 |
|
|
| |
Over 80% Adhere to Long-Acting
CAB+RPV Despite Prior Non-Adherence
|
| |
| |
IDWeek, October 16-19, 2024, Los Angeles
Mark Mascolini
People with a record of poor antiretroviral adherence and virologic failure responded and adhered well to cabotegravir plus rilpivirine (CAB+RPV) injected every 2 months in a San Diego Ryan White-funded clinic [1]. In this 63-person retrospective analysis, only low CD4 count when starting CAB+RPV and active substance use predicted treatment failure; other sociodemographic and clinical variables did not.
Elizabeth Hastie and colleagues at the University of California, San Diego Owen Clinic cited evidence that about 45% of antiretroviral-treated people in the United States adhere poorly to therapy [2]. Factors tied to poor adherence in prior research include female and transgender identity, nonwhite race, low education level, poverty, unemployment, and young age [3]. A network meta-analysis linked text-messaging, adherence counseling and education, personal support interventions (like peer support), and cognitive behavioral therapy to better antiretroviral adherence [4]. But this meta-analysis found that "the effects of even the most effective interventions were slight, and might wane after the intervention is withdrawn" [4].
The US FDA licensed copackaged CAB+RPV injected every 2 months for people with a viral load already below 50 copies. In March 2024, IAS-USA antiretroviral therapy (ART) guidelines said CAB+RPV could also be considered for some groups with a detectable viral load: those with persistent inability to take oral ART, high risk of disease progression (CD4 count below 200 or history of AIDS complications), HIV susceptible to CAB and RPV, and referral for substance use and mental health treatment.
The US LATITUDE trial randomized 293 people with a viral load below 200 copies and adherence problems to CAB+RPV or oral ART. LATITUDE defined poor adherence as a viral load above 200 copies at least twice or loss to follow-up (failure to keep study visits). Twenty-eight failures in the CAB+RPV group and 47 in the oral group translated into a 14.4% lower probability of failure with CAB+RPV-meaning CAB+RPV was superior to daily oral ART for people who faced adherence challenges [5]. The Owen Clinic investigators reproduced LATITUDE parameters in a retrospective, observational, real-world analysis of antiretroviral-treated people in their care. But they avoided one feature of LATITUDE that never appears in real-world populations: economic incentives and compensation.
The Owen Clinic study population consisted of people with antiretroviral adherence challenges who started CAB+RPV from November 2021 to September 2023. The researchers defined adherence problems as a viral load at or above 200 copies in the past 12 months and EITHER poor response to oral ART (2 viral loads at or above 200 copies separated by at least 4 weeks in the past 18 months despite prescription of oral ART) OR loss to follow-up, that is, no contact with an HIV provider for 6 months or more and not taking ART for 7 days or more.
Unlike participants in the LATITUDE trial, people in the Owen Clinic retrospective study had no induction phase to reach an undetectable viral load before starting injected CAB+RPV. But they could take other antiretrovirals to help them suppress HIV, particularly if they had a high viral load, for example, above 10,000 copies. The primary outcome was ART discontinuation or virologic failure (a viral load at or above 200 copies) within 24 to 48 weeks of starting CAB+RPV.
Sixty-three people began CAB+RPV and had 24 weeks of outcome data in their charts; 54 people had 48-week outcome data. Demographics were similar in the 24- and 48-week groups: average age 44.2 and 44.7, 46.0% and 48.2% white, 15.9% and 13.0% black, 38.3% and 35.2% Hispanic, 73.0% and 74.1% male at birth, and average body mass index 26.5 kg/m2 and 26.3 kg/m2. About 40% of the study group had ever injected drugs (compared with 15% in the LATITUDE trial), and one third currently used methamphetamine. About half had anxiety or depression. Almost two thirds used Medicaid, 8% used Medicare only, and 15% used commercial insurance.
Just over 40% of the study group had a viral load above 50 copies when they started CAB+RPV, median CD4 count stood at 488 (compared with 270 in LATITUDE), and median years since HIV diagnosis at 14.2. Only 7 people had a viral load above 10,000 copies when starting CAB+RPV. Sixty cohort members took CAB+RPV every 2 months, while 3 started with a dose every 1 month followed by every 2 months. Only 10 people (16%) had a late CAB+RPV injection during the study period.
At CAB+RPV week 24, only 12 people (19% of 63) met the primary endpoint of virologic failure (6 people) or discontinuation (6 people). Three of the 6 with virologic failure returned to an undetectable viral load without changing their CAB+RPV regimen. Among the 6 discontinuations, 3 resulted from loss to follow-up, 2 reflected participant choice, and 1 resulted from a death unrelated to ART failure.
At week 48, only 10 people (18.5% of 54) met the primary endpoint, 5 with virologic failure and 5 with discontinuations. Forty-four people (81.5% of 54) had a viral load below 200 copies at week 48. Kaplan-Meier analysis indicated that 75% of the study group did not have virologic failure or discontinue ART through 800 days.
Multiple logistic regression analysis tied only two variables to CAB+RPV failure: low CD4 count when starting CAB+RPV (P = 0.04) and active substance use (P = 0.03). This analysis did not link race, ethnicity, insurance status, psychiatric comorbidity, history of injecting drugs, or late injection of CAB+RPV to failure of this regimen.
The Owen Clinic team noted that their 48-week 18.5% failure rate with CAB+RPV compares well with the 24.1% cumulative failure of that combination in the randomized LATITUDE trial [5]. They believe their real-world retrospective findings add to evidence that injected long-acting antiretrovirals like CAB+RPV can promote sustained HIV control in people with a history of poor adherence, including people with psychiatric comorbidities and socioeconomic challenges.
References
1. Hastie E, Hill L, Bamford I, Martin TCS. Long-acting injectable HIV treatment in individuals with adherence challenges: real-world insights from Southern California. IDWeek, October 16-19, 2024, Los Angeles. Abstract 157.
2. Benson C, Wang X, Dunn KJ, et al. Antiretroviral adherence, d
rug resistance, and the impact of social determinants of health in HIV-1 patients in the US. AIDS Behav. 2020;24:3562-3573. doi: 10.1007/s10461-020-02937-8. https://link.springer.com/article/10.1007/s10461-020-02937-8
3. Mate KKV, Engler K, Lessard D, Lebouché B. Barriers to adherence to antiretroviral therapy: identifying priority areas for people with HIV and healthcare professionals. Int J STD AIDS. 2023;34:677-686. doi: 10.1177/09564624231169329. https://journals.sagepub.com/doi/full/10.1177/09564624231169329
4. Kanters S, Park JJ, Chan K, et al. Interventions to improve adherence to antiretroviral therapy: a systematic review and network meta-analysis. Lancet HIV. 2017;4:e31-e40. doi:10.1016/S2352-3018(16)30206-5. https://www.thelancet.com/journals/lanhiv/article/PIIS2352-3018(16)30206-5/fulltext
5. Rana AI, Bao Y, Zheng L, et al. Long-acting injectable CAB/RPV is superior to oral ART in PWH with adherence challenges. ACTG A5359. Conference on Retroviruses and Opportunistic Infections (CROI), March 3-6, 2024, Denver. Abstract 212. https://www.croiconference.org/wp-content/uploads/sites/2/resources/2024/croi2024-abstract-ebook-v3.pdf
|
| |
|
|
|
|
|
