Decay characteristics of HIV-1-infected compartments during combination therapy
Analysis of changes in viral load after initiation of treatment with potent antiretroviral agents has provided substantial insight into the dynamics of human immunodeficiency virus type 1 (HIV-1). The concentration of HIV-1 in plasma drops by approximately 99% in the first two weeks of treatment owi...
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| Veröffentlicht in: | Nature (London) 1997-05, Vol.387 (6629), p.188-191 |
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| creator | Perelson, Alan S Essunger, Paulina Cao, Yunzhen Vesanen, Mika Hurley, Arlene Saksela, Kalle Markowitz, Martin Ho, David D |
| description | Analysis of changes in viral load after initiation of treatment with potent antiretroviral agents has provided substantial insight into the dynamics of human immunodeficiency virus type 1 (HIV-1). The concentration of HIV-1 in plasma drops by approximately 99% in the first two weeks of treatment owing to the rapid elimination of free virus with a half-life (t1/2) of < or =6 hours and loss of productively infected cells with a t1/2 of 1.6 days. Here we show that with combination therapy this initial decrease is followed by a slower second-phase decay of plasma viraemia. Detailed mathematical analysis shows that the loss of long-lived infected cells (t1/2 of 1-4 weeks) is a major contributor to the second phase, whereas the activation of latently infected lymphocytes (t1/2 of 0.5-2 weeks) is only a minor source. Based on these decay characteristics, we estimate that 2.3-3.1 years of a completely inhibitory treatment would be required to eliminate HIV-1 from these compartments. To eradicate HIV-1 completely, even longer treatment may be needed because of the possible existence of undetected viral compartments or sanctuary sites. |
| doi_str_mv | 10.1038/387188a0 |
| format | Article |
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Antiparasitic agents ; Antiretroviral agents ; Antiviral agents ; Biological and medical sciences ; CD4-Positive T-Lymphocytes - virology ; Decay ; Drug therapy ; Drug Therapy, Combination ; Half-Life ; HIV ; HIV Infections - drug therapy ; HIV Infections - virology ; HIV Protease Inhibitors - therapeutic use ; HIV-1 - physiology ; Human immunodeficiency virus ; human immunodeficiency virus 1 ; Humans ; Isoquinolines - therapeutic use ; Lamivudine - therapeutic use ; Leukocytes, Mononuclear - virology ; Lymphocytes ; Macrophages - virology ; Mathematics ; Medical research ; Medical sciences ; Models, Biological ; Nelfinavir ; Pharmacology. 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Academic</collection><jtitle>Nature (London)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Perelson, Alan S</au><au>Essunger, Paulina</au><au>Cao, Yunzhen</au><au>Vesanen, Mika</au><au>Hurley, Arlene</au><au>Saksela, Kalle</au><au>Markowitz, Martin</au><au>Ho, David D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Decay characteristics of HIV-1-infected compartments during combination therapy</atitle><jtitle>Nature (London)</jtitle><addtitle>Nature</addtitle><date>1997-05-08</date><risdate>1997</risdate><volume>387</volume><issue>6629</issue><spage>188</spage><epage>191</epage><pages>188-191</pages><issn>0028-0836</issn><eissn>1476-4687</eissn><coden>NATUAS</coden><abstract>Analysis of changes in viral load after initiation of treatment with potent antiretroviral agents has provided substantial insight into the dynamics of human immunodeficiency virus type 1 (HIV-1). The concentration of HIV-1 in plasma drops by approximately 99% in the first two weeks of treatment owing to the rapid elimination of free virus with a half-life (t1/2) of < or =6 hours and loss of productively infected cells with a t1/2 of 1.6 days. Here we show that with combination therapy this initial decrease is followed by a slower second-phase decay of plasma viraemia. Detailed mathematical analysis shows that the loss of long-lived infected cells (t1/2 of 1-4 weeks) is a major contributor to the second phase, whereas the activation of latently infected lymphocytes (t1/2 of 0.5-2 weeks) is only a minor source. Based on these decay characteristics, we estimate that 2.3-3.1 years of a completely inhibitory treatment would be required to eliminate HIV-1 from these compartments. To eradicate HIV-1 completely, even longer treatment may be needed because of the possible existence of undetected viral compartments or sanctuary sites.</abstract><cop>London</cop><pub>Nature Publishing</pub><pmid>9144290</pmid><doi>10.1038/387188a0</doi><tpages>4</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0028-0836 |
| ispartof | Nature (London), 1997-05, Vol.387 (6629), p.188-191 |
| issn | 0028-0836 1476-4687 |
| language | eng |
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| source | MEDLINE; Nature; Alma/SFX Local Collection |
| subjects | AIDS/HIV Anti-HIV Agents - therapeutic use Antibiotics. Antiinfectious agents. Antiparasitic agents Antiretroviral agents Antiviral agents Biological and medical sciences CD4-Positive T-Lymphocytes - virology Decay Drug therapy Drug Therapy, Combination Half-Life HIV HIV Infections - drug therapy HIV Infections - virology HIV Protease Inhibitors - therapeutic use HIV-1 - physiology Human immunodeficiency virus human immunodeficiency virus 1 Humans Isoquinolines - therapeutic use Lamivudine - therapeutic use Leukocytes, Mononuclear - virology Lymphocytes Macrophages - virology Mathematics Medical research Medical sciences Models, Biological Nelfinavir Pharmacology. Drug treatments Proviruses - physiology Reverse Transcriptase Inhibitors - therapeutic use RNA, Viral - blood Sulfonic Acids - therapeutic use Viral Load Viremia Virus Latency Zidovudine - therapeutic use |
| title | Decay characteristics of HIV-1-infected compartments during combination therapy |
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