A new paradigm for antiretroviral delivery: long-acting cabotegravir and rilpivirine for the treatment and prevention of HIV

Abstract

Purpose of review Cabotegravir (CAB) and rilpivirine (RPV) is the first long-acting injectable antiretroviral therapy (ART) option approved for virologically suppressed adults with HIV-1. In addition, long-acting CAB is a promising agent for HIV preexposure prophylaxis (PrEP). This review focuses on phase 3 clinical trial results and implementation considerations for these long-acting ART and PrEP strategies. Recent findings Long-acting CAB and RPV administered every 4 weeks demonstrated noninferiority to oral ART through week 96 in both the ATLAS and FLAIR studies, whereas ATLAS-2M found similar efficacy through 96 weeks when the long-acting injectable ART was administered every 8 weeks instead of every 4 weeks. For prevention, two phase 3 trials were stopped early due to fewer incident HIV infections in participants receiving long-acting CAB every 8 weeks compared with daily oral tenofovir disoproxil fumarate–emtricitabine for PrEP. The long-acting therapies were well tolerated across all clinical trials. Summary Clinical trial results support the use of long-acting CAB for HIV PrEP and long-acting CAB and RPV as a switch strategy for adults with HIV-1 who are first virologically suppressed with oral ART. Implementation challenges persist, and data are urgently needed in populations who may benefit most from long-acting therapy, including adolescents, pregnant individuals, and those with barriers to medication adherence.

Realizing the promise of long-acting antiretroviral treatment strategies for individuals with HIV and adherence challenges: an illustrative case series

“…Likewise, the FDA and insurance providers have set similar criteria for LAI-ART eligibility–patients must be virologically suppressed on the current oral regimen, have VL < 50 copies/ml, and have no reported history of virologic failure [ 7 , 16 ]. Based on the general perspective that LAI-ART is an effective tool for improving adherence for individuals like those presented in this case series, and considering the high levels of reported adherence and acceptability of the LAI-ART, such limiting criteria potentially exclude those that need the drug the most [ 17 , 18 ]. These cases also highlight that in some patients, LAI-ART have a potential benefit of reducing pill burden in patients who may still require oral medications.…”

NPs safely prescribing long-acting HIV medications

“…In discussing options for ART, NPs should employ shared decision making to learn about and respect patients' values and preferences and provide potential alternatives to the route of medication administration where appropriate. 19,20 ■ Advantages Advantages of prescribing an ER injectable ART over oral includes a less frequent dosing schedule, decreased pill burden, convenience, and avoidance of DDIs at the level of the GI tract. 14,20 Additionally, injectable ART administered in a clinic can provide privacy in that patients do not need to store HIV medications at home.…”

“…19,20 ■ Advantages Advantages of prescribing an ER injectable ART over oral includes a less frequent dosing schedule, decreased pill burden, convenience, and avoidance of DDIs at the level of the GI tract. 14,20 Additionally, injectable ART administered in a clinic can provide privacy in that patients do not need to store HIV medications at home. 21 A study on patient perception found that 57% of participants were likely to accept long-acting injectable ART.…”

“…NPs should assess for barriers to ART, including drug resistance, comorbidities, mental health and substance use disorders, DDIs, presence of drug toxicities or adverse reactions, difficulty accessing medications, high costs, stigma, low health literacy, competing priorities related to life events, caregiving demands, and unstable housing as well as for discrepancies in self-reported medication adherence and viral load results. In discussing options for ART, NPs should employ shared decision making to learn about and respect patients' values and preferences and provide potential alternatives to the route of medication administration where appropriate 19,20…”

Atherosclerosis by Virus Infection—A Short Review

“…Antivirals to treat HIV exist, but it has been reported that some drugs, such as ritonavir or efavirenz, can cause dyslipidemia and atherosclerosis [ 90 , 91 ]. Pre-exposure prophylaxis (PrEP) treatment was the only option to prevent HIV infection, but the U.S., the FDA has recently approved the first injection drug Apretude to prevent HIV infection [ 92 , 93 , 94 , 95 , 96 ]. Additionally, it has been reported that various antiretroviral drug treatments including Ritonavir, Saquinavir, Nelfinavir, Indinavir, Efavirenz, and Tenofovir alafenamide can increase the levels of human blood lipids and the incidence of atherosclerosis [ 97 ].…”