scholarly journals Evidence that Low-Level Viremias during Effective Highly Active Antiretroviral Therapy Result from Two Processes: Expression of Archival Virus and Replication of Virus

2005 ◽  
Vol 79 (15) ◽  
pp. 9625-9634 ◽  
Author(s):  
Nicole H. Tobin ◽  
Gerald H. Learn ◽  
Sarah E. Holte ◽  
Yang Wang ◽  
Ann J. Melvin ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Highly Active Antiretroviral Therapy ◽  
Drug Resistant ◽  
Plasma Virus ◽  
Highly Active ◽  
Infected Cells ◽  
Resistant Mutants ◽  
Viral Sequences ◽  
Hiv 1 ◽  
Selection Of

ABSTRACT Episodes of low-level viremia (LLV), with plasma human immunodeficiency virus type 1 (HIV-1) RNA levels ranging from 50 to 400 copies (c)/ml, occur commonly during highly active antiretroviral therapy (HAART). LLV has been associated with virologic failure of HAART in some studies, while in others LLV did not appear to affect the clinical outcome. To understand the processes leading to LLV, genetic analyses were used to determine whether plasma virions emanated from archived or from newly evolved viral genomes. Episodes of LLV (plasma HIV-1 RNA, 50 to 379 [median, 77] c/ml) were detected in 21/37 (57%) HIV-1-infected children with median plasma HIV-1 RNA levels of <50 c/ml during 79 patient years of HAART. Viral sequences were derived by direct sequencing of PCR products from 21 plasma specimens diluted to end point. In phylogenetic analysis, LLV viral sequences grouped with virus from early in the course of infection in 8/11 subjects. Six specimens had multiple identical viral sequences, suggesting origin from clonally expanded infected cells. LLV plasma virus evolved over time, indicating viral replication, in 3/11 subjects. Two of these had frequent LLV, including the selection of drug-resistant mutants. In summary, plasma virus from episodes of LLV during effective HAART appeared to originate from two distinct processes, (i) clonal outgrowth from long-lived HIV-1-infected cells, presumably following activation and proliferation of these cells, and (ii) ongoing viral replication that included the selection of new drug-resistant mutants. These observations provide a plausible explanation for the divergent clinical outcomes previously associated with LLV.

scholarly journals Multiple Viral Genetic Analyses Detect Low-Level Human Immunodeficiency Virus Type 1 Replication during Effective Highly Active Antiretroviral Therapy

2003 ◽  
Vol 77 (10) ◽  
pp. 5721-5730 ◽  
Author(s):  
Lisa M. Frenkel ◽  
Yang Wang ◽  
Gerald H. Learn ◽  
Jennifer L. McKernan ◽  
Giovanina M. Ellis ◽  
...  
Keyword(s):  
Viral Replication ◽  
Highly Active Antiretroviral Therapy ◽  
Genetic Distances ◽  
Drug Resistant ◽  
Highly Active ◽  
Immunodeficiency Virus ◽  
Resistant Mutants ◽  
Hiv 1 ◽  
Selection Of

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 <50 copies/ml and that combinations of four or five antiretroviral drugs suppress viral replication even after short-term virologic failure of three-drug HAART and despite ongoing accumulation of drug-resistant mutants. Furthermore, the decrease of cellular HIV-1 DNA to low absolute levels in those without genetic evidence of viral replication suggests that monitoring viral DNA during HAART may gauge low-level replication.

Drug-resistant mutants of HIV-1 in patients exhibiting increasing CD4 cell count despite virological failure of highly active antiretroviral therapy

AIDS ◽  
2001 ◽  
Vol 15 (17) ◽  
pp. 2325-2327 ◽  
Author(s):  
Andrea Antinori ◽  
Giuseppina Liuzzi ◽  
Antonella Cingolani ◽  
Ada Bertoli ◽  
Simona Di Giambenedetto ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Cell Count ◽  
Virological Failure ◽  
Highly Active Antiretroviral Therapy ◽  
Drug Resistant ◽  
Cd4 Cell Count ◽  
Highly Active ◽  
Resistant Mutants ◽  
Cd4 Cell ◽  
Hiv 1

Modifications of HIV-1 DNA and Provirus-Infected Cells During 24 Months of Intermittent Highly Active Antiretroviral Therapy

