Real-World Uptake and Clinical Outcomes of Long-Acting Injectable Cabotegravir/Rilpivirine in the United States, 2021–2023

Abstract

Background:

Long-acting injectable antiretroviral therapy offers an alternative to daily oral regimens for people with HIV. We assessed national uptake and characteristics of persons prescribed injectable cabotegravir/rilpivirine (CAB/RPV) in the United States from 2021 to 2023.

Methods:

We conducted a retrospective cohort study using HealthVerity Marketplace, a national claims database with pharmacy, medical, and laboratory data. People with HIV with ≥1 closed, approved prescription claim for CAB/RPV or oral ART were identified. Demographic, clinical, and payer characteristics, viral load (VL), and CD4 counts were examined.

Results:

From 2021 to 2023, 4087 individuals were prescribed CAB/RPV (21,698 prescriptions), comprising 1.3% of all ART prescriptions by 2023. CAB/RPV recipients were more likely to be aged 25–44 and enrolled in Medicaid. CAB/RPV prescribing was disproportionately low in the Southern United States and among adults 55 years and older, despite higher HIV prevalence in these groups. Among individuals with a detectable VL at initiation (52.2%), 7.2% had viremia (≥200 copies/mL). Among those with ≥1 follow-up VL (n = 2234), 1.8% experienced confirmed virologic failure, defined as ≥2 VLs ≥200 copies/mL. CD4 counts remained stable, with median values near 700 cells/mm³ pre- and postinitiation.

Conclusion:

While CAB/RPV uptake is increasing, its use remains modest and uneven. High rates of virologic suppression support its real-world effectiveness, but disparities by age, region, and payer point to persistent barriers. Continued real-world monitoring and targeted implementation strategies are critical to fully realizing the potential of long-acting injectable ART.

BACKGROUND

Long-acting injectable antiretroviral therapy (LAI-ART) offers an alternative to daily oral regimens and represents a major advance in HIV treatment. Injectable cabotegravir/rilpivirine (CAB/RPV), approved by the US Food and Drug Administration in 2021, provides a maintenance option that may reduce adherence challenges related to pill fatigue, stigma, and medication storage.^1–3 Clinical trials have shown that every-eight-week CAB/RPV injection is noninferior to daily oral ART and is highly preferred by many people with HIV (PWH).^1–6

Early real-world studies have similarly shown high levels of patient acceptance and durable viral suppression but have also identified substantial implementation challenges, including staffing demands, clinic workflow constraints, and insurance-related barriers.^7–9 A national survey of Ryan White–funded clinics conducted early in the CAB/RPV rollout found that only 52% felt prepared to implement LAI-ART, citing logistical and structural challenges.⁷ More recent assessments of US clinics indicate that, despite growing familiarity with CAB/RPV, issues with scheduling, care coordination, and payer navigation continue to limit broader adoption.^10,11

To better understand early implementation in the United States, we used a large national health insurance claims database to characterize CAB/RPV prescribing patterns and the demographic, clinical, and payer characteristics of individuals receiving CAB/RPV. We also described oral ART prescribing to contextualize CAB/RPV use within the broader ART landscape, although we do not assess comparative treatment effectiveness. These findings may help inform strategies to optimize LAI-ART delivery and expand access.

METHODS

We conducted a retrospective cohort study using deidentified data from HealthVerity Marketplace, a national administrative claims database containing pharmacy and medical claims, inpatient and outpatient encounters, and linked laboratory test results.¹² The data set includes individuals insured through Medicaid, Medicare, Medicare Advantage, and commercial plans across the United States and Puerto Rico.

Study Population

PWH 18 years and older were identified by International Classification of Diseases, Tenth Revision (ICD-10) diagnosis codes B20 or Z21 and required to have ≥1 pharmacy claim for CAB/RPV or any oral ART between January 1, 2021, and August 31, 2023. Individuals with incomplete claims data or without a confirmed HIV diagnosis were excluded. CAB/RPV initiation was defined as the earliest CAB/RPV injection claim (Fig. 1).

FIGURE 1.

Monthly number of prescriptions of oral ART and injectable cabotegravir/rilpivirine, HealthVerity real-world data — longitudinal database — United States and Puerto Rico, January 2021 through May 2023*. *Data after May 2023 were excluded from the figure due to reporting lags.

