To dose-adjust or not to dose-adjust: lamivudine dose in kidney impairment
Karam Mounzer1, Laurence Brunet2, Christina M Wyatt3
1Philadelphia FIGHT, Philadelphia, PA.
Objectives:
To assess the risk of adverse diagnoses and laboratory abnormalities associated with a 300 or 150 mg daily dose of lamivudine (3TC) initiated by people with HIV (PWH) with an estimated glomerular filtration rate (eGFR) between at least 30 and 49 ml/min per 1.73 m2 or less.
Design:
Longitudinal study based on electronic health records of 539 PWH with eGFR between at least 30 and 49 ml/min per 1.73 m2 or less from the Observational Pharmaco-Epidemiology Research and Analysis (OPERA) cohort.
Methods:
Common unintended effects of 3TC were evaluated as composite outcomes. We estimated the incidence (univariate Poisson regression) and association between dose and incident composite outcomes (multivariate Poisson regression) among PWH without the relevant diagnoses or laboratory abnormalities at 3TC initiation.
Results:
PWH initiating 150 mg 3TC had higher HIV RNA, lower eGFR, and more comorbidities than those initiating 300 mg 3TC. The prevalence of relevant diagnoses and laboratory abnormalities was similar in both groups. The most common lab abnormality was low hemoglobin. There was no statistically significant difference in incident adverse diagnoses/severe lab abnormalities with 300 mg versus 150 mg [incidence rate ratio (IRR): 1.51; 95% confidence interval (CI) 0.59--3.92). However, a statistically significant association was observed when gastrointestinal symptoms/moderate lab abnormalities were included in the outcome (IRR: 3.07, 95% CI 1.12--8.40).
Conclusion:
As 3TC is a well tolerated drug with a wide therapeutic window, dose adjustment may be unnecessary among PWH with eGFR between at least 30 and 49 ml/min per 1.73 m2 or less. Clinical judgement is key when weighing the risks and benefits of 3TC dose adjustment for PWH experiencing gastrointestinal symptoms or moderate lab abnormalities.
Insights
For people with HIV and reduced kidney function (eGFR 30-49 mL/min), lamivudine (3TC) 300mg daily showed similar safety to 150mg daily. Dose adjustment may not be needed, but monitor for GI symptoms.
Area of Science:
- Pharmacology
- Infectious Diseases
- Nephrology
Background:
- Lamivudine (3TC) is a key antiretroviral therapy component.
- Understanding optimal dosing in patients with reduced kidney function is crucial for safety and efficacy.
- Previous guidelines suggested dose reduction for 3TC in moderate renal impairment.
Purpose of the Study:
- To evaluate the safety of 300mg versus 150mg daily doses of lamivudine (3TC) in people with HIV (PWH) and an estimated glomerular filtration rate (eGFR) of 30-49 mL/min/1.73 m².
- To assess the risk of adverse diagnoses and laboratory abnormalities associated with different 3TC doses in this population.
Main Methods:
- A longitudinal study utilizing electronic health records from the Observational Pharmaco-Epidemiology Research and Analysis (OPERA) cohort.
- Included 539 PWH with eGFR 30-49 mL/min/1.73 m² initiating 3TC.
- Incidence and association of composite outcomes (adverse diagnoses/laboratory abnormalities) were analyzed using Poisson regression.
Main Results:
- PWH initiating 150mg 3TC had higher HIV RNA, lower eGFR, and more comorbidities than those initiating 300mg.
- The prevalence of adverse diagnoses and laboratory abnormalities was similar between the 300mg and 150mg groups.
- No significant difference in severe adverse events; however, a significant association was found with gastrointestinal symptoms/moderate lab abnormalities when included (IRR: 3.07).
Conclusions:
- Lamivudine (3TC) is generally well-tolerated in PWH with eGFR 30-49 mL/min/1.73 m², suggesting dose adjustment may not be routinely necessary.
- Clinical judgment is essential when considering 3TC dose adjustments, particularly for patients experiencing gastrointestinal symptoms or moderate laboratory abnormalities.
- The findings support the wide therapeutic window of 3TC in this specific patient group.
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