2008 ◽  
Vol 48 (1) ◽  
pp. 68-71 ◽  
Author(s):  
Lucia Palmisano ◽  
Marina Giuliano ◽  
Flavia Chiarotti ◽  
Marisa Zanchetta ◽  
Mauro Andreotti ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Highly Active Antiretroviral Therapy ◽  
Highly Active ◽  
Infected Cells ◽  
Hiv 1

scholarly journals Neutralizing Antibodies Do Not Mediate Suppression of Human Immunodeficiency Virus Type 1 in Elite Suppressors or Selection of Plasma Virus Variants in Patients on Highly Active Antiretroviral Therapy

2006 ◽  
Vol 80 (10) ◽  
pp. 4758-4770 ◽  
Author(s):  
Justin R. Bailey ◽  
Kara G. Lassen ◽  
Hung-Chih Yang ◽  
Thomas C. Quinn ◽  
Stuart C. Ray ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Highly Active Antiretroviral Therapy ◽  
Neutralizing Antibodies ◽  
Progressive Disease ◽  
Plasma Virus ◽  
Highly Active ◽  
Immunodeficiency Virus ◽  
Elite Suppressors ◽  
Hiv 1

ABSTRACT Neutralizing antibodies (NAb) against autologous virus can reach high titers in human immunodeficiency virus type 1 (HIV-1)-infected patients with progressive disease. Less is known about the role of NAb in HIV-1-infected patients with viral loads of <50 copies/ml of plasma, including patients on effective highly active antiretroviral therapy (HAART) and elite suppressors, who control HIV-1 replication without antiretroviral therapy. In this study, we analyzed full-length env sequences from plasma viruses and proviruses in resting CD4+ T cells of HAART-treated patients, elite suppressors, and untreated HIV-1-infected patients with progressive disease. For each patient group, we assessed plasma virus neutralization by autologous, contemporaneous plasma. The degree of env diversity, the number of N-linked glycosylation sites, and the lengths of variable loops were all lower in elite suppressors than in HAART-treated and untreated viremic patients. Both elite suppressors and HAART-treated patients had lower titers of NAb against HIV-1 lab strains than those of untreated viremic patients. Surprisingly, titers of NAb against autologous, contemporaneous plasma viruses were similarly low in chronic progressors, elite suppressors, and HAART-treated patients. In elite suppressors and HAART-treated patients, titers of NAb against autologous plasma viruses also did not differ significantly from titers against autologous proviruses from resting CD4+ T cells. These results suggest that high-titer NAb are not required for maintenance of viral suppression in elite suppressors and that NAb do not select plasma virus variants in most HAART-treated patients. Both drug-mediated and natural suppression of HIV-1 replication to levels below 50 copies/ml may limit the stimulation and maintenance of effective NAb responses.

scholarly journals Recovery of Replication-Competent Residual HIV-1 from Plasma of a Patient Receiving Prolonged, Suppressive Highly Active Antiretroviral Therapy

2010 ◽  
Vol 84 (16) ◽  
pp. 8348-8352 ◽  
Author(s):  
Gautam K. Sahu ◽  
Juan C. Sarria ◽  
Miles W. Cloyd
Keyword(s):  
Antiretroviral Therapy ◽  
Highly Active Antiretroviral Therapy ◽  
Host Cells ◽  
Drug Resistant ◽  
Residual Viremia ◽  
Viral Genomes ◽  
Highly Active ◽  
Hiv 1 ◽  
Adherence To Therapy

ABSTRACT The clinical significance of persistent residual viremia in patients on prolonged highly active antiretroviral therapy (HAART) is not clear. Moreover, it remains to be demonstrated whether residual viremia consists of viruses capable of spreading infection in vivo upon termination of therapy. Using residual viral RNAs (vRNAs) isolated from a HAART-treated patient's plasma, we cloned full-length viral genomes and found that most of them could produce infectious, replication-competent HIVs when transfected into TZM-bl cells, suggesting that residual viruses produced in the absence of therapy can initiate fresh cycles of infection and spread in host cells. The data further indicate that residual viremia may pose a major concern with regard to the emergence of drug-resistant HIVs during periods of low adherence to therapy.

Sign in / Sign up

Export Citation Format

Share Document