Sociodemographic, Clinical, and Prescription Characteristics

Demographic variables included age and sex. Clinical and social variables included diagnoses of depression, anxiety, bipolar disorder, schizophrenia, and substance use disorders, identified using ICD-10 codes recorded at any time during the study period. Prescription-related characteristics included year and region of prescription, payer type, and the number of unique payers within the month of prescription.

Laboratory Measures

Viral load (VL) at initiation was defined as the most recent VL within the 3 months before or on the day of CAB/RPV initiation. Viral suppression was defined as VL <200 copies/mL. All VL results obtained after CAB/RPV initiation were included, and virologic outcomes were assessed among individuals with at least one postinitiation VL measurement. Confirmed virologic failure was defined as ≥2 consecutive VLs ≥ 200 copies/mL. CD4 counts at initiation were defined as those obtained within 12 months before initiation; all subsequent CD4 results recorded after initiation were included. Laboratory data were not imputed, and missing VL or CD4 measurements were treated as unavailable rather than as clinical outcomes.

Statistical Analysis

Demographic, clinical, payer, and prescription characteristics were summarized using descriptive statistics. Differences between individuals prescribed CAB/RPV and those prescribed oral ART were assessed using χ² tests or two-sample Z tests for proportions. A Bonferroni correction was applied to account for multiple comparisons, with statistical significance set at P < 0.0014. Analyses were conducted using SAS version 9.4 (SAS Institute Inc, Cary, NC).

Ethical Review

This activity was reviewed by CDC, deemed not research, and was conducted consistent with applicable federal law and CDC policy^§. ^§See e.g., 45 C.F.R. part 46, 21 C.F.R. part 56; 42 U.S.C. §241(d); 5 U.S.C. §552a; 44 U.S.C. §3501 et seq.

RESULTS

Overall Prescription Trends

Between January 2021 and August 2023, 4087 unique PWH were prescribed CAB/RPV, accounting for 21,698 total prescriptions during the study period (Tables 1 and 2). By contrast, 208,196 individuals were prescribed only oral ART, with a total of 3,469,191 prescriptions. CAB/RPV prescriptions increased substantially over time, rising from 1410 prescriptions in 2021 to 11,051 in 2022 and 9237 prescriptions from January to August 2023 Figure 1.

TABLE 1.

Characteristics of Persons Prescribed Long-Acting Cabotegravir/Rilpivirine, United States and Puerto Rico, January 2021–August 2023

Characteristic	Oral ART* (n = 208,196), No. (%)	Injectable CAB/RPV† (n =4087), No. (%)	% CAB/RPV Among all Patients	P ‡
Age§
13–24	13,176 (6.3)	170 (4.2)	1.3	<0.001
25–34	49,649 (23.8)	1126 (27.6)	2.2	<0.001
35–44	45,280 (21.7)	1092 (26.7)	2.4	<0.001
45–54	40,812 (19.6)	860 (21.0)	2.1	0.02
55–64	45,068 (21.6)	654 (16.0)	1.4	<0.001
65+	13,471 (6.5)	184 (4.5)	1.3	<0.001
Patient sex||
Male	156,031 (74.9)	2890 (70.7)	1.8	<0.001
Female	52,153 (25.0)	1197 (29.3)	2.3	<0.001
Clinical and social variables¶	n = 200,758 evaluable	n = 3965 evaluable
Alcohol use disorder	22,845 (11.4)	448 (11.3)	1.9	0.87
Cannabis use disorder	20,796 (10.4)	526 (13.3)	2.5	<0.001
Cocaine use disorder	13,603 (6.8)	251 (6.3)	1.8	0.27
Opioid use disorder	16,038 (8.0)	309 (7.8)	1.9	0.65
Substance use disorder#	80,420 (40.1)	1893 (47.7)	2.3	<0.001
Depression	66,865 (33.3)	1660 (41.9)	2.4	<0.001
Anxiety	68,437 (34.1)	1580 (39.8)	2.3	<0.001
Bipolar disorder	21,079 (10.5)	517 (13.0)	2.4	<0.001
Schizophrenia	8119 (4.0)	149 (3.8)	1.8	0.37
Homelessness	10,204 (5.1)	184 (4.6)	1.8	0.21

^*Patients with no CAB/RPV prescriptions and at least one oral ART prescription during the study period.

