During IDWeek 2019 in Washington DC, Joe Eron from UNC Chapel Hill and Paula Teichner from ViiV Healthcare presented data from two studies, ATLAS (NCT02951052) and FLAIR (NCT02938520), that compared long-acting (LA) antiretroviral therapy (ART) using cabotegravir (CAB) and rilpivirine (RPV) injected once monthly versus daily oral three drug ART, bringing more detailed information to results that were previously published in August 2019.
Today, HIV infections can be well controlled with ART, to a degree where the viral load is not detectable anymore. With ViiV’s Juluca (dolutegravir/rilpivirine) and Dovato (dolutegravir/lamivudine) two two-drug regimen therapies are available and with once-daily pills like Gilead’s Biktarvy (bictegravir/emtricitabine/TAF) and ViiV’s Triumeq (abacavir/dolutegravir/lamivudine), both HI-virus integrase inhibitors, many safe and tolerable treatment options exist.
However, taking pills daily, even it is only one, can be inconvenient for some patients and lead to compliance issues, which can subsequently result in viral resistance.
ATLAS and FLAIR (both include the letters L and A for long-acting therapies, funded by ViiV Healthcare and Janssen Pharmaceuticals) showed that long-acting CAB and RPV, given once per month, and in one arm of the study once every two months to patients with suppressed viral loads, showed non-inferiority in comparison with conventional oral ART with three components.
ATLAS data on injection side reactions were presented (intramuscular injection of 2ml of each CAB and RPV, 3ml in the eight week arm), and while pain was reported in 70% of cases during early injections with higher volumes, lasting in average for three days, after 48 weeks 85% of CAB+RPV LA recipients rated pain as very acceptable. Participants enrolled in this trial were on oral ART for four years on average, and most preferred the once a month injection over taking pills daily.
Furthermore, oral bridging is possible, meaning that when a patient knows they will not be able to receive their monthly injection, oral ART (CAB 30mg+RPV 25mg) can be given starting on the day of the missed injection, to keep viral loads down. Data from seven participants showed that oral bridging was able to keep the viral load under the detection level of 50 c/ml (viral count per ml), showing that ART LA injection and oral ART can be combined to best serve patient needs.
Opinions of panellists still differed as to which patient group will benefit most from LA ART, since people with good oral ART adherence will see no need to switch, and patients with weak adherence have to follow regular hospital/doctor’s office visits. However, with this new option, these patients might be able to maintain a low viral load for an extended period of time and avoid or postpone the onset of viral resistance. A potential problem might be the logistics of LA therapy since people who are willing to switch from pills taken once daily at home will now have to receive an injection from trained personnel, which will take limited time and money from already cash-strapped health care systems.
NDA application for the once-monthly LA CAB and RPV was submitted to the FDA and approval is expected at the end of the year.
IDWeek is the joint annual meeting of the Infectious Diseases Society of America (IDSA), Society for Healthcare Epidemiology of America (SHEA), the HIV Medical Association (HIVMA), and the Pediatric Infectious Diseases Society (PIDS).
GlobalData (2019). Expert Insight: Reducing Treatment Burden and Drug Exposure: The Next Step in HIV Management?, August 2019, GDHC2629EI
ViiV Adds the First 2-Drug STR for Treatment-Naïve Patients to Its Growing HIV Arsenal, April 2019
GlobalData (2018). Human Immunodeficiency Virus (HIV): Competitive Landscape to 2026, February 2019, GDHC003CL.