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 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 Retrospective analysis of HHV-8 viremia and cellular viral load in HIV-seropositive patients receiving interleukin 2 in combination with antiretroviral therapy

Blood ◽  
2002 ◽  
Vol 100 (5) ◽  
pp. 1575-1578 ◽  
Author(s):  
Mauro Malnati ◽  
Francesco Broccolo ◽  
Silvia Nozza ◽  
Loredana Sarmati ◽  
Silvia Ghezzi ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Interleukin 2 ◽  
Human Herpesvirus ◽  
Kaposi Sarcoma ◽  
Plasma Viremia ◽  
Herpesvirus 8 ◽  
Sequential Samples ◽  
Antibody Titers ◽  
Hiv Seropositive

The combination of interleukin 2 (IL-2) and antiretroviral therapy (ART) represents an emerging strategy in the treatment of patients infected with HIV. Aside from its immunomodulatory role, however, IL-2 may induce replication of human herpesvirus 8 (HHV-8)/Kaposi sarcoma (KS)–associated herpesvirus. We retrospectively evaluated HHV-8 plasma viremia and cellular load, as well as anti–HHV-8 antibody titers, in sequential samples from 84 patients receiving ART alone or in combination with IL-2. At baseline, HHV-8 plasma viremia was present only in 2 HHV-8–seropositive patients in whom KS subsequently developed during or immediately after termination of IL-2 therapy. The level of viremia increased during follow-up and peaked at the time of the clinical manifestation of KS. Moreover, transient peaks of HHV-8 viremia were temporally associated with administration of IL-2. HHV-8 plasma viremia was never detected in the other 47 patients receiving IL-2 nor in 35 controls treated only with ART. Thus, IL-2 therapy seems safe in most patients infected with both HIV and HHV-8, except for those with detectable HHV-8 viremia, who may not be eligible for IL-2 treatment.

scholarly journals Virologic and Immunologic Features of Simian Immunodeficiency Virus Control Post-ART Interruption in Rhesus Macaques

2020 ◽  
Vol 94 (14) ◽  
Author(s):  
Zachary Strongin ◽  
Luca Micci ◽  
Rémi Fromentin ◽  
Justin Harper ◽  
Julia McBrien ◽  
...  
Keyword(s):  
T Cell ◽  
Antiretroviral Therapy ◽  
Dna Content ◽  
Th17 Cells ◽  
Rhesus Macaques ◽  
Cd4 T Cell ◽  
Plasma Viremia ◽  
Lower Plasma ◽  
Viral Control ◽  
Immunodeficiency Virus

ABSTRACT Antiretroviral therapy (ART) cannot eradicate human immunodeficiency virus (HIV) and a rapid rebound of virus replication follows analytical treatment interruption (ATI) in the vast majority of HIV-infected individuals. Sustained control of HIV replication without ART has been documented in a subset of individuals, defined as posttreatment controllers (PTCs). The key determinants of post-ART viral control remain largely unclear. Here, we identified 7 SIVmac239-infected rhesus macaques (RMs), defined as PTCs, who started ART 8 weeks postinfection, continued ART for >7 months, and controlled plasma viremia at <104 copies/ml for up to 8 months after ATI and <200 copies/ml at the latest time point. We characterized immunologic and virologic features associated with post-ART SIV control in blood, lymph node (LN), and colorectal (RB) biopsy samples compared to 15 noncontroller (NC) RMs. Before ART initiation, PTCs had higher CD4 T cell counts, lower plasma viremia, and SIV-DNA content in blood and LN compared to NCs, but had similar CD8 T cell function. While levels of intestinal CD4 T cells were similar, PTCs had higher frequencies of Th17 cells. On ART, PTCs had significantly lower levels of residual plasma viremia and SIV-DNA content in blood and tissues. After ATI, SIV-DNA content rapidly increased in NCs, while it remained stable or even decreased in PTCs. Finally, PTCs showed immunologic benefits of viral control after ATI, including higher CD4 T cell levels and reduced immune activation. Overall, lower plasma viremia, reduced cell-associated SIV-DNA, and preserved Th17 homeostasis, including at pre-ART, are the main features associated with sustained viral control after ATI in SIV-infected RMs. IMPORTANCE While effective, antiretroviral therapy is not a cure for HIV infection. Therefore, there is great interest in achieving viral remission in the absence of antiretroviral therapy. Posttreatment controllers represent a small subset of individuals who are able to control HIV after cessation of antiretroviral therapy, but characteristics associated with these individuals have been largely limited to peripheral blood analysis. Here, we identified 7 SIV-infected rhesus macaques that mirrored the human posttreatment controller phenotype and performed immunologic and virologic analysis of blood, lymph node, and colorectal biopsy samples to further understand the characteristics that distinguish them from noncontrollers. Lower viral burden and preservation of immune homeostasis, including intestinal Th17 cells, both before and after ART, were shown to be two major factors associated with the ability to achieve posttreatment control. Overall, these results move the field further toward understanding of important characteristics of viral control in the absence of antiretroviral therapy.

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