Disease Prevalence and Incidence
HIV is responsible for causing a condition that gradually weakens the immune system.1 HIV is transmitted via body fluids such as blood, semen, genital secretions, and breast milk; most commonly from unprotected sexual intercourse or through sharing contaminated needles and syringes with an infected person.2 HIV gradually destroys the immune system by selectively destroying CD4 immune cells, which are critical for fighting infections. This compromises the immune system’s ability to mount an effective immunological response to opportunistic pathogens over time. HIV infection can progress to AIDS and ultimately death if left untreated. The fatality of HIV has been significantly reduced since the mid-1990s after the invention of highly active forms of antiretroviral (ARV) therapy (ART).4 Since then, ART has improved steadily with the availability of newer and potent combination therapies. Treatments are aimed at lowering the level of HIV in the body, thereby slowing the spread of the virus and helping the immune system respond to other infections. Patients now have a better opportunity to live a longer, healthier life and decrease their risk of transmitting the virus to others. Newer ARTs have significantly reduced HIV-associated morbidity and mortality and HIV is largely considered a manageable chronic condition.4 Starting treatment early can increase the probability of living a near-normal lifespan. Patient group input provided to CADTH Common Drug Review (CDR) in relation to this review indicates that stigma is a major concern.
Surveillance data from the Public Health Agency of Canada estimate that, in Canada, a cumulative total of 84,409 cases of HIV had been reported by the end of 2016.3 The incidence rate in 2016 was 6.4 per 100,000 population, or 2,344 newly reported cases. The number of reported HIV cases is in decline, although there have been periods of fluctuations.3 The incidence of reported HIV cases declined from 2008 to 2014, but the national diagnosis rate increased by 11.6% in 2016 from the numbers in 2015. Ontario accounted for the highest number and proportion of reported HIV cases in 2016 (37.6%), followed by Quebec (25.3%) and Alberta (12.0%).3 The provincial and territorial HIV diagnosis rates varied notably across the country, with the highest diagnosis rates found in Saskatchewan (7.4%, 15.1 per 100,000), Manitoba (5.4%, 9.5 per 100,000), Quebec (7.1 per 100,000) and Alberta (6.6 per 100,000).3 Age distribution showed that the highest incidence of HIV cases was in people 30 to 39 years old (28.7%) and among males (76.7%). Among adults with known exposure (61.6% of all cases), the most common exposure categories were “men who have sex with men” (44.1%), followed by heterosexual contact (32.3%), and injection drug use (15.1%). Race/ethnicity distribution showed that the following races accounted for the most commonly reported HIV cases: white (40.4%), black (21.9%), and Indigenous (21.2%).3
Standards of Therapy
The clinical expert consulted for this review indicated that the US Department of Health and Human Services (DHHS) Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV4 inform clinical practice in Canada. According to the recommendations, ARV regimens for treatment-naive patients generally consists of two nucleoside reverse transcriptase inhibitors (NRTIs) in combination with a third active ARV drug from one of three classes: an integrase strand transfer inhibitor (InSTI), a non-nucleoside reverse transcriptase inhibitor (NNRTI), or a protease inhibitor (PI) with a pharmacokinetic enhancer (booster) (cobicistat or ritonavir).4 The following regimens are recommended by the DHHS panel for initial treatment among newly diagnosed patients: bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC), dolutegravir/abacavir/lamivudine (DTG/ABC/3TC — only for patients who are HLA-B*5701 negative), dolutegravir/tenofovir disoproxil fumarate/emtricitabine (DTG/TDF)/FTC), and raltegravir/TDF/FTC; with 3TC as an alternative to FTC and TDF used in consideration of bone and renal toxicities and lipid levels.4 Notably, doravirine/TDF/3TC (DOR/TDF/3TC) and DOR plus TAF/FTC are recommended as initial regimens in certain clinical situations, including patients at high cardiac risk and hyperlipidemia.4
Once initiated, ARTs should be continued with the following key treatment goals: maximally and durably suppress plasma HIV ribonucleic acid (RNA) below detectable limits (< 50 copies/mL); restore and preserve immunologic function (increase CD4 cell count); reduce HIV-associated morbidity; prolong the duration and quality of survival; and prevent HIV transmission. Current ARTs are not curative; they require lifelong administration and therefore high levels of adherence to achieve treatment goals.4 To simplify ARV regimens and support long-term adherence, several single-table regimens (STRs) are available, alongside non-STRs, providing clinicians and patients with an array of therapeutic options.
For treatment-experienced patients with viral suppression, the DHHS guidelines do not provide a list of recommended therapies; the selection of a new ARV regimen should be based instead on patients’ previous ART histories, including virologic responses, past ART-associated toxicities and intolerances, resistance-test results, drug-drug interactions, and pill burden, in addition to other non-clinical considerations. For switching to a two-drug regimen, the DHHS guidelines include two regimen options with strong supporting evidence: a boosted PI plus FTC or 3TC, or DTG plus rilpivirine. Switching to a monotherapy regimen is not recommended due to a lack of efficacy and development of treatment resistance.4
According to the clinical expert, there is no pressing therapeutic need that is unmet by current ARV therapies. However, new regimens (preferably STRs) that are effective, safe, and tolerable would be welcome.
Drug
DOR (Pifeltro, 100 mg) is an oral tablet indicated, in combination with other antiretroviral medicinal products, for the treatment of HIV-1 infection in adults without past or present evidence of viral resistance to doravirine. The Health Canada recommended dose is one 100 mg tablet taken orally once daily with or without food. Reimbursement is being sought by the manufacturer in accordance with the indication.
DOR is an NNRTI of HIV-1. NNRTIs act by binding to and blocking HIV reverse transcriptase (an enzyme essential to the HIV replication cycle), thereby preventing HIV from replicating.10
The objective of this systematic review was to evaluate the beneficial and harmful effects of DOR, in combination with other ARV medicinal products, for the treatment of HIV-1 infection in adults without past or present evidence of viral resistance to DOR.
A table describing key characteristics of STRs and other commonly recommended ARV regimens is presented in .
Key Characteristics of Commonly Recommended Antiretroviral Therapy Regimens.
