Switching From TDF to TAF or Dual-Therapy Regimens in HIV Patients

A consistent proportion of people with HIV are switching from tenofovir disoproxil fumarate (TDF)-based therapy to other alternative regimens, according to a study recently published in the Journal of Antimicrobial Agents.

People with HIV can achieve and maintain a lifetime of viral suppression with the combination antiretroviral therapy (cART) currently available. Guidelines recommend the use of a 3-drug combination regimen when switching patients who have suppressed viral loads, have never experienced virologic failure, and have no evidence of drug resistance. Growing evidence suggests some dual-therapy regimens (DT) may also optimally maintain virologic suppression. A goal while switching from TDF-based therapy is to decrease short- or long-term toxicity; TDF is associated with mild renal impairment and could progress to nephrotoxicity.

Treatment advances increase possibilities for patients to switch to regimens with more favorable toxicity profiles while maintaining efficacy. In recent years, there has been an increase in switching from TDF-containing regimens due to the availability of alternative nucleoside reverse transcriptase inhibitors (NRTIs) like tenofovir alafenamide/emtricitabine (TAF/FTC) and the use of partially or totally NRTI-sparing DT combinations. Previous studies have shown no change in viral suppression when patients switch from TDF to TAF. Key factors associated with stopping TDF therapy include anchor drugs (boosted protease inhibitors [PI/b] and INSTI) and eGFR decline. The study evaluated the association between most recent eGFR values and risk of switching from TDF to TAF or DT.

Patients included in the analyses were from the Italian Cohort Naïve Antiretrovirals (ICONA) Foundation cohort, an Italian multicenter prospective observational cohort study set up in 1997 with more than 16,000 patients infected with HIV-1 who are naïve from ART at the time of enrollment and have follow-up care in Italy In total, 1486 HIV+ patients were included between January 2016 and December 2019; these patients were initiated on a TDF-based regimen for the first time, achieved HIV-RNA of 50 or less copies/mL, and followed for a median of 16 months. The primary outcomes of this study were to accurately estimate the 2-year rate of switching from TDF- to TAF-based cART or DT and to study the association between changing regimens and eGFR changes from baseline. The secondary outcome of this study was to evaluate the same switching outcomes with anchor drugs used with TDF at initiation. Kaplan-Meier curves and Cox regression models were used to estimate the time from TDF switch to TAF or DT.

The median age of all included patients was 36 (interquartile range [IQR], 30-42) years, and the median baseline CKD-EPI eGFR was 99.92 (IQR, 86.4, 111.4) mL/min/1.73 m². A higher proportion of patients with a HIV-RNA 50 or less copies/mL switched from TDF to TAF (46.7%; 95% CI, 42.8-48.5%) than to DT (3.5%; 95% CI, 2.6-4.7%). Patients receiving INSTI at baseline had a significantly higher probability of switching to TAF vs patients receiving NNRTIs and PI/b at baseline (P <.0001). There was a higher risk associated with switching to DT (P <.001) but not TAF-based cART (P =.617) if patients had an eGFR less than 60 mL/min/1.73 m² both as a time-fixed covariate at baseline or as a current value.

Study authors conclude the “analysis shows that a consistent proportion of people with a VL ≤50 copies/mL in recent years have been switched from TDF to alternative strategies,” with a switch to TAF-based cART more common than DT.

Reference

Vergori A, Gagliardini R, Gianotti N, et al. Switching from TDF to TAF or dual therapy (DT)-based regimens in HIV-infected individuals with viral load ≤50 copies/mL: does eGFR matter? Published online September 10, 2020. Int J Antimicrob Agents. doi:10.1016/j.ijantimicag.2020.106154