Abstract
Objectives
This study aimed to assess eligibility for long-acting injectable (LAI) cabotegravir/rilpivirine among people with HIV (PWH), identify factors associated with initiation and examine provider prescribing patterns in an urban academic clinic in the USA.
Patients and methods
We conducted a retrospective cohort analysis among PWH at the University of Chicago HIV clinic from 1 January 2021 to 31 May 2023. Eligibility criteria for LAI cabotegravir/rilpivirine included HIV-1 RNA <50 copies/mL for ≥3 months, no active hepatitis B, no resistance to rilpivirine or cabotegravir and no treatment failure history. Logistic regression identified factors associated with initiation among eligible PWH as well as prescribing patterns of providers.
Results
Of 657 PWH, 413 (63%) were eligible for LAI cabotegravir/rilpivirine. Median age was 45, 33% were women, 84% Black, 70% had permanent housing, 52% employed, 56% on Medicaid, 9% had active substance use and 26% had psychiatric comorbidities. Among those eligible, 64 PWH (15%) initiated LAI cabotegravir/rilpivirine. In multivariate analysis, younger age was the only factor associated with LAI cabotegravir/rilpivirine initiation [OR 0.96, 95% CI (0.94, 0.99), P = 0.01]. Prescribing patterns varied widely among the 13 providers, with initiation rates ranging from 0% to 33% (P < 0.001). Two providers, covering 40% of eligible patients, were responsible for 70% of initiations.
Conclusions
In our urban HIV clinic, 63% of PWH were eligible for LAI cabotegravir/rilpivirine, and 15% initiated it within 2.5 years post-approval. Age and provider patterns significantly influenced LAI cabotegravir/rilpivirine uptake. Understanding factors driving LAI cabotegravir/rilpivirine uptake is key to expanding its reach.
Introduction
Long-acting injectable (LAI) cabotegravir/rilpivirine is a new formulation of antiretroviral therapy (ART) available for select people with HIV (PWH) since 2021. This two-drug regimen, administered as a monthly or bimonthly intramuscular injection, has US FDA approval as a switching option in PWH who have maintained virological suppression on a stable antiretroviral regimen, with no history of treatment failure and no known or suspected resistance to either drug.1 The introduction of the first long-acting ART combination marks a significant milestone in HIV treatment, as adherence to and persistence with oral ART continue to pose challenges for many people living with HIV, despite significant advancements in the potency, safety and simplicity of ART regimens.2–4 In 2021, 34% of PWH in the USA had not achieved sustained virological suppression with large disparities across race/ethnicity, sexual and gender identity and geographical regions.5 Most common barriers to adherence encompass psycho-social and structural challenges such as stigma, housing and/or food insecurity, mental health issues, insurance gaps, substance use or competing priorities.6–12 By reducing pill burden, lowering the risk of inadvertent HIV disclosure, improving adherence and mitigating stigma, LAI cabotegravir/rilpivirine holds promise to address some of these challenges and promote sustained virological suppression.13–16
However, LAI cabotegravir/rilpivirine integration into HIV clinics has faced challenges, despite a positive reception from PWH and providers.15–22 Barriers to implementation have emerged across multiple levels resulting in a slower-than-anticipated rollout. The establishment of new processes and organizational frameworks for LAI ART delivery in clinics, along with limitations in time, space and staff, has significantly contributed to this delay.15–17,23 While policy, clinic/health systems and community-level factors are crucial for implementation, providers also have a central role in raising awareness of LAI cabotegravir/rilpivirine and offering it to PWH. Despite the patient–provider interaction being an important driver for ART uptake, discussion about LAI cabotegravir/rilpivirine occurred in only a minority of HIV clinical visits during the early implementation phase.23,24 These disparities in patient awareness, along with structural, social and political barriers, have the potential to deepen HIV health inequities by delaying access to long-acting therapy for PWH who may benefit the most from this new treatment. While numerous studies have reported early treatment outcomes after implementing LAI cabotegravir/rilpivirine,25–29 little is known about the proportion of individuals eligible for this treatment within a large HIV cohort, whether disparities in treatment adoption occurred among eligible patients after early implementation, and the influence of providers on treatment initiation.
In this study, we evaluated eligibility for LAI cabotegravir/rilpivirine among PWH in a Ryan White-funded HIV clinic serving a primarily Black population in an Ending the HIV Epidemic priority jurisdiction in the USA, assessed factors associated with treatment initiation and examined provider prescribing patterns across the clinic to identify potential disparities in LAI-CAB/RPV uptake among eligible PWH.
