scholarly journals Residual plasma viremia and infectious HIV-1 recovery from resting memory CD4 cells in patients on antiretroviral therapy: results from ACTG A5173

2013 ◽  
Author(s):  
Rajesh T Gandhi ◽  
◽  
Ronald J Bosch ◽  
Evgenia Aga ◽  
Margaret A Bedison ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Plasma Viremia ◽  
Cd4 Cells ◽  
Hiv 1 ◽  
Residual Plasma Viremia

scholarly journals 108. Selective Decay of Intact HIV-1 Proviral DNA on Antiretroviral Therapy

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S183-S183
Author(s):  
Rajesh Gandhi ◽  
Joshua Cyktor ◽  
Ronald Bosch ◽  
Hanna Mar ◽  
Gregory Laird ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Panel Member ◽  
Plasma Viremia ◽  
Research Support ◽  
Review Panel ◽  
Proviral Dna ◽  
Hiv 1 ◽  
Over Time ◽  
Residual Plasma Viremia ◽  
Research Grant

Abstract Background HIV-1 proviruses persist in people on antiretroviral therapy (ART) but most are defective and do not constitute a replication-competent reservoir. The decay of infected cells carrying intact compared with defective HIV-1 proviruses has not been well-defined in people on ART. Methods We separately quantified intact and defective proviruses (using an intact proviral DNA assay), residual plasma viremia, and markers of inflammation and activation in people on long-term ART. Longitudinal measurements were done at three timepoints: timepoint 1 was a median of 7.1 years on ART; timepoint 2 was a median of 3.7 years later; timepoint 3 was a median of 5.5 years after timepoint 1 and a median 12 years after starting ART (Figure 1). Figure 1: Study timepoints Results Among 40 participants tested longitudinally from a median of 7.1 years to 12 years after ART initiation, intact provirus levels declined significantly over time (median half-life 7.1 years; 95% confidence interval [CI], 3.9, 18), whereas defective provirus levels did not decrease. The median half-life of total HIV-1 DNA was 41.6 years (95% CI, 13.6, 75). When we evaluated the change in proviral DNA per year, intact proviral DNA declined significantly more (p< 0.001) than defective proviral DNA (the latter did not change) (Figure 2). The proportion of all proviruses that were intact diminished over time on ART, from about 10% at the first on-ART timepoint to about 5% at the last timepoint (Figure 3). At timepoint 1, intact provirus levels on ART correlated with total HIV-1 DNA and residual plasma viremia, but there was no evidence for associations between intact provirus levels and inflammation or immune activation. Figure 2: Percent change in HIV-1 proviral DNA per year Figure 3: Total HIV-1 proviruses (grey bars) and the percentage of intact proviruses (red lines, displaying median, Q1, Q3) by timepoint. Conclusion Cells containing intact, replication-competent proviruses are selectively lost during suppressive ART. Defining the mechanisms involved should inform strategies to accelerate HIV-1 reservoir depletion. Disclosures Rajesh Gandhi, MD, Merck (Advisor or Review Panel member) Gregory Laird, PhD, Accelevir Diagnostics (Shareholder, Other Financial or Material Support, Employee) Albine Martin, PhD, Accelevir Diagnostics (Shareholder, Other Financial or Material Support, Employee) Bernard Macatangay, MD, Gilead (Grant/Research Support) Joseph J. Eron, MD, Gilead Sciences (Consultant, Research Grant or Support)Janssen (Consultant, Research Grant or Support)Merck (Consultant)ViiV Healthcare (Consultant, Research Grant or Support) Janet Siliciano, PhD, Gilead (Advisor or Review Panel member)US Military HIV Research Program (Advisor or Review Panel member) John Mellors, MD, Abound Bio (Shareholder)Accelevir Diagnostics (Consultant)Co-Crystal Pharmaceuticals (Shareholder)Gilead (Consultant, Grant/Research Support)Merck (Consultant)

scholarly journals Selective Decay of Intact HIV-1 Proviral DNA on Antiretroviral Therapy

2020 ◽  
Author(s):  
Rajesh T Gandhi ◽  
Joshua C Cyktor ◽  
Ronald J Bosch ◽  
Hanna Mar ◽  
Gregory M Laird ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Half Life ◽  
Plasma Viremia ◽  
Art Initiation ◽  
Markers Of Inflammation ◽  
Infected Cells ◽  
Selective Decay ◽  
Hiv 1 ◽  
Over Time ◽  
Residual Plasma Viremia

