scholarly journals Factors associated with proviral DNA HIV-1 tropism in antiretroviral therapy-treated patients with fully suppressed plasma HIV viral load: implications for the clinical use of CCR5 antagonists

2010 ◽  
Vol 65 (4) ◽  
pp. 749-751 ◽  
Author(s):  
C. Soulie ◽  
S. Fourati ◽  
S. Lambert-Niclot ◽  
I. Malet ◽  
M. Wirden ◽  
...  
Keyword(s):  
Viral Load ◽  
Antiretroviral Therapy ◽  
Clinical Use ◽  
Hiv Viral Load ◽  
Factors Associated ◽  
Proviral Dna ◽  
Ccr5 Antagonists ◽  
Hiv 1

scholarly journals Early ART-initiation Reduces HIV-1 Proviral DNA Levels in Children from the CHER Trial

2021 ◽  
Author(s):  
Helen Payne ◽  
Man Chan ◽  
Sarah Watters ◽  
Kennedy Otwombe ◽  
Yuan Hsiao ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Factors Associated ◽  
Proviral Dna ◽  
Art Initiation ◽  
Latent Hiv ◽  
Dna Reduction ◽  
Living With Hiv ◽  
Hiv 1

Abstract BACKGROUND: Reduction of the reservoir of latent HIV-infected cells might increase the possibility of long-term remission in individuals living with HIV. We investigated factors associated with HIV-1 proviral DNA levels in children receiving different antiretroviral therapy (ART) strategies in the Children with HIV Early Antiretroviral Therapy (CHER) trial. METHODS: Infants with HIV <12 weeks old with CD4% ≥25% were randomized in the CHER trial to early limited ART for 40 or 96 weeks (ART-40W, ART-96W), or deferred ART (ART-Def). For ART-Def infants or following ART interruption in ART-40W/ART-96W, ART was started/re-started for clinical progression or CD4% <25%. In 229 participants, HIV-1 proviral DNA was quantified by PCR from stored peripheral blood mononuclear cells from children who had received ≥24 weeks ART and two consecutive undetectable HIV-1 RNA 12-24 weeks apart. HIV-1 proviral DNA was compared between ART-Def and ART-96W at week 96, and in all arms at week 248. Factors associated with HIV-1 proviral DNA levels were evaluated using linear regression.FINDINGS: Longer duration of ART was significantly associated with lower HIV-1 proviral DNA at both 96 (p=0.0003) and 248 weeks (p=0.0011). Higher total CD8 count at ART initiation was associated with lower HIV-1 proviral DNA at both 96 (p=0.0225) and 248 weeks (p=0.0398). Week 248 HIV-1 proviral DNA was significantly higher in those with positive HIV-1 serology at week 84 than those with negative serology (p=0.0042).INTEPRETATION: Longer ART duration is key to HIV-1 proviral DNA reduction. Further understanding is needed of the effects of “immune-attenuation” through early HIV-1 exposure.FUNDING: Wellcome Trust, National Institutes of Health, Medical Research Council.

scholarly journals Early ART-initiation and longer ART duration reduces HIV-1 proviral DNA levels in children from the CHER trial

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Helen Payne ◽  
Man K. Chan ◽  
Sarah A. Watters ◽  
Kennedy Otwombe ◽  
Nei-Yuan Hsiao ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Factors Associated ◽  
Proviral Dna ◽  
Art Initiation ◽  
Latent Hiv ◽  
Dna Reduction ◽  
Living With Hiv ◽  
Hiv 1

Abstract Background Reduction of the reservoir of latent HIV-infected cells might increase the possibility of long-term remission in individuals living with HIV. We investigated factors associated with HIV-1 proviral DNA levels in children receiving different antiretroviral therapy (ART) strategies in the children with HIV early antiretroviral therapy (CHER) trial. Methods Infants with HIV  <  12 weeks old with CD4%  ≥  25% were randomized in the CHER trial to early limited ART for 40 or 96 weeks (ART-40 W, ART-96 W), or deferred ART (ART-Def). For ART-Def infants or following ART interruption in ART-40 W/ART-96 W, ART was started/re-started for clinical progression or CD4%  <  25%. In 229 participants, HIV-1 proviral DNA was quantified by PCR from stored peripheral blood mononuclear cells from children who had received  ≥  24 weeks ART and two consecutive undetectable HIV-1 RNA 12–24 weeks apart. HIV-1 proviral DNA was compared between ART-Def and ART-96 W at week 96, and in all arms at week 248. Factors associated with HIV-1 proviral DNA levels were evaluated using linear regression. Findings Longer duration of ART was significantly associated with lower HIV-1 proviral DNA at both 96 (p  =  0.0003) and 248 weeks (p  =  0.0011). Higher total CD8 count at ART initiation was associated with lower HIV-1 proviral DNA at both 96 (p  =  0.0225) and 248 weeks (p  =  0.0398). Week 248 HIV-1 proviral DNA was significantly higher in those with positive HIV-1 serology at week 84 than those with negative serology (p  =  0.0042). Intepretation Longer ART duration is key to HIV-1 proviral DNA reduction. Further understanding is needed of the effects of “immune-attenuation” through early HIV-1 exposure. Funding Wellcome Trust, National Institutes of Health, Medical Research Council.

