000 | 04304cam a2200313 4500 | ||
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001 | NMDX6590 | ||
008 | 120401t2011 xxu||||| |||| 00| 0 eng d | ||
100 | _aCellerai, C. | ||
240 | _aPLoS One. | ||
245 | _aEarly and prolonged antiretroviral therapy is associated with an HIV-1-specific T-cell profile comparable to that of long-term non-progressors. | ||
260 | _c2011 | ||
500 | _aNMUH Staff Publications | ||
500 | _a6 | ||
520 | _a<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&nbsp;<span class="highlight">antiretroviral</span>&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;<span class="highlight">prolonged</span>&nbsp;period in HIV-1 seroconverters could induce an immuno-virological status similar to that of HIV-1&nbsp;<span class="highlight">long-term</span>&nbsp;<span class="highlight">non-progressors</span>&nbsp;(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&nbsp;<span class="highlight">long-term</span>&nbsp;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>&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;<span class="highlight">HIV-1-specific</span>&nbsp;CD4(+) and CD8(+)&nbsp;<span class="highlight">T-cell</span>&nbsp;functional&nbsp;<span class="highlight">profile</span>&nbsp;in terms of cytokine production and cytotoxic capacity using IFN-γ, IL-2, TNF-α production and perforin expression, respectively.&nbsp;<span class="highlight">Comparable</span>&nbsp;levels of highly polyfunctional&nbsp;<span class="highlight">HIV-1-specific</span>&nbsp;CD4(+) and CD8(+) T-cells were found in LTTS and LTNPs, with low perforin expression on&nbsp;<span class="highlight">HIV-1-specific</span>&nbsp;CD8(+) T-cells, consistent with a polyfunctional/non-cytotoxic&nbsp;<span class="highlight">profile</span>&nbsp;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&nbsp;<span class="highlight">prolonged</span>&nbsp;ART initiated at the time of HIV-1 seroconversion is&nbsp;<span class="highlight">associated</span>&nbsp;with immuno-virological features which resemble those of LTNPs, strengthening the recent emphasis on the positive impact of&nbsp;<span class="highlight">early</span>&nbsp;treatment initiation and paving the way for further interventions to promote virological control after treatment interruption.</span></p></div> | ||
700 | _aHarari, A. | ||
700 | _aStauss, H. | ||
700 | _aYerly, S. | ||
700 | _aGeretti, A.M. | ||
700 | _aCarroll, A. | ||
700 | _aYee, T. | ||
700 | _aAinsworth, J. | ||
700 | _aWilliams, I. | ||
700 | _aSweeney, J. | ||
700 | _aFreedman, A. | ||
700 | _aJohnson, M. | ||
700 | _aPantaleo, G. | ||
700 | _aKinloch-de Loes, S. | ||
856 | _uhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3071718/pdf/pone.0018164.pdf | ||
999 |
_c75755 _d75755 |