Effect of Switching Antiretroviral Treatment Regimen in Patients With Drug-Resistant HIV-1 Infection: Retrospective Observational Cohort Study

Abstract

Background: Evidence on the efficacy of antiretroviral therapy (ART) regimen switches on the mortality of patients with HIV drug resistance (HIVDR) is limited. Objective: We aim to provide policy guidance for ART regimen selection and evaluate the effectiveness of ART regime switches for people living with HIV and HIV-1 drug resistance. Methods: This retrospective observational cohort study included 179 people living with HIV and HIV-1 drug resistance from 2011 to 2020. The time that participants switched treatment regimens either to protease inhibitor (PI)–based ART regimens (PIs) or nonnucleoside reverse transcriptase inhibitor (NNRTI)–based ART regimens (NNRTIs) was taken as an observation starting point and followed up every 12 months. The parametric g-formula was used to estimate the 5-year risk of mortality under the situations of (1) natural course, (2) immediate switch to NNRTIs, (3) immediate switch to PIs, and (4) if CD4(+) T cells<200 switched to PIs. Results: The follow-up time of the 179 patients ranged from 30 to 119 months. The median follow-up time was 90 months. During a follow-up of 15,606 person-months, 27 individuals died in the cohort. The estimated 5-year risk of mortality under natural course, immediate switch to NNRTIs, immediate switch to PIs, and if CD4(+), and switch to PIs if T cells<200 were 11.62% (95% CI 7.82-17.11), 31.88% (95% CI 20.79-44.94), 2.87% (95% CI 0.32-7.07), and 5.30% (95% CI 2.07-10.21), respectively. The risk ratios (RRs) of immediate switch to NNRTIs, immediate switch to PIs, and switch to PIs if CD4(+) T cells<200, compared with natural course mortality rate, were 2.74 (95% CI 2.01-3.47), 0.25 (95% CI: 0.04-0.54), and 0.46 (95% CI 0.22-0.71), respectively. The risk differences were 20.26% (95% CI 10.96-28.61), –8.76% (95% CI –13.34 to –5.09) and –6.32% (95% CI –9.75 to –3.11), respectively. Conclusions: Our study found that a PI-based ART regimen was beneficial for reducing mortality in people living with HIV and HIV-1 drug resistance. More effort should be given to find HIV-1 drug resistance earlier to ensure a timely adjustment to PI-based ART, thereby maximizing the benefit of early switch treatment for people living with HIV and HIV-1 drug resistance.