Effectiveness of simplifying antiretroviral therapy to maintain viral suppression and improve bone and renal health: comparing simplified and non-simplified therapy

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Abstract

Objective

Nucleoside/nucleotide reverse transcriptase inhibitors, particularly tenofovir, can cause long-term side effects such as decreased bone mineral density and estimated glomerular filtration rate. A strategy to mitigate these effects is the simplification of antiretroviral therapy, which involves withdrawing one of the nucleoside/nucleotide reverse transcriptase inhibitors from the therapeutic scheme. While clinical trials and real-world studies have demonstrated that the simplified therapy maintains undetectable viral loads, its impact on bone mineral density and kidney function remains unclear owing to the lack of real-world evidence.

Methods

This retrospective cohort study compared 152 patients who underwent antiretroviral therapy simplification (primarily due to osteopenia, osteoporosis, or decreased estimated glomerular filtration rate) with 306 patients who maintained triple therapy, between April 2013 and September 2022. The simplified regimens included lamivudine plus dolutegravir or ritonavir-boosted darunavir. The groups were analyzed based on their demographic characteristics using Student’s t-test in the case of symmetric data. Therapeutic success (undetectable viral load at the end of follow-up) was assessed using Kaplan Meier survival analysis . The estimated glomerular filtration rate variation before and after simplification was analyzed using the Mann-Whitney test . Pre-and post-simplification bone mineral density values were evaluated using the chi-square test for trends and assessed in the simplified therapy group. A significance level of 5% (α = 0.05) was adopted for all tests.

Results

Simplified antiretroviral therapy was non-inferior to triple therapy in maintaining undetectable viral load. Patients receiving simplified regimens showed a positive variation in estimated glomerular filtration rate. A small subset of patients also exhibited improvements in bone mineral density after antiretroviral therapy simplification.

Conclusions

These findings suggest that simplified therapy is as effective as triple therapy and has the additional benefit of reducing tenofovir-related adverse events.

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