Research Article: Reduced Central Memory CD4+ T Cells and Increased T-Cell Activation Characterise Treatment-Naive Patients Newly Diagnosed at Late Stage of HIV Infection

Date Published: October 27, 2012

Publisher: Hindawi Publishing Corporation

Author(s): Francesca Bai, Camilla Tincati, Esther Merlini, Carlotta Pacioni, Elisabetta Sinigaglia, Giovanni Carpani, Antonella d’Arminio Monforte, Giulia Marchetti.


Objectives. We investigated immune phenotypes of HIV+ patients who present late, considering late presenters (LPs, CD4+ < 350/μL and/or AIDS), advanced HIV disease (AHD, CD4+ < 200/μL and/or AIDS), and AIDS presenters (AIDS-defining condition at presentation, independently from CD4+). Methods. Patients newly diagnosed with HIV at our clinic between 2007–2011 were enrolled. Mann-Whitney/Chi-squared tests and logistic regression were used for statistics. Results. 275 patients were newly diagnosed with HIV between January/2007–March/2011. 130 (47%) were LPs, 79 (29%) showed AHD, and 49 (18%) were AIDS presenters. LP, AHD, and AIDS presenters were older and more frequently heterosexuals. Higher CD8+%, lower CD127+CD4+%, higher CD95+CD8+%, CD38+CD8+%, and CD45R0+CD38+CD8+% characterized LP/AHD/AIDS presentation. In multivariate analysis, older age, heterosexuality, higher CD8+%, and lower CD127+CD4+% were confirmed associated with LP/AHD. Lower CD4+ and higher CD38+CD8+% resulted independently associated with AIDS presentation. Conclusions. CD127 downregulation and immune activation characterize HIV+ patients presenting late and would be studied as additional markers of late presentation.

Partial Text

Despite reduced morbidity and mortality achieved by highly active antiretroviral therapy (HAART) and extensive work encouraging earlier HIV testing, late presentation of HIV remains a relevant clinical problem. Up to 15%–38% of HIV positive patients present late for testing with a low CD4+ T-cell count, high viral load, and severe alterations of their immune system [1]. Focusing on the Italian scenario, 39% of new HIV diagnosis occur late [2]. Compared to patients diagnosed with HIV early in the course of infection, late presenters are at higher probability of clinical progression and treatment-related adverse events and introduce HAART later than recommended by current antiretroviral therapy guidelines [3, 4]. Furthermore, late presentation deeply impacts on healthcare system and community in terms of resource use and higher risk of HIV transmission to sexual partners [5]. Recently, two different classifications of late presentation have been established by the European AIDS Clinical Society [6]: all patients who present with a CD4+ T-cell count less than 350 cells/μL and/or an AIDS-defining condition at, or within a month after, HIV diagnosis are identified as “late presenters.” This definition allows for the identification of patients that should be considered for treatment in accordance with current guidelines. Secondly, focusing on the established risk cutoff for developing opportunistic infections, all patients who present with a CD4+ T-cell count less than 200 cells/μL and/or an AIDS event should be considered to have “advanced HIV disease” [7, 8].

In our clinic, we observed 275 new HIV diagnosis in the period 2007–2011 with no significant differences over time. Still nowadays, the greatest percentages of persons diagnosed with HIV/AIDS are men, of minority ethnicity, and have as principal HIV transmission risk factor sexual contacts. Globally, in our experience, patients who present a new HIV-positive test display a median CD4+ T cells at presentation of 396 cells/μL and, therefore, near the minimum CD4+ count threshold for initiation of HAART, as suggested by the most recent international guidelines [6, 18–20]. In fact, different studies have demonstrated that initiating therapy at CD4+ levels higher than 350 cells/μL improves survival [21]. Furthermore, patients with a CD4+ count between 350 and 500 cells/μL and a HIV-RNA >100.000 copies/mL should be considered for treatment [6]. For this reason, encouraging an earlier recourse to HIV testing and access to care becomes crucial.

A broader definition of immunological features of late presenters could permit a better identification of patients subsets at high risk of clinical progression and reduced immunological response to HAART. Besides CD4+ levels, CD127+ expression on CD4+ T lymphocytes, and T-cell activation could be proposed as novel additional markers of late presentation and advanced HIV disease. Further studies on larger population are needed to confirm immunological patterns associated with late presentation.




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