^†Patients with at least one CAB/RPV prescription during the study period.

^‡Both χ² and two-sample proportion tests were used to compare characteristics of the patient populations. P values from the two-sample Z-test for proportions are shown here.

^§Age was missing for 740 individuals in the oral ART group and 1 in the CAB/RPV group. Age was estimated by subtracting the year of birth from the year of the earliest recorded prescription during the study period.

^||Sex was missing for 12 individuals in the oral ART category.

^¶Number of patients with clinical and social variable ICD10 diagnoses documented during study period; 200,758 of the 208,196 patients prescribed oral ART and 3965 of the 4087 patients prescribed CAB/RPV had diagnosis code data available in HealthVerity.

^#Substance use disorder included parent ICD-10 codes F10, F11, F12, F13, F14, F15, F16, F17, F18, and F19.

ART, antiretroviral therapy; CAB/RPV, cabotegravir/rilpivirine; ICD-10, International Classification of Diseases, 10th Revision.

TABLE 2.

Characteristics of Prescriptions of Oral ART and Long-Acting Cabotegravir/Rilpivirine, United States and Puerto Rico, January 2021–August 2023

Characteristic	Oral ART* (n = 3,469,191), No. (%)	Injectable CAB/RPV† (n = 21,698), No. (%)	% CAB/RPV Among all ART	P ‡
Prescription year§
2021	1,344,575 (38.8)	1410 (6.5)	0.10	<0.001
2022	1,431,532 (41.3)	11,051 (50.9)	0.77	<0.001
2023 (January to August)	693,084 (20.0)	9237 (42.6)	1.32	<0.001
Region||
Midwest	395,720 (11.4)	1970 (9.1)	0.50	<0.001
Northeast	941,101 (27.1)	7026 (32.4)	0.74	<0.001
South	1,400,948 (40.4)	7215 (33.3)	0.51	<0.001
West	685,373 (19.8)	5312 (24.5)	0.77	<0.001
Puerto Rico	6136 (0.2)	5 (0.0)	0.08	<0.001
Unknown	39,913 (1.2)	170 (0.8)	0.42	<0.001
Number of payers¶
0	316,086 (9.1)	2103 (9.7)	0.66	0.003
1	3,152,511 (90.9)	19,593 (90.3)	0.62	0.003
2	594 (0.0)	2 (0.0)	0.34	0.374
Payer type# (if number of payers = 1)
Medicaid	1,696,146 (53.8)	14,926 (76.2)	0.87	<0.001
Medicare	665 (0.0)	11 (0.1)	1.63	<0.001
Medicare advantage	418,105 (13.3)	1869 (9.5)	0.44	<0.001
Commercial	1,013,519 (32.1)	2708 (13.8)	0.27	<0.001
Unknown	24,076 (0.8)	79 (0.4)	0.33	<0.001

^*Oral ART prescriptions among patients with no CAB/RPV prescriptions and at least one oral ART prescription during the study period.

^†CAB/RPV prescriptions among patients with at least one CAB/RPV prescription during the study period.

^‡Both χ² and two-sample proportion tests were used to compare characteristics of the patient populations. P values from the two-sample Z-test for proportions are shown here.

^§Year of pharmacy prescription.

^||Region of prescription (Midwest: IA, IL, IN, KS, MI, MN, MO, ND, NE, OH, SD, WI; Northeast: CT, MA, ME, NH, NJ, NY, PA, RI, VT; South: AL, AR, DC, DE, FL, GA, KY, LA, MD, MS, NC, OK, SC, TN, TX, VA, WV; West: AK, AZ, CA, CO, HI, ID, MT, NM, NV, OR, UT, WA, WY).

^¶Number of unique payers with pharmacy benefits within the month and year of the patient prescribed the medication.

^#Type of payer among prescriptions with only one unique payer.

ART, antiretroviral therapy; CAB/RPV, cabotegravir/rilpivirine; ICD-10, International Classification of Diseases, 10th Revision.

