Nucleoside Reverse-Transcriptase Inhibitor Resistance Mutations Predict Virological Failure in Human Immunodeficiency Virus-Positive Patients During Lamivudine Plus Dolutegravir Maintenance Therapy in Clinical Practice

Borghetti, Alberto; Giacomelli, Andrea; Borghi, Vanni; Ciccullo, Arturo; Dusina, Alex; Fabbiani, Massimiliano; Rusconi, Stefano; Zazzi, Maurizio; Mussini, Cristina; Giambenedetto, Simona Di

doi:10.1093/ofid/ofab103

Cited by 11 publications

(8 citation statements)

References 11 publications

(17 reference statements)

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“…Characteristics of the 5 real-world cohorts that met all search criteria and were included in the meta-analysis are summarized in Table 1 and indicated by lead cohort publication. Of these cohorts, 2 used similar criteria to define VF [ 13 , 14 ]; 3 reported VF outcomes at all time points [ 13 , 14 , 16 ].…”

Section: Resultsmentioning

confidence: 99%

“…Key findings related to VF in RWE cohorts are summarized in Table 2 . One cohort observed that presence of M184V/I had no impact on virologic suppression with DTG + 3TC [ 19 ], and another found that presence of M184V/I did not predict VF [ 17 ] but did predict shorter time to VF (vs absence [ 16 ]); 3 cohorts found that evidence of M184V/I did not affect probability of VF for ≥1 year [ 13 , 14 , 18 ].…”

Section: Resultsmentioning

confidence: 99%

“…Most VF definitions were consistent in the interventional sensitivity analysis but less consistent in RWE sensitivity analyses. In 4 of 5 RWE studies, VF criteria included a single elevated VL ranging from ≥200 to >1000 copies/mL [ 13 , 14 , 16 , 18 ]. Without details on which individuals met which criteria, VF may be underreported in studies with less stringent definitions.…”

Section: Discussionmentioning

confidence: 99%

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Virologic Response to Dolutegravir Plus Lamivudine in People With Suppressed Human Immunodeficiency Virus Type 1 and Historical M184V/I: A Systematic Literature Review and Meta-analysis

Kabra,

Barber,

Allavena

et al. 2023

Open Forum Infectious Diseases

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Background To investigate the impact of the M184V/I mutation on virologic response to dolutegravir (DTG) + lamivudine (3TC) in suppressed-switch populations, a meta-analysis was performed using virologic outcomes from people with HIV-1 (PWH) with and without M184V/I before DTG + 3TC switch in real-world studies identified via systematic literature review. Sensitivity analyses were performed using data from PWH with M184V/I in interventional studies identified via targeted literature review. Methods Single-arm meta-analyses using common- and random-effects models were used to estimate proportions of PWH with virologic failure (VF) among real-world populations with and without M184V/I and interventional study participants with M184V/I at 24, 48, and 96 weeks. Results Literature reviews identified 5 real-world studies from 3907 publications and 51 abstracts meeting inclusion criteria and 5 interventional studies from 1789 publications and 3 abstracts. All time points had low VF incidence in PWH with M184V/I (real-world: 1.43%-3.81%; interventional: 0.00%) and without (real-world: 0.73%-2.37%). Meta-analysis–estimated proportions (95% CI) with VF were low at Weeks 24, 48, and 96, respectively, for PWH with M184V/I (real-world: 0.01 [0.00-0.04], 0.03 [0.01-0.06], and 0.04 [0.01-0.07]; interventional: 0.00 [0.00-0.02], 0.00 [0.00-0.01], and 0.00 [0.00-0.03]) and without (real-world: 0.00 [0.00-0.02], 0.02 [0.01-0.04], and 0.02 [0.00-0.05]). One real-world study (n=712) reported treatment-emergent M184V at VF in 1/652 (0.15%) PWH without prior M184V/I. Conclusions Results suggest that prior M184V/I has minimal impact on virologic suppression after switching to DTG + 3TC and provide reassurance when considering switching regimens in virologically suppressed PWH with incomplete treatment history or limited treatment options.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Virologic Response to Dolutegravir Plus Lamivudine in People With Suppressed Human Immunodeficiency Virus Type 1 and Historical M184V/I: A Systematic Literature Review and Meta-analysis

