Comparing Intermittent Injectable Cabotegravir + Rilpivirine vs Daily Oral HIV Treatments: SOLAR Study Highlights

Cabotegravir + rilpivirine (CAB+RPV LA), a long-acting injectable regimen for patients with human immunodeficiency virus (HIV), was demonstrated to be as effective as daily bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) in a clinical trial known as the SOLAR study.¹The SOLAR study, funded by ViiV Healthcare, is the first randomized, large head-to-head trial to test whether CAB+RPV LA was noninferior to BIC/FTC/TAF in patients with virologically suppressed HIV-1. 

The open-label, multicenter SOLAR study enrolled 670 people. Participants were randomized 1:2 to continue receiving once-daily BIC/FTC/TAF (n=223) or switch to CAB+RPV LA administered once every 2 months (n=447).¹ 

The primary endpoint was the proportion of participants with HIV-1 RNA ≥50 c/mL, using the FDA Snapshot algorithm and a 4% noninferiority margin. At 12 months, the primary endpoint was met, with CAB+RPV LA demonstrating noninferiority compared to BIC/FTC/TAF (mITT-E; CAB+RPV LA: 5/447 [1%], BIC/FTC/TAF: 1/223 [<1%], adjusted difference: 0.7%, 95% confidence interval [-0.7, 2.0]).¹ 

Additionally, virologic suppression rates were similar between groups, at 90% and 93% in the CAB+RPV LA and BIC/FTC/TAF arms, respectively (adjusted difference: -2.7%, 95% CI [-7.0, 1.7]).¹ 

Regarding safety, drug-related adverse events (AEs) occurred in 20% of participants receiving CAB+RPV LA and <1% of BIC/FTC/TAF recipients. The most common drug-related AEs were fever (3%), headache (2%), fatigue (2%), and diarrhea (2%) in the CAB+RPV LA group vs weight gain (<1%) and abnormal hepatic function (<1%) in the BIC/FTC/TAF group.¹ 

A phase 3b clinical trial, referred to as ATLAS-2M, also compared the effectiveness of CAB+RPV LA administered every 2 months versus every 4 weeks in adults with HIV-1. The study duration was 152 weeks and aimed to determine if the longer dosing interval was noninferior in terms of efficacy and safety.² 

The endpoints of the study included the proportion of participants with HIV-1 RNA above and below 50 copies/mL, virologic failure, and the safety and tolerability of the treatment. A total of 1045 participants were included, with 522 randomly receiving CAB+RPV LA every 8 weeks and 523 randomly receiving it every 4 weeks.² 

The study found that the longer dosing interval was noninferior to the shorter interval, with 2.7% and 1.0% of participants having HIV-1 RNA above 50 copies/mL, respectively.² At the end of the 152-week period, 87% of participants in both groups maintained HIV-1 RNA below 50 copies/mL. A small percentage of participants experienced virologic failure, with more cases in every 8-week dosing group. Some participants who experienced virologic failure developed mutations associated with resistance to the treatment. The safety profiles of both dosing regimens were similar, with no new safety concerns observed.² 

Both study’s findings demonstrate that both dosing intervals of CAB+RPV LA provide durable virologic suppression for approximately 3 years and are safe and well-tolerated as a complete regimen for maintaining HIV-1 suppression. 

After following a CAB+RPV LA treatment regimen, patients with HIV demonstrated a preference for CAB+RPV LA due to ease of adherence. The SOLAR study found that “…90% of participants who switched from BIC/FTC/TAF to CAB+RPV LA preferred the complete long-acting regimen to daily pills.”¹ 

Between March 2021 and June 2022, a discrete choice experiment was conducted on people with HIV (PWH) over the age of 18 who were recruited from HIV clinics in Washington State and Atlanta, Georgia. The participants were presented with 17 choice scenarios, each offering 3 options: 2 hypothetical long-acting antiretroviral therapy (LA-ART) regimens and the option to stick with their current daily oral treatment. The LA-ART regimens were described in terms of treatment mode, pain, dosing frequency, location, pre-treatment time with undetectable viral load, pre-treatment negative reaction testing, and "late-dose leeway". Preference weights for all attribute levels were estimated using conditional logistic regression, with an interaction between treatment mode and pain.³ 

A total of 700 participants, with 350 at each site, were enrolled in the study. The median age of the participants was 51 years, ranging from 18 to 73. Most participants, 70%, identified as cisgender male, while 24% identified as cisgender female, and 6% identified as non-binary or transgender. LA oral tablets were the most preferred long-acting antiretroviral therapy (LA-ART) option, followed by annual implants and injections. Preferences also indicated a preference for longer time between doses and administration at home, with clinics being preferred over pharmacies.³ 

