Multiple Viral Genetic Analyses Detect Low-Level Human Immunodeficiency Virus Type 1 Replication during Effective Highly Active Antiretroviral Therapy
| Autor: | Ingrid A. Beck, Gerald H. Learn, Jennifer L. McKernan, Lisa M. Frenkel, Laura Heath, Diane M. Pawluk, Yang Wang, Paul Lewis, Giovanina M. Ellis, Nicole H. Tobin, Sarah Holte, James I. Mullins, Shannon M. De Vange, Kathleen M. Mohan, Ann J. Melvin, Wilscott E. Naugler, Madhumita Mahalanabis |
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| Rok vydání: | 2003 |
| Předmět: |
Molecular Sequence Data
Immunology Mutant HIV Infections Drug resistance Biology Virus Replication Microbiology Evolution Molecular chemistry.chemical_compound Antiretroviral Therapy Highly Active Virology Drug Resistance Viral Genotype Humans Child Phylogeny Infant RNA Sequence Analysis DNA Viral replication chemistry Child Preschool Insect Science Viral evolution DNA Viral HIV-1 RNA Viral Pathogenesis and Immunity Viral load DNA |
| Zdroj: | Journal of Virology. 77:5721-5730 |
| ISSN: | 1098-5514 0022-538X |
| DOI: | 10.1128/jvi.77.10.5721-5730.2003 |
| Popis: | To evaluate human immunodeficiency virus type 1 (HIV-1) replication and selection of drug-resistant viruses during seemingly effective highly active antiretroviral therapy (HAART), multiple HIV-1 env and pol sequences were analyzed and viral DNA levels were quantified from nucleoside analog-experienced children prior to and during a median of 5.1 (range, 1.8 to 6.4) years of HAART. Viral replication was detected at different rates, with apparently increasing sensitivity: 1 of 10 by phylogenetic analysis; 2 of 10 by viral evolution with increasing genetic distances from the most recent common ancestor (MRCA) of infection; 3 of 10 by selection of drug-resistant mutants; and 6 of 10 by maintenance of genetic distances from the MRCA. When four- or five-drug antiretroviral regimens were given to these children, persistent plasma viral rebound did not occur despite the accumulation of highly drug-resistant genotypes. Among the four children without genetic evidence of viral replication, a statistically significant decrease in the genetic distance to the MRCA was detected in three, indicating the persistence of a greater number of early compared to recent viruses, and their HIV-1 DNA decreased by ≥0.9 log 10 , resulting in lower absolute DNA levels ( P = 0.007). This study demonstrates the variable rates of viral replication when HAART has suppressed plasma HIV-1 RNA for years to a median of |
| Databáze: | OpenAIRE |
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