Kabra,

Barber,

Allavena

et al. 2023

Open Forum Infectious Diseases

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“…A very similar case has been reported [ 18 ]. In line with these considerations, the TANGO trial [ 19 ] found the combination of M184V/I and at least one TAM and previous failure on an INSTI-based regimen to predict failure upon switching to lamivudine and dolutegravir, highlighting the importance of an optimal NRTI backbone for virologic success. Although the overall finding from the NADIA trial [ 15 ] was noninferiority between dolutegravir and ritonavir boosted darunavir (darunavir/r) in combination with either tenofovir or zidovudine as second-line treatment, four patients failing dolutegravir had confirmed major drug resistance mutations versus none failing darunavir/r.…”

Section: Discussionmentioning

confidence: 99%

Emergence of the G118R Pan-Integrase Resistance Mutation as a Result of Low Compliance to a Dolutegravir-Based cART

Mens

Fjordside

Fonager

et al. 2022

Infectious Disease Reports

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HIV-1 resistance towards integrase inhibitors is a potential threat of the success of HIV-1 combination treatment. G118R is a rare drug resistance mutation conferring pan-integrase resistance. Here, we describe the occurrence of G118R in a HIV-1 subtype-B-positive individual with major compliance problems, detected while the patient was on dolutegravir-based cART. We speculate the pre-selection of M184I/V aided the occurrence of G118R in this case, and discuss the robustness of dolutegravir-based therapies.

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“…Indeed, clinical and virological characteristics of each single subject should be considered before choosing drugs either for ART-naïve or -experienced PLWH. In particular, late presentation, tolerability to previous drugs, patient's lifestyle , drug-drug interactions, viral subtype, history of previous virological failures or transmitted resistance and even residual viremia can play a role in the maintenance of the long-term efficacy of ART [15,16]. In addition, definitive data on the long-term success of the newest therapeutic strategies are still lacking due to their recent introduction in clinical practice, and the best way to study them throughout time, is still object of debate and research.…”

Section: Introductionmentioning

confidence: 99%

Optimizing the antiretroviral treatment focusing on long-term effectiveness and a person-centred approach. Consensus Guidance Using a Delphi Process

Maggiolo

Caputo

Bonora

et al. 2022

Preprint

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BackgroundModern antiretroviral therapy (ART) offers several treatment options characterized by high efficacy and tolerability, and new strategies with new drugs are now available for the treatment of HIV infection. As definitive data on the long-term success of these new strategies are lacking, a panel of infectious diseases specialists was convened to develop a consensus on how to tailor and follow in time a person-centered ART approach.MethodsPanelists used a Delphi technique to develop a list of statements describing preferred management approaches for ART and patient monitoring and quality of life evaluation. Panelists provided level of agreement and feedback on consensus statements generated and refined them from the first round through 2 subsequent rounds of voting.ResultsNinety infectious diseases specialists from different Infectious Diseases Centres in Italy participated in the consensus process. A consensus was reached on virological and immunological parameters to use to monitor long term efficacy of antiretroviral treatment, while there was no consensus on the use of specific inflammation and immune-activation markers in clinical routine. The panel agreed on the need of an antiretroviral treatment with the lowest impact on bone, kidney and cardiovascular toxicity and on the utility of quality of life monitoring during the standard follow up of people living with HIV.ConclusionsThe consensus statements developed by a panel of infectious diseases specialists may provide guidance to practitioners for a person-centered approach aimed at obtaining long-term virological and clinical success for people living with HIV.Key pointsA panel of experts in the care of HIV infection expressed their consensus on which could be the best strategy to achieve and maintain long-term effectiveness in course of antiretroviral therapy, using Delphi methodology.

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Nucleoside Reverse-Transcriptase Inhibitor Resistance Mutations Predict Virological Failure in Human Immunodeficiency Virus-Positive Patients During Lamivudine Plus Dolutegravir Maintenance Therapy in Clinical Practice

Cited by 11 publications

References 11 publications

Virologic Response to Dolutegravir Plus Lamivudine in People With Suppressed Human Immunodeficiency Virus Type 1 and Historical M184V/I: A Systematic Literature Review and Meta-analysis

Virologic Response to Dolutegravir Plus Lamivudine in People With Suppressed Human Immunodeficiency Virus Type 1 and Historical M184V/I: A Systematic Literature Review and Meta-analysis

Emergence of the G118R Pan-Integrase Resistance Mutation as a Result of Low Compliance to a Dolutegravir-Based cART

Optimizing the antiretroviral treatment focusing on long-term effectiveness and a person-centred approach. Consensus Guidance Using a Delphi Process

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