Abatacept Pharmacokinetics and Exposure Response in Patients Hospitalized With COVID-19: A Secondary Analysis of the ACTIV-1 IM Randomized Clinical Trial.

Importance: The pharmacokinetics of abatacept and the association between abatacept exposure and outcomes in patients with severe COVID-19 are unknown. Objective: To characterize abatacept pharmacokinetics, relate drug exposure with clinical outcomes, and evaluate the need for dosage adjustments. Design, Setting, and Participants: This study is a secondary analysis of data from the ACTIV-1 (Accelerating COVID-19 Therapeutic Interventions and Vaccines) Immune Modulator (IM) randomized clinical trial conducted between October 16, 2020, and December 31, 2021. The trial included hospitalized adults who received abatacept in addition to standard of care for treatment of COVID-19 pneumonia. Data analysis was performed between September 2022 and February 2024. Exposure: Single intravenous infusion of abatacept (10 mg/kg with a maximum dose of 1000 mg). Main Outcomes and Measures: Mortality at day 28 was the primary outcome of interest, and time to recovery at day 28 was the secondary outcome. Drug exposure was assessed using the projected area under the serum concentration time curve over 28 days (AUC0-28). Logistic regression modeling was used to analyze the association between drug exposure and 28-day mortality, adjusted for age, sex, and disease severity. The association between time to recovery and abatacept exposure was examined using Fine-Gray modeling with death as a competing risk, and was adjusted for age, sex, and disease severity. Results: Of the 509 patients who received abatacept, 395 patients with 848 serum samples were included in the population pharmacokinetic analysis. Their median age was 55 (range, 19-89) years and most (250 [63.3%]) were men. Abatacept clearance increased with body weight and more severe disease activity at baseline. Drug exposure was higher in patients who survived vs those who died, with a median AUC0-28 of 21 428 (range, 8462-43 378) mg × h/L vs 18 262 (range, 9628-27 507) mg × h/L (P < .001). Controlling for age, sex, and disease severity, an increase of 5000 units in AUC0-28 was associated with lower odds of mortality at day 28 (OR, 0.52 [95% CI, 0.35-0.79]; P = .002). For an AUC0-28 of 19 400 mg × h/L or less, there was a higher probability of recovery at day 28 (hazard ratio, 2.63 [95% CI, 1.70-4.08] for every 5000-unit increase; P < .001). Controlling for age, sex, and disease severity, every 5000-unit increase in AUC0-28 was also associated with lower odds of a composite safety event at 28 days (OR, 0.46 [95% CI, 0.33-0.63]; P < .001). Using the dosing regimen studied in the ACTIV-1 IM trial, 121 of the 395 patients (30.6%) would not achieve an abatacept exposure of at least 19 400 mg × h/L, particularly at the extremes of body weight. Using a modified, higher-dose regimen, only 12 patients (3.0%) would not achieve the hypothesized target abatacept exposure. Conclusions and Relevance: In this study, patients who were hospitalized with severe COVID-19 and achieved higher projected abatacept exposure had reduced mortality and a higher probability of recovery with fewer safety events. However, abatacept clearance was high in this population, and the current abatacept dosing (10 mg/kg intravenously with a maximum of 1000 mg) may not achieve optimal exposure in all patients. Trial Registration: ClinicalTrials.gov Identifier: NCT04593940.

Time to first annual HIV care visit and associated factors for patients in care for HIV infection in 10 US cities.

BACKGROUND: Visiting a medical provider less frequently than clinical circumstances would suggest is appropriate has been reported to be associated with worse clinical outcomes for patients living with HIV infection. Patients with less frequent attendance to HIV care also may be systematically underrepresented in research or surveillance studies that enroll patients sequentially over a specified enrollment period - for example several months. For both reasons, understanding factors associated with time to care visit is important. METHODS: We used data from the Adult and Adolescent Spectrum of HIV Disease (ASD) project, a multi-site clinical outcomes surveillance system that enrolled and followed patients in care for HIV prospectively from 1990 to 2004. For this analysis, we used data from all patients observed in ASD at least one time before 1 January 2003, and who had at least one HIV care visit in 2003. We documented time to first annual HIV care visit for each patient, and used Kaplan-Meier plots and proportional hazards regression to describe factors associated with longer time to care visit. RESULTS: A total of 12,135 patients had ≥1 care visit during 2003 and were included in the analysis. Of these, 81%, 88%, and 95% had their first visit within three, four, and six months, respectively. In multivariate analysis, having a delayed (later) care visit was associated with not ever having had an AIDS diagnosis, having an HIV RNA concentration ≥10,000 copies/mL, having a current CD4 count <100 cells/µL, having no health insurance, and not being currently prescribed antiretroviral therapy. Having a delayed care visit was not associated with race/ethnicity or age. CONCLUSIONS: Having a delayed first annual HIV care visit was associated with higher viremia, lower CD4 cell count, and lack of health insurance. Interventions to address these factors are likely to ameliorate some of the consequences of HIV. For studies enrolling patients in care for HIV over a finite time period, an enrollment period of four-six months should sufficiently reflect the patient population seen in a one-year period, including those attending care infrequently.

Short report: migration among persons living with HIV.

Data from the first national probability sample of persons with HIV, the HIV Cost of Services and Utilization Survey (HCSUS), are used to examine migration patterns among persons with HIV/AIDS in the USA. Persons with serious illness may choose to relocate to receive better care or support. This migration has implications for the distribution of resources. This study describes the frequency and reasons that persons with HIV move to different communities. An analytic file of 3014 respondents was obtained from the first national probability sample of persons with HIV/AIDS, the HCSUS. A migration section of the baseline questionnaire questioned respondents on their residential history. Persons were defined as movers if they moved across state lines or to a non-contiguous county after knowing they were HIV positive but before the HCSUS baseline interview. Forty percent of movers said that their HIV status was a very important factor in their decision to move. Although earlier studies of limited generalizability found movement among the HIV population from urban to rural counties, this study found only eight percent of HIV migration was from urban to rural counties, just slightly more than the migration from rural to urban counties. In addition, the vast majority of people who were moving were not moving to return home. Major factors in the decision to move included being near caregivers and being in a community with shared needs and interests. Significant numbers of persons also moved to obtain care from a physician knowledgeable in HIV treatment or to get away from discrimination. Financial assistance and the availability of Medicaid also played a prominent role in many decisions to move. Persons with HIV/AIDS are more likely to move than non-infected persons in the general population. Moreover, they are almost twice as likely to be moving out-of-state. Persons with HIV who move are similar to persons with HIV who do not move on most demographic characteristics including age, region of the country, and income.