The Case for Greater Access for Once-Daily Single Tablet Regimens to Treat HIV Infection in Europe

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In recent decades, the prognosis for those diagnosed with Human Immunodeficiency Virus (HIV) has dramatically improved. Advancements in pharmacotherapies and antiretroviral medications have been paramount in this change. One of the defining innovations was the combination antiretroviral therapies (cART) involving different classes of medications to combat HIV infection. To address the need for patients to ingest multiple pills per day, co-formulated, once-daily fixeddose combination (FDC) single tablet regimens (STR) soon evolved, significantly mitigating the pill burden associated with a multi-tablet regimen (MTR). Some of the more popular once-daily FDC STRs today are combinations of two nucleoside reverse transcriptase inhibitors (NRTIs) and one non-nucleotide reverse transcriptase inhibitor (NNRTI) such as Atripla® (combining efavirnez, emtricitabine, and tenofovir disoproxil) and Eviplera®/Complera® (combining emtricitabine, tenofovir disoproxil, and rilpivirine), while use of integrase inhibitor-containing STRs such as Stribild® (combining elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil) and Triumeq® (combining dolutegravir, abacavir and lamuivudine) and STRs replacing tenofovir disoproxil (TDF) with tenofovir alafenamide (TAF) are increasingly being used. Although the acquisition costs for STRs are typically higher than the total cost for the separate equivalent components, STRs have been shown to positively impact patient outcomes through improving medication adherence and effectiveness, while being judged as a cost-effective therapeutic option. Despite these findings, the stringent market access for STRs seen across Europe does not reflect their demonstrated clinical and economic benefits. Indeed, Payers and Health Technology Assessment (HTA) decision-makers in the big EU-5 markets have instead enacted policies and issued recommendations making access to these therapies more difficult.

The convenience benefits associated with STRs have enhanced therapeutic effectiveness and adherence. A recently published meta-analysis by Clay et al (2015) found that after 48 weeks of treatment, significantly better viral load suppression was found in the STR groups in comparison to the MTR group (P=0.0003); in addition, the odds of adherence associated with an STR regimen was found to be 2.37 times higher than with an MTR (P<0.0001). As higher treatment adherence in HIV has been shown to improve viral load suppression, drug resistance, and survival while increasing patient quality-of-life (QoL), this finding is of considerable importance. Finally, among key efficacy and safety domains (including change in CD4 cell count at 48 weeks, tolerability/ discontinuation, mortality, and Grade 3 or 4 adverse events), outcomes associated with STR were found to be comparable to MTR. More recently, a prospective multicenter study in Spain and France found that Atripla® was associated with a significantly lower virological failure rate than both an MTR containing the same compounds as Atripla® and other MTRs containing different compounds.

STRs are not only associated with benefits in efficacy, adherence, and QoL, but have been demonstrated to be economically attractive as well in comparison to MTRs. Several European studies have looked into the cost-effectiveness and overall annual costs of an STR versus an MTR. Newly diagnosed HIV patients in a Milan hospital, for instance, incurred considerably lower mean annual costs starting on an STR rather than an MTR (€9,213 vs. €14,277). Another Italian study found that STRs were more cost-effective (more Quality-adjusted Life Years (QALYs)) than a number of MTRs, including tenofovir/emtricitabine plus raltegravir and abacavir/lamivudine plus atazanavir/ritonavir. With some individual HIV drugs increasingly available as generic medications, a debate has en-sued concerning the possibility of incorporating generics into cART and breaking apart once-daily STRs to realize potential cost savings on the long-term. Sweet et al (2016) developed a simulation model of lifetime health and economic outcomes; STRs had an incremental costeffectiveness ratio of $26,384 per QALY gained, indicating a good value for money under the normal cost-effectiveness thresholds (adopted by various HTA entities) despite substantial price reductions of generic medications.