Early and prolonged antiretroviral therapy is associated with an HIV-1-specific T-cell profile comparable to that of long-term non-progressors.
<h4>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 c...
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2011
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oai:doaj.org-article:b262d415a2514fc4899f27eac687b6592021-11-18T06:56:13ZEarly and prolonged antiretroviral therapy is associated with an HIV-1-specific T-cell profile comparable to that of long-term non-progressors.1932-620310.1371/journal.pone.0018164https://doaj.org/article/b262d415a2514fc4899f27eac687b6592011-04-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21483676/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>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>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>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.Cristina CelleraiAlexandre HarariHans StaussSabine YerlyAnna-Maria GerettiAnne CarrollThynn YeeJonathan AinsworthIan WilliamsJohn SweeneyAndrew FreedmanMargaret JohnsonGiuseppe PantaleoSabine Kinloch-de LoesPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 4, p e18164 (2011) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Cristina Cellerai Alexandre Harari Hans Stauss Sabine Yerly Anna-Maria Geretti Anne Carroll Thynn Yee Jonathan Ainsworth Ian Williams John Sweeney Andrew Freedman Margaret Johnson Giuseppe Pantaleo Sabine Kinloch-de Loes Early and prolonged antiretroviral therapy is associated with an HIV-1-specific T-cell profile comparable to that of long-term non-progressors. |
| description |
<h4>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>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>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. |
| format |
article |
| author |
Cristina Cellerai Alexandre Harari Hans Stauss Sabine Yerly Anna-Maria Geretti Anne Carroll Thynn Yee Jonathan Ainsworth Ian Williams John Sweeney Andrew Freedman Margaret Johnson Giuseppe Pantaleo Sabine Kinloch-de Loes |
| author_facet |
Cristina Cellerai Alexandre Harari Hans Stauss Sabine Yerly Anna-Maria Geretti Anne Carroll Thynn Yee Jonathan Ainsworth Ian Williams John Sweeney Andrew Freedman Margaret Johnson Giuseppe Pantaleo Sabine Kinloch-de Loes |
| author_sort |
Cristina Cellerai |
| title |
Early and prolonged antiretroviral therapy is associated with an HIV-1-specific T-cell profile comparable to that of long-term non-progressors. |
| title_short |
Early and prolonged antiretroviral therapy is associated with an HIV-1-specific T-cell profile comparable to that of long-term non-progressors. |
| title_full |
Early and prolonged antiretroviral therapy is associated with an HIV-1-specific T-cell profile comparable to that of long-term non-progressors. |
| title_fullStr |
Early and prolonged antiretroviral therapy is associated with an HIV-1-specific T-cell profile comparable to that of long-term non-progressors. |
| title_full_unstemmed |
Early and prolonged antiretroviral therapy is associated with an HIV-1-specific T-cell profile comparable to that of long-term non-progressors. |
| title_sort |
early and prolonged antiretroviral therapy is associated with an hiv-1-specific t-cell profile comparable to that of long-term non-progressors. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2011 |
| url |
https://doaj.org/article/b262d415a2514fc4899f27eac687b659 |
| work_keys_str_mv |
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| _version_ |
1718424188841099264 |