Patients and methods
Study setting and population
The University of Chicago HIV clinic, a Ryan White-funded clinic on Chicago’s South Side, serves approximately 650 PWH who are predominantly Black (85%), consistent with the racial make-up of the surrounding community. The overall virological suppression rate in the clinic is approximately 80%, two-thirds of patients are retained in care by standard metrics and about 60% have Medicaid as their primary insurance.30 The University of Chicago HIV clinic is part of a larger infectious diseases clinic staffed by approximately 20 providers with diverse backgrounds, clinical focuses and responsibilities. This leads to significant variations in the number of PWH that each provider manages. After the FDA’s approval of LAI cabotegravir/rilpivirine on 21 January 2021, a pharmacy-centred model was created to support initiation and injection adherence. The implementation and impact of this programme on LAI cabotegravir/rilpivirine initiations have been previously described.31 Briefly, interested and potentially eligible patients were referred to the hospital specialty pharmacy through an order in the electronic medical record (EMR) after discussion with a provider. Upon receiving referrals, experienced pharmacists confirmed patient eligibility, provided education and counselling, handled prior authorizations and scheduling, conducted follow-up communications and tracked injection schedules. LAI cabotegravir/rilpivirine was covered on Medicaid and ADAP formularies in Illinois on 1 October 2021 and 1 January 2023, respectively.
Study design
We conducted a single-centre retrospective analysis including all people with HIV-1, aged 18 years or older, who attended the University of Chicago HIV clinic at least once between 1 January 2021 and 31 May 2023 and who had at least two viral load measurements available during this period. The study objectives were the following: (i) to evaluate the proportion of PWH eligible for LAI cabotegravir/rilpivirine and compare their basic socio-demographic characteristics with those who were not eligible; (ii) to identify factors associated with LAI cabotegravir/rilpivirine initiation among eligible PWH; and (iii) to evaluate and compare LAI cabotegravir/rilpivirine initiation rates among providers in the clinic for eligible PWH. Participants were considered eligible for LAI cabotegravir/rilpivirine if they met all the following criteria according to the Department of Health and Human Services Guidelines at least one during the study period: (i) sustained virologic suppression (VS) (HIV-1 RNA <50 copies/mL) on a stable antiretroviral regimen for at least 3 months; (ii) no resistance-associated mutations (RAM) to rilpivirine or cabotegravir on historical genotypes and/or no history of treatment failure on NNRTI or integrase strand transfer inhibitors (INSTI) and (iii) no active hepatitis B virus infection defined by a positive hepatitis B surface antigen.32 PWH with minor RAM to INSTI or NNRTI, defined as a Sanford genotypic susceptibility score >15, were considered not eligible for LAI cabotegravir/rilpivirine. For PWH with no available HIV genotype, a history of treatment failure was defined as the inability to achieve or maintain an HIV RNA <200 copies/mL 6 months after initiating a NNRTI and/or INSTI therapy. The study flowchart (Figure 1) summarizes the steps taken to determine participant eligibility for LAI cabotegravir/rilpivirine. The pharmacy tracking system was used to identify PWH who initiated LAI cabotegravir/rilpivirine treatment, defined as having received at least one injection within the study period.
Figure 1.
Flowchart of PWH eligible for and initiating LAI cabotegravir/rilpivirine. PWH, people with HIV; LAI-CAB/RPV, long-acting injectable cabotegravir/rilpivirine; RAM, resistance-associated mutations; VS, virally suppressed; NNRTI, non-nucleoside reverse transcriptase inhibitor; INSTI, integrase strand transfer inhibitor.
Data collection
We used an automated data extraction process to collect basic characteristics from the EMR, including age, sex, race/ethnicity, zip code, primary insurance, follow-up visit dates with provider, HIV-1 RNA viral load and CD4 count values during the study period. For PWH who were VS for at least 3 months, we performed manual medical record abstraction to collect the following information from free text note and ICD-10 codes: housing status (permanent, temporary, unstable, homeless according to the Ryan White HIV/AIDS programme definitions), employment status, date of HIV diagnosis, any active substance use (alcohol use disorder and/or current use of stimulants, opioids, hallucinogens or other drugs), psychiatric comorbidities, oral and injectable comedications, HBV status, HIV genotype history and past and current exposure to NNRTI and/or INSTI. The study electronic case report form (eCRF) is available in the Appendix.
