Transmission of Integrase Strand-Transfer Inhibitor Multidrug-Resistant HIV-1: Case Report and Response to Raltegravir-Containing Antiretroviral Therapy

Young, Benjamin; Fransen, Signe; Greenberg, Kenneth S.; Thomas, Amy; Martens, S.; Clair, Marty St.; Petropoulos, Christos J.; Ha, Belinda

doi:10.3851/imp1748

Cited by 66 publications

(41 citation statements)

References 14 publications

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“…Participants had documented absence of genotypic resistance to reverse transcriptase and protease inhibitors; integrase genotyping was not required since transmitted integrase resistance remains rare. (6, 7) There were no limitations on CD4 cell count at entry. This study was approved by the ethics committee at each site, and all participants gave written informed consent before study enrollment.…”

Section: Methodsmentioning

confidence: 99%

Efficacy and Tolerability of 3 Nonnucleoside Reverse Transcriptase Inhibitor–Sparing Antiretroviral Regimens for Treatment-Naive Volunteers Infected With HIV-1

Lennox¹,

Landovitz²,

Ribaudo³

et al. 2014

Ann Intern Med

238

179

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Background Non-nucleoside reverse transcriptase (NNRTI) inhibitor-based antiretroviral therapy is not suitable for all treatment-naïve HIV-infected persons. Objective Perform a rigorous evaluation of three NNRTI-sparing initial antiretroviral regimens to demonstrate equivalence for virologic efficacy and tolerability. Design Phase-III, 1:1:1 randomized, open label, >96 week study. Setting Fifty-seven sites in United States and Puerto Rico. Patients Treatment naïve, ≥18 years, HIV-1 RNA >1000 copies/mL, no nucleoside reverse transcriptase or protease inhibitor resistance. Intervention Atazanavir 300 mg with ritonavir 100 mg, daily; or raltegravir 400 mg twice daily; or darunavir 800 mg with ritonavir 100 mg, daily; plus emtricitabine 200 mg + tenofovir disoproxil fumarate 300 mg daily. Measurements Virologic failure defined as confirmed HIV-1 RNA >1000 copies/mL between 16 and 24 weeks, or >200 copies/mL at or after 24 weeks; tolerability failure defined as discontinuation of atazanavir, raltegravir or darunavir for toxicity. A secondary endpoint was a combination of virologic efficacy and tolerability. Results Among 1,809 participants all pairwise comparisons of incidence of virologic failure over 96-weeks demonstrated equivalence within ±10%. Raltegravir and ritonavir-boosted darunavir were equivalent for tolerability, whereas ritonavir-boosted atazanavir resulted in a 12.7% and a 9.2% higher incidence of tolerability discontinuation than raltegravir and ritonavir-boosted darunavir respectively, primarily due to hyperbilirubinemia. For combined virologic efficacy and tolerability ritonavir-boosted darunavir was superior to ritonavir-boosted atazanavir, and raltegravir was superior to both protease inhibitors. Antiretroviral resistance at time of virologic failure was rare but more likely with raltegravir. Limitations Open label; ritonavir not provided Conclusions Over 2 years all three regimens attain high and equivalent rates of virologic control. Regimens containing raltegravir or ritonavir-boosted darunavir have superior tolerability compared to the ritonavir-boosted atazanavir regimen. Primary Funding Source National Institute of Allergy and Infectious Diseases

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Section: Methodsmentioning

confidence: 99%

Efficacy and Tolerability of 3 Nonnucleoside Reverse Transcriptase Inhibitor–Sparing Antiretroviral Regimens for Treatment-Naive Volunteers Infected With HIV-1

Lennox¹,

Landovitz²,

Ribaudo³

et al. 2014

Ann Intern Med

238

179

View full text Add to dashboard Cite

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“…The most common PI SDRMs were L90M, M46I/L, I85V, I54V, N88D, I84V, D30N, G73S, and they occurred less frequently (Bertagnolio et al, 2016; Rhee et al, 2015a). Although transmitted INSTI-associated resistance has been practically absent in ongoing surveillance efforts (Casadella et al, 2015; Doyle et al, 2015; Stekler et al, 2015), there have been at least four case reports of INSTI-associated TDR (Boyd et al, 2011; Varghese et al, 2016; Volpe et al, 2015; Young et al, 2011). …”

