Participants on dolutegravir re-suppress HIV RNA after virologic failure: updated data from the ADVANCE trial

2021 ◽  
Author(s):  
Toby Pepperrell ◽  
Willem Daniel Francois Venter ◽  
Kaitlyn McCann ◽  
Bronwyn Bosch ◽  
Melissa Tibbatts ◽  
...  
Keyword(s):  
Virological Failure ◽  
Virologic Failure ◽  
Hiv Rna ◽  
Suppressive Capacity

Abstract Following evidence of HIV RNA re-suppression on DTG-based regimens, we assess the re-suppressive capacity of ADVANCE participants on TAF/FTC+DTG, TDF/FTC+DTG and TDF/FTC/EFV. Viraemic participants were able to re-suppress within 3 follow-up visits of protocol-defined virological failure (PDVF) in 77/121(64%), 85/126(67%) and 44/138(32%) cases respectively (DTG regimens vs. TDF/FTC/EFV; p<0.001).

scholarly journals 1766. Sustained Viral Suppression with Dolutegravir and Boosted Darunavir Dual Therapy Among Highly Treatment-Experienced Individuals

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S64-S64
Author(s):  
Kellie Hawkins ◽  
Brian Montague ◽  
Sarah Rowan ◽  
Margaret Mclees ◽  
Robert Beum ◽  
...  
Keyword(s):  
Viral Suppression ◽  
Virologic Failure ◽  
Dual Therapy ◽  
Hiv Rna ◽  
Sustained Viral Suppression ◽  
System Data ◽  
Health System Data ◽  
Dual Class ◽  
Reasons For Use

Abstract Background The use of antiretroviral (ARV) dual therapy for treatment of HIV is increasing; raltegravir with boosted darunavir (bDRV) is recommended in certain clinical situations in DHHS guidelines. Dolutegravir (DTG) with bDRV has not been widely studied. We sought to determine the effectiveness of DTG/bDRV in treatment experienced patients. Methods This retrospective cohort study evaluated viral suppression in patients prescribed DTG/bDRV dual therapy within a large urban health system. Data collected included demographics, cumulative ARV exposure, reasons for use, regimen start/stop dates, and viral suppression (HIV-RNA ≤200). Follow-up was defined as the number of days from start of regimen until last HIV-RNA determination on the study regimen. Results From January 1, 2013 to December 31, 2017, 60 patients received DTG/bDRV dual therapy: 15% were female, median age was 56, 83% were ≥3 class ARV-experienced, and median time since starting ARVs was 20 years. Median follow-up on DTG/bDRV was 444 days (IQR 273–808). Viral suppression was achieved by 59 of 60 (98%) patients at some point on DTG/bDRV. When stratified by baseline viral suppression, 46 of 46 (100%) who had baseline viral suppression maintained viral suppression in comparison to 11 of 14 (79%) without baseline viral suppression (table). The most common reasons for DTG/bDRV were simplification in setting of prior resistance (47%), toxicity reduction (39%), and virologic failure (15%). At study end, 53 of 60 (88%) were still on DTG/bDRV and the most common reason for stopping was drug interactions. Conclusion In a highly treatment-experienced cohort of patients, DTG/bDRV dual therapy demonstrated sustained rates of viral suppression, even in those who were failing therapy prior to initiating the regimen. Further study of this potent, simple, high-barrier dual class regimen is warranted. Disclosures S. Rowan, Gilead Sciences: Investigator, Research grant. S. C. Johnson, Viiv Healthcare: Scientific Advisor, Consulting fee.

Virological failure at one year in triple-class experienced patients switching to raltegravir-based regimens is not predicted by baseline factors

2012 ◽  
Vol 23 (7) ◽  
pp. 459-463 ◽  
Author(s):  
R Bucciardini ◽  
G D'ettorre ◽  
S Baroncelli ◽  
G Ceccarelli ◽  
G Parruti ◽  
...  
Keyword(s):  
Virological Failure ◽  
High Rate ◽  
Hiv Rna ◽  
Drug Classes ◽  
Route Of Transmission ◽  
Related Quality ◽  
Health Related ◽  
Baseline Factors ◽  
One Year

