Antiretroviral resistance at virological failure in the NEAT 001/ANRS 143 trial: raltegravir plus darunavir/ritonavir or tenofovir/emtricitabine plus darunavir/ritonavir as first-line ART

Lambert-Niclot, Sidonie; George, Elizabeth C.; Pozniak, Anton; White, Ellen; Schwimmer, Christine; Jessen, Heiko; Johnson, Margaret; Dunn, David; Perno, Carlo Federico; Clotet, Bonaventura; Plettenberg, Andreas; Blaxhult, Anders; Palmisano, Lucia; Wittkop, Linda; Calvez,; Marcelin, Anne–Geneviève; Raffi, François; Neat,

doi:10.1093/jac/dkv427

Cited by 23 publications

(21 citation statements)

References 24 publications

(32 reference statements)

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“…27 Darunavir/ritonavir plus raltegravir was noninferior to darunavir/ritonavir plus 2 NRTIs, but the2-drug regimen had higher rates of treatment failure in patients with a CD4 cell count below 200/μL or an HIV RNA level above 100 000 copies/mL. 28 …”

Section: Recommended Initial Regimensmentioning

confidence: 99%

Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults

Saag

Benson

Gandhi

et al. 2018

JAMA

498

280

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IMPORTANCE Antiretroviral therapy (ART) is the cornerstone of prevention and management of HIV infection. OBJECTIVE To evaluate new data and treatments and incorporate this information into updated recommendations for initiating therapy, monitoring individuals starting therapy, changing regimens, and preventing HIV infection for individuals at risk. EVIDENCE REVIEW New evidence collected since the International Antiviral Society–USA 2016 recommendations via monthly PubMed and EMBASE literature searches up to April 2018; data presented at peer-reviewed scientific conferences. A volunteer panel of experts in HIV research and patient care considered these data and updated previous recommendations. FINDINGS ART is recommended for virtually all HIV-infected individuals, as soon as possible after HIV diagnosis. Immediate initiation (eg, rapid start), if clinically appropriate, requires adequate staffing, specialized services, and careful selection of medical therapy. An integrase strand transfer inhibitor (InSTI) plus 2 nucleoside reverse transcriptase inhibitors (NRTIs) is generally recommended for initial therapy, with unique patient circumstances (eg, concomitant diseases and conditions, potential for pregnancy, cost) guiding the treatment choice. CD4 cell count, HIV RNA level, genotype, and other laboratory tests for general health and co-infections are recommended at specified points before and during ART. If a regimen switch is indicated, treatment history, tolerability, adherence, and drug resistance history should first be assessed; 2 or 3 active drugs are recommended for a new regimen. HIV testing is recommended at least once for anyone who has ever been sexually active and more often for individuals at ongoing risk for infection. Preexposure prophylaxis with tenofovir disoproxil fumarate/emtricitabine and appropriate monitoring is recommended for individuals at risk for HIV. CONCLUSIONS AND RELEVANCE Advances in HIV prevention and treatment with antiretroviral drugs continue to improve clinical management and outcomes for individuals at risk for and living with HIV.

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Section: Recommended Initial Regimensmentioning

confidence: 99%

Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults

Saag

Benson

Gandhi

et al. 2018

JAMA

498

280

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“…INSTI efficacy and tolerability have been shown in both na€ ıve and previously treated patients [5][6][7][8][9]. Clinical trials with various INSTIs have shown different rates of emergent drug resistance, indicating a higher genetic barrier for DTG and BIC [8][9][10][11][12][13][14][15][16]. However, the heterogeneity of HIV-1-infected patients and several other factors may influence INSTI treatment outcome and emergent resistance in the clinical setting [17,18].…”

