scholarly journals 318. Tenofovir Alafenamide (TAF) vs. Tenofovir Disoproxil Fumarate (TDF) in Hispanic/Latinx and Black Participants: Efficacy, Bone and Renal Safety Results from a Pooled Analysis of 7 Clinical Trials

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S168-S169
Author(s):  
Edwin DeJesus ◽  
Jaime Federico Andrade Villanueva ◽  
Jose Ramon Arribas Lopez ◽  
Cynthia Brinson ◽  
Gordon Crofoot ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Pooled Analysis ◽  
Retinol Binding Protein ◽  
Virologic Suppression ◽  
Mineral Density ◽  
Art Initiation ◽  
Treatment Naïve ◽  
Tenofovir Alafenamide ◽  
Renal Tubular ◽  
Hiv 1

Abstract Background People of color are underrepresented in clinical trials. TAF has shown improved renal and bone safety vs. TDF. We pooled 7 studies to evaluate efficacy/safety of TAF vs. TDF for ART initiation/switch in Hispanic/Latinx and Black participants. Methods Data from Hispanic/Latinx and Black adults who initiated/switched to TAF or TDF in 7 randomized trials (2 treatment-naïve, 5 suppressed switch) were analyzed. TAF-based regimens (elvitegravir/cobicistat/emtricitabine [FTC]/TAF, rilpivirine/FTC/TAF, FTC/TAF, or bictegravir/FTC/TAF) were compared with TDF-based regimens. Virologic suppression (VS; HIV-1 RNA < 50 c/mL, FDA snapshot) and % change in bone mineral density (BMD) and renal tubular biomarkers urine β-2-microglobulin (B2M):creatinine (Cr) ratio and retinol binding protein (RBP):Cr ratio are reported at W96. Results The pooled population (N = 5,825) included 1138 Hispanic/Latinx and 1324 Black participants. Treatment-naïve participants (n = 1,733) were 15% female, 25% Black, 19% Hispanic/Latino, with median age 34 years, HIV-1 RNA 4.6 log10 c/mL, CD4 405 cells/mm3. Switch participants (n = 4,092) were 13% female, 22% Black, 20% Hispanic/Latino, median age 45 years, CD4 653 cells/mm3. There was no difference in VS rate with TAF vs. TDF in any group. VS rate (TAF vs. TDF) in naïve participants: 88% vs. 84% (Hispanic/Latinx); 78 vs. 79% (Black); 87% vs. 85% (overall). VS (TAF vs. TDF) was well maintained in switch participants: 91% both arms (Hispanic/Latinx); 86% vs. 87% (Black); 90% vs. 88% (overall). TAF and TDF were well tolerated with few discontinuations due to adverse events (0.6–2%) in all groups. At W96 there was less impact on renal biomarkers in all groups initiating TAF (P < 0.001; table), and decreases in BMD were smaller (P < 0.005; table) vs. TDF. All groups switching from TDF to TAF experienced decreases in tubular proteinuria and improvements in BMD (both P < 0.001; table) at W96. Conclusion Hispanic/Latinx and Black participants who initiated/switched to TAF had significantly improved bone and renal parameters vs. TDF, with similar VS rates at W96. Efficacy and biomarkers were similar to the overall study population. These data in >2,400 Hispanic/Latinx and Black PLH demonstrate noninferior efficacy and safety advantages with TAF vs. TDF. Disclosures All authors: No reported disclosures.

scholarly journals A Randomized Trial of Bictegravir or Dolutegravir with Emtricitabine and Tenofovir Alafenamide (F/TAF) Followed by Open Label Switch to Bictegravir/F/TAF Fixed Dose Combination

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S426-S427 ◽  
Author(s):  
Paul E Sax ◽  
Edwin Dejesus ◽  
Gordon Crofoot ◽  
Douglas Ward ◽  
Paul Benson ◽  
...  
Keyword(s):  
Adverse Event ◽  
Fixed Dose ◽  
Virologic Suppression ◽  
Research Support ◽  
Open Label ◽  
Treatment Naïve ◽  
Dose Combination ◽  
Tenofovir Alafenamide ◽  
Hiv 1 ◽  
Research Grant

