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PD-1 Expression in HIV-Specific CD8+ T cells Before Antiretroviral Therapy Is Associated With HIV Persistence

Ghiglione, Yanina, MSc, PhD*; Trifone, César, MSc*; Salido, Jimena, MSc*; Rhodes, Ajantha, BSc (Hons); Ruiz, María Julia, MD, PhD*,‡; Polo, María Laura, MSc, PhD*; Salomón, Horacio, PhD*; Laufer, Natalia, MD, PhD*,§; Sued, Omar, MD, PhD; Lewin, Sharon R., MBBS (Hons), PhD†,¶; Turk, Gabriela, MSc, PhD*

JAIDS Journal of Acquired Immune Deficiency Syndromes: January 1, 2019 - Volume 80 - Issue 1 - p 1–6
doi: 10.1097/QAI.0000000000001887
Rapid Communication

Background: The persistence of latently infected T cells remains the principal barrier to HIV cure. Understanding how the early immune responses shape persistence of HIV on antiretroviral therapy (ART) will be fundamental for potential eradication. Here, we aimed to determine the relationship between CD8+ T-cell function and phenotype before therapy and HIV persistence on ART.

Methods: Blood samples from 29 individuals enrolled during primary HIV infection (at baseline and every 3 months up to 2 years post-ART initiation) were obtained. HIV-specific T-cell function and expression of the activation markers were evaluated before ART by flow cytometry. Cell-associated HIV DNA and unspliced (US)-RNA were quantified in purified CD4+ T cells by real-time polymerase chain reaction. Data were analyzed using nonparametric statistics.

Results: Elevated immune activation, dominance of monofunctional CD8+ T cells, and skewed distribution of memory profile were observed before ART. After ART initiation, HIV DNA and US-RNA levels rapidly diminished, reaching a plateau by 30 weeks after ART. The proportion of baseline HIV-specific effector memory and terminal effector CD8+ T cells directly correlated with HIV DNA levels at 1 year after ART. A strong positive correlation was observed between the proportion of bulk and HIV-specific PD-1High CD8+ T cells measured before ART and HIV DNA at 1 year after ART.

Conclusions: A higher proportion of terminally differentiated CD8+ T cells and increased PD1 expression were associated with HIV persistence on ART after treatment of primary infection. Thus, the quality of the early CD8+ T-cell immune response may serve as a predictor of HIV persistence on ART.

*CONICET-Universidad de Buenos Aires, Instituto de Investigaciones Biomédicas en Retrovirus y Sida (INBIRS), Buenos Aires, Argentina;

Peter Doherty Institute for Infection and Immunity, The University of Melbourne and Royal Melbourne Hospital, Melbourne, Victoria, Australia;

Currently, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, Quebec, Canada;

§Hospital General de Agudos “Dr. JA Fernández”, Unidad Enfermedades Infecciosas, Buenos Aires, Argentina;

Fundación Huésped, Buenos Aires, Argentina; and

Department of Infectious Diseases, Alfred Health and Monash University, Melbourne, Australia.

Correspondence to: Yanina Ghiglione, MSc, PhD, Instituto de Investigaciones Biomédicas en Retrovirus y SIDA INBIRS, Universidad de Buenos Aires-CONICET, Paraguay 2155 Piso 11, C1121ABG—Buenos Aires, Argentina (e-mail: yghiglione@fmed.uba.ar).

Supported by grants from the Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT; PICT2015, Grant # 1004) and the HIV Research Trust (2015) to Y.G.; from ANPCyT/GlaxoSmithKline (PICTO-GSK, Grant # 2013/0006) and from Universidad de Buenos Aires (UBACyT 2013-2016, Grant # 20020120200263BA and UBACyT 2017, Grant # 20020160100008BA) to G.T. S.R.L. is supported by the National Institutes of Health (Grant numbers U19 AI096109 and UM1AI126611) and the National Health and Medical Research Council of Australia. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

The authors have no conflicts of interest to disclose.

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Received July 24, 2018

Accepted October 01, 2018

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