Data analysis
Descriptive statistics were used to summarize the characteristics of patients eligible for LAI CAB-RPV, including medians and IQR for continuous variables and frequencies and percentages for categorical variables. Basic socio-demographic characteristics of PWH eligible for LAI cabotegravir/rilpivirine were compared to those who were not eligible using a Wilcoxon rank-sum test for continuous variables and chi-square or Fisher’s exact tests for categorical variables. We used a logistic regression model to evaluate the factors associated with LAI cabotegravir/rilpivirine initiation among eligible patients. Bivariable logistic regression models included a priori variables likely to be associated with LAI cabotegravir/rilpivirine initiation such as age, time from HIV diagnosis, employment status, active psychiatric comorbidities, taking other daily pills or receiving another injection treatment. Covariates identified as possible factors in the bivariable analysis (P < 0.30) were retained for the multivariable model. Model results are presented as OR and 95% CI (upper bound, lower bound). We also conducted a sensitivity analysis where we replicated the multivariate model including all PWH with an unknown or incomplete ART history as eligible for LAI cabotegravir/rilpivirine. The provider analysis included all healthcare professionals (physicians, physician assistants, nurse practitioners) authorized to prescribe LAI-CAB/RPV who managed at least 10 PWH at the UChicago HIV clinic during the study period. For each eligible patient, we determined the provider who was seen the most frequently over the study period. In cases where there were ties (two or more providers were seen the same number of times), we chose the provider seen earliest. We compared the proportion of LAI cabotegravir/rilpivirine initiation among eligible PWH by provider using a Fisher’s exact test, as well as in bivariable logistic regression models. In these models, we examined if individual providers, as well as if including provider information overall, improved the prediction of LAI cabotegravir/rilpivirine initiation. Lastly, we compared initiation rates among eligible patients seen by one, two or more than three providers during the study period to evaluate the impact of provider switches on LAI cabotegravir/rilpivirine initiation. All P-values and confidence intervals were two-sided, with statistical significance of P ≤ 0.05, unless otherwise noted (such as for bivariable analyses, P = 0.3). Statistical analyses were performed using SAS software version 9.4 (Cary, NC, USA). This project was formally determined to be quality improvement, not human subjects research, and was therefore not overseen by the Institutional Review Board, per the University of Chicago Medicine institutional policy. As a quality improvement project, data were collected as part of routine clinical care, and consent was not obtained for this retrospective review.
Results
Eligibility for LAI cabotegravir/rilpivirine
From 1 January 2021 to 31 May 2023, 657 people with HIV-1 were included in the analysis. The median age was 45 (IQR 32–58) years, 67% were men, 85% identified as Black, 3.5% as Hispanic, and 58% had Medicaid insurance. Figure 1 describes the flowchart for determining LAI cabotegravir/rilpivirine eligibility and details the reasons for non-eligibility based on the availability of genotypic testing. Among the 255 PWH virally suppressed for at least 3 months with a genotype, 24 (9.4%) had RAM to CAB, RPV, or both (Table S1, available as Supplementary data at JAC Online). Overall, among the 657 PWH included, 413 (62.8%) met the eligibility criteria for LAI cabotegravir/rilpivirine. There was no significant difference in terms of age, sex, race/ethnicity or primary insurance between PWH who were eligible versus those who were not in the cohort (Table S2). However, the median number of visits was higher among eligible PWH compared to those not eligible (three versus two visits, P < 0.001).
Characteristics of PWH eligible for LAI cabotegravir/rilpivirine
Among the 413 PWH eligible for LAI cabotegravir/rilpivirine, the median age was 45 years, 67% were men, 84% identified as Black, 4% as Hispanic, 52% were employed, 70% had permanent housing, and 56% had Medicaid insurance. Nine per cent reported active substance use, 26% had a psychiatric comorbidity, and 69% were prescribed at least one daily oral medication aside from their HIV treatment (Table 1). The median time (IQR) from HIV diagnosis was 9 (3–18) years, 52% had an HIV genotype available in the EMR, and 6% had a confirmed CD4 count <200/mm² at the first visit; they were eligible for LAI cabotegravir/rilpivirine. Of the 413 PWH eligible, 64 (15%) started LAI cabotegravir/rilpivirine over the study period. The median time (IQR) from the first eligible visit to LAI cabotegravir/rilpivirine initiation was 10 months (IQR: 3–15).
Table 1.