We evaluated rates and determinants of virological failure in triple-class experienced patients receiving raltegravir-based regimens from a national observational study over 48 weeks, defined by any one of the following: (1) no HIV-RNA suppression to undetectable levels (<50 copies/mL) during follow-up; (2) detectable viral load after obtaining undetectable levels; and (3) leaving the study before 48 weeks. Among 101 eligible patients, 26 (25.7%; 95% CI 17.2–34.2) had virological failure. No significant differences between patients with and without virological failure were observed for gender, age, route of transmission, baseline CD4/HIV-RNA, CDC group, hepatitis B or C co-infections, resistance (based on the last genotype available), type and number of concomitant drug classes, concomitant use of darunavir, atazanavir, etravirine, enfuvirtide or maraviroc, and health-related quality-of-life measures. A high rate of treatment response was observed. The analyses did not identify any baseline factor associated with failure, including resistance status. Even if we cannot exclude the presence of pre-existing minority resistant variants not captured by genotypic tests, the lack of baseline predictors of failure suggests the need to monitor patients closely during follow up for other factors, such as potential drug interactions and reduced levels of adherence, which may favour virological failure.

scholarly journals Determinants of Viral Resuppression or Persistent Virologic Failure After Initial Failure With Second-Line Antiretroviral Treatment Among Asian Children and Adolescents With HIV

2019 ◽  
Vol 9 (2) ◽  
pp. 253-256
Author(s):  
Sirinya Teeraananchai ◽  
Stephen J Kerr ◽  
Monica Gandhi ◽  
Viet Chau Do ◽  
Lam Van Nguyen ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Protease Inhibitor ◽  
Antiretroviral Treatment ◽  
Virologic Failure ◽  
Second Line ◽  
Hiv Rna ◽  
Immunodeficiency Virus ◽  
Asian Children ◽  
Perinatally Acquired

Abstract Of 56 children with perinatally acquired human immunodeficiency virus (HIV) who had been prescribed second-line protease inhibitor–based antiretroviral therapy and had ≥1 previous episode of viral failure (HIV RNA, ≥1000 copies/mL), 46% had ≥1, 34% had ≥2, and 23% had ≥3 consecutive episodes of viral failure during the 2 years of follow-up. Two of these children experienced a major protease inhibitor mutation.

scholarly journals The Successful Application of a National Peer Advisory Committee for Physicians Who Provide Salvage Regimens to Heavily Antiretroviral-Experienced Patients in Mexican Human Immunodeficiency Virus Clinics

2014 ◽  
Vol 1 (2) ◽  
Author(s):  
Juan J. Calva ◽  
Juan Sierra-Madero ◽  
Luis E. Soto-Ramírez ◽  
Pedro Aguilar-Salinas
Keyword(s):  
Human Immunodeficiency Virus ◽  
Advisory Committee ◽  
Virologic Failure ◽  
Clinical Skills ◽  
Virologic Response ◽  
Routine Practice ◽  
Salvage Regimen ◽  
Hiv Rna ◽  
Immunodeficiency Virus

Background.  Designing optimal antiretroviral (ARV) salvage regimens for multiclass drug-resistant, human immunodeficiency virus (HIV)-infected patients demands specific clinical skills. Our aim was to assess the virologic and immunologic effects of the treatment recommendations drafted by a peer advisory board to physicians caring for heavily ARV-experienced patients. Methods.  We conducted a nationwide, HIV clinic-based, cohort study in Mexico. Adults infected with HIV were assessed for a median of 33 months (interquartile range [IQR] = 22–43 months). These patients had experienced the virologic failure of at least 2 prior ARV regimens and had detectable viremia while currently being treated; their physicians had received therapeutic advice, by a panel of experts, regarding the ARV salvage regimen. The primary endpoint was the incidence of loss of virologic response (plasma HIV-RNA levels of &lt;200 copies per mL, followed by levels above this threshold) during the follow-up assessment using an observed-failure competing risks regression analysis. Results.  A total of 611 patients were observed (median ARV therapy exposure = 10.5 years; median prior regimens = 4). The probabilities of virologic failure were 11.9%, 14.4%, 16.9%, and 19.4% at the 12-, 24-, 36-, and 48-month follow-up assessments, respectively. Of the 531 patients who achieved a confirmed plasma HIV-RNA level below 200 copies per mL, the median increase in blood CD4+ T-cell count was 162 cells per mL (IQR = 45–304 cells per mL). Conclusions.  In routine practice, a high rate of patients with extensive ARV experience, who received an optimized salvage regimen recommended by a peer advisory committee, achieved a long-term sustained virologic response and immune reconstitution.

