The last decade has transformed the EU5’s HIV treatment landscape. The norm used to be a daily cocktail of antiretrovirals (ARVs) taken at intervals throughout the day and often accompanied by unpleasant side-effects. The advent of the Single Tablet Regimen (STR) offered a revolutionary alternative.
STRs consist of several different classes of ARV in one pill that can be taken once a day; more convenient for the patient, STRs result in improved adherence and better treatment outcomes. The EU5’s first STR – Atripla – was launched by a Gilead/BMS joint venture in 2008. Gilead followed up with Eviplera in 2011 and Stribild in 2013, largely dominating the ARV market.
With the recent launch of Triumeq from ViiV – whose owner, GSK, brought the first HIV treatment to market in the late 1980s – this looks set to change. Here we discuss how the HIV STR landscape has evolved, the importance of the patient/physician relationship, and what lies ahead for this dynamic disease area.
The advent of STRs
Several different classes of ARV exist to treat HIV. The NRTIs (nucleoside reverse transcriptase inhibitors) came first in the late 1980s, followed by NNRTIs (non-nucleoside reverse transcriptase inhibitors), PIs (protease inhibitors) and, more recently, EIs (entry inhibitors) and IIs (integrase inhibitors). It was found that combining two NRTIs with one NNRTI or PI or II created a far more effective treatment than any one ARV, and was also durable against viral resistance. This type of combination therapy is known as highly active antiretroviral therapy (HAART), and remains the recommended treatment for HIV today.
STRs retain the benefits of HAART but with the added advantages of reduced dosing frequency and pill burden. Ipsos’ HIV Therapy Monitor data shows that the top reason for prescribing an STR is convenience. Convenience is important to both patient and physician; if a patient can easily adhere to his or her regimen then the virus is kept at bay and drug resistance is less likely to develop. Conversely, missed doses undermine treatment success and may require the patient to be switched, further complicating the treatment paradigm.
Staggered launches
The STRs’ attractive features explain their rapid uptake across the EU5. However, no doubt driven by local market healthcare systems, both Eviplera and Stribild had staggered launches in the EU5; Eviplera first took off in France, Germany and the UK, Stribild in Germany and the UK. The uptake of STRs has been slower in Italy in particular. Viiv’s Triumeq is now following a similar pattern. Although it gained EU approval in September 2014, it has only launched in Germany and the UK so far. However, the II component of Triumeq (dolutegravir, brand name Tivicay) has experienced rapid uptake in Germany and is competing with established antiretrovirals. If this is any indication of physicians’ future prescribing of Triumeq, ViiV’s product will have a strong start in this market where over 50% of initiating and switching patients are now prescribed an STR.
As the first non-Gilead STR, it will be interesting to see how Triumeq affects the more established STRs. Although Atripla and Eviplera contain NNRTIs, both of the newer products – Stribild and Triumeq – contain IIs. IIs are more potent, with fewer side effects and drug interactions and the top reason for prescribing them is their good tolerability profile. The question is, which II-containing STR will physicians prescribe? The first generation II STR, Stribild – based on firsthand experience, clinical trial/safety data, and the drug company’s reputation – or the new II STR by ViiV?
The HIV patient population is unique and physicians’ choice of drugs must be prudently balanced
No two HIV patients are the same
HIV treatments have come a long way, but with greater choice comes harder treatment decisions – and key differentiators between drugs become critical. Decisions are further complicated by the HIV patient population being universally different and also including high-risk patients, ie intravenous drug users (12%), patients co-infected with other diseases (17%) and serodiscordant couples. As patients differ so do their barriers to adherence, whether this be complexity of the dosing regimen, side effects experienced, psychosocial issues or concomitant diseases where drug-to-drug interactions must be managed.
Treatment success: a physician/patient union
The onus of treatment success is no longer solely on the patient but on a patient/physician partnership. With a move towards the holistic healthcare of patients – which must be balanced against efficient use of limited healthcare budgets – a physician’s choice of the best possible treatment is imperative. This relationship must be fostered early, with the physician understanding the patients’ needs, views, preferences and ecosystem.
Options and improvements
Despite STRs’ rapid uptake, the flexibility offered by differing treatment classes remains essential – especially for difficult-to-treat patients where toxicity and side-effects must be managed. As our data shows, physicians’ primary reason for choosing a particular treatment class varies; IIs differentiate themselves from PIs and STRs based on few drug-to-drug interactions, while PIs’ main appeal is potency in reducing viral load and safety during pregnancy. Improvements to ingrained treatment options are also happening. Explorations of cheaper regimens which don’t contain an NRTI – termed ‘Nuc-sparing’ – are highest in Spain and Italy (both at 9% share ) with Prezista being the top choice. Since the advent of ARVs, the life expectancy of HIV patients has increased to be on par with those unaffected; however, long-term side-effects associated with NRTIs include lipodystrophy, kidney disease, and premature ageing. Nuc-sparing regimens have thus been suggested for treatment-experienced patients demonstrating toxicity or resistance to one or more NRTIs.
With Triumeq signalling the approval of the first STR without tenofovir disoproxil fumarate (TDF) it can, uniquely, be used in those patients with impaired kidney function. Gilead, in hot pursuit, is in phase III of development of a new regimen where TDF has been substituted with tenofovir alafenamide fumarate (TAF). TAF is more potent than TDF and can be administered at a much lower dose, dramatically reducing side effects.
What will the future bring?
The HIV patient population is unique and physicians’ choice of an increasing array of drugs must be balanced prudently against the needs and lifestyle of the patient, particularly when that patient is taking other drugs for a concomitant condition. With competition hotting up in the HIV arena, new treatment options and improvements to established drugs are welcomed by physicians and can only mean good news for patients. How the HIV landscape will continue to evolve is highly anticipated and expected to be firmly monitored. As the clash of the titans begins, will ViiV – whose owners, GSK, have the longest heritage in the field of HIV treatment – match or surpass the continued commitment and improvement of Gilead? Or will the longest-standing player in the HIV STR field retain its dominant position?