Early and Prolonged Antiretroviral Therapy Is Associated with an HIV-1-Specific T-Cell Profile Comparable to That of Long-Term Non-Progressors

Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
PLoS ONE (Impact Factor: 3.23). 04/2011; 6(4):e18164. DOI: 10.1371/journal.pone.0018164
Source: PubMed


Intervention with antiretroviral treatment (ART) and control of viral replication at the time of HIV-1 seroconversion may curtail cumulative immunological damage. We have therefore hypothesized that ART maintenance over a very prolonged period in HIV-1 seroconverters could induce an immuno-virological status similar to that of HIV-1 long-term non-progressors (LTNPs).
We have investigated a cohort of 20 HIV-1 seroconverters on long-term ART (LTTS) and compared it to one of 15 LTNPs. Residual viral replication and reservoirs in peripheral blood, as measured by cell-associated HIV-1 RNA and DNA, respectively, were demonstrated to be similarly low in both cohorts. These two virologically matched cohorts were then comprehensively analysed by polychromatic flow cytometry for HIV-1-specific CD4(+) and CD8(+) T-cell functional profile in terms of cytokine production and cytotoxic capacity using IFN-γ, IL-2, TNF-α production and perforin expression, respectively. Comparable levels of highly polyfunctional HIV-1-specific CD4(+) and CD8(+) T-cells were found in LTTS and LTNPs, with low perforin expression on HIV-1-specific CD8(+) T-cells, consistent with a polyfunctional/non-cytotoxic profile in a context of low viral burden.
Our results indicate that prolonged ART initiated at the time of HIV-1 seroconversion is associated with immuno-virological features which resemble those of LTNPs, strengthening the recent emphasis on the positive impact of early treatment initiation and paving the way for further interventions to promote virological control after treatment interruption.

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    • "Although their viral reservoirs have been shown to be low, replication-competent viruses can still be found in these individuals (Blankson et al., 2007; Buzon et al., 2014). LTNPs display strong HIV-1-specific T cells responses with polyfunctionality, thereby suggesting a role of T cell immunity in viremia control (Cellerai et al., 2011). "
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    • "p=0.016) supports the second hypothesis. Therefore, although performed with different methodological approaches and type of patients, our study, at least in part, complements that of Simonetta et al. [17] by demonstrating that a long lasting effective cART restores Treg homeostasis, most likely by hampering HIV replication in the periphery and into the lymphoid sanctuaries [30, 31]. "
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    • "This early destruction of the CD4 memory T-cell pool coupled with rapid establishment of a viral reservoir suggests that current strategies alone, which work to suppress replication of virus, are unlikely to result in eradication of the viral reservoir from the host, or facilitate reconstitution of immunity (Richman et al., 2009; Deeks et al., 2012). Nonetheless, in LTNP and other HIV-1+ individuals receiving multi-targeted drug treatment at the initial acute stages of infection, the proviral reservoir has been described as significantly reduced compared to those treated at a later chronic stage of infection (Pires et al., 2004; Cellerai et al., 2011; Ananworanich et al., 2012). "
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