Characteristics of PWH eligible for LAI cabotegravir/rilpivirine
| PWH eligible for LAI-CAB/RPV (n = 413) | PWH who did not start LAI-CAB/RPV (n = 349) | PWH who started LAI-CAB/RPV (n = 64) | |
|---|---|---|---|
| Median age (years)—IQR | 45 (3 258) | 48 (3 360) | 33.5 (2 944.5) |
| Age categories—no. (%) | |||
| < 30 | 64 (15.5%) | 43 (12.3%) | 21 (32.8%) |
| 30–50 | 179 (43.3%) | 146 (41.8%) | 33 (51.6%) |
| > 50 | 170 (41.2%) | 160 (45.9%) | 10 (15.6%) |
| Sex assigned at birth—no. (%) | |||
| Men | 278 (67.3%) | 234 (67.1%) | 44 (68.8%) |
| Women | 135 (32.7%) | 115 (33.0%) | 20 (31.3%) |
| Race/ethnicity—no. (%) | |||
| Black | 346 (83.8%) | 294 (84.2%) | 52 (81.3%) |
| Hispanic | 16 (3.9%) | 13 (3.7%) | 3 (4.7%) |
| White | 34 (8.2%) | 29 (8.3%) | 5 (7.8%) |
| Asian | 3 (0.7%) | 2 (0.6%) | 1 (1.6%) |
| Other (more than one) | 3 (0.7%) | 3 (0.9%) | 0 (0.0%) |
| Missing data/unknown/patient declined | 11 (2.7%) | 8 (2.3%) | 3 (4.7%) |
| Housing—no. (%) | |||
| Permanent | 288 (69.7%) | 245 (70.2%) | 43 (67.2%) |
| Temporary | 30 (7.7%) | 24 (6.9%) | 6 (9.4%) |
| Unstable | 22 (5.3%) | 17 (4.9%) | 5 (7.8%) |
| Homeless | 1 (0.2%) | 1 (0.3%) | 0 (0.0%) |
| Unknown | 72 (17.4%) | 62 (17.8%) | 10 (15.6%) |
| Employment status—no. (%) | |||
| Employed | 216 (52.3%) | 174 (49.6%) | 43 (67.2%) |
| Unemployed | 47 (11.4%) | 42 (12.0%) | 5 (7.8%) |
| Retired | 41 (10.3%) | 37 (10.6%) | 4 (6.3%) |
| Student | 1 (0.3%) | 1 (0.3%) | 0 (0.0%) |
| Disability | 70 (17.0%) | 63 (18.1%) | 7 (10.9%) |
| Unknown | 38 (9.2%) | 33 (9.5%) | 5 (7.8%) |
| Primary insurance—no. (%) | |||
| Medicare | 6 (1.5%) | 5 (1.4%) | 1 (1.6%) |
| Medicaid | 230 (55.7%) | 192 (55.0%) | 38 (59.4%) |
| Private | 176 (42.6%) | 151 (43.3%) | 25 (39.1%) |
| Missing data | 1 (0.2%) | 1 (0.3%) | 0 (0.0%) |
| Time from HIV diagnosis (years)—median (IQR) (missing n = 19) | 9 (3, 18) | 11 (3, 19) | 6 (3, 11) |
| Active substance use | |||
| At least one substance—no. (%) | 37 (9.0%) | 32 (9.2%) | 5 (7.8%) |
| Stimulants | 16 (3.9%) | 13 (3.7%) | 3 (4.7%) |
| Alcohol use disorder | 18 (4.4%) | 17 (4.9%) | 1 (1.6%) |
| Opioid | 6 (1.5%) | 5 (1.4%) | 1 (1.6%) |
| Hallucinogen | 3 (0.7%) | 3 (0.9%) | 0 (0.0%) |
| Active psychiatric comorbidities | |||
| At least one mental illness—no. (%) | 108 (26.2%) | 96 (27.5%) | 12 (18.8%) |
| Anxiety disorders | 20 (4.8%) | 17 (4.9%) | 3 (4.7%) |
| Depression or bipolar disorder | 81 (19.6%) | 72 (20.6%) | 9 (14.1%) |
| Post-traumatic stress disorder | 5 (1.2%) | 5 (1.4%) | 0 (0.0%) |
| Schizophrenia or psychosis | 10 (2.4%) | 9 (2.6%) | 1 (1.6%) |
| Other psychiatric disorders | 6 (1.5%) | 6 (1.7%) | 0 (0.0%) |
| Other chronic medication | |||
| At least one other chronic medication—no. (%) | 295 (71.4%) | 259 (74.2%) | 36 (56.2%) |
| At least one other daily pill—no. (%) | 286 (69.3%) | 255 (73.1%) | 31 (48.4%) |
| Number of oral drugs—median (IQR) | 3 (2, 5) | 3 (2, 6) | 2 (1, 3) |
| At least one injectable druga—no. (%) | 52 (12.8%) | 42 (12.0%) | 11 (17.2%) |
| Number of injectable treatments—median (IQR) | 0 (0, 0) | 0 (0, 0) | 0 (0, 1) |
| HIV genotype available—no. (%) | 214 (51.8%) | 184 (52.7%) | 30 (46.9%) |
| CD4 count | |||
| Median CD4 over the study period (IQR) | 607 (437, 807) | 601 (436, 806) | 624 (447, 844) |
| Confirmed CD4 <200/mm3—no. (%) | 25 (6.1%) | 21 (6.0%) | 4 (6.3%) |
| Missing data | 4 (1.0%) | 3 (0.9%) | 1 (1.6%) |
PWH, people with HIV; LAI-CAB/RPV, long-acting injectable cabotegravir/rilpivirine; RAM, resistance-associated mutations.