Patient Characteristics

Among CAB/RPV recipients, 54.3% were aged 25–44, compared with 45.5% of oral ART recipients (P < 0.001) (Table 1). Individuals 55 years and older comprised 20.5% of the CAB/RPV group, compared with 28.1% of those prescribed oral ART (P < 0.001). Men represented 70.7% of CAB/RPV recipients and 74.9% of oral ART recipients (P < 0.001).

Diagnoses of mental health and substance use disorders were more prevalent among CAB/RPV recipients, with notable differences observed for depression (41.9% vs. 33.3%), anxiety (39.8% vs. 34.1%), bipolar disorder (13.0% vs. 10.5%), and cannabis use disorder (13.3% vs. 10.4%) (all P < 0.001; Table 1).

Prescription Characteristics and Payer Distribution

Of the 21,698 CAB/RPV prescriptions, 76.2% were covered by Medicaid, compared with 53.8% of oral ART prescriptions (P < 0.001) (Table 2). Commercial insurance coverage was lower for CAB/RPV (13.8%) than for oral ART (32.1%; P < 0.001). Regionally, CAB/RPV represented 0.50% of all ART prescriptions in the Midwest and 0.51% in the South, compared with 0.74% in the Northeast and 0.77% in the West (all P < 0.001).

Virologic and Immunologic Outcomes of CAB/RPV Recipients

Of the 3611 individuals prescribed CAB/RPV, 2134 (59.1%) had a documented VL result within 3 months before or on the day of initiation (data not displayed in Tables). Among these, 1980 (92.8%) were virologically suppressed (<200 copies/mL), while 154 (7.2%) had detectable viremia (≥200 copies/mL), with a median VL of 1414 copies/mL (IQR 378–5909) among those who were not virally suppressed. VL monitoring after initiation was assessed over the study observation period (January 2021–August 2023). Among individuals with at least one follow-up VL test, the median duration of follow-up was 251 days (IQR 119–399).

Among 2234 CAB/RPV patients with at least one VL test after initiation, 39 (1.8%) met criteria for confirmed virologic failure, 53 (2.4%) had a last recorded VL ≥ 200 copies/mL, 129 (5.8%) had any VL test ≥200 copies/mL, and 161 (7.2%) had at least one VL test ≥50 copies/mL. Among the 154 individuals with detectable viremia at initiation, 107 had a follow-up VL while on CAB/RPV, of whom 90 (84.1%) were virally suppressed at their last measurement during treatment.

Within the 12 months before or at CAB/RPV initiation, 2642 individuals (72.3%) had CD4 testing, with CD4 ≥500 cells/mm³ in 74.5%, 200–499 cells/mm³ in 21.9%, and <200 cells/mm³ in 3.6% (median 701; IQR: 494–918). After initiation, 2182 individuals (60.4%) had CD4 results and 915 (25.3%) had ≥3 tests. CD4 counts remained stable: 75.4% had CD4 ≥500 cells/mm³ at their last measurement, 21.3% had 200–499 cells/mm³, and 3.3% had <200 cells/mm³ (median 701; IQR: 504–924).

DISCUSSION

In this national analysis of pharmacy and laboratory claims data, we evaluated the real-world uptake and clinical outcomes of long-acting injectable CAB/RPV among PWH in the United States and Puerto Rico from 2021 to 2023. While prescribing increased over time, CAB/RPV still only comprised 1.3% of all ART use by 2023, signaling early implementation challenges and barriers to broader uptake.

Demographic trends revealed prescribing disparities not fully explained by the underlying distribution of PWH in the United States and Puerto Rico. More than half of CAB/RPV recipients were aged 25–44, while only 16% were 55 years and older, despite over half of PWH in the United States being 50 years and older.¹³ This aligns with prior research suggesting younger populations may be more likely to adopt LAI-ART, while provider hesitancy, patient concerns about long-term feasibility, and logistical challenges may restrict its use among older adults.¹⁴ However, emerging data demonstrate that CAB/RPV is safe and effective in older adults with multimorbidity, indicating potential opportunities to expand use in this population.¹⁵

