by Carolyn Chu, MD, MSc, AAHIVS, AAHIVM Chief Medical Officer
June 15, 2021
Mounzer K, Brunet L, Wyatt CM, et al. To dose-adjust or not to dose-adjust: lamivudine dose in kidney impairment. AIDS. 2021 Jul 1; 35(8): 1201-1208. doi: 10.1097/QAD.0000000000002871. PMID: 33710017.
This study aimed to estimate the association between lamivudine (3TC) dose and incidence of adverse diagnoses and laboratory abnormalities among people living with HIV with baseline CKD-EPI eGFR between 30-49 mL/min per 1.73m2 at 3TC initiation. Investigators reviewed routine clinical data from electronic health records of 539 eligible PWH; participants received care at 85 U.S. clinics in 19 states and 1 territory and were followed as part of the OPERA (Observational Pharmaco-Epidemiology Research and Analysis) cohort. No significant difference was observed in incidence of lactic acidosis, paresthesia, peripheral neuropathy, pancreatitis, rhabdomyolysis, anemia, neutropenia, thrombocytopenia, nausea or severe laboratory abnormalities by 3TC dose (full-dose 300mg vs. adjusted-dose 150mg daily, IRR: 1.51, 95% CI: 0.59-3.92). However, risk of [additional] gastrointestinal symptoms and moderate lab abnormalities differed: for people receiving full-dose 3TC, incidence rate was three times that for the adjusted-dose group (IRR: 3.07, 95% CI: 1.12-8.40). Dose-adjusted 3TC was prescribed more frequently for women and sicker PWH (as demonstrated by higher viral load, lower eGFR, higher Veterans Aging Cohort Study index, and/or higher likelihood of several comorbid conditions).
Current ARV guidelines and package inserts recommend dose adjustment of 3TC/FTC (XTC) for CrCl < 50 mL/min. Given the prevalence of renal impairment and chronic kidney disease among PWH, and presence of XTC in nearly all currently-available single-tablet, fixed-dose regimens, the decision of whether to dose adjust XTC (which would require ‘unbundling’ combination formulations at times) is commonly encountered. 3TC is generally a well-tolerated drug with a wide therapeutic index, and many experienced HIV providers defer dose adjustment for patients who appear to be doing well. This study suggests no difference in risk of severe events for full vs. adjusted-dose 3TC, however gastrointestinal symptoms and/or moderate lab abnormalities may be more likely with full-dose 3TC. Clinical judgment and careful assessment of potential adherence and medication access challenges versus possible toxicity are key to ensuring that patients remain virologically suppressed without experiencing bothersome symptoms and/or concerning laboratory abnormalities.
The author has no conflicts of interest to disclose.
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