Real life use of dolutegravir doravirine dual regimen in experienced elderly PLWH with multiple comorbidities and on polypharmacy

Abstract

By increasing life expectancy of people living with HIV, the most clinical challenge is managing both drug-to-drug interactions and comorbidities (especially metabolic). Doravirine (DOR), a new non-nucleoside reverse transcriptase inhibitor, recently approved for the treatment of HIV, could be a good companion of dolutegravir (DTG) in a dual regimen for experienced elderly patients with multimorbidity and polypharmacy. We herein report our preliminary experience in a small cohort of elderly patients (>50 years of age) with multimorbidity and on polypharmacy who were switched to DOR/DTG dual regimen and followed-up for 3 months. The study was conducted at the Infectious and Tropical Diseases Unit of Padua University Hospital, Italy. Eighteen patients were included, 72.2% males and 27.8% postmenopausal women, mean age was of 61.3 years (7.6), 50% experienced AIDS events. Switches to DOR and DTG were mainly due to high cardiovascular and metabolic risk (72.2%), and interactions among comedications (50%). Antiretrovirals that subjects were switched off were mostly boosted protease inhibitors 66.7%. We observed a viral suppression among all subjects. Interestingly, we observed a statistically significant reduction in body mass index, body weight and waist circumference, eGFR, and a significant increase in serum creatinine levels. No significant changes in CD4+ T cell count was observed from the baseline. Lipid and fasting glucose values did not change significantly. To the best of our knowledge this is the first experience reporting real-life outcome of switch to DTG + DOR in elderly with multimorbidity and on polypharmacy. From our very preliminary data the dual combination of DTG and DOR could be a good treatment strategy for these subjects. However, our findings need to be validated on a greater number of patients.

HIV treatment with dolutegravir and doravirine: rationale for selection and clinical outcomes in a highly treatment experienced population

“…Our single-center service evaluation of small numbers of PWH found that dolutegravir and doravirine alone or in combination with other antiretrovirals appeared safe and achieved virologic suppression in most recipients, consistent with the prior case series of PWH receiving dolutegravir plus doravirine. 7 Our experience underscores the importance of close longitudinal follow-up in PWH receiving less studied ART combinations to detect potential adverse effects, especially in older populations with multiple comorbidities. Larger randomized longitudinal research studies such as the planned Efficacy of Doravirine + Dolutegravir Dual Therapy in the Context of Antiretroviral Therapy Switch (DORDOL) study will assess durability of virologic suppression and inform future clinical guidance regarding this ART combination.…”

“…10 The prior case series of dolutegravir with doravirine in older PWH noted ART simplification as a factor in 69% and polypharmacy in all participants. 7 Dolutegravir and doravirine combinations avoid the drug interaction challenges of cobicistat- or ritonavir-boosted protease inhibitor containing regimens and may mitigate risks from polypharmacy.…”

“…6 Whilst we hypothesize based on the pharmacologic mechanisms of action that dolutegravir taken with doravirine would be safe and effective as HIV treatment, and both agents are FDA-approved individually, no prospective clinical trial data supports use of this combination, with clinical data limited to a single small case series of 18 elderly PWH in Italy who all achieved virologic suppression on dolutegravir with doravirine as a two-drug ART regimen, with one discontinuation for psychiatric side effects. 7 We conducted a service evaluation of dolutegravir with doravirine use in our clinic in order to establish why PWH were switched to this unusual regimen and to verify that this combination was able to safely achieve adequate virologic suppression.…”

Real-life use of Doravirine in treatment-experienced people living with HIV: A multicenter Italian study

“…This approach is consistent with other studies, in whom the main reasons for the switch were high cardiovascular/metabolic risk, treatment simplification, drug-to-drug interaction and toxicity. [14][15][16] This suggests that clinicians look at DOR as a drug useful to improve the management of metabolic issues in clinical practice.…”

“…Data regarding the use of this new NNRTI in a real-life setting are still scarce, [14][15][16] and it is important to define how clinicians have interpreted the role of DOR in the current HIV armamentarium. Therefore, this study aimed to describe the reasons leading clinicians to switch patients to a DOR-containing regimen and its role in clinical practice.…”