BACKGROUND: Heavily treatment-experienced adults with multidrug-resistant (MDR) HIV-1 infection have limited remaining antiretroviral treatment options and are typically treated with optimized background therapy (OBT) based on individual resistance profiles. Composition and cost of OBT are not well described in the literature. This study assesses the characteristics and cost of OBT for participants in a phase 3 clinical trial for adults with MDR HIV-1 treated with ibalizumab plus OBT (TMB-301; 2015-2016).
METHODS: Patient-level antiretroviral therapy regimens were analyzed at baseline using descriptive statistics. Costs of individual antiretroviral drugs were applied using wholesale acquisition costs (2017) to calculate annual OBT costs. Outcomes included composition of OBT; number of antiretroviral drugs; use of fixed-dose combination and investigational drugs; and annual cost, with and without generic drug use.
RESULTS: Among trial participants (n=40), the most frequent antiretroviral drugs used as part of OBT were tenofovir disoproxil fumarate (DF) (72.5% total, 62.5% as emtricitabine/tenofovir DF, 10% as tenofovir DF alone), dolutegravir (60%), ritonavir (57.5%), darunavir (65% total, 50% boosted with ritonavir, 15% as darunavir/cobicistat), investigational agent (42.5%), and etravirine (12.5%). Other antiretroviral drugs were used by ≤ 10% of participants. All protease inhibitors were boosted. On average, OBT consisted of 4.7 antiretroviral drugs (range: 1-7), with more drugs used by those treated with an investigational agent (mean: 5.5; range: 3-7) than by those not treated with an investigational agent (mean: 4.0; range: 1-6). As part of OBT, 85% of participants used ≥ 1 (range: 0-2) fixed-dose combination drug.
Assuming brand prices and standard dosing for all antiretroviral drugs, the mean annual cost of OBT was $51,551 (range: $18,697-$105,533). Annual OBT costs were higher among those treated with an investigational agent (mean: $56,797; range: $19,086-$105,533) than among those not treated with an investigational agent (mean: $47,673; range: $18,697-$78,920). Few participants’ OBT regimens included drugs with generic options available (7.5%); costs for these participants were 6%-41% lower if generic options were used.
CONCLUSIONS: For heavily treatment-experienced patients with MDR HIV-1 infection, the composition of OBT is heterogenous with high associated costs. New, potent therapies with a new mechanism of action are needed for this patient population.
