Dual therapy with renally adjusted lamivudine and dolutegravir: a switch strategy to manage comorbidity and toxicity in older, suppressed patients?

Abstract

Objectives The aim of the study was to evaluate the efficacy of dual therapy with lamivudine (3TC), with dose adjustment for renal function, and dolutegravir (DTG) in a subgroup of patients fully suppressed on treatment who were switched because of concerns about comorbidity and toxicity on their current triple drug regimen. Methods A retrospective evaluation of clinical and pathological parameters from an electronic patient record from a single centre was carried out. Results There were no virological failures in 52 patients with a median age of 60.5 years. The median duration of follow‐on dual therapy was 2.29 years (28 months; range 1.10–3.34 years). In 25 of 52 (48%) cases, the dose of 3TC was adjusted taking into account reduced renal function, and none of these patients experienced virological failure. Four additional patients discontinued early, because of side effects of the switch, with no failure. Conclusions This retrospective review suggests that 3TC and DTG may be effective in controlling viral load in older patients with comorbidities. This regimen appears to be a useful option in the context of comorbidities (including renal impairment) and polypharmacy in older patients. However, this review has been conducted in one centre and in a small population of patients. Therefore, further multicentre trials involving larger populations of patients are needed.

HIV Treatment with the Two-Drug Regimen Dolutegravir Plus Lamivudine in Real-world Clinical Practice: A Systematic Literature Review

“…This analysis included 5017 PWH who were reported to be using dolutegravir plus lamivudine. In 20 studies that reported data for sex, the majority of PWH treated with dolutegravir plus lamivudine were male (range, 60-97%) [29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48]. In five of seven studies with reported racial demographics, C 90% of PWH were identified as White [30,32,33,42,43,46,47].…”

“…Among studies that reported information on prior regimens (n = 1958), many PWH switched to dolutegravir plus lamivudine from 3DRs (n = 1718; 88%) [29,35,42,43,48,49,54,57]. Primary reasons for switching to dolutegravir plus lamivudine included toxicity of the previous regimen [48,52], avoidance of drug interactions [36,48,52,53], treatment regimen simplification [34,48,52,58], and comorbidities (including cardiovascular, renal, and bone disease) [34,53,58]. Of the comorbidities reported at baseline, bone, hypertension, liver, and metabolic comorbidities were most prevalent (Table 1) [32].…”

“…Six studies (all in virologically suppressed PWH) switching to dolutegravir plus lamivudine assessed serum creatinine levels and estimated glomerular filtration rate (eGFR) measured by creatinine clearance (Table 3) [34,36,42,52,69,70]. Although increases in serum creatinine [52,69] and decreases in eGFR [36,70] were reported, changes were minimal and generally not considered to be clinically significant.…”

Dolutegravir Plus Lamivudine Two-Drug Regimen: Safety, Efficacy and Diagnostic Considerations for Its Use in Real-Life Clinical Practice—A Refined Approach in the COVID-19 Era

“…Real-life data consistently report an overall excellent tolerability of DTG/3TC, with an absence/low incidence of toxicity [ 15 , 62 , 73 , 76 , 78 , 81 , 106 , 107 ], and improvements in CD4 count [ 62 , 73 , 76 , 78 ], CD4:CD8 ratio [ 62 , 74 , 78 , 107 ], and lipid profile [ 62 , 73 , 74 , 76 , 77 , 78 ], when DTG/3TC is used as initial or switch strategy. Patients begin to report significant improvements in symptom distress and treatment satisfaction after the first few months of initial treatment [ 15 ].…”

“…Interestingly, a recent case review reported no virologic failure in 25 patients who switched to DTG/dose-adjusted 3TC once daily, over a median time of 2.5 years of observation [ 106 ]. This proof-of-concept contributes to the provision of further confidence that simplification to once-a-day therapy with DTG and dose-adjusted 3TC may, in fact, be a viable solution in those patients with compromised renal functionality.…”