CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

however, dosing algorithms (weight band or mg/kg) are not aligned for the two drugs nor with available formulations (P=150 mg; H=100 mg), over- complicating implementation. Further, pharmacokinetic (PK) rationale for dosing P by weight is lacking in adults. Here, we provide PK evidence supporting flat (non-weight based) P dosing in adults and simplified weight band dosing in children, easily implementable with current formulations. Methods: A population PK model of P was established based on PK data from 9 clinical studies (n=863 adults). The impact of weight, HIV, age and other factors on PK were examined using nonlinear mixed effect approaches. For H in adults and P and H in children, previously published models were used. Dosing simulations were performed with current and proposed regimens for 1HP (adults only) and 3HP using established PK models. PK metrics (eg, time above MIC, AUC) were compared by regimen and relevant patient factors (eg, HIV status, weight). Results: Weight-based dosing of P in adults is not justified by population PK and results in lower P exposures in low weight individuals who receive smaller doses. Flat P dosing (600 mg in 1HP or 900 mg in 3HP) would ensure equal exposure across adults of all sizes. However, stratification by HIV status may be warranted. HIV+ patients require at least 30% higher P doses to account for reduced bioavailability (ie, 1200 mg P weekly in HIV+ produces similar exposures as 900 mg P weekly in HIV-). In children, aligning H and P weight bands delivered equal exposures to the current guidelines and utilized available formulations (Table 1). Future coformulation of 300/300 HP in a child-friendly tablet could further simplify therapy. For H, dosing stratification by NAT2 genotype is justified, when possible, as it is the main driver of drug exposure discrepancies, not weight. Conclusion: 3HP dosing recommendations can be simplified to improve implementation without compromising clinical efficacy. Further, flat dosing of P in adults should be recommended to avoid underexposure in low weight people and HIV+ adults need 30% higher P doses to match exposures in HIV- adults. 730 INCREASED HLA-DR EXPRESSION IN MONOCYTES OF PERSONS WITH HIV AND LATENT TB INFECTION Moises A. Huaman 1 , Steven Juchnowski 2 , David A. Zidar 2 , Cissy Kityo 3 , Sophie Nalukwago 3 , Rashidah Nazzinda 3 , Carl J. Fichtenbaum 1 , Chris T. Longenecker 2 1 University of Cincinnati, Cincinnati, OH, USA, 2 Case Western Reserve University, Cleveland, OH, USA, 3 Joint Clinical Research Centre, Kampala, Uganda Background: Persistent monocyte activation contributes to the increased risk of end-organ complications in persons with HIV (PWH). Whether Mycobacterium tuberculosis (Mtb) coinfection has an effect on monocyte activation in PWH is unknown. We hypothesized that there would be greater monocyte activation phenotypes in PWH with Mtb coinfection. Methods: Cross-sectional study within a cohort of HIV-infected and -uninfected participants enrolled at the Joint Clinical Research Centre in Kampala, Uganda. Participants were ≥45 years with at least one traditional cardiovascular disease risk factor. PWH had to be on stable antiretroviral therapy with HIV viral load ≤1,000 copies/mL within the 6 months prior to study entry. Participants completed a TB questionnaire and had a QuantiFERON TB (QFT) test. Latent TB infection (LTBI) was defined by a positive QFT and no TB symptoms. Prior active TB was defined by self-report and/or medical records review. Persons without evidence of Mtb infection had a negative QFT, no TB symptoms, and denied prior TB. Fresh blood samples were stained with monocyte subset markers (CD14, CD16), CD62p, CD69, CX3CR1, HLA-DR, and tissue factor, and examined with flow cytometry. Results: We included 125 participants (83 PWH and 42 without HIV) with flow cytometry data and defined TB status in this analysis. Median CD4 count was 556 cells/uL in PWH. PWH had a higher frequency of total monocytes (4.3% vs 3.2%; p<0.001) and inflammatory monocyte subset (15.5% vs 11.7%; p=0.016) compared to those without HIV. Among PWH, prior TB was associated

