Sara Hurtado Bares

Background: Long-acting injectable (LAI) cabotegravir/rilpivirine (CAB/RPV) is an effective human immunodeficiency virus-1 (HIV) treatment, but barriers, such as financial considerations, limit implementation. Understanding the real-world financial impact is essential for program sustainability and equitable access. Methods: This retrospective cohort study at the University of Nebraska Medical Center, Specialty Care Center (May 2022 to December 2024), evaluated people with HIV (PWH) receiving LAI CAB/RPV via buy-and-bill acquisition. We assessed annual staff time, program income (PI), and patient costs (PCs). The primary endpoint was annual PI adjusted for staff time per patient compared with a modeled oral antiretroviral therapy (ART) comparator (bictegravir/emtricitabine/tenofovir alafenamide) using the Wilcoxon signed-rank test. PI and PC were compared across study years and payer mix with Kruskal-Wallis test. Multivariate regression models explored factors predicting PI losses. Results: The study included 110 PWH receiving 862 injections. LAI CAB/RPV required more annual staff time per participant than oral ART (7.4 vs 3.7 hours). Median annual PI per participant hour managed was significantly lower for LAI CAB/RPV versus the oral ART model across all study years (P < .001). Despite this, the LAI program remained financially viable (median PI: $2163/injection) with minimal PC; 91% of injections had $0 cost-sharing. PI losses occurred in 4.9% of injections and was associated with Medicaid coverage, lack of AIDS Drug Assistance Program (ADAP) coverage, and insurance changes. Conclusions: Although LAI CAB/RPV requires double the staff time and generates less time-adjusted PI than oral ART, buy-and-bill LAI programs can remain financially viable. Payer mix and insurance stability are essential to ensuring sustainability and equitable access.

Objectives: Long-acting injectable (LAI) cabotegravir/rilpivirine demonstrates substantial inter- and intraindividual variability in trough concentrations during the first year of use. We aimed to characterize trough concentration variability of cabotegravir and rilpivirine after >12 months of continuous use. Methods: We conducted a prospective pharmacokinetic study in virologically suppressed people with HIV receiving bimonthly LAI cabotegravir/rilpivirine 600 mg/900 mg. Plasma trough samples were collected prior to three consecutive doses over 6 months for drug quantitation. Primary outcomes were inter- and intraindividual variability defined as coefficient of variation (CV) and intraclass correlation coefficient (ICC). Secondary outcomes included concentrations below the proposed 4x-protein-adjusted 90% inhibitory concentration (PA-IC90) for cabotegravir (4x-PA-IC90 = 664 ng/mL) and rilpivirine (4x-PA-IC90 = 48 ng/mL). Results: Among 50 participants, 150 samples were collected. Participants were primarily male (80%) with a median age of 45 years and a body mass index of 28 kg/m2. Median interindividual CVs were high for both cabotegravir [58%, interquartile range (IQR): 15, 59] and rilpivirine (52%, IQR: 18, 59). Median intraindividual CVs were moderate for both cabotegravir (24%, IQR: 15, 39) and rilpivirine (23%, IQR: 15, 39), with ICCs indicating good intraindividual agreement for cabotegravir (0.82) and moderate intraindividual agreement for rilpivirine (0.72). Twelve (8%) cabotegravir concentrations in 8 participants and 24 (16%) rilpivirine concentrations in 16 participants were below 4x-PA-IC90; however, all participants maintained virologic suppression throughout the study period. Conclusions: After one year of continuous use, inter- and intraindividual variability persists for cabotegravir and rilpivirine, indicating that clinical decisions should not be based on only one trough concentration.

We present a case of emergent integrase strand transfer inhibitor resistance following rifamycin-based latent tuberculosis infection (LTBI) treatment in a patient with HIV. This case highlights the risks associated with modifying antiretroviral therapy during LTBI treatment and illustrates how archived genotype results can directly impact clinical decision-making.

Immune reconstitution inflammatory syndrome (IRIS) is a well-described complication following initiation of antiretroviral therapy (ART) in people with HIV. In this case report, we describe the complex clinical presentation of a 27-year-old ART-naïve male with advanced HIV who developed Kaposi sarcoma-associated IRIS (KS-IRIS) with visceral involvement and pericardial effusion shortly after starting ART. We review known risk factors for KS-IRIS, its clinical manifestations including rare cardiac involvement and paradoxical worsening with steroid use, as well as current evidence for chemotherapeutic and antiviral treatment strategies.

Our retrospective review included 186 patients who received a doxycycline postexposure prophylaxis (doxy-PEP) prescription, with 56% missing ≥1 quarterly sexually transmitted infection (STI) screening visit. Of attended visits, 63% included guideline-recommended multisite STI screenings. As doxy-PEP use grows, improving patient engagement is essential to ensure long-term effectiveness.

Long-acting injectable cabotegravir plus rilpivirine offers an alternative to daily oral antiretroviral therapy, but insurance-related barriers can disrupt implementation. We examined the frequency and impact of insurance changes in a United States cohort and found that nearly half of patients experienced insurance changes, which could lead to delayed injections.

Implementation of a long-acting injectable antiretroviral treatment program requires substantial multidisciplinary effort, particularly for program coordination, coverage/billing, and patient support/retention. As our program scaled to 113 patients over 2.5 years, a total of 2.25 full-time equivalents were required. Despite operational demands, clinical outcomes were favorable, supporting real-world feasibility and scalability.

Given the melanocortin-4 receptor's (MC4R) importance in obesity, we examined associations between MC4R gene variants and weight following a switch to integrase inhibitor-containing antiretroviral therapy among participants in Advancing Clinical Therapeutics Globally studies. Among 529 persons with HIV (median age: 50 years, 29% non-Hispanic Black, 22% female), 62% were overweight or obese at integrase strand transfer inhibitor switch, and 62% switched to raltegravir. In adjusted linear models, three variants were associated (P < .05) with weight change after switch in all participants or in prespecified subgroups. These exploratory findings are consistent with the role of melanocortins in appetite and weight and suggest a neuroendocrine contribution to integrase inhibitor-related weight gain.

We present pharmacokinetic data on long-acting cabotegravir/rilpivirine (LA CAB/RPV) from two patients during their second and third trimesters. Monthly LA CAB/RPV dosing maintained concentrations above the proposed efficacy thresholds while bimonthly dosing resulted in subtherapeutic RPV concentrations. This highlights the potential of monthly LA CAB/RPV dosing in pregnancy.

Long-acting cabotegravir/rilpivirine offers a low incidence of virologic failure. However, drug resistance can develop after discontinuation without an effective replacement regimen due to its long pharmacokinetic tail. We present a case of sustained virologic suppression 18 months after discontinuation of long-acting cabotegravir/rilpivirine despite inadequate adherence to oral antiretroviral therapy.