scholarly journals 936. Evaluating the Impact of Polypharmacy on Virologic Success in People with HIV

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S501-S502
Author(s):  
Humberto R Jimenez ◽  
Naana Boachie ◽  
Sangwon Park ◽  
Jin Suh
Keyword(s):  
Hiv Transmission ◽  
Virologic Failure ◽  
Descriptive Analysis ◽  
Virologic Response ◽  
Transmission Risk ◽  
Pill Burden ◽  
Cross Sectional ◽  
Hiv Rna ◽  
Aids Diagnosis ◽  
The Impact

Abstract Background As people with HIV (PWH) have experienced reductions in antiretroviral pill burden, there has been an increase in medications to manage non-AIDS-related co-morbidities. Previous studies have linked virologic failure to an increased pill burden. This study assessed whether polypharmacy and other variables affect success of HIV management in our population. Methods A retrospective, cross-sectional analysis of PWH receiving care at a Ryan White-funded clinic in New Jersey was performed. Eligible patients were ≥18 years old, had ≥2 visits in 2019 and were receiving antiretroviral therapy (ART). The primary endpoints were to determine the effect polypharmacy (defined as 5 or more non-ART pills per day) on virologic response rates (HIV RNA &lt; 200 copies/mL). Secondary endpoints accounted for the impact of age, gender, race/ethnicity, HIV transmission risk factor, and AIDS diagnosis on virologic response. A descriptive analysis of comorbidities and medication classes was also completed. Logistic regression, chi square and student’s t test were used for statistical analysis. Results 964 patients were included in the analysis, with 355 (37%) meeting the criteria for polypharmacy. Most patients were male (60%) and the mean age was 49 years of age. The racial/ethnic breakdown was 46% Hispanic, 45% Black and 8% White. Polypharmacy was associated with higher rates of virologic success compared to those with a lower pill burden: 94% vs 86% had an HIV RNA &lt; 200 copies/mL (P=0.0003), respectively. ART pill burden was statistically, but not clinically higher among those with polypharmacy (1.34 vs 1.45, P=0.025). Virologic response was found to be higher among Hispanics and Whites in comparison to Black patients (OR 2.2, CI 1.4-3.5 and 3.0, CI 1.1-8.2). Patients with an AIDS diagnosis were less likely to achieve virologic response (OR 0.64, CI 0.42-0.99). Conclusion Patients with polypharmacy were more likely to achieve virologic success than paitents with a low pill burden in our population. Disclosures Humberto R. Jimenez, PharmD, BCPS, AAHIVP, Gilead (Speaker’s Bureau)

scholarly journals A Low Level of Darunavir Resistance–Associated Mutation Emergence in Patients With Virological Failure During Long-term Use of Darunavir in People With HIV. The ANRS CO3 Aquitaine Cohort

2020 ◽  
Vol 7 (12) ◽  
Author(s):  
Hélène Chaussade ◽  
Camille Tumiotto ◽  
Fabien Le Marec ◽  
Olivier Leleux ◽  
Lucile Lefèvre ◽  
...  
Keyword(s):  
Protease Inhibitor ◽  
Virological Failure ◽  
Resistance Test ◽  
Resistance Testing ◽  
Factors Associated ◽  
Viral Loads ◽  
Hiv Resistance ◽  
Baseline Characteristics

Abstract Background Ritonavir-boosted darunavir (DRV/r) is a protease inhibitor (PI) indicated for the treatment of naïve and pretreated HIV-infected patients since 2007. Our study aims to describe DRV/r-treated patients experiencing virological failure (VF) documented with HIV resistance testing. Methods Data from patients belonging to the ANRS CO3 Aquitaine Cohort treated with a regimen including DRV/r between February 2007 and December 2015 were analyzed. Baseline characteristics of patients experiencing VF (defined by 2 consecutive plasma viral loads &gt;50 copies/mL) were compared with those without VF. We then described factors associated with VF as emergence of IAS DRV resistance–associated mutations (RAMs). Results Among the 1458 patients treated at least once with a DRV/r-based regimen, 270 (18.5%) patients experienced VF during follow-up, including 240 with at least 1 genotype resistance test (GRT). DRV RAMs were detected in 29 patients (12%). Among them, 25/29 patients had ≥2 DRV RAMs before DRV/r initiation, all of whom had experienced VF during previous PI treatments. For 18/29, DRV/r was maintained after VF, and controlled viremia was restored after modification of DRV-associated antiretroviral molecules or increased DRV dose. Finally, only 6/29 patients selected new DRV RAMs after DRV/r initiation. All of these experienced previous VFs while on other PIs. Conclusions These results highlight the efficacy and robustness of DRV/r, as the emergence of DRV RAMs appeared in &lt;0.4% of patients receiving a DRV/r-based regimen in our large cohort.

