Early and prolonged antiretroviral therapy is associated with an HIV-1-specific T-cell profile comparable to that of long-term non-progressors.
Cellerai, C.
Early and prolonged antiretroviral therapy is associated with an HIV-1-specific T-cell profile comparable to that of long-term non-progressors. - 2011
NMUH Staff Publications 6
<div style="line-height: 17.999801635742188px;"><h4 style="margin: 0px 0.25em 0px 0px; text-transform: uppercase; float: left;"><span style="font-size: 8pt;">BACKGROUND:</span></h4><p style="margin: 0px 0px 0.5em;"><span style="font-size: 8pt;">Intervention with <span class="highlight">antiretroviral</span> 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 <span class="highlight">prolonged</span> period in HIV-1 seroconverters could induce an immuno-virological status similar to that of HIV-1 <span class="highlight">long-term</span> <span class="highlight">non-progressors</span> (LTNPs).</span></p><h4 style="margin: 0px 0.25em 0px 0px; text-transform: uppercase; float: left;"><span style="font-size: 8pt;">METHODOLOGY/PRINCIPAL FINDINGS:</span></h4><p style="margin: 0px 0px 0.5em;"><span style="font-size: 8pt;">We have investigated a cohort of 20 HIV-1 seroconverters on <span class="highlight">long-term</span> ART (LTTS) and compared it to one of 15 LTNPs. Residual viral replication and reservoirs in peripheral blood, as measured by cell-<span class="highlight">associated</span> 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 <span class="highlight">HIV-1-specific</span> CD4(+) and CD8(+) <span class="highlight">T-cell</span> functional <span class="highlight">profile</span> in terms of cytokine production and cytotoxic capacity using IFN-γ, IL-2, TNF-α production and perforin expression, respectively. <span class="highlight">Comparable</span> levels of highly polyfunctional <span class="highlight">HIV-1-specific</span> CD4(+) and CD8(+) T-cells were found in LTTS and LTNPs, with low perforin expression on <span class="highlight">HIV-1-specific</span> CD8(+) T-cells, consistent with a polyfunctional/non-cytotoxic <span class="highlight">profile</span> in a context of low viral burden.</span></p><h4 style="margin: 0px 0.25em 0px 0px; text-transform: uppercase; float: left;"><span style="font-size: 8pt;">CONCLUSIONS:</span></h4><p style="margin: 0px 0px 0.5em;"><span style="font-size: 8pt;">Our results indicate that <span class="highlight">prolonged</span> ART initiated at the time of HIV-1 seroconversion is <span class="highlight">associated</span> with immuno-virological features which resemble those of LTNPs, strengthening the recent emphasis on the positive impact of <span class="highlight">early</span> treatment initiation and paving the way for further interventions to promote virological control after treatment interruption.</span></p></div>
Early and prolonged antiretroviral therapy is associated with an HIV-1-specific T-cell profile comparable to that of long-term non-progressors. - 2011
NMUH Staff Publications 6
<div style="line-height: 17.999801635742188px;"><h4 style="margin: 0px 0.25em 0px 0px; text-transform: uppercase; float: left;"><span style="font-size: 8pt;">BACKGROUND:</span></h4><p style="margin: 0px 0px 0.5em;"><span style="font-size: 8pt;">Intervention with <span class="highlight">antiretroviral</span> 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 <span class="highlight">prolonged</span> period in HIV-1 seroconverters could induce an immuno-virological status similar to that of HIV-1 <span class="highlight">long-term</span> <span class="highlight">non-progressors</span> (LTNPs).</span></p><h4 style="margin: 0px 0.25em 0px 0px; text-transform: uppercase; float: left;"><span style="font-size: 8pt;">METHODOLOGY/PRINCIPAL FINDINGS:</span></h4><p style="margin: 0px 0px 0.5em;"><span style="font-size: 8pt;">We have investigated a cohort of 20 HIV-1 seroconverters on <span class="highlight">long-term</span> ART (LTTS) and compared it to one of 15 LTNPs. Residual viral replication and reservoirs in peripheral blood, as measured by cell-<span class="highlight">associated</span> 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 <span class="highlight">HIV-1-specific</span> CD4(+) and CD8(+) <span class="highlight">T-cell</span> functional <span class="highlight">profile</span> in terms of cytokine production and cytotoxic capacity using IFN-γ, IL-2, TNF-α production and perforin expression, respectively. <span class="highlight">Comparable</span> levels of highly polyfunctional <span class="highlight">HIV-1-specific</span> CD4(+) and CD8(+) T-cells were found in LTTS and LTNPs, with low perforin expression on <span class="highlight">HIV-1-specific</span> CD8(+) T-cells, consistent with a polyfunctional/non-cytotoxic <span class="highlight">profile</span> in a context of low viral burden.</span></p><h4 style="margin: 0px 0.25em 0px 0px; text-transform: uppercase; float: left;"><span style="font-size: 8pt;">CONCLUSIONS:</span></h4><p style="margin: 0px 0px 0.5em;"><span style="font-size: 8pt;">Our results indicate that <span class="highlight">prolonged</span> ART initiated at the time of HIV-1 seroconversion is <span class="highlight">associated</span> with immuno-virological features which resemble those of LTNPs, strengthening the recent emphasis on the positive impact of <span class="highlight">early</span> treatment initiation and paving the way for further interventions to promote virological control after treatment interruption.</span></p></div>