aInjection medications include insulin, liraglutide, semaglutide, testosterone, adalimumab and evolocumab.
Factors associated with LA cabotegravir/rilpivirine initiation
In the bivariable model, PWH who initiated LAI cabotegravir/rilpivirine were significantly younger (34 versus 48 years) with 0.95 times the odds for each additional year of age [OR 0.95, 95% CI (0.93, 0.97), P < 0.001], diagnosed with HIV more recently (6 versus 11 years) with 0.96 times the odds for each additional year since diagnosis [OR 0.96, 95% CI (0.93, 0.99), P = 0.009], were more likely to be employed [OR 2.22, 95% CI (1.20, 4.11), P = 0.01] and were less likely to take additional daily medications aside from their HIV treatment [OR 0.35, 95% CI (0.20, 0.60), P < 0.001]. Variables that did not meet the 0.05 significance level, but did meet the P = 0.3 level for inclusion in multivariable models included use of injectable treatments and psychiatric comorbidities. Indeed, initiators tended to be more likely to receive injectable medications for conditions other than HIV [OR 1.52, 95% CI (0.74, 3.13), P = 0.26] and more likely to have psychiatric comorbidities [OR 1.64, 95% CI (0.84, 3.21), P = 0.15]. In multivariable analysis, younger age remained significantly associated with LAI cabotegravir/rilpivirine initiation, with 0.96 times the odds of initiation for each year of increasing age [OR 0.96, 95% CI (0.94, 0.99), P = 0.01] (Table 2). No other variables, including receiving an injectable medications for others conditions than HIV [OR 2.23, 95% CI (0.98, 5.08), P = 0.06], having psychiatric comorbidities [OR 0.87, 95% CI (0.41, 1.84), P = 0.71] or taking oral daily medication other than ART [OR 0.60, 95% CI (0.30, 1.22), P = 0.16] were significant in the multivariable model. In the sensitivity analysis including participants with incomplete or unknown HIV history (n = 466), similar results were obtained with younger age remaining independently associated with LAI cabotegravir/rilpivirine initiation [OR 0.96, 95% CI (0.94, 0.99), P = 0.004] (Table S3). Mirroring the results of our previous model, receiving an injectable medication [OR 0.53, 95% CI (0.24, 1.17), P = 0.12], having psychiatric comorbidities [OR 0.74, 95% CI (0.37, 1.49), P = 0.40] and taking oral daily medication other than ART [OR 0.66, 95% CI (0.34, 1.29), P = 0.22] were not significant in the multivariate model.
Table 2.
