HIV DNA Decay in a Treatment-Naive Patient Starting Dolutegravir Plus Lamivudine with Resistance Mutations to Integrase Inhibitors: A Case Report

2020 ◽  
Vol 36 (4) ◽  
pp. 256-257 ◽  
Author(s):  
Arturo Ciccullo ◽  
Gianmaria Baldin ◽  
Francesca Lombardi ◽  
Alberto Borghetti ◽  
Simona Di Giambenedetto
Keyword(s):  
Case Report ◽  
Integrase Inhibitors ◽  
Resistance Mutations ◽  
Naive Patient ◽  
Hiv Dna ◽  
Treatment Naïve

Prevalence of Primary Resistance Mutations to Integrase Inhibitors in Treatment-Naïve and -Experienced Patients Infected With B and Non-B HIV-1 Variants

2013 ◽  
Vol 14 (1) ◽  
pp. 10-16 ◽  
Author(s):  
Carolina Gutiérrez ◽  
Beatriz Hernández-Novoa ◽  
María Jesús Pérez-Elías ◽  
Ana María Moreno ◽  
África Holguín ◽  
...  
Keyword(s):  
Integrase Inhibitors ◽  
Resistance Mutations ◽  
Primary Resistance ◽  
Treatment Naïve ◽  
Hiv 1

Drug Resistance Mutations of HIV Type 1 Non-B Viruses to Integrase Inhibitors in Treatment-Naive Patients from Sub-Saharan Countries and Discordant Interpretations

2012 ◽  
Vol 28 (9) ◽  
pp. 1157-1160 ◽  
Author(s):  
Marjorie Monleau ◽  
Avelin F. Aghokeng ◽  
Benedicte A. Nkano ◽  
Marie-Laure Chaix ◽  
Martine Peeters, and the AC11/AC12 ANRS Wor
Keyword(s):  
Drug Resistance ◽  
Integrase Inhibitors ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
Treatment Naïve ◽  
Hiv Type 1 ◽  
Sub Saharan

scholarly journals Coexistence of follicular lymphoma and an unclassifiable myeloproliferative neoplasm in a treatment-naïve patient: A case report

2015 ◽  
Vol 11 (2) ◽  
pp. 1469-1473
Author(s):  
GYEONGMIN JEONG ◽  
JINHYONG KIM ◽  
SEEUN HAN ◽  
JONGMIN LEE ◽  
KYUNGHYE PARK ◽  
...  
Keyword(s):  
Case Report ◽  
Follicular Lymphoma ◽  
Myeloproliferative Neoplasm ◽  
Naive Patient ◽  
Treatment Naïve

scholarly journals Contribution of Gag and protease to variation in susceptibility to protease inhibitors between different strains of subtype B human immunodeficiency virus type 1

2014 ◽  
Vol 95 (1) ◽  
pp. 190-200 ◽  
Author(s):  
Katherine A. Sutherland ◽  
Jean L. Mbisa ◽  
Patricia A. Cane ◽  
Deenan Pillay ◽  
Chris M. Parry
Keyword(s):  
Human Immunodeficiency Virus ◽  
Protease Inhibitors ◽  
Significant Variation ◽  
Reference Strain ◽  
Resistance Mutations ◽  
Naive Patient ◽  
Subtype B ◽  
Immunodeficiency Virus ◽  
Treatment Naïve

Recent reports have shown that human immunodeficiency virus type 1 (HIV-1) Gag can directly affect susceptibility to protease inhibitors (PIs) in the absence of known resistance mutations in protease. Inclusion of co-evolved Gag alongside protease in phenotypic drug susceptibility assays can alter PI susceptibility in comparison with protease with a WT Gag. Using a single-replication-cycle assay encompassing full-length Gag together with protease we demonstrated significant variation in PI susceptibility between a number of PI-naïve subtype B viruses. Six publicly available subtype B molecular clones, namely HXB2, NL4-3, SF2, YU2, JRFL and 89.6, displayed up to nine-fold reduced PI susceptibility in comparison with the assay reference strain. For two molecular clones, YU2 and JRFL, Gag contributed solely to the observed reduction in susceptibility, with the N-terminal region of Gag contributing significantly. Gag and protease from treatment-naïve, patient-derived viruses also demonstrated significant variation in susceptibility, with up to a 17-fold reduction to atazanavir in comparison with the assay reference strain. In contrast to the molecular clones, protease was the main determinant of the reduced susceptibility. Common polymorphisms in protease, including I13V, L63P and A71T, were shown to contribute to this reduction in PI susceptibility, in the absence of major resistance mutations. This study demonstrated significant variation in PI susceptibility of treatment-naïve patient viruses, and provided further evidence of the independent role of Gag, the protease substrate and in particular the N-terminus of Gag in PI susceptibility. It also highlighted the importance of considering co-evolved Gag and protease when assessing PI susceptibility.

