HIV Program and Division of Infectious Diseases
Brigham and Women's Hospital
Professor of Medicine
Harvard Medical School
Paul E. Sax, MD, has disclosed that he has received consulting fees from Gilead Sciences, GlaxoSmithKline, Janssen, Merck, and ViiV Healthcare and funds for research support from Gilead Sciences, GlaxoSmithKline, Merck, and ViiV Healthcare.
Thematically inherent at any modern HIV conference is a focus on emerging ART strategies. The 10th IAS Conference on HIV Science in Mexico City, occurring earlier this summer, was no different, including discussion of therapeutic agents with novel mechanisms of action, efficacy and safety of 2-drug regimens, and—the main topic we will consider here—perceived acceptability of long-acting (LA) injectable therapy.
ATLAS and FLAIR: Pooled Analysis Confirms Noninferior Efficacy of LA CAB Plus RPV vs 3-Drug Oral ART
A pooled efficacy analysis of 2 multicenter, randomized phase III trials investigating LA injectable ART was reported at IAS 2019. ATLAS (enrolling virologically suppressed patients with no previous treatment failure) and FLAIR (enrolling ART-naive patients who received 20 weeks of oral induction with dolutegravir/abacavir/lamivudine before randomization) both compared intramuscular injection of LA cabotegravir (CAB) plus rilpivirine (RPV) every 4 weeks with daily oral 3-drug ART. All patients in an injectable treatment arm received a 4-week lead-in of oral CAB plus RPV to monitor for adverse events prior to receipt of a LA dose.
The primary endpoint for both trials was the proportion of patients with HIV-1 RNA ≥ 50 copies/mL at Week 48, and each study individually reported noninferiority of the 2-drug LA injectable regimen at CROI 2019. The pooled analysis presented at IAS 2019 combined data from both trials and reached an equivalent conclusion with < 2% of patients experiencing virologic nonresponse with either treatment strategy. This further supports the noninferior efficacy of monthly injectable CAB plus RPV compared with daily oral 3-drug ART.
ATLAS: Patient-Reported Outcomes Reinforce Preference for Injectable ART – Among Those Willing to Try It
The novel information regarding LA injectable CAB plus RPV presented at IAS 2019 featured patient-reported outcomes. These data addressed important outstanding questions regarding how LA injectable ART may affect patients: 1) Will certain patients be accepting of injectable treatment and 2) will injection-site reactions (ISRs) deter them from continuing their use of injectable ART? In short, the answers to these questions are “yes” and “probably not,” respectively.
Patient-reported outcomes from the ATLAS study revealed that individuals who switched to injectable CAB plus RPV from oral ART reported significantly greater increases in treatment acceptance at Weeks 8, 24, and 48 compared with those continuing their baseline oral regimen. In addition, although ISRs occurred in approximately 21% of the total injections administered through Week 48, 90% of LA CAB plus RPV recipients completing the Perception of Injection (PIN) questionnaire scored ISRs as very or totally acceptable. These data suggest that ISRs, although they do occur, are not tremendously bothersome to patients.
Finally, the outcome that I found most impressive was that patients in the ATLAS trial who switched to LA CAB plus RPV from daily oral ART reported significant improvements in treatment satisfaction. In fact, 97% of survey respondents said that they preferred the LA injectable ART delivery over pills. Thus, not only may patients be accepting of ART injections, they may also be more satisfied and prefer the injections to their current oral regimen.
Take-home Message: Convenience Wins
Overall, among patients who chose to commence LA CAB plus RPV, there were extremely high rates of treatment satisfaction, low rates of severe ISRs, and a preference for injectable delivery. It is important to remember that the patients in these studies enrolled with the knowledge that there would be a 50% chance of receiving injectable therapy and, as such, may represent a subset of individuals more accepting of injectable therapy in general.
However, if the injections were very painful or burdensome or negatively affected their quality of life, this would have been reflected in their treatment acceptance and satisfaction responses. I think this is good news. Going forward, if virologically suppressed patients with no history of treatment failure express interest in injectable ART, there is a high likelihood that they will succeed and be satisfied with their choice. Of importance, this will provide patients with the option of switching from daily therapy to treatment administered only 12 times per year.
Following IAS 2019, near the end of August, primary results for the ATLAS-2M study were publicly reported, confirming the noninferior virologic efficacy of administering LA injectable CAB plus RPV every 8 weeks vs every 4 weeks in virologically suppressed patients. The once-monthly dosing strategy is currently under FDA review, with action expected by the end of the year. If ATLAS-2M data were included in the regulatory filing and approval extends to bimonthly dosing, I expect LA CAB plus RPV to be even more compelling to patients. Despite any anticipated logistical barriers to administration, 6—or even 12—injections per year reduces the burden of 365 days of oral treatment and may be preferable to certain patients.
Do you foresee patient interest in LA injectable ART in the future? I invite you to join the discussion by posting a comment. For more details on this and other key issues addressed at IAS 2019, review more Conference Coverage from CCO here.