Abstract Background HIV-1 proviruses persist in people on antiretroviral therapy (ART) but most are defective and do not constitute a replication-competent reservoir. The decay of infected cells carrying intact compared with defective HIV-1 proviruses has not been well defined in people on ART. Methods We separately quantified intact and defective proviruses, residual plasma viremia, and markers of inflammation and activation in people on long-term ART. Results Among 40 participants tested longitudinally from a median of 7.1 years to 12 years after ART initiation, intact provirus levels declined significantly over time (median half-life, 7.1 years; 95% confidence interval [CI], 3.9–18), whereas defective provirus levels did not decrease. The median half-life of total HIV-1 DNA was 41.6 years (95% CI, 13.6–75). The proportion of all proviruses that were intact diminished over time on ART, from about 10% at the first on-ART time point to about 5% at the last. Intact provirus levels on ART correlated with total HIV-1 DNA and residual plasma viremia, but there was no evidence for associations between intact provirus levels and inflammation or immune activation. Conclusions Cells containing intact, replication-competent proviruses are selectively lost during suppressive ART. Defining the mechanisms involved should inform strategies to accelerate HIV-1 reservoir depletion.

scholarly journals Replicate Aptima Assay for Quantifying Residual Plasma Viremia in Individuals on Antiretroviral Therapy

2020 ◽  
Vol 58 (12) ◽  
Author(s):  
Sonia Bakkour ◽  
Xutao Deng ◽  
Peter Bacchetti ◽  
Eduard Grebe ◽  
Leilani Montalvo ◽  
...  
Keyword(s):  
Viral Load ◽  
Antiretroviral Therapy ◽  
False Negative ◽  
Study Cohort ◽  
Plasma Samples ◽  
Plasma Viremia ◽  
Viral Loads ◽  
The Impact ◽  
Hiv 1 ◽  
Residual Plasma Viremia

ABSTRACT Detection of residual plasma viremia in antiretroviral therapy (ART)-suppressed HIV-infected individuals is critical for characterizing the latent reservoir and evaluating the impact of cure interventions. Ultracentrifugation-based single-copy assays are sensitive but labor intensive. Fully automated replicate testing using a standard clinical viral load assay was evaluated as a high-throughput alternative for the quantification of low-level viremia. Four plasma samples from blood donors with acute HIV-1 infection and one viral culture supernatant were serially diluted into 25-ml samples to nominal viral loads ranging from 39 to <0.5 copies (cp)/ml. Each dilution was tested with 45 replicates (reps) using 0.5 ml/rep with the Aptima HIV-1 Quant assay. The nominal and estimated viral loads based on the single-hit Poisson model were compared, and a hybrid Poisson digital model for calibrated viral load estimation was derived. Testing performed using 45 reps on longitudinal plasma samples from 50 ART-suppressed individuals in the Reservoir Assay Validation and Evaluation Network (RAVEN) study cohort (range of 1 to 19 years of continuous ART suppression) showed a median viral load of 0.54 cp/ml (interquartile range [IQR], 0.22 to 1.46 cp/ml) and a 14% (95% confidence interval [CI], 9% to 19%) decline in viral load for each additional year in duration suppressed. Within the RAVEN cohort, the expected false-negative rate for detection at lower rep numbers using 9 and 18 reps was 26% and 14%, respectively. Residual plasma viremia levels positively correlated with cell-associated HIV RNA and DNA. The performance characteristics of the replicate Aptima assay support its use for quantifying residual plasma viremia to study the latent HIV reservoir and cure interventions.

scholarly journals Continued Slow Decay of the Residual Plasma Viremia Level in HIV-1–Infected Adults Receiving Long-term Antiretroviral Therapy

2015 ◽  
Vol 213 (4) ◽  
pp. 556-560 ◽  
Author(s):  
Sharon A. Riddler ◽  
Evgenia Aga ◽  
Ronald J. Bosch ◽  
Barbara Bastow ◽  
Margaret Bedison ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Plasma Viremia ◽  
Slow Decay ◽  
Viremia Level ◽  
Hiv 1 ◽  
Residual Plasma Viremia

scholarly journals Relationship Between Residual Plasma Viremia and the Size of HIV Proviral DNA Reservoirs in Infected Individuals Receiving Effective Antiretroviral Therapy