Factors associated with LAI cabotegravir/rilpivirine initiation among eligible PWH
| PWH eligible for LAI-CAB/RPV (n = 413) | PWH who started LAI-CAB/RPV (n = 64) | Univariate modela | Multivariate modela | |||
|---|---|---|---|---|---|---|
| OR (95% CI) | P-value | OR (95% CI) | P-value | |||
| Age (years) | 45 (32, 58) | 33.5 (29, 44.5) | 0.95 (0.93, 0.97) | <0.001 | 0.96 (0.94, 0.99) | 0.01 |
| Time from HIV diagnosis (years) | 9 (3, 18) | 6 (3, 11) | 0.96 (0.93, 0.99) | 0.009 | 0.99 (0.96, 1.03) | 0.74 |
| Employed | ||||||
| Yes | 216 (52.3%) | 43 (67.2%) | 2.22 (1.20, 4.11) | 0.01 | 1.15 (0.57, 2.33) | 0.70 |
| No | 159 (38.5%) | 16 (25.0%) | Reference | Reference | ||
| Psychiatric comorbidities | ||||||
| Yesb | 108 (26.2%) | 12 (18.8%) | 1.64 (0.84, 3.21) | 0.15 | 0.87 (0.41, 1.84) | 0.71 |
| No | 305 (73.9%) | 52 (81.3%) | Reference | Reference | ||
| Other oral daily pills | ||||||
| Yes | 286 (69.3%) | 31 (48.4%) | 0.35 (0.20, 0.60) | <0.001 | 0.60 (0.30, 1.22) | 0.16 |
| No | 127 (30.8%) | 33 (51.6%) | Reference | Reference | ||
| Injectable medication | ||||||
| Yes | 52 (12.8%) | 11 (17.2%) | 1.52 (0.74, 3.13) | 0.26 | 2.23 (0.98, 5.08) | 0.06 |
| No | 307 (88.0%) | 53 (82.8%) | Reference | Reference | ||
PWH, people with HIV; LAI-CAB/RPV, long-acting injectable cabotegravir/rilpivirine; OR, odds ratio; CI, confidence interval.
aA total of 54 participants were removed from the model for missing data related to employment status and/or time from HIV diagnosis.
bAnxiety disorders, depression or bipolar disorder, post-traumatic stress disorder (PTSD), schizophrenia or psychosis, other psychiatric disorders.
Provider prescribing patterns for LAI cabotegravir/rilpivirine
Five providers saw fewer than 10 eligible patients and were not included in this analysis. The provider prescribing patterns analysis included 13 providers managing 399 eligible PWH. Of the included providers, 11/13 (85%) were infectious diseases-trained, 12 (92%) were physicians (MD/DO), and 1 (8%) was an advanced practice provider. At the start of the study period, five providers had been in practice for 1–5 years, three for 6–10 years, and five for >10 years. The proportion of LAI cabotegravir/rilpivirine initiation per provider varied widely, ranging from 0% to 33% (Figure 2). Bivariable logistic regression models examining the effect of each provider on LAI cabotegravir/rilpivirine initiation resulted in no significant associations for individual providers. However, the inclusion of provider information overall was significant in predicting who initiated LAI cabotegravir/rilpivirine (P = 0.03). When testing the proportion of patients who did and did not initiate LAI cabotegravir/rilpivirine by provider, significant differences were seen using Fisher’s exact test (P < 0.001). Providers M and L, who managed 40% of eligible patients, drove 70% of LAI cabotegravir/rilpivirine initiations. These two providers had a significantly younger pool of eligible patients with a median age (IQR) of 34 (29–46) years, compared to the rest of the providers, whose patients had a median age of 52 (38–62) (P < 0.001). During the study period, eligible PWH were seen by one or more providers, with 235 (58.9%) managed by a single provider, 131 (32.8%) by two providers, 30 (7.5%) by three providers and 3 by four providers (0.08%). The number of providers seen by PWH did not significantly impact LAI cabotegravir/rilpivirine initiation rates (one provider, 58.5% initiations; two providers, 32.9% initiations; three providers, 7.7% initiations; four providers, 0.9% initiations; Fisher’s exact test P = 0.99).
Figure 2.
Rate of LAI cabotegravir/rilpivirine initiation among eligible PWH per clinic’s providers. LAI-CAB/RPV, long-acting injectable cabotegravir/rilpivirine.
Discussion
In the University of Chicago HIV clinic serving primarily Black PWH, 63% of the 655 PWH in the clinic were eligible for LAI cabotegravir/rilpivirine, and 15% of those eligible initiated it within 2.5 years after FDA approval. Younger age was strongly associated with treatment initiation. Other factors such as taking oral daily medication other than ART or receiving an injectable medication for other conditions other than HIV also emerged as potential factors related to LAI cabotegravir/rilpivirine initiation across our different analyses, yet did not reach statistical significance. Important variations in prescribing patterns were identified, suggesting that providers may significantly influence the initiation of LAI cabotegravir/rilpivirine. Importantly, there were no differences in initiation by insurance status.
