellular immunity are exposed to an increased risk of morbidity and mortality during long‐term follow‐up, although the underlying mechanisms remain poorly understood. We aim to describe clinical outcomes and factors associated with the worse immune recovery and all‐cause mortality in people living with HIV (PLWH) from Latin America following ART initiation.MethodsRetrospective cohort study using the CCASAnet database: PLWH ≥18 years of age at ART initiation using a three drug‐based combination therapy and with medical follow‐up for ≥24 months after ART initiation and undetectable viral load were included. Patients were divided into four immune recovery groups based on rounded quartiles of increase in CD4 T‐cell count at 2 years of treatment (<150, [150, 250), [250, 350] and >350 cells/mm3). Primary outcomes included all‐cause mortality, AIDS‐defining events and non‐communicable diseases that occurred >2 years after ART initiation. Factors associated with an increase in CD4 T‐cell count at 2 years of treatment were evaluated using a cumulative probability model with a logit link.ResultsIn our cohort of 4496 Latin American PLWH, we found that patients with the lowest CD4 increase (<150) had the lowest survival probability at 10 years of follow‐up. Lower increase in CD4 count following therapy initiation (and remarkably not a lower baseline CD4 T‐cell count) and older age were risk factors for all‐cause mortality. We also found that older age, male sex and higher baseline CD4 T‐cell count were associated with lower CD4 count increase following therapy initiation.ConclusionsOur study shows that PLWH with lower increases in CD4 count have lower survival probabilities. CD4 increase during follow‐up might be a better predictor of mortality in undetectable PLWH than baseline CD4 count. Therefore, it should be included as a routine clinical variable to assess immune recovery and overall survival.

Funder

Fondo de Financiamiento de Centros de Investigación en Áreas Prioritarias

Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases

Publisher

Wiley

Reference23 articles.

1. UNAIDS.Global HIV Statistics. Fact Sheet 2021.2021.

2. United Nations Joint Programme on HIV/AIDS (UNAIDS).UNAIDS Data 2019 [Internet].2019. Accesed July 7 2023. Available from:https://www.unaids.org/sites/default/files/media_asset/2019‐UNAIDS‐data_en.pdf_aidsinfo.unaids.org

3. HIV infection

4. Lower CD4+ T Lymphocyte Nadirs May Indicate Limited Immune Reconstitution in HIV-1 Infected Individuals on Potent Antiretroviral Therapy: Analysis of Immunophenotypic Marker Results of AACTG 5067

5. Incomplete Immune Recovery in HIV Infection: Mechanisms, Relevance for Clinical Care, and Possible Solutions

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