scholarly journals Factors associated with HIV viral load suppression on antiretroviral therapy in Vietnam

2016 ◽  
Vol 2 (2) ◽  
pp. 94-101 ◽  
Author(s):  
Suresh Rangarajan ◽  
Donn J. Colby ◽  
Le Truong Giang ◽  
Duc Duong Bui ◽  
Huu Hung Nguyen ◽  
...  
Keyword(s):  
Viral Load ◽  
Antiretroviral Therapy ◽  
Viral Load Suppression ◽  
Hiv Viral Load ◽  
Factors Associated

Factors associated with HIV-1 virological failure in an outpatient clinic for HIV-infected people in Haiphong, Vietnam

2011 ◽  
Vol 22 (11) ◽  
pp. 659-664 ◽  
Author(s):  
D T M Huong ◽  
W Bannister ◽  
P T Phong ◽  
O Kirk ◽  
L Peters
Keyword(s):  
Viral Load ◽  
Virological Failure ◽  
Hiv Transmission ◽  
Clinical Stage ◽  
World Health ◽  
Hiv Viral Load ◽  
Heterosexual Intercourse ◽  
Infected People ◽  
Factors Associated ◽  
Hiv 1

The objective of our study was to investigate factors associated with virological failure in 100 consecutive HIV-1 infected Vietnamese adults who initiated antiretroviral therapy (ART) from June 2007 to June 2008. Data were collected from medical records, and a structured questionnaire was used in individual interviews to investigate factors associated with adherence to ART. Plasma HIV viral load was measured at the time of the interview. The median age was 35 years, 35% were women and heterosexual intercourse was the most common mode of HIV transmission (61 %). After a median of 14 months since starting ART, 23% had detectable HIV-1 viral load (≥400 copies/mL). Patients who had developed a World Health Organization (WHO) clinical stage 4 condition at the time of initiation of ART were more likely to experience virological failure than those in stages 1-3, odds ratio (OR): 5.20 (95% confidence interval [CI] 1.34-20.11), P = 0.017. Patients who reported that their health status was evaluated by a physician at each visit were less likely to experience virological failure, OR: 0.02 (95% CI 0.00-0.24), P = 0.002.

scholarly journals STING and cGAS gene expressions were downregulated among HIV-1-infected persons after antiretroviral therapy

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Lorena Leticia Peixoto de Lima ◽  
Allysson Quintino Tenório de Oliveira ◽  
Tuane Carolina Ferreira Moura ◽  
Ednelza da Silva Graça Amoras ◽  
Sandra Souza Lima ◽  
...  
Keyword(s):  
Gene Expression ◽  
Viral Load ◽  
T Cell ◽  
Antiretroviral Therapy ◽  
Cell Count ◽  
Enzyme Linked Immunosorbent Assay ◽  
Type I ◽  
Α Level ◽  
The Impact ◽  
Hiv 1

Abstract Background The HIV-1 epidemic is still considered a global public health problem, but great advances have been made in fighting it by antiretroviral therapy (ART). ART has a considerable impact on viral replication and host immunity. The production of type I interferon (IFN) is key to the innate immune response to viral infections. The STING and cGAS proteins have proven roles in the antiviral cascade. The present study aimed to evaluate the impact of ART on innate immunity, which was represented by STING and cGAS gene expression and plasma IFN-α level. Methods This cohort study evaluated a group of 33 individuals who were initially naïve to therapy and who were treated at a reference center and reassessed 12 months after starting ART. Gene expression levels and viral load were evaluated by real-time PCR, CD4+ and CD8+ T lymphocyte counts by flow cytometry, and IFN-α level by enzyme-linked immunosorbent assay. Results From before to after ART, the CD4+ T cell count and the CD4+/CD8+ ratio significantly increased (p < 0.0001), the CD8+ T cell count slightly decreased, and viral load decreased to undetectable levels in most of the group (84.85%). The expression of STING and cGAS significantly decreased (p = 0.0034 and p = 0.0001, respectively) after the use of ART, but IFN-α did not (p = 0.1558). Among the markers evaluated, the only markers that showed a correlation with each other were STING and CD4+ T at the time of the first collection. Conclusions ART provided immune recovery and viral suppression to the studied group and indirectly downregulated the STING and cGAS genes. In contrast, ART did not influence IFN-α. The expression of STING and cGAS was not correlated with the plasma level of IFN-α, which suggests that there is another pathway regulating this cytokine in addition to the STING–cGAS pathway.

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&lt; 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)

Proviral HIV-1 DNA in subjects followed since primary HIV-1 infection who suppress plasma viral load after one year of highly active antiretroviral therapy

AIDS ◽  
2001 ◽  
Vol 15 (6) ◽  
pp. 665-673 ◽  
Author(s):  
Nicole Ngo-Giang-Huong ◽  
Christiane Deveau ◽  
Isabelle Da Silva ◽  
Isabelle Pellegrin ◽  
Alain Venet ◽  
...  
Keyword(s):  
Viral Load ◽  
Antiretroviral Therapy ◽  
Highly Active Antiretroviral Therapy ◽  
Plasma Viral Load ◽  
Highly Active ◽  
One Year ◽  
Hiv 1
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