scholarly journals Predictors of virological failure among people living with HIV receiving first line antiretroviral treatment in Myanmar: retrospective cohort analysis

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Anita Mesic ◽  
Alexander Spina ◽  
Htay Thet Mar ◽  
Phone Thit ◽  
Tom Decroo ◽  
...  
Keyword(s):  
Viral Load ◽  
Virological Failure ◽  
Antiretroviral Treatment ◽  
People Living With Hiv ◽  
First Line ◽  
Hiv Viral Load ◽  
Loss To Follow Up ◽  
History Of ◽  
Living With Hiv

Abstract Background Progress toward the global target for 95% virological suppression among those on antiretroviral treatment (ART) is still suboptimal. We describe the viral load (VL) cascade, the incidence of virological failure and associated risk factors among people living with HIV receiving first-line ART in an HIV cohort in Myanmar treated by the Médecins Sans Frontières in collaboration with the Ministry of Health and Sports Myanmar. Methods We conducted a retrospective cohort study, including adult patients with at least one HIV viral load test result and having received of at least 6 months’ standard first-line ART. The incidence rate of virological failure (HIV viral load ≥ 1000 copies/mL) was calculated. Multivariable Cox’s regression was performed to identify risk factors for virological failure. Results We included 25,260 patients with a median age of 33.1 years (interquartile range, IQR 28.0–39.1) and a median observation time of 5.4 years (IQR 3.7–7.9). Virological failure was documented in 3,579 (14.2%) participants, resulting in an overall incidence rate for failure of 2.5 per 100 person-years of follow-up. Among those who had a follow-up viral load result, 1,258 (57.1%) had confirmed virological failure, of which 836 (66.5%) were switched to second-line treatment. An increased hazard for failure was associated with age ≤ 19 years (adjusted hazard ratio, aHR 1.51; 95% confidence intervals, CI 1.20–1.89; p < 0.001), baseline tuberculosis (aHR 1.39; 95% CI 1.14–1.49; p < 0.001), a history of low-level viremia (aHR 1.60; 95% CI 1.42–1.81; p < 0.001), or a history of loss-to-follow-up (aHR 1.24; 95% CI 1.41–1.52; p = 0.041) and being on the same regimen (aHR 1.37; 95% CI 1.07–1.76; p < 0.001). Cumulative appointment delay was not significantly associated with failure after controlling for covariates. Conclusions VL monitoring is an important tool to improve programme outcomes, however limited coverage of VL testing and acting on test results hampers its full potential. In our cohort children and adolescents, PLHIV with history of loss-to-follow-up or those with low-viremia are at the highest risk of virological failure and might require more frequent virological monitoring than is currently recommended.

scholarly journals INSTI-Based Triple Regimens in Treatment-Naïve HIV-Infected Patients Are Associated With HIV-RNA Viral Load Suppression at Ultralow Levels

2019 ◽  
Vol 6 (5) ◽  
Author(s):  
Sidonie Lambert-Niclot ◽  
Anders Boyd ◽  
Djeneba Fofana ◽  
Nadia Valin ◽  
Marc Wirden ◽  
...  
Keyword(s):  
Multivariable Analysis ◽  
Female Gender ◽  
Strand Transfer ◽  
University Hospitals ◽  
Viral Load Suppression ◽  
Hiv Rna ◽  
Art Initiation ◽  
Treatment Naïve ◽  
Hiv 1

