Usefulness of an HIV DNA resistance genotypic test in patients who are candidates for a switch to the rilpivirine/emtricitabine/tenofovir disoproxil fumarate combination

Lambert-Niclot, Sidonie; Allavena, Clotilde; Grudé, Maxime; Flandre, Philippe; Sayon, Sophie; Andre, Elodie Baumfeld; Wirden, Marc; Rodallec, Audrey; Jovelin, T; Katlama, Christine; Cálvez, Vincent; Raffi, François; Marcelin, Anne–Geneviève

doi:10.1093/jac/dkw146

Cited by 18 publications

(13 citation statements)

References 11 publications

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“…Outside the guidelines, in the absence of prior plasma genotype data, it has been suggested that a proviral DNA genotype in peripheral blood mononuclear cells (PBMCs) in the virologically suppressed patient might provide information on archived mutations .…”

Section: Considering the Evidence For Switch – What The Guidelines Saymentioning

confidence: 99%

Switching regimens in virologically suppressed HIV‐1‐infected patients: evidence base and rationale for integrase strand transfer inhibitor (INSTI)‐containing regimens

Raffi¹,

Eßer

Nunnari

et al. 2016

HIV Medicine

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In an era when most individuals with treated HIV infection can expect to live into old age, clinicians should proactively review their patients' current and future treatment needs and challenges. Clinical guidelines acknowledge that, in the setting of virological suppression, treatment switch may yield benefits in terms of tolerability, regimen simplification, adherence, convenience and long-term health considerations, particularly in the context of ageing. In this paper, we review evidence from six key clinical studies on switching virologically suppressed patients to regimens based on integrase strand transfer inhibitors (INSTIs), the antiretroviral class increasingly preferred as initial therapy in clinical guidelines. We review these studies and focus on the virological efficacy, safety, and tolerability of switching to INSTI-based regimens in suppressed HIV-positive individuals. We review the early switch studies SWITCHMRK and SPIRAL [assessing a switch from a ritonavir-boosted protease inhibitor (PI/r) to raltegravir (RAL)-containing regimens], together with data from STRATEGY-PI [assessing a switch to elvitegravir (EVG)-containing regimens; EVG/cobicistat (COBI)/emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) vs. remaining on a PI/r-containing regimen], STRATEGY-NNRTI [assessing a switch to EVG/COBI/FTC/TDF vs. continuation of a nonnucleoside reverse transcriptase inhibitor (NNRTI) and two nucleoside reverse transcriptase inhibitors (NRTIs)], STRIIVING [assessing a switch to a dolutegravir (DTG)-containing regimen (abacavir (ABC)/lamivudine (3TC)/DTG) vs. staying on the background regimen], and GS study 109 [assessing a switch to EVG/COBI/FTC/tenofovir alafenamide fumarate (TAF) vs. continuation of FTC/TDF-based regimens]. Switching to INSTI-containing regimens has been shown to support good virological efficacy, with evidence from two studies demonstrating superior virological efficacy for a switch to EVG-containing regimens. In addition, switching to INSTI regimens was associated with improved tolerability and greater reported patient satisfaction and outcomes in some studies. INSTI-based regimens offer an important contemporary switch option that may be tailored to meet and optimize the needs of many patients.

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Section: Considering the Evidence For Switch – What The Guidelines Saymentioning

confidence: 99%

Switching regimens in virologically suppressed HIV‐1‐infected patients: evidence base and rationale for integrase strand transfer inhibitor (INSTI)‐containing regimens

Raffi¹,

Eßer

Nunnari

et al. 2016

HIV Medicine

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“… 17 Other studies showed that switch regimens, as bictegravir/emtricitabine/tenofovir alafenamide and abacavir/lamivudine/dolutegravir triple therapy and ART-PRO for dual therapy, were successful in the absence of historical M184V in baseline PBMCs. 18 , 19 The choice of ART in the clinic has always been based on the study of genotype mutations by Sanger sequencing. Some studies have showed that choosing treatment based on ultradeep mutations has a limited impact on virological outcomes.…”