P21 Prevalence of antiretroviral resistance mutations in treatment-naive HIV-1-infected patients in South London

HIV Medicine ◽  
2000 ◽  
Vol 1 (3) ◽  
pp. 179-179
Author(s):  
Am Geretti ◽  
M Smith ◽  
M Donati ◽  
P Easterbrook ◽  
M Zuckerman
Keyword(s):  
Resistance Mutations ◽  
Antiretroviral Resistance ◽  
Treatment Naïve ◽  
Hiv 1

Amivantamab in combination with lazertinib for the treatment of osimertinib-relapsed, chemotherapy-naïve EGFR mutant (EGFRm) non-small cell lung cancer (NSCLC) and potential biomarkers for response.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9006-9006
Author(s):  
Joshua Bauml ◽  
Byoung Chul Cho ◽  
Keunchil Park ◽  
Ki Hyeong Lee ◽  
EUN KYUNG CHO ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Progression Free Survival ◽  
Complete Response ◽  
Combination Regimen ◽  
Resistance Mutations ◽  
Tumor Biopsy ◽  
Potential Biomarker ◽  
Treatment Naïve ◽  
Exon 19 Deletion ◽  
Potential Biomarkers

9006 Background: Preliminary efficacy was observed with the combination of amivantamab, an EGFR-MET bispecific antibody, and lazertinib, a 3rd-generation tyrosine kinase inhibitor, in both treatment-naïve and osimertinib (osi)-relapsed patients (pts) with EGFRm NSCLC (Cho Ann Oncol 2020;31:S813). We present updated results of the combination in osi-relapsed pts, including an analysis of potential biomarkers of response. Methods: Pts with EGFR exon 19 deletion or L858R mutation NSCLC, who had progressed on osi without intervening chemotherapy, were enrolled in the combination cohort of the ongoing CHRYSALIS study (NCT02609776). With pre-treatment tumor biopsies and ctDNA collected prospectively, pts received the combination dose of 1050/1400 mg amivantamab + 240 mg lazertinib to assess safety and efficacy in the osi-relapsed population. Response was assessed by investigator per RECIST v1.1. Osi-resistance mutations or amplifications in EGFR/MET identified by next-generation sequencing (NGS) in either ctDNA or tumor biopsy (biomarker-positive [pos]), were evaluated for enriching response. Immunohistochemistry (IHC) staining for EGFR and MET expression was also explored as a potential biomarker for response. Results: Of the 45 osi-relapsed pts, 36% (95% CI, 22–51) had a confirmed response (1 complete response and 15 partial responses [PR]). At a median follow-up of 8.2 mo (1.0–11.8), 20/45 pts (44%) remain on treatment. With 11/16 pts (69%) continuing in response (2.6–9.6+ mo), median duration of response has not been reached (NR). The median progression-free survival (mPFS) was 4.9 mo (95% CI, 3.7–8.3). In total, 44/45 pts were evaluable by ctDNA and 29/45 by tumor NGS. Genetic testing identified 17 biomarker-pos pts, of whom 8 (47%) responded. Of the remaining 28 pts, 8 (29%) responded. Among these 28 pts, 18 had unknown mechanisms of osi-resistance (8 PR) and 10 had non-EGFR/MET mechanisms of resistance identified (none responded). The mPFS (95% CI) for biomarker-pos and remaining pts was 6.7 mo (3.4–NR) and 4.1 mo (1.4–9.5), respectively. Adequate tissue was available for 20 pts to perform IHC testing for EGFR and MET–9/10 (90%) IHC high (combined EGFR+MET H score>400) pts responded to treatment, while 1/10 IHC low pts responded to treatment. Conclusions: Treatment with the combination of amivantamab and lazertinib yielded responses in 36% of chemotherapy-naïve pts who progressed on osi. Among these pts, genetic EGFR and MET-based biomarkers of resistance identified a subgroup of pts more likely to respond to amivantamab and lazertinib, although additional pts lacking identified resistance markers also responded. An IHC-based approach may identify pts most likely to benefit from the combination regimen, but further investigation is warranted. Clinical trial information: NCT02609776.

