Enhanced Immunological Recovery With Early Start of Antiretroviral Therapy During Acute or Early HIV Infection–Results of Italian Network of ACuTe HIV InfectiON (INACTION) Retrospective Study

Antonio Muscatello, Silvia Nozza, Massimiliano Fabbiani, Ilaria De Benedetto, Marco Ripa, Raffaele Dell’Acqua, Andrea Antinori, Carmela Pinnetti, Andrea Calcagno, Micol Ferrara, Emanuele Focà, Eugenia Quiros-Roldan, Diego Ripamonti, Marco Campus, Benedetto Maurizio Celesia, Carlo Torti, Lucio Cosco, Antonio Di Biagio, Stefano Rusconi, Giulia Marchetti, Cristina Mussini, Roberto Gulminetti, Antonella Cingolani, Gabriella D’Ettorre, Giordano Madeddu, Antonina Franco, Giancarlo Orofino, Nicola Squillace, Andrea Gori, Giuseppe Tambussi, Alessandra Bandera

Abstract


Background: Viral load peak and immune activation occur shortly after exposure during acute or early HIV infection (AEHI). We aimed to define the benefit of early start of antiretroviral treatment (ART) during AEHI in terms of immunological recovery, virological suppression, and treatment discontinuation.

Setting: Patients diagnosed with AEHI (Fiebig stages I-V) during 2008-2014 from an analysis of 20 Italian centers.

Methods: This was an observational, retrospective, and multicenter study. We investigated the effect of early ART (defined as initiation within 3 months from AEHI diagnosis) on time to virological suppression, optimal immunological recovery (defined as CD4 count ≥ 500/µL, CD4 ≥ 30%, and CD4/CD8 ≥ 1), and first-line ART regimen discontinuation by Cox regression analysis.

Results: There were 321 patients with AEHI included in the study (82.9% in Fiebig stage III-V). At diagnosis, the median viral load was 5.67 log10copies/mL and the median CD4 count was 456 cells/µL. Overall, 70.6% of patients started early ART (median time from HIV diagnosis to ART initiation 12 days, IQR 6-27). Higher baseline viral load and AEHI diagnosis during 2012-2014 were independently associated with early ART. HBV co-infection, baseline CD4/CD8 ≥ 1, lower baseline HIV-RNA, and AEHI diagnosis in recent years (2012-2014) were independently associated with a shorter time to virological suppression. Early ART emerged as an independent predictor of optimal immunological recovery after adjustment for baseline CD4 (absolute and percentage count) and CD4/CD8 ratio. The only independent predictor of first-line ART discontinuation was an initial ART regimen including > 3 drugs.

Conclusions: In a large cohort of well-characterized patients with AEHI, we confirmed the beneficial role of early ART on CD4+ T-cell recovery and on rates of CD4/CD8 ratio normalization. Moreover, we recognized baseline CD4/CD8 ratio as an independent factor influencing time to virological response in the setting of AEHI, thus giving new insights into research of immunological markers associated with virological control.


Keywords


acute/early HIV infection; early antiretroviral treatment; optimal immunological recovery; intensified antiretroviral regimen

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