CD4/CD8 ratio normalisation and non-AIDS-related events in individuals with HIV who achieve viral load suppression with antiretroviral therapy: An observational cohort study

Antonella Cingolani, Roberto Cauda, Andrea De Luca, Cristina Mussini, Patrizia Lorenzini, Alessandro Cozzi-Lepri, Giuseppe Lapadula, Giulia Marchetti, Emanuele Nicastri, Miriam Lichtner, Andrea Antinori, Andrea Gori, Antonella D'Arminio Monforte, M. Andreoni, G. Angarano, A. D'Arminio Monforte, F. Castelli, G. Di Perri, M. Galli, A. LazzarinP. Viale, A. Castagna, S. Lo Caputo, M. Puoti, P. Bonfanti, S. Bonora, A. De Luca, Giordano Madeddu, F. Maggiolo, L. Monno, E. Quiros Roldan, A. Giacometti, A. Costantini, S. Mazzoccato, C. Santoro, C. Suardi, E. Vanino, G. Verucchi, C. Minardi, T. Quirino, C. Abeli, P. E Manconi, P. Piano, J. Vecchiet, K. Falasca, L. Sighinolfi, D. Segala, F. Mazzotta, G. Cassola, C. Viscoli, A. Alessandrini, R. Piscopo, G. Mazzarello, C. Mastroianni, V. Belvisi, I. Caramma, A. Chiodera, A. P. Castelli, G. Rizzardini, A. L. Ridolfo, R. Piolini, S. Salpietro, L. Carenzi, M. C. Moioli, C. Tincati, C. Puzzolante, N. Abrescia, A. Chirianni, M. G. Guida, M. Gargiulo, F. Baldelli, D. Francisci, G. Parruti, T. Ursini, G. Magnani, M. A. Ursitti, V. Vullo, A. D'Avino, L. Gallo, R. Acinapura, M. Capozzi, R. Libertone, G. Tebano, A. Cattelan, L. Sasset, M. S. Mura, B. Rossetti, P. Caramello, G. C. Orofino, M. Sciandra, M. Bassetti, A. Londero, G. Pellizzer, V. Manfrin

Risultato della ricerca: Contributo in rivistaArticolo in rivista

145 Citazioni (Scopus)

Abstract

Background: In patients with HIV, immune reconstitution after antiretroviral therapy (ART) is often incomplete. We assessed the probability of patients reaching a CD4/CD8 ratio of 1 or more after the start of ART and its association with the onset of non-AIDS-defining events and death. Methods: We did an analysis of the ICONA cohort, which recruited treatment-naive patients with HIV in Italy. We included participants in the cohort who started ART, reached an undetectable viral load (≤80 copies per mL), and had a CD4/CD8 ratio of less than 0·8 at the time of an undetectable viral load. We defined ratio normalisation in patients as two consecutive values of 1 or more. We used Kaplan-Meier curves to estimate the cumulative probability of ratio normalisation. We then used Poisson regression models to identify factors independently associated with normalisation and with progression to non-AIDS-defining events or death. Findings: We included 3236 participants, enrolled between Jan 22, 1997, and Feb 25, 2013. At the start of ART, median CD4/CD8 ratio in our population was 0·39 (IQR 0·26-0·55). 458 (14%) patients reached a CD4/CD8 ratio of 1 or more; the estimated probability of normalisation was 4·4% (95% CI 3·7-5·2) by 1 year from baseline, 11·5% (10·2-13·0) by 2 years, and 29·4% (26·7-32·4) by 5 years. Factors associated with normalisation were high pre-ART CD4 cell counts, a high CD4/CD8 ratio at baseline, and negative cytomegalovirus serological findings. The incidence rate of non-AIDS-defining events for patients with a CD4/CD8 ratio of less than 0·30 (4·2 per 100 patient-years, 95% CI 3·4-5·3) was double that for those with a ratio of 0·30-0·45 (2·3, 2·1-2·5) or more than 0·45 (2·2, 1·7-2·9). A ratio of less than 0·30 was independently associated with an increased risk of non-AIDS-defining events or death compared with one of more than 0·45. Interpretation: Few patients had normalised CD4/CD8 ratios, even though they had viral suppression. Low ratios were associated with increased risk of serious events and deaths. The CD4/CD8 ratio could be used by clinicians to identity patients at risk of non-AIDS-related events. Funding: AbbVie, Bristol-Myers Squibb, Gilead, Janssen, Merck Sharp & Dohme, ViiV Italy.
Lingua originaleEnglish
pagine (da-a)98-106
Numero di pagine9
RivistaTHE LANCET. HIV
Volume2
DOI
Stato di pubblicazionePubblicato - 2015

Keywords

  • Adult
  • Anti-HIV Agents
  • CD4 Lymphocyte Count
  • CD4-CD8 Ratio
  • Cohort Studies
  • Epidemiology
  • Female
  • HIV Infections
  • HIV-1
  • Humans
  • Immunology
  • Infectious Diseases
  • Italy
  • Male
  • Middle Aged
  • Viral Load
  • Virology

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