Diversity of HIV-1 subtypes and transmitted drug-resistance mutations among minority HIV-1 variants in a Turkish cohort

2021 ◽  
Vol 19 ◽  
Author(s):  
Rabia Can Sarinoglu ◽  
Uluhan Sili ◽  
Ufuk Hasdemir ◽  
Burak Aksu ◽  
Guner Soyletir ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Transcriptase Inhibitor ◽  
Transmitted Drug Resistance ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
Subtype B ◽  
Treatment Naïve ◽  
Reverse Transcriptase Inhibitor ◽  
Hiv 1

Background: The World Health Organization (WHO) recommends the surveillance of transmitted drug resistance mutations (TDRMs) to ensure the effectiveness and sustainability of HIV treatment programs. Objective: Our aim was to determine the TDRMs and evaluate the distribution of HIV-1 subtypes using and compared next-generation sequencing (NGS) and Sanger-based sequencing (SBS) in a cohort of 44 antiretroviral treatment-naïve patients. Methods: All samples that were referred to the microbiology laboratory for HIV drug resistance analysis between December 2016 and February 2018 were included in the study. After exclusions, 44 treatment-naive adult patients with a viral load of >1000 copies/mL were analyzed. DNA sequencing for reverse transcriptase and protease regions was performed using both DeepChek ABL single round kit and Sanger-based ViroSeq HIV-1 Genotyping System. The mutations and HIV-1 subtypes were analyzed using the Stanford HIVdb version 8.6.1 Genotypic Resistance software, and TDRMs were assessed using the WHO surveillance drug-resistance mutation database. HIV-1 subtypes were confirmed by constructing a maximum-likelihood phylogenetic tree using Los Alamos IQ-Tree software. Results: NGS identified nucleos(t)ide reverse transcriptase inhibitor (NRTI)-TDRMs in 9.1% of the patients, non-nucleos(t)ide reverse transcriptase inhibitor (NNRTI)-TDRMs in 6.8% of the patients, and protease inhibitor (PI)-TDRMs in 18.2% of the patients at a detection threshold of ≥1%. Using SBS, 2.3% and 6.8% of the patients were found to have NRTI- and NNRTI-TDRMs, respectively, but no major PI mutations were detected. M41L, L74I, K65R, M184V, and M184I related to NRTI, K103N to NNRTI, and N83D, M46I, I84V, V82A, L24I, L90M, I54V to the PI sites were identified using NGS. Most mutations were found in low-abundance (frequency range: 1.0% - 4.7%) HIV-1 variants, except M41L and K103N. The subtypes of the isolates were found as follows; 61.4% subtype B, 18.2% subtype B/CRF02_AG recombinant, 13.6% subtype A, 4.5% CRF43_02G, and 2.3% CRF02_AG. All TDRMs, except K65R, were detected in HIV-1 subtype B isolates.. Conclusion: The high diversity of protease site TDRMs in the minority HIV-1 variants and prevalence of CRFs were remarkable in this study. All minority HIV-1 variants were missed by conventional sequencing. TDRM prevalence among minority variants appears to be decreasing over time at our center.

scholarly journals Effectiveness, Safety, and Costs of a Treatment Switch to Dolutegravir Plus Rilpivirine Dual Therapy in Treatment-Experienced HIV Patients

2017 ◽  
Vol 52 (1) ◽  
pp. 11-18 ◽  
Author(s):  
José Luis Revuelta-Herrero ◽  
Esther Chamorro-de-Vega ◽  
Carmen Guadalupe Rodríguez-González ◽  
Roberto Alonso ◽  
Ana Herranz-Alonso ◽  
...  
Keyword(s):  
Drug Interaction ◽  
Viral Load ◽  
Dual Therapy ◽  
Art Adherence ◽  
Integrase Inhibitors ◽  
Resistance Mutations ◽  
Safe Strategy ◽  
Treatment Switch ◽  
Effectiveness Endpoint ◽  
All Treatment

Background: Evidence about the use of dolutegravir (DTG) and rilpivirine (RPV) as an antiretroviral therapy (ART) in treatment-experienced patients is scarce. Objective: To explore the effectiveness, safety, and costs of switching to a DTG plus RPV regimen in this population. Methods: This observational, prospective study included all treatment-experienced patients who switched to DTG plus RPV between November 2014 and July 2016. Patients were excluded if resistance mutations to integrase inhibitors or RPV were found. The effectiveness endpoint was the proportion of patients who achieved virological suppression (viral load [VL] <50 copies/mL) at week 48 (W48). Safety (incidence of adverse events leading to discontinuation and laboratory abnormalities), adherence, and costs were analyzed. Results: A total of 35 patients were included, and 91.4% were virologically suppressed at baseline. Patients were treated with ART for a median of 14 years (interquartile range = 7-20). At W48, 91.4% of patients were virologically suppressed (95% CI = 77.0-98.2). Two of the 3 patients not suppressed at baseline achieved undetectable VL at W48, and 2 patients discontinued DTG plus RPV (intolerance and a drug-drug interaction). None of the virologically suppressed patients at baseline showed virological rebound through W48. There were no significant changes in lipid, liver, and renal profiles. The proportion of patients with an ART adherence >90% increased from 65.6% to 93.8% ( P = 0.004). The annual per-patient ART costs dropped by €665 ( P = 0.265). Conclusions: Switching to DTG plus RPV seems to be an effective and safe strategy. Significant improvements in patients’ adherence and costs were achieved.

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