Latest advances in the efficacy, tolerability, and monotherapy of integrase inhibitors

Tang, Qi; Lu, Hongzhou

doi:10.5582/bst.2017.01194

Cited by 6 publications

(6 citation statements)

References 15 publications

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“…INSTIs are the most recent class of antiretrovirals for treating HIV-1 infection [6] and include the first-generation agents raltegravir and elvitegravir and the second-generation agents dolutegravir and bictegravir. Like dolutegravir [31], the latest INSTI bictegravir has a high genetic barrier to the development of resistance (Sect.…”

Section: Place In the Management Of Hiv-1 Infectionmentioning

confidence: 99%

“…These INSTIs are available as single-agent formulations and/or single-tablet regimens (STRs) [6, 7], the latter of which are convenient, easy to take and have potential adherence advantages [1]. These STRs generally comprise an INSTI plus two NRTIs (e.g.…”

Section: Introductionmentioning

confidence: 99%

“…Until recently, the INSTI class included only raltegravir and elvitegravir (the limitations of which include a lower genetic barrier to resistance than some other agents and considerable cross resistance) and the second-generation INSTI dolutegravir (which has a more favourable resistance profile) [1, 5]. These INSTIs are available as single-agent formulations and/or single-tablet regimens (STRs) [6, 7], the latter of which are convenient, easy to take and have potential adherence advantages [1]. These STRs generally comprise an INSTI plus two NRTIs (e.g.…”

Section: Introductionmentioning

confidence: 99%

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Bictegravir/Emtricitabine/Tenofovir Alafenamide: A Review in HIV-1 Infection

Deeks

2018

Drugs

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Bictegravir is a new integrase strand transfer inhibitor (INSTI) with a high genetic barrier to the development of HIV-1 resistance. The drug is co-formulated with the nucleos(t)ide reverse transcriptase inhibitors emtricitabine and tenofovir alafenamide (AF) in a single-tablet regimen (STR) for the once-daily treatment of HIV-1 infection in adults (bictegravir/emtricitabine/tenofovir AF; Biktarvy®). In phase 3 trials, bictegravir/emtricitabine/tenofovir AF was noninferior to dolutegravir-based therapy (dolutegravir/abacavir/lamivudine or dolutegravir plus emtricitabine/tenofovir AF) in establishing virological suppression in treatment-naïve adults through 96 weeks’ treatment and, similarly, was noninferior to ongoing dolutegravir/abacavir/lamivudine or boosted elvitegravir- or protease inhibitor (PI)-based therapy in preventing virological rebound over 48 weeks in treatment-experienced patients. No resistance emerged to any of the antiretrovirals in the STR. Bictegravir/emtricitabine/tenofovir AF is generally well tolerated, requires no prior HLA-B*5701 testing (making it more suitable for ‘rapid start’ treatment), fulfils the antiretroviral regimen requirement for patients with hepatitis B virus (HBV) co-infection (i.e. contains tenofovir AF and emtricitabine, both of which are active against HBV) and can be used in renally impaired patients with creatinine clearance (CRCL) ≥ 30 mL/min. Thus, although cost-effectiveness analyses would be beneficial, current data indicate that bictegravir/emtricitabine/tenofovir AF is a convenient initial and subsequent treatment option for adults with HIV-1 infection, including those co-infected with HBV, and provides the first non-pharmacologically boosted, INSTI-based, triple-combination STR suitable for patients with CRCL 30–50 mL/min.

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Section: Place In the Management Of Hiv-1 Infectionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Bictegravir/Emtricitabine/Tenofovir Alafenamide: A Review in HIV-1 Infection

Deeks

2018

Drugs

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“…Our study recommends that physicians prescribe fixed-dose combination regimens, favoring once-daily integrase inhibitor–based regimens. Use of complex ART regimens with the inclusion of protease inhibitors may trigger gastrointestinal symptoms and potential loss of adherence by our adolescent or young adult study youth, whereas efficacy of integrase inhibitor (integrase strand transfer inhibitor; INSTI)–based ARTs is successful in suppressing virus more rapidly than non-INSTI- based therapy [37]. By recommending fixed-dose combination once-daily integrase inhibitor–based regimens, we can minimize pill burden and the possibility of ART side effects.…”

Section: Methodsmentioning

confidence: 99%

Acute HIV Infection in Youth: Protocol for the Adolescent Trials Network 147 (ATN147) Comprehensive Adolescent Research and Engagement Studies (CARES) Study

et al. 2019

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BackgroundEarly treatment studies have shown that prompt treatment of HIV with combination antiretroviral therapy (cART) can limit the size of latent viral reservoirs, thereby providing clinical and public health benefits. Studies have demonstrated that adolescents have a greater capacity for immune reconstitution than adults. Nevertheless, adolescents who acquired HIV through sexual transmission have not been included in early treatment studies because of challenges in identification and adherence to cART.ObjectiveThis study aimed to identify and promptly treat with cART youth aged 12 to 24 years in Los Angeles and New Orleans who have acute, recent, or established HIV infection, as determined by Fiebig stages 1 to 6 determined by viral RNA polymerase chain reaction, p24 antigen presence, and HIV-1 antigen Western blot. The protocol recommends treatment on the day of diagnosis when feasible. Surveillance and dedicated behavioral strategies are used to retain them in care and optimize adherence. Through serial follow-up, HIV biomarkers and response to antiretroviral therapy (ART) are assessed. The study aims to assess viral dynamics, decay and persistence of viral reservoirs over time, and correlate these data with the duration of viral suppression.MethodsA total of 72 youth (36 acutely infected and 36 treatment naïve controls) are enrolled across clinical sites using a current community-based strategy and direct referrals. Youth are prescribed ART according to the standard of care HIV-1 management guidelines and followed for a period of 2 years. Assessments are conducted at specific time points throughout these 2 years of follow-up for monitoring of adherence to ART, viral load, magnitude of HIV reservoirs, and presence of coinfections.ResultsThe study began enrolling youth in July 2017 across study sites in Los Angeles and New Orleans. As of September 30, 2018, a total of 37 youth were enrolled, 12 with recently acquired, 16 with established HIV infection as determined by Fiebig staging, and 9 pending determination of Fiebig status. Recruitment and enrollment are ongoing.ConclusionsWe hypothesize that the size of the HIV reservoir and immune activation markers will be different across groups treated with cART, that is, those with acute or recent HIV infection and those with established infection. Adolescents treated early who are virally suppressed will have diminished HIV reservoirs than those with established infection. These youth may be potential candidates for a possible HIV vaccine and additional HIV remission intervention trials. Our study will inform future studies of viral remission strategies.International Registered Report Identifier (IRRID)DERR1-10.2196/10807

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“…Use of complex ART regimens with the inclusion of protease inhibitors may trigger gastrointestinal symptoms and potential loss of adherence by our adolescent/young adult study youth while efficacy of integrase inhibitor (INSTI) based ARTs is successful in suppressing virus more rapidly than non-INSTI based therapy [36]. By recommending fixed dose combination once daily integrase-inhibitor based regimens, we can minimize pill burden and the possibility of ART side effects.…”

Section: Treatmentmentioning

confidence: 99%