Section: Transmitted Drug Resistancementioning

confidence: 99%

HIV-1 drug resistance and resistance testing

Clutter

Jordan

Bertagnolio

et al. 2016

Infection, Genetics and Evolution

257

204

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The global scale-up of antiretroviral (ARV) therapy (ART) has led to dramatic reductions in HIV-1 mortality and incidence. However, HIV drug resistance (HIVDR) poses a potential threat to the long-term success of ART and is emerging as a threat to the elimination of AIDS as a public health problem by 2030. In this review we describe the genetic mechanisms, epidemiology, and management of HIVDR at both individual and population levels across diverse economic and geographic settings. To describe the genetic mechanisms of HIVDR, we review the genetic barriers to resistance for the most commonly used ARVs and describe the extent of cross-resistance between them. To describe the epidemiology of HIVDR, we summarize the prevalence and patterns of transmitted drug resistance (TDR) and acquired drug resistance (ADR) in both high-income and low- and middle-income countries (LMICs). We also review to two categories of HIVDR with important public health relevance: (i) pre-treatment drug resistance (PDR), a World Health Organization-recommended HIVDR surveillance metric and (ii) and pre-exposure prophylaxis (PrEP)-related drug resistance, a type of ADR that can impact clinical outcomes if present at the time of treatment initiation. To summarize the implications of HIVDR for patient management, we review the role of genotypic resistance testing and treatment practices in both high-income and LMIC settings. In high-income countries where drug resistance testing is part of routine care, such an understanding can help clinicians prevent virological failure and accumulation of further HIVDR on an individual level by selecting the most efficacious regimens for their patients. Although there is reduced access to diagnostic testing and to many ARVs in LMIC, understanding the scientific basis and clinical implications of HIVDR is useful in all regions in order to shape appropriate surveillance, inform treatment algorithms, and manage difficult cases.

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“…Currently, transmitted INSTI resistance is infrequent with a few cases documented. [8][9][10] Furthermore, INSTIs overall have fewer central nervous system and metabolic side effects than NNRTIs and PIs, respectively. [11][12][13][14][15][16][17] The single tablet regimen containing the INSTI EVG, boosted by cobicistat (COBI) plus the NRTIs emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF) (EVG/COBI/FTC/TDF; STRIBILD) is currently approved in the United States for ARV-naive patients.…”

Section: Introductionmentioning

confidence: 99%

Baseline Antiretroviral Resistance Mutations and Treatment-Emergent Resistance in HIV-1 RNA-Suppressed Patients Switching to EVG/COBI/FTC/TDF or Continuing on Their PI-, NNRTI-, or RAL-Based Regimen

Andreatta

Kulkarni

Abram

et al. 2015

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Switching antiretroviral regimens to EVG/COBI/FTC/TDF in HIV-1 RNA-suppressed FTC/TDF-sensitive patients resulted in maintained virologic suppression through 48 weeks. Similar virologic success rates were achieved irrespective of the presence of preexisting resistance mutations or subtype. The lack of emergent resistance through 48 weeks supports utility of EVG/COBI/FTC/TDF for treatment-experienced patients seeking regimen modification or simplification.

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Transmission of Integrase Strand-Transfer Inhibitor Multidrug-Resistant HIV-1: Case Report and Response to Raltegravir-Containing Antiretroviral Therapy

Cited by 66 publications

References 14 publications

Efficacy and Tolerability of 3 Nonnucleoside Reverse Transcriptase Inhibitor–Sparing Antiretroviral Regimens for Treatment-Naive Volunteers Infected With HIV-1

Efficacy and Tolerability of 3 Nonnucleoside Reverse Transcriptase Inhibitor–Sparing Antiretroviral Regimens for Treatment-Naive Volunteers Infected With HIV-1

HIV-1 drug resistance and resistance testing

Baseline Antiretroviral Resistance Mutations and Treatment-Emergent Resistance in HIV-1 RNA-Suppressed Patients Switching to EVG/COBI/FTC/TDF or Continuing on Their PI-, NNRTI-, or RAL-Based Regimen

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