FDA Approves Two Fixed Dose HIV Treatments
New combination therapy gains approval for adult and pediatric patients with HIV-1.
Yesterday, the FDA granted approval to 2 different fixed dose drugs to treat HIV-1: Symfi Lo tablets, which is a combination of efavirenz (EFV) 400-mg, lamivudine (3TC) 300-mg, tenofovir disoproxil fumarate (TDF) 300-mg, and Biktarvy, which is a combination of bictegravir, emtricitabine, and tenofovir alafenamide.
Symfi Lo is indicated to treat adults and children weighing at least 35 kg who are HIV positive, according to the FDA.
Prior to initiating therapy, the FDA advises health care providers to test patients for hepatitis B virus and obtain estimated creatinine clearance (CrCL), urine glucose, and urine protein.
The recommended dose of Symfi Lo tablets is 1 oral tablet once per day on an empty stomach, preferably before bed, according to an FDA release. The FDA noted that taking the treatment at bedtime may make nervous system symptoms more tolerable.
The drug is not recommended for patients with CrCL less than 50-mL/min or patients with end-stage renal disease that requires hemodialysis, according to the FDA. Additionally, it is not recommended for patients with moderate-to-severe hepatic impairment and should be used cautiously in those with mild impairment.
Common adverse events seen in the ENCORE1 study, which included 630 treatment-naïve patients treated with the combination, included mild-to-moderate gastrointestinal events, dizziness, abnormal dreams, and rash, according to the FDA.
The efficacy of the treatment regimen was established in Trial 903 and ENCORE1.
The ENCORE1 clinical trial compared treatment efficacy in 630 treatment-naïve patients with HIV-1. Patients were randomized 1:1 to receive EFV 400-mg plus TDF 300-mg and FTC 200-mg once daily or EFV 600-mg plus TDF 300-mg/FTC 200-mg once daily.
Mean baseline CD4+ cell count was 273 cells/mm3 and median baseline viral load was 56,469 copies/mL, according to the release. Approximately 34% of subjects had baseline viral load of ≥ 100,000 copies/mL.
The researchers found that slightly more patients taking the EFV 400-mg dose regimen responded to treatment at 48 weeks, while virologic failure was similar for both therapies, according to the FDA.
The mean increase at Week 48 from baseline in CD4+ cell count was 183 cells/mm3 for the EFV 400-mg cohort and 158 cells/mm3 for the EFV 600 mg cohort, according to the release.
During the 48-week period, 11 patients in the 400-mg arm and 5 subjects in the 600-mg arm experienced a new CDC Class C event, the FDA concluded.
Biktarvy is indicated as a complete regimen for patients with HIV-1 who are treatment-naïve or who are virologically suppressed on a stable antiretroviral treatment for at least 3 months, according to the FDA.
The agency noted that this treatment requires the same testing as Symfi Lo prior to administration. Biktarvy is also not recommended for patients with estimated CRCL lower than 30-mL/minute or for those with severe hepatic impairment.
The safety of Biktarvy was explored in 2 randomized clinical trials, Trial 1489 and Trial 1490, which enrolled 1274 treatment-naïve patients with HIV. In the studies, 634 patients were treated with once-daily oral Biktarvy.
The most common adverse reactions include diarrhea, nausea, and headache, according to the FDA.
Safety was also explored in trials of virologically suppressed adults who were switched from established ART regimens to Biktarvy. The FDA noted that the safety profile in virologically suppressed adult subjects was similar to those of treatment-naïve patients, according to the release.
The FDA warned that co-administration of Biktarvy with drugs that are substrates of organic cation transporter 2 and multidrug and toxin extrusion transporter 1 may increase plasma concentrations.