scholarly journals Cost-Efficacy of Antiretroviral Regimens Recommended in Treatment-Naive HIV-Infected Adults. A Single Center Experience

Processes ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 956
Author(s):  
Raluca Jipa ◽  
Iulia Nedelcu ◽  
Eliza Manea ◽  
Anca Damalan ◽  
Adriana Hristea
Keyword(s):  
Similar Efficacy ◽  
Strand Transfer ◽  
Software Application ◽  
Single Center Experience ◽  
Combined Antiretroviral Therapy ◽  
Treatment Naïve ◽  
Cost Efficacy ◽  
Transfer Inhibitor ◽  
The Cost ◽  
Integrase Strand Transfer Inhibitor

We aimed to assess the prescription trends of combined antiretroviral therapy (cART) in one infectious diseases department and the cost-efficacy (C/E) of different regimens used in treatment-naïve patients. The C/E was assessed with a software application developed by a group of researchers in Spain. The efficacy was already calculated in the application. The costs included the local cost of antiretrovirals and other direct costs specific to our institution. In the software application, the C/E reference regimen was ABC/3TC/DTG. In total, 181 HIV-infected patients were diagnosed and initiated cART during 2015–2019. The proportion of patients treated with integrase-strand transfer inhibitor (INSTI)-based regimens increased from 2015–2018 (54%) to the end of 2019 (81%). The relative C/E ranged from 0.90 to 1.28 for the evaluated INSTI-based regimens. Among INSTI-based regimens, ABC/3TC/DTG and TAF/FTC/EVG/c are the regimens with similar efficacy and relative C/E.

scholarly journals Might dolutegravir be part of a functional cure for HIV?

2016 ◽  
Vol 62 (5) ◽  
pp. 375-382 ◽  
Author(s):  
Mark A. Wainberg ◽  
Ying-Shan Han ◽  
Thibault Mesplède
Keyword(s):  
First Generation ◽  
Strand Transfer ◽  
Resistance Mutations ◽  
Functional Cure ◽  
Viral Reservoirs ◽  
Genetic Barrier ◽  
Clinical Resistance ◽  
Treatment Naïve ◽  
Transfer Inhibitor ◽  
Integrase Strand Transfer Inhibitor

Antiretroviral therapy (ART) has greatly decreased HIV-related morbidity and mortality. However, HIV can establish viral reservoirs that evade both the immune system and ART. Dolutegravir (DTG) is a second-generation integrase strand transfer inhibitor (INSTI) related to the first-generation INSTIs raltegravir (RAL) and elvitegravir (EVG). DTG shows a higher genetic barrier to the development of HIV-1 resistance than RAL and EVG. More interestingly, clinical resistance mutations to DTG in treatment-naïve patients have not been observed to date. This review summarizes recent studies on strategies toward a cure for HIV, explores resistance profiles of DTG, and discusses how DTG might help in finding a functional cure for HIV.

scholarly journals Canary in the Coal Mine? Transmitted Mutations Conferring Resistance to All Integrase Strand Transfer Inhibitors in a Treatment-Naive Patient

2018 ◽  
Vol 5 (11) ◽  
Author(s):  
Kara S McGee ◽  
Nwora Lance Okeke ◽  
Christopher B Hurt ◽  
Mehri S McKellar
Keyword(s):  
Human Immunodeficiency Virus ◽  
Drug Resistance ◽  
Transmitted Drug Resistance ◽  
Strand Transfer ◽  
Naive Patient ◽  
Immunodeficiency Virus ◽  
Integrase Strand Transfer Inhibitors ◽  
Treatment Naïve ◽  
Transfer Inhibitor ◽  
Integrase Strand Transfer Inhibitor

Abstract Transmitted drug resistance to the integrase strand transfer inhibitor (INSTI) class of antiretrovirals is very rare. We present a case of a treatment-naive female patient with human immunodeficiency virus harboring resistance to all INSTIs, including bictegravir and dolutegravir.

scholarly journals Emergent Resistance to Dolutegravir Among INSTI-Naïve Patients on First-line or Second-line Antiretroviral Therapy: A Review of Published Cases

2020 ◽  
Vol 7 (6) ◽  
Author(s):  
Muge Cevik ◽  
Chloe Orkin ◽  
Paul E Sax
Keyword(s):  
Virological Failure ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Poor Adherence ◽  
Clinical Aspects ◽  
Strand Transfer ◽  
Treatment Naïve ◽  
Transfer Inhibitor ◽  
Integrase Strand Transfer Inhibitor

Abstract None of the licensing studies of dolutegravir (DTG) reported any treatment-emergent resistance among DTG-treated individuals, though virological failure in treatment-naïve and treatment-experienced, integrase strand transfer inhibitor (INSTI)–naïve individuals has been reported in clinical practice. While the spectrum of dolutegravir-selected mutations and their effects on clinical outcome have been described, the clinical characteristics of these rare but important virological failure cases are often overlooked. In this perspective piece, we focus on key clinical aspects of emergent resistance to DTG among treatment-naïve and treatment-experienced INSTI-naïve patients, with an aim to inform clinical decision-making. Poor adherence and HIV disease factors contribute to emergent drug resistance, even in regimens with high resistance barriers. Patients with severe immunosuppression or poor adherence are under-represented in licensing studies, and these patients may be at higher risk of treatment failure with DTG resistance, which requires close clinical and laboratory follow-up.