While numerous studies have focused on early patient outcomes after implementing LAI cabotegravir/rilpivirine,25–29 few have explored the proportion of PWH eligible for this treatment in large HIV cohorts. Our analysis revealed that 37% of PWH at the University of Chicago HIV clinic were ineligible for LAI cabotegravir/rilpivirine. This ineligibility rate is lower than the approximately 70% reported in the Washington DC cohort and close to the 33% found among VS patients in the University of North Carolina HIV clinical cohort.33,34 Our study aligned with data from an Italian study, where ineligibility rates ranged from 31% to 47%.35 The differences across studies can be explained in part by the variability in the approaches and criteria used to define LAI cabotegravir/rilpivirine eligibility. Most cases of non-eligibility in our cohort (60%) were due to not achieving viral suppression on oral ART rather than a history of failure on NNRTIs and/or INSTIs. With a large proportion of eligible PWH, ∼15% initiated LAI cabotegravir/rilpivirine initiation in our clinic, which was higher than previously reported in other programmes.33,36 Notably, in the 2.5 years following FDA approval, only 23/1469 (2%) of eligible patients according to the FDA package insert started LAI cabotegravir/rilpivirine across the 14 sites of the Washington DC cohort.33 The early development of a pharmacy-centred, hospital-based delivery likely facilitated the initiation of LAI cabotegravir/rilpivirine in our medium-sized clinic.31 Interestingly, patient insurance status was not associated with LAI cabotegravir/rilpivirine initiation in our clinic, possibly because PWH covered by Medicaid gained early access to the treatment in Illinois. Younger age was independently associated with LAI cabotegravir/rilpivirine initiation among eligible PWH in our cohort, with half of the initiations occurring in people under 34 years, which is consistent with previous studies.33,37 Other factors such as taking oral daily medication other than ART or receiving injectable medications for other conditions than HIV also emerged as potential factors related to LAI cabotegravir/rilpivirine initiation. The strong overlap between younger age and these factors, along with the small number of PWH initiating LAI cabotegravir/rilpivirine, may have limited the model’s ability to assess their independent associations with treatment initiation. Additional studies will be needed to confirm if these trends in our analysis are significant in larger studies.
While younger age was a key driver of LAI cabotegravir/rilpivirine initiation following early implementation, PWH who were expected to benefit most from LAI ART introduction, such as those with psychiatric comorbidities, substance use, or unstable housing, showed similar initiation rates to other patients in the cohort. These PWH may be overrepresented among those who did not achieve viral suppression, rendering them ineligible for LAI cabotegravir/rilpivirine according to the study eligibility criteria. This is an important focus for further studies. These differences in treatment uptake among certain patient profiles may be explained by how patients are made aware of LAI cabotegravir/rilpivirine within the clinic. Our analysis of provider prescribing patterns is particularly insightful in this regard, as it shows the significant impact of providers on initiation. Notable discrepancies in LAI cabotegravir/rilpivirine initiation rates were observed between providers in the clinic, with two providers accounting for 70% of initiations. The outsized impact of these two providers on LAI cabotegravir/rilpivirine initiation at the clinic level may be partially explained by the fact that they have a younger patient population compared to other providers. However, there were also variations in initiation rates among providers with similarly aged patients, suggesting that factors other than age contribute to differences in initiation among providers. Providers’ varying attitudes towards informing PWH about LAI cabotegravir/rilpivirine should also be considered. Qualitative analyses revealed that providers considered younger PWH and those not taking other medications to be more suitable candidates for LAI ART.19 Providers were also particularly excited to offer LAI cabotegravir/rilpivirine to PWH struggling with adherence to oral ART.16 These perceptions may shape how providers inform PWH about LAI cabotegravir/rilpivirine, which may lead them to selectively discuss LAI ART with certain patients. This difference between providers in initiation rates might also be explained by other factors, such as differential training, experience and comfort in managing ART, workload and time constraints or relationship with the pharmaceutical industry (i.e. advisory boards). Furthermore, not all PWH are interested in switching to injectable treatment. Although most PWH react positively to LAI ART, some remain sceptical about it. In a survey conducted in May 2021 across three academic HIV clinics, including our own, 8% and 5% of participants reported they probably or definitely would not try LAI CAB/RPV, respectively.23 The common dealbreakers included fear of needles and anticipated pain, difficulty integrating injections into daily routines and/or challenges in attending appointments.15 While it is unclear how many PWH were informed about or declined LAI-CAB/RPV in this analysis, the varying initiation rates among providers suggest significant differences in the shared decision-making process regarding injectable ART. Further exploration is needed to understand the factors influencing this process and ensure that patients are adequately informed and involved in decisions about their treatment options.