Abstract Background Integrase strand transfer inhibitors (INSTIs) are widely recommended for initial HIV-1 treatment. Bictegravir (BIC, B) is a novel, once-daily INSTI with potent antiviral activity being developed in coformulation with emtricitabine and tenofovir alafenamide (F/TAF). Methods In this Phase 2 study, treatment naïve, HIV-infected adults were randomized 2:1 to receive blinded treatment with BIC or dolutegravir (DTG) coadministered with open label F/TAF (200/25 mg). After all participants completed 48 weeks, they were unblinded and switched to a single fixed-dose combination tablet of B/F/TAF 50/200/25 mg. The proportion of participants with HIV-1 RNA &lt;50 copies/mL (c/mL) was assessed at Week (W) 24 and W48 of the blinded phase and 12 weeks after switching to open label B/F/TAF (W72). Results Of 98 participants enrolled in the blinded treatment phase, 65 were randomized to BIC+F/TAF and 33 to DTG+F/TAF. Most were male, had asymptomatic HIV infection, with median HIV-1 RNA 4.4–4.5 log10 c/mL. The proportion of subjects with HIV-1 RNA &lt;50 c/mL at W24 was 97% for the BIC arm and 94% for the DTG arm, and at W48 was 97% and 91%, respectively (Table). All 92 participants who completed the blinded phase were switched to B/F/TAF at W60. At W72 or 12 weeks after switching to open-label B/F/TAF, 99% (91/92) maintained HIV-1 RNA &lt;50 c/mL (98% prior BIC arm [N = 62]; 100% prior DTG arm [N = 30]) and one individual withdrew prior to the analysis. No viral resistance was detected in participants treated with BIC. No participants discontinued open label B/F/TAF due to an adverse event, there were no treatment-related serious adverse events and no deaths. One individual on BIC previously discontinued due to an adverse event of urticaria following the W24 visit. Conclusion All participants switched from DTG+F/TAF to open-label B/F/TAF maintained virologic suppression, with none discontinuing due to adverse events. During 72 weeks of follow-up, no treatment-emergent resistance to any components was detected in participants taking B/F/TAF. B/F/TAF demonstrated durable virologic suppression in naïve patients through W72 and was safe and effective after switching from DTG + F/TAF, further study in treatment naïve and experienced populations is warranted. Disclosures P. E. Sax, Gilead: Consultant and Investigator, Consulting fee, Research grant and Research support; BMS: Consultant and Investigator, Consulting fee, Research grant and Research support; GlaxoSmithKline/ViiV: Consultant and Investigator, Consulting fee, Research grant and Research support; AbbVie: Consultant, Consulting fee; Janssen: Consultant, Consulting fee; Merck: Consultant, Consulting fee; E. Dejesus, Gilead Sciences: Consultant, Investigator and Speaker’s Bureau, Consulting fee and Speaker honorarium; Janssen: Consultant, Investigator and Speaker’s Bureau, Consulting fee and Speaker honorarium; G. Crofoot, Gilead: Investigator and Scientific Advisor, Advisory honorarium and Research grant; ViiV: Investigator and Scientific Advisor, Advisory honorarium, Research grant and Research support; D. Ward, Gilead: Investigator, Research support; P. Benson, Gilead Sciences: Investigator, Shareholder and Speaker’s Bureau, Research support and Speaker honorarium; ViiV Healthcare: Investigator, Research support; L. Wei, Gilead: Employee and Shareholder, Salary; K. White, Gilead Sciences, Inc.: Employee and Shareholder, Salary; S. Collins, Gilead: Employee and Shareholder, Salary; H. Martin, Gilead Sciences: Employee, Salary; A. Cheng, Gilead: Employee and Shareholder, Salary; E. Quirk, Gilead: Employee and Shareholder, Salary

scholarly journals Resistance Analysis of Bictegravir-Emtricitabine-Tenofovir Alafenamide in HIV-1 Treatment-Naive Patients through 48 Weeks