Section: Discussionmentioning

confidence: 99%

Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure

Ory

Beltrán-Pavez

Gutiérrez

et al. 2021

Journal of Antimicrobial Chemotherapy

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Objectives We analysed the prevalence of M184V/I and/or K65R/E/N mutations archived in proviral DNA (pDNA) in youths with perinatal HIV, virological control and who previously carried these resistance mutations in historic plasma samples. Methods We included vertically HIV-infected youths/young adults aged ≥10 years in the Madrid Cohort of HIV-1 Infected Children and Adolescents, exposed to lamivudine and/or emtricitabine, with M184V/I and/or K65R/E/N in historic plasma samples, on antiretroviral therapy (ART), virologically suppressed (HIV-1 RNA <50 copies/mL), and with available PBMCs in the Spanish HIV BioBank. Genomic DNA was extracted from PBMCs and HIV-1 RT gene was amplified and sequenced for resistance testing by Stanford HIV Resistance tool. Results Among the 225 patients under follow-up in the study cohort, 13 (5.8%) met selection criteria, and RT sequences were recovered in 12 (92.3%) of them. All but one were Spaniards, carrying subtype B, with a median age at PBMCs sampling of 21.3 years (IQR: 15.6–23.1) with 4 years (IQR 2.1–6.5) of suppressed viral load (VL). Nine (75%) youths did not present M184V/I in pDNA after at least 1 year of viral suppression. In December 2019, the remaining three subjects carrying M184V/I in pDNA maintained suppressed viraemia, and two still used emtricitabine in ART. Conclusions The prevalence of resistance mutations to lamivudine and emtricitabine in pDNA in a cohort of youths perinatally infected with HIV who remain with undetectable VL, previously lamivudine and/or emtricitabine experienced, was infrequent. Our results indicate that ART including lamivudine or emtricitabine may also be safe and successful in youths with perinatal HIV with previous experience of and resistances to these drugs detected in plasma.

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“…[18][19][20][21] Lambert-Niclot et al found good concordance between DNA and RNA GRT only in absence of prior virological failure. 11 DNA GRT could be useful in a virologically suppressed patient in the absence of prior RNA GRT, or in case of history of virological failure while receiving NNRTI and no RNA GRT at the time of failure. Use of rilpivirine should be avoided if resistance-associated mutations are detected using a DNA GRT.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies suggest an interest of proviral DNA GRT before switching therapy in patients successfully suppressed when no historical RNA resistance test is available. 11,12 In France, November 2016 and May 2017 updates of national guidelines proposed to realize proviral DNA GRT in PBMC in patients with virological failure with low-level viremia and unsuccessful RNA resistance test and in patients successfully suppressed when no historical RNA resistance test is available and a switch of therapy is planned. 2 However, several issues have been raised concerning HIV proviral DNA GRT.…”

Section: Introductionmentioning

confidence: 99%

Virological Outcome After Choice of Antiretroviral Regimen Guided by Proviral HIV-1 DNA Genotyping in a Real-Life Cohort of HIV-Infected Patients

Meybeck

Alidjinou²,

Huleux

et al. 2020

AIDS Patient Care and STDs

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Issues have been raised concerning clinical relevance of HIV-1 proviral DNA genotypic resistance test (DNA GRT). To assess impact of DNA GRT on choice of antiretroviral therapy (ART) and subsequent virological outcome, we retrospectively reviewed decision-making and viral load (VL) evolution following DNA GRT performed in our center between January 2012 and December 2017, except those prescribed within the framework of a clinical trial. A total of 304 DNA GRTs were included, 185 (62%) performed in a context of virological success. Only 34% of tests were followed by ART change, more frequently in situation of virological success (39% vs. 26%, p = 0.02). In this situation, ART change guided by DNA GRT led to VL >20 copies/mL after 6 months in 5% of cases. In multivariate analysis, higher HIV DNA quantification (p = 0.01) was associated with occurrence of viremia. A higher nadir of CD4 count (p = 0.04) and a longer time with VL <20 copies/mL (p = 0.04) were independently associated with a lower risk of viremia. In situation of low-level viremia, ART change guided by DNA GRT led to VL <20 copies/mL after 6 months in 52% of cases, while decision to maintain the same treatment led to VL <20 copies/mL in 74% of cases. In multivariate analysis, longer time with VL >20 copies/mL (p = 0.02) was associated with persistence of virological replication. In conclusion, in situation of virological success, use of DNA GRT in addition to analysis of historical RNA GRT to guide ART optimization appears safe. Its prescription framework in situation of low-level viremia deserves to be better defined.

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Usefulness of an HIV DNA resistance genotypic test in patients who are candidates for a switch to the rilpivirine/emtricitabine/tenofovir disoproxil fumarate combination

Cited by 18 publications

References 11 publications

Switching regimens in virologically suppressed HIV‐1‐infected patients: evidence base and rationale for integrase strand transfer inhibitor (INSTI)‐containing regimens

Switching regimens in virologically suppressed HIV‐1‐infected patients: evidence base and rationale for integrase strand transfer inhibitor (INSTI)‐containing regimens

Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure

Virological Outcome After Choice of Antiretroviral Regimen Guided by Proviral HIV-1 DNA Genotyping in a Real-Life Cohort of HIV-Infected Patients

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