Posthoc analysis of the EMERALD trial reveal the combination regimen of D/C/F/TAF performs well in HIV-positive patients across different race, gender, and age subgroups, who may have failed previous antiviral regimens.
Although significant advances have been made in the treatment of HIV, certain patient populations continue to face barriers to viral suppression. Treatment-experienced patients from diverse backgrounds who may have struggled with adherence in the past are facing the issue of drug resistance and therefore, new treatment options for these patients need to be developed and made available. The 48-week results of a posthoc analysis of clinical trial testing 1 of these new agents in treatment-experienced patients—the EMERALD trial—were recently presented at the 25th Annual Conference on Retroviruses and Opportunistic Infections (CROI) and the results look promising.
For the phase 3, randomized (2:1), non-inferiority trial, investigators studied the efficacy and safety of switching to darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg vs continuing use of a boosted protease inhibitor (PI) +emtricitabine/tenofovir disoproxil fumarate (control) in 1141 treatment-experienced, virologically-suppressed HIV-1—infected adults with a viral load [VL] of <50 copies [c]/mL for ≥2 months. One VL ≥50 and <200 c/mL was allowed in 12 months before screening and previous non-darunavir virologic failure [VF] was also allowed.
According to the study authors, “the primary endpoint was the proportion of patients with virologic rebound (confirmed VL ≥50 c/mL or premature discontinuation with last VL ≥50 c/mL) cumulative through Week 48. Virologic response was defined as VL <50 c/mL (FDA snapshot). Safety was assessed by adverse events (AEs) and changes in bone mineral density and eGFR from baseline to Week 48. Results were evaluated in subgroups by age (≤50 vs >50 y), gender, and race (non-black/African American [AA] vs black/AA). A total of 382 (33.5%) [of the patients] were >50 years of age; 205 (18.0%) were women, and 237 (20.8%) were black/AA.”
Contagion® sat down with the lead investigator, Gregory D. Huhn, MD, an infectious disease specialist in the Cook County Health system in Chicago, Illinois, who shared with us what made this trial unique (see video, below).
The results of the trial revealed that the virologic rebound rate in the D/C/F/TAF arm was 2.5% vs 2.1% in the control arm. These results were consistent across gender, age, and race subgroups. Furthermore, Dr. Huhn shared with us that, “virologic response rates were similar for D/C/F/TAF (94.9%) and control (93.7%) in the total population and consistent across subgroups.” There was no resistance to the study drugs observed and the overall rates of AEs—and subsequent discontinuations because of an AE—were not statistically significant across groups. Dr. Huhn elaborated on these results further in our interview (see video, below).
Based on these results, the study investigators concluded that switching the treatment-experienced adults infected with HIV-1 to D/C/F/TAF “led to low rates of cumulative virologic rebound over 48 weeks that was overall non-inferior to the continuation of prior antiretroviral therapy.” In addition, patients across all subgroups who received D/C/F/TAF experienced lower rebound rates and improved bone safety and renal function versus those patients in the control group.
We asked Dr. Huhn to explain what the results of this study mean for clinicians who are in the field treating patients in these populations. He stated that “despite significant progress [in the field of HIV], clinical challenges remain in patients with diverse backgrounds that may have had problems with adherence in the past or [who are] at risk of drug resistance. I think the results here—the posthoc analysis, the data from EMERALD—speaks to the real-life experiences that providers confront in treating different patient populations that have had different levels of experience. D/C/F/TAF is in use in Europe, and if it is approved here [in the United States] it will offer a simplified, single-tablet regimen for providers to have at their disposal. [It can be used as] an option to introduce in treatment-naïve patients or to switch patients that may be at risk for adherence factors that may lead toward drug resistance. In fact, the World Health Organization advocates to start newly diagnosed patients on antiretroviral therapy within 1 week of diagnosis, and this drug—given the very high barrier to resistance of darunavir—would be an option for that patient, without [even having] baseline genotype. [It will also work] for those patients who have extensive treatment history, with no darunavir resistance.”
Janssen submitted their New Drug Application for D/C/F/TAF in September 2017 based on the results of EMERALD and the AMBER trials. Clinicians in the United States can hope to have access to this first-of-its-kind boosted PI single-tablet regimen potentially by Summer 2018.