2019 ◽  
Vol 63 (5) ◽  
Author(s):  
Rima K. Acosta ◽  
Madeleine Willkom ◽  
Ross Martin ◽  
Silvia Chang ◽  
Xuelian Wei ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Transcriptase Inhibitor ◽  
Virologic Suppression ◽  
Strand Transfer ◽  
Primary Drug Resistance ◽  
Treatment Naïve ◽  
Tenofovir Alafenamide ◽  
Inhibitor Resistance ◽  
Reverse Transcriptase Inhibitor ◽  
Hiv 1

ABSTRACT In clinical studies GS-US-380-1489 (study 1489) and GS-US-380-1490 (study 1490), bictegravir-emtricitabine-tenofovir alafenamide (B-F-TAF), dolutegravir-abacavir-lamivudine (DTG-ABC-3TC), and dolutegravir plus emtricitabine-tenofovir alafenamide (DTG+F-TAF) treatment achieved high rates of virologic suppression in HIV-1 treatment-naive participants through week 48. Preexisting primary drug resistance was present at levels of 1.3% integrase strand transfer inhibitor resistance (INSTI-R), 2.7% nucleoside reverse transcriptase inhibitor resistance (NRTI-R), 14.1% nonnucleoside reverse transcriptase inhibitor resistance (NNRTI-R), and 3.5% protease inhibitor resistance (PI-R) in the 1,274 participants from these studies. These mutations did not affect treatment outcomes. Resistance analyses in 13 virologic failures found no emergent resistance to study drugs.

scholarly journals Week 96 results of a phase 3 trial of darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-naive HIV-1 patients

AIDS ◽  
2020 ◽  
Vol 34 (5) ◽  
pp. 707-718 ◽  
Author(s):  
Chloe Orkin ◽  
Joseph J. Eron ◽  
Jürgen Rockstroh ◽  
Daniel Podzamczer ◽  
Stefan Esser ◽  
...  
Keyword(s):  
Phase 3 ◽  
Treatment Naïve ◽  
Tenofovir Alafenamide ◽  
Hiv 1

scholarly journals 2509. Pooled Resistance Analyses of Darunavir (DRV) Once Daily (QD) Regimens and Formulations Across 10 Clinical Studies of Treatment-Naïve (TN) and Treatment-Experienced (TE) Patients with Human Immunodeficiency Virus (HIV)-1 Infection

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S870-S871 ◽  
Author(s):  
Erkki Lathouwers ◽  
Sareh Seyedkazemi ◽  
Donghan Luo ◽  
Kimberley Brown ◽  
Sandra De Meyer ◽  
...  
Keyword(s):  
Clinical Studies ◽  
Virologic Failure ◽  
Transcriptase Inhibitor ◽  
Resistance Testing ◽  
Resistance Development ◽  
Single Tablet Regimen ◽  
Treatment Naïve ◽  
Tenofovir Alafenamide ◽  
Hiv 1 ◽  
Phenotypic Susceptibility