Insurance coverage and reimbursement barriers also seemed to influence uptake. Medicaid covered more than three-quarters of CAB/RPV prescriptions, whereas commercial insurance covered only 13.8%, despite covering nearly one-third of oral ART prescriptions. Commercial plans often require prior authorization, and CAB/RPV may be billed under either the pharmacy or medical benefit, each with distinct coverage rules, cost-sharing structures, and documentation requirements. These challenges can delay approval or deter prescribing altogether.¹⁶ Even public programs have meaningful restrictions: as of 2024, over half of Medicaid programs required prior authorization and many AIDS Drug Assistance Programs had not yet added CAB/RPV to their formularies.¹⁶ Such administrative barriers may impede both initiation and continuity, particularly for clinics with limited staffing or billing capacity.^7,8

Geographic disparities in CAB/RPV uptake were evident. Although the Southern United States comprises more than half of PWH nationally, it accounted for only one-third of CAB/RPV prescriptions, whereas oral ART prescribing from the same source more closely matched regional HIV prevalence.¹³ This discrepancy likely reflects broader structural barriers—such as uneven Medicaid expansion, clinic capacity, and provider familiarity with LAI-ART—that may disproportionately limit adoption in the South.^8,11,16,17 Addressing these factors will be critical to supporting equitable scale-up.

CAB/RPV recipients had higher rates of depression, anxiety, and substance use disorders compared with individuals prescribed oral ART. These patterns may reflect provider decisions to prioritize LAI-ART to individuals perceived at greater risk for adherence challenges and also patient perceived preference for nondaily regimens among those who experience stigma, pill fatigue, or difficulty maintaining adherence.^2,18–20 Ensuring adequate support, such as navigator programs, flexible scheduling, or appointment reminders, will be critical to maintaining continuity for these populations.

Virologic outcomes among CAB/RPV recipients were reassuring. Among those with ≥1 follow-up VL, 97.6% were suppressed at their last test, and confirmed virologic failure was uncommon (1.8%). Importantly, among individuals who initiated CAB/RPV with detectable viremia, 84.1% achieved viral suppression—reinforcing the potential of CAB/RPV to support individuals with recent viremia or adherence challenges.^19,21 However, incomplete laboratory capture remains a limitation: nearly one-third of all recipients lacked a follow-up VL, and 40.9% lacked a baseline VL, complicating population-wide outcome estimates and emphasizing the need for more complete monitoring in future evaluations.

Innovative service models may help reduce logistical barriers to LAI-ART delivery and support broader CAB/RPV uptake. Pharmacy-led injection programs, mobile or community-based administration, and home-based injections by trained caregivers have demonstrated improved feasibility, acceptability, and persistence in early studies.^22–25 Structured implementation strategies—such as coordinated scheduling, bundled lab-and-injection visits, navigation support, and reminder systems—may further enhance continuity of care.^24,25 Ensuring adequate reimbursement pathways across pharmacy and medical benefits will be critical for scaling these models and sustaining clinic capacity

This study has several limitations. The HealthVerity Marketplace data set includes only insured individuals with documented pharmacy and laboratory claims, excluding uninsured populations and those receiving care in closed systems such as public health clinics or integrated health systems. Geographic representation therefore likely reflects the distribution of contributing data partners and may not align with the true regional burden of HIV. Variability in payer coverage, formulary restrictions, and provider practices may also influence CAB/RPV prescribing patterns, limiting generalizability. Laboratory data were incomplete for many individuals, restricting the comprehensive assessment of virologic and immunologic outcomes Owing to limitations in data availability—including loss of access to additional laboratory and oral ART data—this study was not designed to compare the effectiveness of CAB/RPV with oral ART, but rather to describe the characteristics and prescription patterns of these groups within a shared data source. Future work using more diverse data sources and multivariable modeling will be important to clarify predictors of CAB/RPV uptake, persistence, and regional or payer-level disparities.

CONCLUSION

Despite strong clinical evidence supporting its use, CAB/RPV uptake remains limited and uneven across populations, regions, and insurance types. Most individuals prescribed CAB/RPV maintained virologic suppression, and confirmed virologic failure was uncommon, underscoring its effectiveness in real-world settings. Addressing insurance-related barriers, expanding administration options, and strengthening clinical infrastructure will be essential to improving access and optimizing outcomes for PWH. Continued real-world monitoring and targeted implementation strategies are critical to fully realizing the potential of LAI-ART.