This study has several limitations. First, we conducted a retrospective single-centre study in an academic urban HIV clinic serving primarily Black PWH, which may limit the generalizability of our findings to other settings. Second, certain factors were not taken into account when assessing patients’ eligibility for LAI cabotegravir/rilpivirine, such as pregnancy, potential drug–drug interactions, hepatic impairment or contraindications to intramuscular injection. Therefore, the proportion of PWH eligible for LAI cabotegravir/rilpivirine may have been overestimated. Third, some of the variables included in the model such as employment, the use of other medications or psychiatric comorbidities may have varied over time for each patient during their eligibility period to LAI ART. It is unclear whether this change over time can influence the results of the model. Fourth, the lack of systematic tracking in the EMR regarding LAI cabotegravir/rilpivirine discussions and potential refusals limited the ability to understand the reasons for differences in initiation rates between providers. Lastly, due to the limited number of LAI cabotegravir/rilpivirine initiations and significant overlap among these variables within the same persons, we were not able to fully determine whether certain variables, besides age, were independently correlated with treatment initiation. Despite these limitations, we think this study provides valuable insights into understanding the reach of LAI cabotegravir/rilpivirine among eligible PWH and factors associated with treatment initiations in a large HIV cohort.
To conclude, in the University of Chicago HIV clinic, which primarily serves Black PWH on Chicago’s South Side, nearly two-thirds of PWH were eligible for LAI cabotegravir/rilpivirine, and 15% of those eligible initiated this treatment within 2.5 years after FDA approval. Younger age was strongly associated with treatment initiations, and a trend was also observed for receiving other injectable treatments. Providers had a large impact on uptake with notable differences in initiation rates, suggesting differences between providers in the decision-making process regarding injectable ART. A better understanding of the factors that influence LAI cabotegravir/rilpivirine use among providers is needed to expand its reach and ensure that all PWH can discuss this new treatment option with their provider.
Supplementary Material
Acknowledgements
We acknowledge the patients at the University of Chicago HIV clinic.
Contributor Information
Geoffroy Liegeon, Department of Medicine, The University of Chicago, Chicago, IL, USA.
Eleanor Friedman, Department of Medicine, The University of Chicago, Chicago, IL, USA.
Christopher Kaperak, Department of Medicine, The University of Chicago, Chicago, IL, USA.
Paul Djuricich, Department of Pharmacy, The University of Chicago, Chicago, IL, USA.
Alicia Dawdani, Department of Medicine, The University of Chicago, Chicago, IL, USA.
Sophie Plotkin, Department of Medicine, The University of Chicago, Chicago, IL, USA.
Jessica Schmitt, Department of Medicine, The University of Chicago, Chicago, IL, USA.
Aniruddha Hazra, Department of Medicine, The University of Chicago, Chicago, IL, USA.
Katerina A Christopoulos, Division of HIV, ID, and Global Medicine, University of California San Francisco, San Francisco, CA, USA.
John A Schneider, Department of Medicine, The University of Chicago, Chicago, IL, USA.
Moira C McNulty, Department of Medicine, The University of Chicago, Chicago, IL, USA.
Funding
K.A.C., J.A.S., and M.C.M. were supported by the National Institutes of Health (PI: K.A.C., R01 MH123396). K.A.C. was also supported by the National Institute of Allergy and Infectious Diseases (K24 AI167805). G.L. was supported by a grant from the ANRS | Maladies Infectieuses Emergentes and by the young researcher scholarship from the Collège Français des Universitaires de Maladies Infectieuses.
Transparency declarations
G.L. has participated in advisory boards for ViiV Healthcare. M.C.M. has served on an advisory board for Gilead Sciences, Inc. K.A.C. has been a medical advisory board member for Gilead Sciences and a workshop participant for Janssen. All other authors declare no competing interests.
Author contributions
M.C.M., P.D., A.H. and J.A.S. implemented LAI-CAB/RPV in the University of Chicago HIV clinic. G.L., M.C.M., K.A.C. and J.A.S. designed the study. G.L., C.K., A.D. and S.P. collected the data. G.L., M.C.M. and E.F. designed the analysis. E.F. conducted the analysis. G.L., M.C.M., E.F. and C.K. reviewed the analysis and validated the final results. G.L. wrote the first draft of the report. All authors critically reviewed and approved the manuscript.
Supplementary data
Tables S1–S3 are available as Supplementary data at JAC Online.
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