728 HIGH LEVELS OF ALCOHOL USE ASSOCIATED WITH LATENT TB INFECTION IN HIV-POSITIVE ADULTS Sarah B. Puryear 1 , Robin Fatch 1 , Brian Beesiga 2 , Allen Kekibiina 3 , Sara Lodi 4 , Kara Marson 1 , Nneka I. Emenyonu 1 , Winnie R. Muyindike 3 , Dalsone Kwarisiima 5 , Judith A. Hahn 1 , Gabriel Chamie 1 1 University of California San Francisco, San Francisco, CA, USA, 2 Infectious Diseases Research Collaboration, Kampala, Uganda, 3 Mbarara University of Science and Technology, Mbarara, Uganda, 4 Boston University, Boston, MA, USA, 5 Makerere University, Kampala, Uganda Background: HIV infection and heavy alcohol use are risk factors for tuberculosis (TB) disease, but it is unknown if TB infection varies by level of alcohol use among people living with HIV (PLWH). We examined associations between level of alcohol use and tuberculin skin test (TST) positivity among PLWH with heavy alcohol use, to inform TB prevention. Methods: We evaluated adults screened (2018-19) for enrollment in an ongoing randomized controlled trial of economic incentives to reduce heavy alcohol use and improve isoniazid preventive therapy (IPT) completion in HIV/TB+ drinkers in rural Uganda. Adults had TSTs placed if they were HIV+ on ART ≥6 months, reported no history of TB or IPT, endorsed hazardous drinking and had a positive urine ethyl glucuronide test (alcohol biomarker). Alcohol use was measured by the Alcohol Use Disorders Identification Test-C (AUDIT-C). Hazardous use was a score ≥3 if female and ≥4 if male and was stratified into medium (AUDIT-C 4-5 men/3-5 women), high (6-7) and very high (8-12) levels. Positive TST was defined as induration ≥5mm 48-72 hours after placement; TST results outside the testing window were excluded. We conducted logistic regression with robust standard errors to evaluate associations between drinking levels and TST-positivity, adjusting for age, sex, and study site. Results: Among 729 HIV+ hazardous drinkers who underwent TST placement, 617 (85%) returned for TST reading on time. Among those with TST results, 217 (35%) were TST-positive, 452 (73%) were male, median age was 40 years (IQR 32-48) and median AUDIT-C score was 6 (IQR 5-8). Drinking levels were: 42% medium, 31% high and 28% very high. TST-positivity by drinking level was: medium 31%, high 33%, very high 45%. In the multivariate model, very-high level use was significantly associated with TST- positivity compared to medium level drinking (aOR 1.61, 95%CI: 1.03-2.50, p=0.04). High level drinking had a non-significant association with TST-positivity compared to medium level use (aOR 1.05, 95%CI: 0.69-1.59, p=0.83). Conclusion: Very high-level alcohol use was associated with increased TST-positivity among a cohort of PLWH. Potential mechanisms of increased TB infection are unclear but may include more time spent in high transmission environments (e.g. bars) or high-risk social networks. Our findings suggest higher prevalence of latent TB may be a contributor to drinkers’ higher risk of TB disease. These results underscore the importance of advancing TB prevention efforts for HIV+ drinkers. 729 PRAGMATIC DOSING RECOMMENDATIONS OF RIFAPENTINE-CONTAINING REGIMENS FOR LATENT TB

Poster Abstracts

Kendra K. Radtke 1 , Jennifer E. Hibma 1 , Radojka M. Savic 1 1 University of California San Francisco, San Francisco, CA, USA

Background: Two short-course regimens containing rifapentine (P) and isoniazid (H) have demonstrated efficacy in preventing tuberculosis (TB) disease: 1 month of daily H and P (1HP) and 3 months of weekly H and P (3HP). Weight-based dosing of both drugs is recommended in adults and children;

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