Raltegravir: Its use in the Treatment of HIV Infection

2009 ◽  
Vol 1 ◽  
pp. CMT.S32
Author(s):  
Marianne Harris
Keyword(s):  
Hiv Infection ◽  
Safety Data ◽  
Resistance Testing ◽  
Strand Transfer ◽  
Antiretroviral Agents ◽  
First Line Therapy ◽  
Effective Option ◽  
Treatment Naïve ◽  
Transfer Inhibitor ◽  
Integrase Strand Transfer Inhibitor

Raltegravir is the first integrase strand transfer inhibitor to be approved for the treatment of HIV infection. Administered orally in doses of 400 mg twice daily, it is well-tolerated and has minimal drug-drug interactions with coadministered antiretrovirals and other agents. In clinical trials including treatment-experienced and treatment-naïve HIV-infected adults, raltegravir in combination with other antiretroviral agents has demonstrated a rapid and potent virologic effect and a generally benign safety profile. Like other antiretrovirals, raltegravir should ideally be given with two additional agents to which the patient's virus is susceptible based on results of resistance testing. In this context, raltegravir offers a safe and effective option as a component of combination therapy in treatment-experienced patients who are infected with HIV-1 strains showing evidence of resistance to other antiretroviral agents. Pending the availability of longer-term efficacy and safety data, raltegravir cannot currently be recommended as part of first-line therapy for treatment-naïve patients.

Inflammatory Myositis Secondary to Anti-Retroviral Therapy in a Child; Case Report and Review of the Literature

2021 ◽  
pp. 1-7
Author(s):  
Marie Monaghan ◽  
Charlotte Loh ◽  
Stephen Jones ◽  
Agyepong Oware ◽  
Kathryn Urankar ◽  
...  
Keyword(s):  
Drug Regimen ◽  
Dramatic Improvement ◽  
Strand Transfer ◽  
Inflammatory Myositis ◽  
Once Daily ◽  
Immune Mediated ◽  
Show Evidence ◽  
Transfer Inhibitor ◽  
Integrase Strand Transfer Inhibitor

Here, we describe a five year old girl with congenital HIV who had a six-week onset of rapidly deteriorating mobility and progressive proximal muscle weakness, associated with a raised Creatine Kinase (CK) level of 4330 U/L [25–200 U/L], subsequently diagnosed with an inflammatory myositis. Potential causes were investigated by paediatric neurology and immunology teams. Her viral load had been undetectable over the preceding two years, excluding a primary HIV myositis. While MRI scanning did not show evidence of definite myositis, a muscle biopsy showed evidence of an inflammatory process, comprising a moderate endomysial, perimysial and perivascular mononuclear (CD8 + T cell) infiltrate with increased MHC expression. No particular features of dermatomyositis or immune-mediated necrotising myopathy were identified and there were no features of an inclusion body myositis. Given the absence of active HIV infection, the role of anti-retroviral medications was considered. She had had a recent switch in medication, from twice daily Raltegravir (an Integrase Strand Transfer Inhibitor, INSTI) to once daily Dolutegravir (an INSTI) while continuing on an established daily protocol of Abacavir and Lamivudine (Nucleoside Reverse Transcriptase Inhibitors). Changing the Dolutegravir back to Raltegravir, in combination with continuing Lamivudine and Abacavir for two months made no difference to her weakness or CK levels. Moreover, this drug regimen had been well-tolerated over the preceding 19 month period. Changing the anti-retroviral regime completely to a single drug class (Protease Inhibitors) of Ritonavir and Darunavir, resulted in a dramatic improvement in her symptomatology. Within ten days she regained the ability to stand and walk, with a reduction in her CK from 1700 U/L at time of switch to 403 U/L [25–200]. This case highlights the potential risk of developing inflammatory myositis from anti-retrovirals even 19 months into treatment.

Progressive emergence of an S153F plus R263K combination of integrase mutations in the proviral DNA of one individual successfully treated with dolutegravir

2020 ◽  
Author(s):  
Hanh T Pham ◽  
Brunna M Alves ◽  
Sunbin Yoo ◽  
Meng A Xiao ◽  
Jing Leng ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Dna Binding ◽  
Drug Resistant ◽  
Strand Transfer ◽  
Viral Genomes ◽  
Proviral Dna ◽  
Viral Loads ◽  
Subtype B ◽  
Transfer Inhibitor ◽  
Integrase Strand Transfer Inhibitor

Abstract Objectives The development of HIV drug resistance against the integrase strand transfer inhibitor dolutegravir is rare. We report here the transient detection, by near full-genome ultradeep sequencing, of minority HIV-1 subtype B variants bearing the S153F and R263K integrase substitutions in the proviral DNA from blood cells of one patient who successfully initiated dolutegravir-based ART, over 24 weeks. Our objective was to study the effects of these substitutions. Methods Strand transfer and DNA-binding activities of recombinant integrase proteins were measured in cell-free assays. Cell-based resistance, infectivity and replicative capacities were measured using molecular clones. Structural modelling was performed to understand experimental results. Results R263K emerged first, followed by the addition of S153F at Week 12. By Week 24, both mutations remained present, but at lower prevalence. We confirmed the coexistence of S153F and R263K on single viral genomes. Combining S153F or S153Y with R263K decreased integration and viral replicative capacity and conferred high levels of drug resistance against all integrase inhibitors. Alone, S153Y and S153F did little to infectivity or dolutegravir resistance. We identified altered DNA binding as a mechanism of resistance. The patient remained with undetectable viral loads at all timepoints. Conclusions Drug-resistant minority variants have often been reported under suppressive ART. Our study adds to these observations by unravelling a progression towards higher levels of resistance through a novel pathway despite continuous undetectable viral loads. Poorly replicative HIV drug-resistant minority proviral variants did not compromise viral suppression in one individual treated with dolutegravir.

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