A Comparison of the Risk of Viral Load Blips in Human Immunodeficiency Virus Patients on Two-Drug Versus Three-Drug Antiretroviral Regimens

<b>Background/Objectives</b>: The objective of this retrospective, multicenter cohort study was to compare the incidence of viral load blips between two-drug and three-drug antiretroviral therapy regimens in human immunodeficiency virus (HIV) patients. <b>Methods</b>: A total of 121 patients were included, with 44 receiving two-drug regimens (e.g., dolutegravir/lamivudine) and 77 receiving three-drug regimens (e.g., bictegravir/tenofovir alafenamide/emtricitabine) at the time of analysis. The primary outcome was the occurrence of viral blips, defined as transient HIV-RNA elevations ≥ 50 copies/mL; a sensitivity analysis used ≥20 copies/mL. <b>Results</b>: Generalized estimating equation models adjusted for clinical covariates showed no significant difference in the odds of blip occurrence comparing three-drug with two-drug regimens, both for blips ≥ 50 (odds ratio [OR]: 2.64; 95% confidence interval [CI]: 0.91-7.70; <i>p</i> = 0.075) and ≥20 (OR: 1.76; 95% CI: 0.76-4.08; <i>p</i> = 0.190). In the two- and three-drug groups, the predicted probabilities of blips were 1.4% and 3.7% (<i>p</i> = 0.075) for blips ≥ 50, and 6.9% and 11.5% (<i>p</i> = 0.190) for ≥20, respectively. No virologic failure was observed. <b>Conclusions</b>: These findings suggest that two-drug regimens provide virologic control comparable to three-drug regimens and may be a viable clinical option due to fewer drug interactions, lower toxicity, and reduced cost.