2011 ◽  
Vol 204 (1) ◽  
pp. 135-138 ◽  
Author(s):  
Tae-Wook Chun ◽  
Danielle Murray ◽  
J. Shawn Justement ◽  
Claire W. Hallahan ◽  
Susan Moir ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Plasma Viremia ◽  
Proviral Dna ◽  
Hiv Proviral Dna ◽  
Residual Plasma Viremia

scholarly journals Transient loss of detectable HIV-1 RNA following brentuximab vedotin anti-CD30 therapy for Hodgkin lymphoma

2018 ◽  
Vol 2 (23) ◽  
pp. 3479-3482 ◽  
Author(s):  
Chia-Ching Wang ◽  
Cassandra Thanh ◽  
Erica A. Gibson ◽  
Maya Ball-Burack ◽  
Louise E. Hogan ◽  
...  
Keyword(s):  
T Cell ◽  
Hodgkin Lymphoma ◽  
Brentuximab Vedotin ◽  
Cd4 T Cell ◽  
Plasma Viremia ◽  
Hiv Rna ◽  
Key Points ◽  
Transient Loss ◽  
Hiv 1 ◽  
Residual Plasma Viremia

Key Points Anti-CD30 therapy for Hodgkin lymphoma led to transient loss of detectable CD4+ T-cell HIV RNA and a decrease in residual plasma viremia. Targeting nonviral markers expressed on HIV-1 transcriptionally active cells may lead to reduced measures of HIV-1 persistence.

scholarly journals Human Immunodeficiency Virus Type 1 Monoclonal Antibodies Suppress Acute Simian-Human Immunodeficiency Virus Viremia and Limit Seeding of Cell-Associated Viral Reservoirs

2015 ◽  
Vol 90 (3) ◽  
pp. 1321-1332 ◽  
Author(s):  
Diane L. Bolton ◽  
Amarendra Pegu ◽  
Keyun Wang ◽  
Kathleen McGinnis ◽  
Martha Nason ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Clinical Trials ◽  
Monoclonal Antibodies ◽  
Antiretroviral Therapy ◽  
Envelope Glycoprotein ◽  
Plasma Viremia ◽  
Immunodeficiency Virus ◽  
Acute Hiv ◽  
Hiv 1

ABSTRACTCombination antiretroviral therapy (cART) administered shortly after human immunodeficiency virus type 1 (HIV-1) infection can suppress viremia and limit seeding of the viral reservoir, but lifelong treatment is required for the majority of patients. Highly potent broadly neutralizing HIV-1 monoclonal antibodies (MAbs) can reduce plasma viremia when administered during chronic HIV-1 infection, but the therapeutic potential of these antibodies during acute infection is unknown. We tested the ability of HIV-1 envelope glycoprotein-specific broadly neutralizing MAbs to suppress acute simian-human immunodeficiency virus (SHIV) replication in rhesus macaques. Four groups of macaques were infected with SHIV-SF162P3 and received (i) the CD4-binding-site MAb VRC01; (ii) a combination of a more potent clonal relative of VRC01 (VRC07-523) and a V3 glycan-dependent MAb (PGT121); (iii) daily cART, all on day 10, just prior to expected peak plasma viremia; or (iv) no treatment. Daily cART was initiated 11 days after MAb administration and was continued for 13 weeks in all treated animals. Over a period of 11 days after a single administration, MAb treatment significantly reduced peak viremia, accelerated the decay slope, and reduced total viral replication compared to untreated controls. Proviral DNA in lymph node CD4 T cells was also diminished after treatment with the dual MAb. These data demonstrate the virological effect of potent MAbs and support future clinical trials that investigate HIV-1-neutralizing MAbs as adjunctive therapy with cART during acute HIV-1 infection.IMPORTANCETreatment of chronic HIV-1 infection with potent broadly neutralizing HIV-1 MAbs has been shown to significantly reduce plasma viremia. However, the antiviral effect of MAb treatment during acute HIV-1 infection is unknown. Here, we demonstrate that MAbs targeting the HIV-1 envelope glycoprotein both suppress acute SHIV plasma viremia and limit CD4 T cell-associated viral DNA. These findings provide support for clinical trials of MAbs as adjunctive therapy with antiretroviral therapy during acute HIV-1 infection.

Sign in / Sign up

Export Citation Format

Share Document