Infectious Diseases Society of America (IDSA)’nın düzenlediği IDWeek 2015™’de sunulan araştırmada, araştırıcılar önceden tedavi deneyimi olan HIV hastalarında tenofovir alafenamid bazlı tedavi rejimine geçilmesinin virolojik baskılamayı sürdürdüğünü; ayrıca böbrek ve kemiklerde güvenli kullanımda iyileşme kaydedildiğini bildirdi.
SAN DIEGO — Treatment-experienced HIV patients who switched to a tenofovir alafenamide-based regimen maintained virologic suppression and saw significant improvements in renal and bone safety, researchers reported.
Tenofovir alafenamide (TAF), an investigational prodrug of tenofovir (TFV) coformulated with elvitegravir, cobicistat and emtricitabine (E/C/F/TAF), has demonstrated potent antiviral activity at approximately one-tenth the dose of the current TFV drug, Viread (tenofovir disoproxil fumarate, Gilead Sciences; TDF). Additionally, the reduced toxicity of TAF has made it an attractive option for treatment-experienced patients.
Improved safety profile
In one presentation, Melanie Thompson, MD, from the AIDS Research Consortium of Atlanta, discussed week 48 data from a study of virologically suppressed adults taking Stribild (elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate, Gilead Sciences; E/C/F/TDF) who switched to a single tablet of E/C/F/TAF. A subset of 459 virologically suppressed patients from a larger study were randomly assigned in a 2:1 ratio to receive open-label E/C/F/TAF or to remain on their TDF-based regimen. Thompson said baseline characteristics were similar between the two groups.
No treatment-related serious adverse events were reported. Two patients discontinued treatment due to increases in serum creatinine; both of these patients belonged to the TDF arm.
Additionally, “those who switched to TAF saw improvement in their kidney function, measured by serum creatinine and by urinary proteins, and they also saw improvement in bone density when they switched to TAF off of the TDF-containing regimen,” Thompson told Infectious Disease News.
Patients taking E/C/F/TAF had statistically significant increases in lipid levels since baseline, the clinical significance of which is still unclear, according to Thompson. Lipid-modifying medications were initiated by 7.8% of patients on a TAF-based regimen and 6.5% of patients on a TDF-based regimen.
According to Thompson, TAF delivers high levels of tenofovir directly into HIV target cells, yielding 91% lower plasma TFV levels compared with TDF. This may account for the improved safety profile of the drug.
“I think what we’re seeing is that there is less circulating tenofovir, which is the active agent, in plasma, and so there is less bystander effect on these off-target organs like kidney and bone, but where we want tenofovir to be concentrated is in the lymphoid cells, and so that’s what TAF does,” she told Infectious Disease News.
In a separate presentation, Gregory Huhn, MD, MPHTM, assistant professor of infectious diseases at Rush University Medical Center, said the simplification of treatment by switching from a multi-tablet regimen to E/C/F/TAF plus the protease inhibitor Prezista (darunavir, Janssen; DRV) also led to improved outcomes in virologically suppressed adults with multidrug resistance.
According to Huhn, 135 patients on a DRV-containing regimen for at least 4 months with two prior treatment failures and resistance to at least two classes of drugs were randomly assigned to open-label E/C/F/TAF plus DRV (n = 89) or continued with their baseline regimen (BR). Huhn said baseline characteristics between the two groups were relatively well-balanced.
The median number of pills per regimen at study entry was 5, with 65% of patients taking a twice-daily regimen — a majority whom had been prescribed a TDF-based regimen. Viral suppression was maintained by week 24 in 97% of patients in the switch arm vs. 91% in the BR arm, with a proportional difference of 5.3% (95% CI, –3.4% to 17.4%). At week 48, 94% of patients who switched to a TAF-based regimen and 76% of BR patients maintained virologic control — a proportional difference of 18.3% (95% CI, 3.5% to 33%).
“With these figures, statistical superiority was established in the switch arm,” Huhn said.
The researchers saw no evidence of the emergence of drug resistance in patients receiving E/C/F/TAF plus DRV. One participant with viral rebound developed resistance in the BR arm.
There was a slightly higher adverse event rate in the switch arm (92% vs. 78%), “which may be due to the open-label study design in patients initiating a novel therapy,” Huhn said.
The researchers reported no serious drug-related adverse events, and no adverse events led to treatment discontinuation.
Additionally, they saw no significant difference in the estimated glomerular filtration rate at week 48 with E/C/F/TAF plus DRV (+ 7.4 mL/min) vs. BR (+ 3.9 mL/min). TAF also was associated with greater treatment satisfaction among patients, the researchers said.
“For treatment-experienced individuals with two-class or greater resistance on complex, high-pill burden regimens, switching to E/C/F/TAF plus darunavir provides a simple, once-daily, two-pill option with superior efficacy and comparable tolerability,” Huhn concluded. – by John Schoen
Huhn G, et al. Abstract 726. Presented at: IDWeek; Oct. 7-11, 2015; San Diego.
Thompson M, et al. Abstract 725. Presented at: IDWeek; Oct. 7-11, 2015; San Diego.
Disclosure: The studies were funded by Gilead Sciences. Please see the full studies for a list of all authors’ relevant financial disclosures.