Abstract
A latent viral reservoir that resides in resting CD4+ T cells represents a major barrier for eradication of HIV infection. We test here the impact of HIV protease inhibitor (PI) based combination anti-retroviral therapy (cART) over nonnucleoside reverse transcriptase inhibitor (NNRTI)-based cART on HIV-1 reactivation and integration in resting CD4+ T cells. This is a prospective cohort study of patients with chronic HIV-1 infection treated with conventional cART with an undetectable viremia. We performed a seven-year study of 47 patients with chronic HIV-infection treated with cART regimens and with undetectable plasma HIV-1 RNA levels for at least 1 year. Of these 47 patients treated with cART, 24 were treated with a PI-based regimen and 23 with a NNRTI-based regimen as their most recent treatment for more than one year. We evaluated the HIV-1 reservoir using reactivation assay and integrated HIV-1 DNA, respectively, in resting CD4+ T cells. Resting CD4+ T cells isolated from PI-treated patients compared to NNRTI-treated patients showed a limited HIV-1 reactivation upon T-cell stimulation (p = 0·024) and a lower level of HIV-1 integration (p = 0·024). Our study indicates that PI-based cART could be more efficient than NNRTI-based cART for limiting HIV-1 reactivation in aviremic chronically infected patients.
Highlights
Among the main features of human immunodeficiency virus-1 (HIV-1) infection are immune suppression and viral persistence[1]
Forty-seven patients with chronic HIV-1 infection treated with combination anti-retroviral therapy (cART) and with undetectable plasma HIV-1 RNA levels (
We did not observe significant differences for nadir median CD4 counts (298·106 versus 333·106 cells/l, P = 0.579), median CD4 counts at initiation of treatment (384·106 versus 349·106 cells/l, P = 0·903), median CD4 counts at the last point (607·106 versus 624·106 cells/l, P = 0·647), and median HIV RNA load at zenith (4·92 versus 4·83 log/ml, P = 0·892) between protease inhibitor (PI)-treated and NNRTI-treated patients (Table 1)
Summary
Among the main features of human immunodeficiency virus-1 (HIV-1) infection are immune suppression and viral persistence[1]. Most of the studies so far have addressed the effect of cART on the decrease of HIV-1 viremia under limit of detection using the classical assays. In contrast to the measurement of viremia in patients on cART, the impact of cART on the size of the cellular reservoirs of HIV-1 has been much less studied. Initiation of cART during primary HIV infection may limit the establishment of viral reservoirs, and very early cART limits the seeding of the HIV reservoir in long-lived central memory CD4+ T cells[6,13,14]. We report here a study indicating a higher efficiency of PI-based cART over NNRTI-based cART for limiting HIV-1 reactivation in CD4+ T cells from aviremic chronically HIV-1 infected patients
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