“Our results suggest that LA oral tablets will be preferred by many patients over their current daily oral treatment, while implants and injections with longer duration may be acceptable to some,” said researchers.³ 

However, a research review in the Journal of the Association of Nurses in AIDS Care noted that significant implementation barriers may exist for patients seeking to first initiate injectable CAB+RPV LA therapy.⁴ 

“One year after approval, myriad implementation barriers threaten the access and sustainability of this life-saving innovation: eligibility issues (viral suppression, drug resistance, and failed oral regimens); injection requires medical provider and transportation to facility; strict medication adherence; life challenges—mental health, homelessness, joblessness; and lack of insurance and high cost,” said researchers.⁴ 

Despite the potential barriers for patients seeking to medicate with CAB+RPV LA injectables, projected benefit research suggests that injectable medication for HIV with support services may lead to the highest rates of viral suppression and engagement in care at 3 years when compared to other treatment regimens.⁵ 

In a demonstration project, researchers found that CAB-RPV was effective in achieving viral suppression in a high percentage of individuals with HIV who had adherence barriers. To further understand the potential impact of CAB-RPV for those with adherence issues, the researchers conducted a long-term projection using the Cost-Effectiveness of Preventing AIDS Complications (CEPAC) model. The study compared 3 strategies: standard-of-care oral integrase inhibitor-based ART (INSTI), ART with supportive social services (INSTI/WS), and CAB-RPV with supportive social services (CAB-RPV/WS). The model outcomes included viral suppression, engagement in care, and life expectancy after three years.⁵ 

A wide variation in the projected viral suppression at 3 years was noted, with rates of 16% for INSTI, 38% for INSTI/WS, and 44% for CAB-RPV/WS. The life expectancy also differs significantly, with 7.4 life-years (LY) for INSTI, 9.0 LY for INSTI/WS, and 9.4 LY for CAB-RPV/WS. Those who start CAB-RPV/WS at lower CD4 counts would experience greater benefits over oral ART in terms of viral suppression and life expectancy. Compared to oral INSTI strategies, CAB-RPV/WS consistently improves viral suppression and life expectancy across plausible key parameter ranges.⁵ 

“These model-based results support that long-acting injectable CAB-RPV with extensive support services for nonsuppressed PWH experiencing adherence barriers is likely to increase viral suppression and improve survival,” said researchers. “A prospective study to provide further evidence is needed.”⁵ 

Findings from each study indicate that CAB+RPV LA not only proves to be efficacious in treating HIV but also emerges as the favored choice among patients with access to this treatment regimen. The clinical outcomes strongly advocate its position as a leading contender for achieving viral suppression in the HIV drug market. 

References  

1. ViiV Healthcare announces positive data demonstrating long-acting injectable Cabenuva (cabotegravir, rilpivirine) is as effective as daily oral Biktarvy (BIC/FTC/TAF) for the treatment of HIV-1. News release. ViiV Healthcare. February 23, 2023. Accessed January 10, 2024.  https://www.gsk.com/en-gb/media/press-releases/viiv-healthcare-announces-positive-12-month-findings-from-the-solar-study/  
2. Overton ET, Richmond G, Rizzardini G, et al. Long-acting cabotegravir and rilpivirine dosed every 2 months in adults with human immunodeficiency virus 1 type 1 infection: 152-week results from ATLAS-2M, a randomized, open-label, phase 3b, noninferiority study. Clin Infect Dis. 2023;76(9), 1646–1654. doi:10.1093/cid/ciad020 
3. Graham SM, Barthold D, Hauber B, et al. US patient preferences for long-acting HIV treatment: A discrete choice experiment. J Int AIDS Soc. 2023;26 suppl 2:e26099. doi:10.1002/jia2.26099 
4. Pinto RM, Hall E, Tomlin R. Injectable long-acting cabotegravir-rilpivirine therapy for people living with HIV/AIDS: Addressing implementation barriers from the start. JANAC. 2023;34(2): 216–220. doi:10.1097/JNC.0000000000000386 
5. Chen W, Gandhi M, Sax PE, et al. Projected benefits of long-acting antiretroviral therapy in nonsuppressed people with human immunodeficiency virus experiencing adherence barriers. Open Forum Infectious Diseases. 2023;10(8). doi:10.1093/ofid/ofad390