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Lamivudine is a nucleoside reverse transcriptase inhibitor (NRTI) widely used for the treatment of HIV (Human Immunodeficiency Virus) infection in combination with other antiretrovirals. It is an effective agent with a long intracellular half-life, allowing for once or twice daily dosing. It also has one of the best tolerability and long-term safety profiles among all antiretroviral agents. However, lamivudine is only available in combinational fixed doses, which can pose a challenge for patients with chronic kidney disease (CKD). CKD is a common comorbidity in HIV-infected patients, with a prevalence of 6.4% in a global study. Patients with CKD require dose adjustments of lamivudine to avoid toxicity. In Sub-Saharan Africa, where the prevalence of CKD is highest, patients with HIV and CKD often do not receive the renal-adjusted doses of lamivudine recommended by national guidelines. This is due to a lack of accessibility to single-agent lamivudine.
This study enrolled a retrospective folder review of 6 patients still battling HIV with CKD, frequenting nephrology and dialysis outpatient clinics. These operate at a tertiary hospital in Kilimanjaro, Tanzania. Each patient's file was accessed both physically and electronically to pinpoint the timing of CKD diagnosis, the transition to a renal-friendly Highly Active Antiretroviral Therapy (HAART) regimen, and post-switch progress. Patients were evaluated for clinical signs and symptoms of lamivudine toxicity. Additionally, laboratory tests such as lipid profiles and liver transaminases were conducted at baseline, three months, and six months into treatment. Creatinine serves as an indicator of renal function.
The mean age of patients was 49 years, with 66% of patients being HIV stage 4 according to WHO classification. All the patients are currently on an Abacavir-based regime, with lamivudine being a common drug in the equation even after the switch. The reason for the switch was mainly Tenofovir-induced nephrotoxicity, leading to a progressive rise in creatinine levels.
About 83.3% of patients had very high creatinine levels exceeding 500 µmol/L, the maximum being 1300 µmol/L. One patient was diagnosed with End Stage Renal Disease and HIV on the same admission and was initiated on an Abacavir-based regime. All patients were well suppressed on the new regime, with the CD4 count being over 400.
None of these patients received lamivudine in the recommended doses. They were exposed to doses almost 10 to 15-fold the evidence-based dose. There was good tolerance of the new regime consisting of lamivudine for three months or more without showing any symptoms and signs of toxicity or laboratory derangements from baseline.
Four patients were on hemodialysis and presented with similar results as the group not on dialysis; hence, dialysis was not a confounder. These patients were also receiving lamivudine at doses much higher than the recommended dose
It is an interesting observation that these six patients have shown tolerance to relatively high doses of lamivudine. Challenges of accessibility of lamivudine tabs of various strengths have raised questions on the need for renal-dose adjustments. More studies are needed to shed light to confirm the safety and possible mechanism of lamivudine tolerance in renal impairment.