Early and prolonged antiretroviral therapy is associated with an HIV-1-specific T-cell profile comparable to that of long-term non-progressors.

By:

Cellerai, C

Contributor(s):

Publication details: 2011Uniform titles:

PLoS One.

Online resources:

Click here to access online

Summary: <div style="line-height: 17.999801635742188px;"><h4 style="margin: 0px 0.25em 0px 0px; text-transform: uppercase; float: left;">BACKGROUND:</h4>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).<h4 style="margin: 0px 0.25em 0px 0px; text-transform: uppercase; float: left;">METHODOLOGY/PRINCIPAL FINDINGS:</h4>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.<h4 style="margin: 0px 0.25em 0px 0px; text-transform: uppercase; float: left;">CONCLUSIONS:</h4>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.</div>

Holdings
Item type	Home library	Collection	Class number	Status	Date due	Barcode
UNKNOWN	Ferriman information and Library Service (North Middlesex) Online	Staff publications for NMDX		Available

NMUH Staff Publications

<div style="line-height: 17.999801635742188px;"><h4 style="margin: 0px 0.25em 0px 0px; text-transform: uppercase; float: left;">BACKGROUND:</h4>Intervention with&nbsp;antiretroviral&nbsp;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&nbsp;prolonged&nbsp;period in HIV-1 seroconverters could induce an immuno-virological status similar to that of HIV-1&nbsp;long-term&nbsp;non-progressors&nbsp;(LTNPs).<h4 style="margin: 0px 0.25em 0px 0px; text-transform: uppercase; float: left;">METHODOLOGY/PRINCIPAL FINDINGS:</h4>We have investigated a cohort of 20 HIV-1 seroconverters on&nbsp;long-term&nbsp;ART (LTTS) and compared it to one of 15 LTNPs. Residual viral replication and reservoirs in peripheral blood, as measured by cell-associated&nbsp;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&nbsp;HIV-1-specific&nbsp;CD4(+) and CD8(+)&nbsp;T-cell&nbsp;functional&nbsp;profile&nbsp;in terms of cytokine production and cytotoxic capacity using IFN-γ, IL-2, TNF-α production and perforin expression, respectively.&nbsp;Comparable&nbsp;levels of highly polyfunctional&nbsp;HIV-1-specific&nbsp;CD4(+) and CD8(+) T-cells were found in LTTS and LTNPs, with low perforin expression on&nbsp;HIV-1-specific&nbsp;CD8(+) T-cells, consistent with a polyfunctional/non-cytotoxic&nbsp;profile&nbsp;in a context of low viral burden.<h4 style="margin: 0px 0.25em 0px 0px; text-transform: uppercase; float: left;">CONCLUSIONS:</h4>Our results indicate that&nbsp;prolonged&nbsp;ART initiated at the time of HIV-1 seroconversion is&nbsp;associated&nbsp;with immuno-virological features which resemble those of LTNPs, strengthening the recent emphasis on the positive impact of&nbsp;early&nbsp;treatment initiation and paving the way for further interventions to promote virological control after treatment interruption.</div>

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