Multiple viral genetic analyses detect low-level human immunodeficiency virus type 1 replication during effective highly active antiretroviral therapy

Lisa M. Frenkel, Yang Wang, Gerald H. Learn, Jennifer L. McKernan, Giovanina M. Ellis, Kathleen M. Mohan, Sarah E. Holte, Shannon M. De Vange, Diane M. Pawluk, Ann J. Melvin, Paul Lewis, Laura M. Heath, Ingrid A. Beck, Madhumita Mahalanabis, Willscott (Scott) Naugler, Nicole H. Tobin, James I. Mullins

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Abstract

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 log10, 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

Original languageEnglish (US)
Pages (from-to)5721-5730
Number of pages10
JournalJournal of Virology
Volume77
Issue number10
DOIs
Publication statusPublished - May 2003

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ASJC Scopus subject areas

  • Immunology

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