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Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (EVG/COBI/FTC/TAF) (Genvoya) Fixed-Dose Combination, Oral Tablet) [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2016 Nov.
Human immunodeficiency virus (HIV) attacks cluster of differentiation 4 (CD4)+ T-cells, components of the immune system necessary for defending the body against infection.1 HIV progressively impairs immune response and, if left untreated, may lead to acquired immunodeficiency syndrome (AIDS), the final stage of HIV where a patient can no longer fight off infections and certain malignancies. HIV is transmitted through bodily fluids, and can be passed from an infected individual to a healthy individual through unprotected sex and sharing of drug needles.2 An infected mother can also pass the virus to her baby during pregnancy or birth (vertical transmission), or breastfeeding. HIV can be divided into two major types: HIV type 1 (HIV-1) and HIV type 2 (HIV-2), between which HIV-1 is the predominant virus worldwide.3
At the end of 2011, Health Canada estimated that 71,300 people (range 58,600 to 84,000) were living with HIV infection in Canada,4 an increase of 11.4% from the 2008 estimate of 64,000. Men who have sex with men (MSM) accounted for 46.7% of the total, injection drugs users 16.9%, heterosexuals 32.5%, and MSM who also inject drugs 3.0%.
In 2011, approximately 95% of reported HIV/AIDS cases were from Ontario (42.6%), Quebec (21.5%), British Columbia (13.4%), Alberta (9.7%), and Saskatchewan (7.7%).5 The incidence in Canada of HIV infection was estimated at 3,175 (range 2,250 to 4,100) cases in 2011, which was comparable to data from 2008.5
The current standard of care for HIV management is to treat with highly active antiretroviral therapy (HAART) with the primary goal of achieving and maintaining maximal suppression of viral load (VL), which leads to restoration and preservation of immunologic function, improvement of quality of life, and reduction of HIV-related morbidity and mortality.6
The choice of the optimal antiretroviral treatment (ART) for an individual patient must take into account drug potency, tolerability, convenience, and known or potential drug interactions, as well as patient comorbidities, ART history, concomitant medication use, and cost.
As viral mutations conferring resistance to ART can occur only during viral replication, the goal of ART is the complete suppression of viral replication, as determined by repeated VL measurements below assay limit.7 Virologic failure occurs when viral suppression is not achieved or maintained. A number of published guidelines are available to assist clinicians in choosing an appropriate first-line therapy. According to the consulting clinical expert for this review, the guidelines published by the US Department of Health and Human Services (DHHS) are the ones most commonly used in Canada.6
The DHHS recommends five regimens for ART-naive patients — four integrase strand transfer inhibitor (INSTI)-based regimens and one ritonavir-boosted protease inhibitor (PI/r)-based regimen, as follows:
In Canada, two of these preferred regimens are available as single-tablet regimens (STRs): Stribild (EVG/COBI/TDF/FTC) and Triumeq (DTG/ABC/3TC). There are two additional STRs available, although they are listed as “alternative” by the DHHS, as follows: Atripla (efavirenz [EFV]/TDF/FTC) and Complera (rilpivirine [RPV]/TDF/FTC). Key characteristics of these regimens are presented in Table 3.
Key Characteristics of Department of Health and Human Services-recommended HIV Regimens for Antiretroviral Therapy-naive Patients Available in Canada.
Apart from virologic failure, changes to ART may be necessary due to adverse events (AEs). Because of the large number of drug options available, careful single or multiple substitutions of the components of an antiretroviral (ARV) regimen can continue to offer optimal virologic suppression with improved tolerability or adherence.
The DHHS does not make specific recommendations for the treatment of ART-experienced patients. Rather, it recommends that a new regimen should include at least two, and preferably three, fully active drugs, which it defines as those that are expected to have “uncompromised activity on the basis of the patient’s treatment history and drug-resistance testing results and/or the drug’s novel mechanism of action.”6
Before modifying a regimen, however, the DHHS notes it is critical to carefully evaluate the cause(s) of virologic failure, including incomplete adherence, poor tolerability, and drug and food interactions, as well as review HIV ribonucleic acid (RNA) and CD4 cell count changes over time, treatment history, and drug-resistance test results. If HIV RNA suppression is not possible with currently approved drugs, it suggests use of investigational drugs; failing that, the choice of regimens should focus on minimizing toxicity and preserving treatment options while maintaining CD4 cell counts to delay clinical progression.
The DHHS recommends that the dosage of medications for HIV infection should be prescribed according to the Tanner staging of puberty and not exclusively by age.8 In particular, it suggests that adolescents in early puberty, i.e., Tanner Stages I and II, should be administered doses on pediatric schedules, whereas those in late puberty, i.e., Tanner Stage V, should follow adult schedules. Nevertheless, the DHHS emphasizes that selection of an initial regimen should be based on the characteristics of the proposed regimen, patient characteristics, and viral resistance test results.
For treatment-naive children aged six years or older, the DHHS recommends treatment initiation with one of three preferred drugs — ritonavir-boosted atazanavir (ATV/r), EFV, or ritonavir-boosted lopinavir (LPV/r) — plus a dual nucleoside/nucleotide analogue reverse transcriptase inhibitor (N[t]RTI) backbone combination. Among children aged 12 years and older, it recommends ABC + 3TC or ABC + FTC as the N(t)RTI backbone. A list of DHHS-recommended alternative and acceptable regimens most relevant to the population under consideration for this review is presented in Table 4.
Department of Health and Human Services-recommended Regimens for Initial Therapy of Infection in Children and Adolescents.
Genvoya (EVG/COBI/FTC/tenofovir alafenamide fumarate [TAF]) has a Health Canada indication for the treatment of HIV-1 infection in adults and pediatric patients 12 years of age and older (weighing ≥ 35 kg) with no known mutations associated with resistance to the individual components of EVG/COBI/FTC/TAF. It is a single-tablet, fixed-dose co-formulation that consists of: EVG 150 mg, COBI 150 mg, FTC 200 mg, and TAF 10 mg. EVG/COBI/FTC/TAF includes the components of Stribild, except that TDF in Stribild has been replaced with TAF. Stribild was recommended for reimbursement by the CADTH Canadian Drug Expert Committee (CDEC) in May 2013 as a complete regimen for ARV treatment-naive HIV-1-infected patients, except those in whom EFV is indicated.9
TAF is a prodrug of tenofovir (TFV) that undergoes intracellular activation by cathepsin A. Due to its increased plasma stability, TAF is proposed to be more efficient than TDF in loading TFV into peripheral blood mononuclear cells. The lower plasma concentrations of TFV with TAF at therapeutic doses minimize the unwanted “off-target” effects typically associated with TDF administration.
At the time of this review, EVG/COBI/FTC/TAF was under review by Health Canada, although it has been approved by the FDA10 and the European Commission11 for similar indications.
Per the DHHS, EVG/COBI/FTC/TAF will also be added as one of the recommended initial regimens for ART-naive adults and adolescents with estimated CrCl ≥ 30 mL/min.12
| Indication under review |
|---|
| For the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults and pediatric patients 12 years of age and older (weighing ≥ 35 kg) with no known mutations associated with resistance to the individual components of EVG/COBI/FTC/TAF. |
| Listing criteria requested by sponsor |
| For treatment-naive and virologically suppressed HIV-1 infected adult and pediatric patients 12 years of age and older with no known mutations associated with resistance to the individual components of EVG/COBI/FTC/TAF. |
Except where otherwise noted, this work is distributed under the terms of a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International licence (CC BY-NC-ND), a copy of which is available at http://creativecommons.org/licenses/by-nc-nd/4.0/
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