Low-level HIV-1 replication and the dynamics of the resting CD4<sup>+ </sup>T cell reservoir for HIV-1 in the setting of HAART
<p>Abstract</p> <p>Background</p> <p>In the setting of highly active antiretroviral therapy (HAART), plasma levels of human immunodeficiency type-1 (HIV-1) rapidly decay to below the limit of detection of standard clinical assays. However, reactivation of remaining late...
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| Format: | Article |
| Language: | English |
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BMC
2008-01-01
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| Series: | BMC Infectious Diseases |
| Online Access: | http://www.biomedcentral.com/1471-2334/8/2 |
| _version_ | 1819037432944787456 |
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| author | Wilke Claus O Siliciano Robert F Sedaghat Ahmad R |
| author_facet | Wilke Claus O Siliciano Robert F Sedaghat Ahmad R |
| author_sort | Wilke Claus O |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>In the setting of highly active antiretroviral therapy (HAART), plasma levels of human immunodeficiency type-1 (HIV-1) rapidly decay to below the limit of detection of standard clinical assays. However, reactivation of remaining latently infected memory CD4<sup>+ </sup>T cells is a source of continued virus production, forcing patients to remain on HAART despite clinically undetectable viral loads. Unfortunately, the latent reservoir decays slowly, with a half-life of up to 44 months, making it the major known obstacle to the eradication of HIV-1 infection. However, the mechanism underlying the long half-life of the latent reservoir is unknown. The most likely potential mechanisms are low-level viral replication and the intrinsic stability of latently infected cells.</p> <p>Methods</p> <p>Here we use a mathematical model of T cell dynamics in the setting of HIV-1 infection to probe the decay characteristics of the latent reservoir upon initiation of HAART. We compare the behavior of this model to patient derived data in order to gain insight into the role of low-level viral replication in the setting of HAART.</p> <p>Results</p> <p>By comparing the behavior of our model to patient derived data, we find that the viral dynamics observed in patients on HAART could be consistent with low-level viral replication but that this replication would not significantly affect the decay rate of the latent reservoir. Rather than low-level replication, the intrinsic stability of latently infected cells and the rate at which they are reactivated primarily determine the observed reservoir decay rate according to the predictions of our model.</p> <p>Conclusion</p> <p>The intrinsic stability of the latent reservoir has important implications for efforts to eradicate HIV-1 infection and suggests that intensified HAART would not accelerate the decay of the latent reservoir.</p> |
| first_indexed | 2024-12-21T08:21:20Z |
| format | Article |
| id | doaj.art-3c6186bc9cd44f089311f3fddbc4f687 |
| institution | Directory Open Access Journal |
| issn | 1471-2334 |
| language | English |
| last_indexed | 2024-12-21T08:21:20Z |
| publishDate | 2008-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Infectious Diseases |
| spelling | doaj.art-3c6186bc9cd44f089311f3fddbc4f6872022-12-21T19:10:25ZengBMCBMC Infectious Diseases1471-23342008-01-0181210.1186/1471-2334-8-2Low-level HIV-1 replication and the dynamics of the resting CD4<sup>+ </sup>T cell reservoir for HIV-1 in the setting of HAARTWilke Claus OSiliciano Robert FSedaghat Ahmad R<p>Abstract</p> <p>Background</p> <p>In the setting of highly active antiretroviral therapy (HAART), plasma levels of human immunodeficiency type-1 (HIV-1) rapidly decay to below the limit of detection of standard clinical assays. However, reactivation of remaining latently infected memory CD4<sup>+ </sup>T cells is a source of continued virus production, forcing patients to remain on HAART despite clinically undetectable viral loads. Unfortunately, the latent reservoir decays slowly, with a half-life of up to 44 months, making it the major known obstacle to the eradication of HIV-1 infection. However, the mechanism underlying the long half-life of the latent reservoir is unknown. The most likely potential mechanisms are low-level viral replication and the intrinsic stability of latently infected cells.</p> <p>Methods</p> <p>Here we use a mathematical model of T cell dynamics in the setting of HIV-1 infection to probe the decay characteristics of the latent reservoir upon initiation of HAART. We compare the behavior of this model to patient derived data in order to gain insight into the role of low-level viral replication in the setting of HAART.</p> <p>Results</p> <p>By comparing the behavior of our model to patient derived data, we find that the viral dynamics observed in patients on HAART could be consistent with low-level viral replication but that this replication would not significantly affect the decay rate of the latent reservoir. Rather than low-level replication, the intrinsic stability of latently infected cells and the rate at which they are reactivated primarily determine the observed reservoir decay rate according to the predictions of our model.</p> <p>Conclusion</p> <p>The intrinsic stability of the latent reservoir has important implications for efforts to eradicate HIV-1 infection and suggests that intensified HAART would not accelerate the decay of the latent reservoir.</p>http://www.biomedcentral.com/1471-2334/8/2 |
| spellingShingle | Wilke Claus O Siliciano Robert F Sedaghat Ahmad R Low-level HIV-1 replication and the dynamics of the resting CD4<sup>+ </sup>T cell reservoir for HIV-1 in the setting of HAART BMC Infectious Diseases |
| title | Low-level HIV-1 replication and the dynamics of the resting CD4<sup>+ </sup>T cell reservoir for HIV-1 in the setting of HAART |
| title_full | Low-level HIV-1 replication and the dynamics of the resting CD4<sup>+ </sup>T cell reservoir for HIV-1 in the setting of HAART |
| title_fullStr | Low-level HIV-1 replication and the dynamics of the resting CD4<sup>+ </sup>T cell reservoir for HIV-1 in the setting of HAART |
| title_full_unstemmed | Low-level HIV-1 replication and the dynamics of the resting CD4<sup>+ </sup>T cell reservoir for HIV-1 in the setting of HAART |
| title_short | Low-level HIV-1 replication and the dynamics of the resting CD4<sup>+ </sup>T cell reservoir for HIV-1 in the setting of HAART |
| title_sort | low level hiv 1 replication and the dynamics of the resting cd4 sup sup t cell reservoir for hiv 1 in the setting of haart |
| url | http://www.biomedcentral.com/1471-2334/8/2 |
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