Abstract Background During antiretroviral therapy (ART), HIV-1-infected patients may present with ultralow (UL) HIV-RNA viral loads (VLs) below quantification levels of current assays. Reasons for UL-VL detection and its relation to virological rebound (VR) are unclear. Methods HIV-1-infected, ART-naïve patients followed at 2 university hospitals were included. All participants had an HIV-RNA &gt;200 copies/mL at ART initiation and achieved a VL &lt;50 copies/mL during ART. UL-VL was determined by the presence/absence of polymerase chain reaction signal detected using a commercially available assay (COBAS, TaqMan, Roche). Random-effects Poisson regression was used for assessing determinants of UL-VL not detected overtime and conditional risk set analysis for VR (1 VL &gt; 200 copies/mL or 2 VL &gt; 50 copies/mL) while accounting for frequency of VL measurements. Results Between 2009 and 2013, 717 patients initiated ART containing 2 nucleos(-t)ide reverse transcriptase inhibitors (NRTIs) plus a non-NRTI (29.4%), a protease inhibitor (58.4%), or an integrase-strand transfer inhibitor (INSTI; 12.1%). During a median (interquartile range) 3.4 (2.3–4.6) years, 676 (94.3%) patients achieved UL-VL not detected. In multivariable analysis, UL-VL not detected overtime was associated with younger age (P &lt; .001), female gender (P = .04), lower baseline VL (P &lt; .001), baseline CD4+ &gt;500 vs &lt;350/mm3 (P &lt; .001), and INSTI-containing ART (P = .009). One hundred thirty-one (18.3%) patients had VR during follow-up, which was independently associated with a CD4/CD8 ratio &lt;0.8 during follow-up (P = .01) and time spent with UL-VL not detected (P &lt; .001). When UL-VL not detected occurred for ≥50% of the follow-up duration (n = 290), faster time to reach UL-VL not detected (P &lt; .001), faster CD4+ T-cell count increase (P = .03), and faster CD4/CD8 ratio increase (P = .001) were observed. Conclusions VL suppression at an ultralow level is associated with INSTI-class ART initiation. Extensive VL suppression below ultralow detection could improve immune reconstitution.

scholarly journals Switching to Tenofovir Alafenamide in Elvitegravir-Based Regimens: Pharmacokinetics and Antiviral Activity in Cerebrospinal Fluid

2019 ◽  
Vol 71 (4) ◽  
pp. 982-988 ◽  
Author(s):  
Qing Ma ◽  
Andrew J Ocque ◽  
Gene D Morse ◽  
Chelsea Sanders ◽  
Alina Burgi ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Antiviral Activity ◽  
Virologic Failure ◽  
Plasma Concentrations ◽  
Open Label ◽  
Assay Sensitivity ◽  
Once Daily ◽  
Hiv Rna ◽  
The Central Nervous System ◽  
Tenofovir Alafenamide

Abstract Background Tenofovir alafenamide fumarate (TAF) co-formulated with elvitegravir (EVG; E), cobicistat (C), and emtricitabine (F), a recommended antiretroviral regimen, was evaluated for distribution and antiviral activity in cerebrospinal fluid (CSF) as well as neurocognitive (NC) performance change in participants switching from E/C/F/tenofovir disoproxil fumarate (TDF) to E/C/F/TAF. Methods This was a 24-week, single-arm, open-label study in treatment-experienced adults living with human immunodeficiency virus (HIV). Nine participants switched from E/C/F/TDF (150/150/200/300 mg once daily) to E/C/F/TAF (150/150/200/10 mg once daily) at week 12. CSF and total plasma concentrations of EVG, TDF, TAF, tenofovir (TFV), and HIV RNA levels were measured at baseline and week 24. NC performance was estimated by the Montreal Cognitive Assessment. Results EVG concentrations in CSF and the CSF:plasma ratio remained stable (P = .203) over time. Following the switch, TFV concentrations in CSF and plasma declined (P = .004), although the TFV CSF:plasma ratio increased (P = .004). At week 24, median TAF plasma concentration was 11.05 ng/mL (range, 2.84–147.1 ng/mL) 2 hours postdose but was below assay sensitivity 6 hours after dosing. TAF was below assay sensitivity in all CSF specimens. HIV RNA was ≤40 copies/mL in all CSF and plasma specimens. Three participants (33%) had NC impairment at baseline and 2 (22%) remained impaired at week 24. Conclusions Switch to E/C/F/TAF was associated with reductions in TFV concentrations in CSF but stable EVG concentrations that exceeded the 50% inhibitory concentration for wild-type HIV, suggesting that EVG achieves therapeutic concentrations in the central nervous system. No virologic failure or significant NC changes were detected following the switch. Clinical Trials Registration NCT02251236.

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