Cell-associated HIV-1-DNA quantitation after highly active antiretroviral therapy-treated primary infection in patients with persistently undetectable plasma HIV-1 RNA

Garrigue, Isabelle; Pellegrin, Isabelle; Hoën, Bruno; Dumon, Béatrice; Harzic, M.; Schrive, Marie-Hélène; Séréni, D.; Fleury, Hervé

doi:10.1097/00002030-200012220-00006

Cited by 45 publications

(24 citation statements)

References 21 publications

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“…The high levels of tat mRNA observed with the ART-treated HIV-2 cohort suggested that the therapeutic regimens used were unable to reduce the rate of de novo cell infection. These data contrast with those for ART-treated HIV-1 ϩ patients, in which virological response is usually associated with a sharp decline in MS mRNA (4,21,62) and in the proportion of MS mRNA relative to US mRNA in PBMC (57), as well as with a progressive decrease in proviral DNA (23,58,59) despite the low-level viremia that can frequently be detected using ultrasensitive assays (17,43).…”

Section: Discussionmentioning

confidence: 63%

“…Viremia levels were similar in the treated and untreated HIV-2 cohorts, due to the low-level viremia detected in some of the ART-treated HIV-2 ϩ patients ( Table 2). Of note, in contrast with the progressive decline in proviral DNA levels usually observed with ART-treated HIV-1 ϩ patients (23,58), proviral DNA did not significantly differ between untreated and treated HIV-2 ϩ patients (Fig. 3A), despite the prolonged treatment.…”

Section: Relationship Of Plasma and Cell-associated Viral Load With Cmentioning

confidence: 72%

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Cell-Associated Viral Burden Provides Evidence of Ongoing Viral Replication in Aviremic HIV-2-Infected Patients

Soares¹,

Tendeiro

Foxall

et al. 2011

J Virol

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Viremia is significantly lower in HIV-2 than in HIV-1 infection, irrespective of disease stage. Nevertheless, the comparable proviral DNA burdens observed for these two infections indicate similar numbers of infected cells. Here we investigated this apparent paradox by assessing cell-associated viral replication. We found that untreated HIV-1-positive (HIV-1 ؉ ) and HIV-2 ؉ individuals, matched for CD4 T cell depletion, exhibited similar gag mRNA levels, indicating that significant viral transcription is occurring in untreated HIV-2 ؉ patients, despite the reduced viremia (undetectable to 2.6 ؋ 10 4 RNA copies/ml). However, tat mRNA transcripts were observed at significantly lower levels in HIV-2 ؉ patients, suggesting that the rate of de novo infection is decreased in these patients. Our data also reveal a direct relationship of gag and tat transcripts with CD4 and CD8 T cell activation, respectively. Antiretroviral therapy (ART)-treated HIV-2 ؉ patients showed persistent viral replication, irrespective of plasma viremia, possibly contributing to the emergence of drug resistance mutations, persistent hyperimmune activation, and poor CD4 T cell recovery that we observed with these individuals. In conclusion, we provide here evidence of significant ongoing viral replication in HIV-2 ؉ patients, further emphasizing the dichotomy between amount of plasma virus and cell-associated viral burden and stressing the need for antiretroviral trials and the definition of therapeutic guidelines for HIV-2 infection.

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Section: Discussionmentioning

confidence: 63%

Section: Relationship Of Plasma and Cell-associated Viral Load With Cmentioning

confidence: 72%

Cell-Associated Viral Burden Provides Evidence of Ongoing Viral Replication in Aviremic HIV-2-Infected Patients

Soares¹,

Tendeiro

Foxall

et al. 2011

J Virol

View full text Add to dashboard Cite

show abstract

“…replication among individuals with plasma HIV-1 RNA below the limits of detection. Data from others' studies similarly suggest that PBMC HIV-1 DNA loads correlate with markers of viral nucleic acid synthesis (2,4,20,27,37,61), as have intracellular viral RNA levels (4) and the ratio of unspliced to multiply spliced HIV-1 mRNA (19). Decreases in total HIV-1 levels associated with viral replication well-suppressed by HAART appear primarily due to decreases in unintegrated HIV-1 DNA (27).…”

Section: Discussionmentioning

confidence: 91%

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

Frenkel¹,

Wang²,

Learn³

et al. 2003

J Virol

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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 <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.

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“…The amount of HCV RNA in each biopsy was quantified by RT-PCR using the Amplicor HCV Monitor 1.0 assay (Roche Diagnostic Systems, Branchburg, NJ; 25). The technique was adapted from the Agence Nationale de Recherche sur le SIDA method used for HIV RNA quantitation in lymph nodes (26). Briefly, 100 l of the proteinase K-digested specimens were mixed with 400 l of Monitor lysis buffer containing guanidine thiocyanate with addition of the Roche-supplied internal quantitative standard (IQS) required for determining RNA levels.…”

Section: Hcv Rna Quantitation In Frozen Liver Tissuesmentioning

confidence: 99%

Immunohistochemical Detection of HCV in Cirrhosis, Dysplastic Nodules, and Hepatocellular Carcinomas with Parallel-Tissue Quantitative RT-PCR

Rullier

Trimoulet

Urbaniak³

et al. 2001

Modern Pathology

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Cell-associated HIV-1-DNA quantitation after highly active antiretroviral therapy-treated primary infection in patients with persistently undetectable plasma HIV-1 RNA

Cited by 45 publications

References 21 publications

Cell-Associated Viral Burden Provides Evidence of Ongoing Viral Replication in Aviremic HIV-2-Infected Patients

Cell-Associated Viral Burden Provides Evidence of Ongoing Viral Replication in Aviremic HIV-2-Infected Patients

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

Immunohistochemical Detection of HCV in Cirrhosis, Dysplastic Nodules, and Hepatocellular Carcinomas with Parallel-Tissue Quantitative RT-PCR

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