Genetic characterization of rebounding HIV-1 after cessation of highly active antiretroviral therapy
| Autor: | Yong Guo, Linqi Zhang, Chris Chung, Alexandria Kim, Bharat Ramratnam, David D. Ho, Xia Jin, Martin Markowitz, Tian He, Bor-Shen Hu, Eva Skulsky, Arlene Hurley |
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| Rok vydání: | 2000 |
| Předmět: |
Adult
Male Lymphoid Tissue viruses HIV Infections Viremia Biology Genes env Article Virus Pharmacotherapy Recurrence Antiretroviral Therapy Highly Active Virus latency medicine Humans virus diseases General Medicine Viral Load medicine.disease Virology CD4 Lymphocyte Count Virus Latency Discontinuation Lymphatic system Viral replication Chronic Disease Immunology Commentary HIV-1 RNA Viral Viral load Polymorphism Restriction Fragment Length |
| Zdroj: | Journal of Clinical Investigation. 106:839-845 |
| ISSN: | 0021-9738 |
| DOI: | 10.1172/jci10565 |
| Popis: | Despite prolonged treatment with highly active antiretroviral therapy (HAART), infectious HIV-1 continues to replicate and to reside latently in resting memory CD4(+) T lymphocytes, creating a major obstacle to HIV-1 eradication. It is therefore not surprising to observe a prompt viral rebound after discontinuation of HAART. The nature of the rebounding virus, however, remains undefined. We now report on the genetic characterization of rebounding viruses in eight patients in whom plasma viremia was undetectable throughout about 3 years of HAART. Taking advantage of the extensive length polymorphism in HIV-1 env, we found that in five patients who did not show HIV-1 replication during treatment, the rebound virus was identical to those isolated from the latent reservoir. In three other patients, two of whom had been free of plasma viremia but had showed some residual viral replication, the rebound virus was genetically different from the latent reservoir virus, corresponding instead to minor viral variants detected during the course of treatment in lymphoid tissues. We conclude that in cases with apparent complete HIV-1 suppression by HAART, viral rebound after cessation of therapy could have originated from the activation of virus from the latent reservoir. In patients with incomplete suppression by chemotherapy, however, the viral rebound is likely triggered by ongoing, low-level replication of HIV-1, perhaps occurring in lymphoid tissues. |
| Databáze: | OpenAIRE |
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