Section: Introductionmentioning

confidence: 99%

Prevalence and determinants of resistance mutations in HIV‐1‐infected patients exposed to integrase inhibitors in a large Italian cohort

et al. 2018

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Objectives The aim of the study was to analyse the prevalence of integrase resistance mutations in integrase strand transfer inhibitor (INSTI)‐experienced HIV‐1‐infected patients and its predictors. Methods We selected HIV‐1 integrase sequences from the Antiviral Response Cohort Analysis (ARCA) database, derived from INSTI‐experienced patients between 2008 and 2017. Differences in the prevalence of resistance to raltegravir (RAL), elvitegravir (EVG) and dolutegravir (DTG) were assessed by χ2 test and predictors of resistance were analysed by logistic regression. Results We included 462 genotypes from INSTI‐exposed individuals: 356 ‘INSTI‐failing' patients and 106 ‘previously INSTI‐exposed' patients (obtained a median of 42 weeks after INSTI discontinuation [interquartile range (IQR) 17–110 weeks]). Overall, at least low‐level resistance (LLR) to any INSTI (Stanford 8.5 algorithm) was detected in 198 (42.9%) cases. The most frequent INSTI resistance mutation was N155H, followed by Q148H/K/R, G140A/C/S, E138A/K/T and Y143C/H/R. Y143R and E138A were more prevalent in viral subtype B versus non‐B [5.2 versus 1.5%, respectively (P = 0.04), and 3.1 versus 0%, respectively (P = 0.02)]. Overall, the Q148H/K/R plus G140A/C/S and/or E138A/K/T pattern, defining an intermediate level of resistance to DTG, was detected in 70 (15%) cases. Independent predictors of at least LLR to any INSTI were current use versus past use of INSTIs, a lower genotypic sensitivity score (GSS) for contemporary antiretroviral drugs used, and having an integrase sequence obtained in calendar year 2016 as compared to 2008–2009. Conclusions The results support integrase resistance testing in INSTI‐experienced patients. Emergence of INSTI resistance is facilitated by the reduced genetic barrier of the regimen as a consequence of resistance to companion drugs. However, INSTI resistance may become undetectable by standard population sequencing upon INSTI discontinuation.

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“…In both treatment-naïve and -experienced populations, integrase inhibitors play a large role in NRTI-sparing 2DRs. Raltegravir was studied in many 2DRs as it was the first INSTI on the market [18,24,25,42]. However, data from randomized-controlled studies largely do not support any additional benefit from the use of a boosted PI with RAL since this regimen is quickly becoming obsolete given that RAL is a first-generation INSTI that is less potent than newer agents such as DTG and BIC.…”

Section: Discussionmentioning

confidence: 99%

“…Of nine non-inferiority studies including a variety of 2DR combinations, non-inferiority was achieved in five studies [15][16][17][18]24] (Table 1) [15][16][17][18][19][20][21][22][23][24][25]. Two studies included maraviroc (MVC) ?…”

Section: Nrti Sparingmentioning

confidence: 99%

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Two’s a Company, Three’s a Crowd: A Review of Initiating or Switching to a Two-Drug Antiretroviral Regimen in Treatment-Naïve and Treatment-Experienced Patients Living with HIV-1

Badowski¹,

Pérez²,

Schwartz³

et al. 2020

Infect Dis Ther

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Introduction: As HIV has become a manageable chronic condition, a renewed and increased interest in challenging traditional three-drug HIV therapies and moving toward two-drug regimens (2DR) for initial or maintenance treatment in people living with HIV (PLWH) has developed. As PLWH are living longer, continual advancements in antiretroviral regimens have been a focus to provide optimal lifelong therapy options. Although early studies may have shown poor outcomes in virologic suppression with 2DR, newer studies and treatment options have emerged to show promise in the management of HIV. The purpose of this review is to evaluate current literature and assess the efficacy of two-drug (2DR) antiretroviral therapy in treatment-naïve and -experienced people living with HIV.

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Antiretroviral resistance at virological failure in the NEAT 001/ANRS 143 trial: raltegravir plus darunavir/ritonavir or tenofovir/emtricitabine plus darunavir/ritonavir as first-line ART

Cited by 23 publications

References 24 publications

Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults

Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults

Prevalence and determinants of resistance mutations in HIV‐1‐infected patients exposed to integrase inhibitors in a large Italian cohort

Two’s a Company, Three’s a Crowd: A Review of Initiating or Switching to a Two-Drug Antiretroviral Regimen in Treatment-Naïve and Treatment-Experienced Patients Living with HIV-1

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