Abstract Background DRV has demonstrated high efficacy and barrier to resistance development across diverse populations, from TN to heavily TE patients. We evaluated resistance data from 10 clinical studies of different DRV 800 mg QD–based antiretroviral regimens and formulations. Methods The analysis included patients from 10 phase 2/3 studies (48–192 weeks in duration) of ritonavir- and cobicistat-boosted DRV 800 mg QD–based regimens in TN and virologically failing or suppressed TE patients with HIV-1 (table). Three were phase 3 studies of the DRV/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg single-tablet regimen (STR). Post-baseline resistance was evaluated in patients experiencing protocol-defined virologic failure (PDVF); definitions and criteria for resistance testing varied slightly among studies. Resistance-associated mutations (RAMs) were based on respective International Antiviral Society–USA mutation lists over time. Results Of the 3,635 patients evaluated, 250 met PDVF criteria and 205 had post-baseline genotypes/phenotypes. Overall, 4 (0.1%) patients developed (or had identified [switch studies]) ≥1 DRV and/or primary protease inhibitor (PI) RAM (table), and only 1 (< 0.1%, ODIN) patient lost DRV phenotypic susceptibility; this TE patient had prior VF with lopinavir. Among those who used a nucleos(t)ide reverse transcriptase inhibitor (NRTI) backbone (mostly emtricitabine [FTC] + tenofovir [TFV]), 12 (0.4%) patients had ≥1 NRTI RAM, including 10 with M184I/V associated with FTC resistance. No TFV RAMs were observed. Among patients receiving D/C/F/TAF (n = 1,949), none had post-baseline DRV, primary PI, or TFV RAMs; only 2 (0.1%) patients developed an FTC RAM. Conclusion Across a large, diverse population using DRV 800 mg QD–based regimens and formulations, resistance development remains rare; 0.1% of patients had ≥1 DRV and/or primary PI RAM post-baseline. Among 3 trials of the D/C/F/TAF STR, no patients developed a DRV or primary PI RAM. After > 10 years of investigating DRV 800 mg QD–based regimens in clinical trials, loss of phenotypic susceptibility to DRV has never been observed in TN or TE virologically suppressed patients and was only once observed in a TE patient with prior VF on multiple antiretrovirals, including a PI. Disclosures All authors: No reported disclosures.

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 Long-term Outcomes in a Large Randomized Trial of HIV-1 Salvage Therapy: 96-Week Results of AIDS Clinical Trials Group A5241 (OPTIONS)

2019 ◽  
Vol 221 (9) ◽  
pp. 1407-1415 ◽  
Author(s):  
Rajesh T Gandhi ◽  
Karen T Tashima ◽  
Laura M Smeaton ◽  
Vincent Vu ◽  
Justin Ritz ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Salvage Therapy ◽  
Virologic Failure ◽  
Virologic Suppression ◽  
Cumulative Activity ◽  
Antiretroviral Medications ◽  
Resistant Group ◽  
Aids Clinical Trials ◽  
Hiv 1

Abstract Background Short-term (48-week) results of the OPTIONS trial showed that nucleoside reverse transcriptase inhibitors (NRTIs) can be safely omitted from salvage therapy as long as the regimen has a cumulative activity of &gt;2 active antiretroviral medications. The long-term durability of this approach and outcomes in persons who have more-extensive HIV-1 drug resistance are uncertain. Methods Participants with virologic failure and anticipated antiretroviral susceptibility received an optimized regimen and were randomized to omit or add NRTIs. A separate group with more resistance (cumulative activity ≤2 active agents) received an optimized regimen including NRTIs. Results At week 96, among 360 participants randomized to omit or add NRTIs, 70% and 65% had HIV-1 RNA &lt;200 copies/mL, respectively. Virologic failure was uncommon after week 48. Younger age and starting fewer new antiretroviral medications were associated with higher odds of virologic failure. In the highly resistant group, 53% had HIV-1 RNA &lt;200 copies/mL at week 96. Conclusions HIV-1 salvage therapy can safely omit NRTIs without compromising efficacy or durability of response as long as the new regimen has a cumulative activity of &gt;2 active drugs. Younger people and those receiving fewer new antiretrovirals require careful monitoring. Even among individuals with more-extensive resistance, most achieve virologic suppression. Clinical Trials Registration NCT00537394.

scholarly journals HIV-1 Tropism Testing and Clinical Management of CCR5 Antagonists: Quebec Review and Recommendations

2013 ◽  
Vol 24 (4) ◽  
pp. 202-208 ◽  
Author(s):  
Cécile Tremblay ◽  
Isabelle Hardy ◽  
Richard Lalonde ◽  
Benoit Trottier ◽  
Irina Tsarevsky ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Clinical Management ◽  
Crucial Role ◽  
Alternative Strategies ◽  
Limited Access ◽  
Ccr5 Receptor ◽  
Treatment Naïve ◽  
Ccr5 Antagonists ◽  
Phenotypic Tests ◽  
Hiv 1

HIV-1 tropism assays play a crucial role in determining the response to CCR5 receptor antagonists. Initially, phenotypic tests were used, but limited access to these tests prompted the development of alternative strategies. Recently, genotyping tropism has been validated using a Canadian technology in clinical trials investigating the use of maraviroc in both experienced and treatment-naive patients. The present guidelines review the evidence supporting the use of genotypic assays and provide recommendations regarding tropism testing in daily clinical management.

scholarly journals 902. Unreturned Pill Bottles in the 1489 and 1490 Clinical Trials: An Important Measure of Poor Adherence that Is Often Ignored in Pill Count Calculations

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S542-S543
Author(s):  
Rima K Acosta ◽  
Grace Q Chen ◽  
Hailin Huang ◽  
Hui Liu ◽  
Kirsten L White
Keyword(s):  
Clinical Trials ◽  
Pill Count ◽  
Return Rate ◽  
Poor Adherence ◽  
Resistance Testing ◽  
Virologic Suppression ◽  
Treatment Groups ◽  
Pill Bottle ◽  
Treatment Naïve ◽  
All Treatment

Abstract Background Adherence to antiretroviral therapy is important for HIV suppression. In clinical trials, adherence is commonly measured by pill count; limitations are that unreturned pills may not have been taken and unreturned pill bottle data are omitted. This analysis focuses on the relationship between unreturned pill bottles as a measure of poor adherence and the overall effect on virologic success rates across all treatment groups. Methods Pill bottle return category (all bottles returned or ≥1 bottle unreturned) and return rates for participants across all treatment groups from two treatment-naïve INSTI clinical trials (Studies 1489 and 1490) were calculated. Association of bottle return category or rates with virologic events through week 144, including last on-treatment observation carried forward (LOCF) outcome, was determined; comparisons used Fisher’s exact or Wilcoxon rank sum test. Results Virologic suppression with ≥95% adherence by pill count can differ for those with unreturned pill bottles (Figure). In these studies, 60% of participants returned all their pill bottles through week 144; if one visit with ≥1 unreturned bottle was allowed, this percentage increased to 81%. The mean bottle return rate was 94% and did not differ by study, treatment arm, or sex. Failure to return pill bottles was significantly associated with lower suppression rates. Additionally, significant differences in pill bottle return rate (p &lt; 0.01) were observed by week 144 LOCF outcome (95% vs 77% mean return rate for those with HIV RNA &lt; 50 c/mL vs ≥50 c/mL), need for resistance testing (95% vs 77% return rate for those not tested vs tested), confirmed virologic failure (VF) (94% vs 90% return rate for those without VF vs with VF) and blip status (95% vs 92% return rate for those without blips vs with blips). HIV-1 Viral Loads of Two Participants with ≥95% Adherence by Pill Count through Week 144 Conclusion In these treatment-naïve INSTI clinical trials, failure to return pill bottles was associated with lower suppression rates. Although the calculated adherence rates in these studies was relatively high (median ≥95%), these calculations did not account for unreturned pill bottles. We believe that assessing adherence by both pill count and pill bottle return rate may provide a more complete picture of adherence in clinical trials. Disclosures Rima K. Acosta, BS, Gilead Sciences, Inc. (Employee, Shareholder) Grace Q. Chen, BS, Gilead Sciences, Inc. (Employee) Hailin Huang, PhD, Gilead Sciences, Inc. (Employee, Shareholder) Hui Liu, PhD, Gilead Sciences, Inc. (Employee, Shareholder) Kirsten L. White, PhD, Gilead Sciences, Inc (Employee, Shareholder)

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