835. Improvement in Diet Attenuates Antiretroviral Therapy (ART) Associated Weight Gain in Persons with Human Immunodeficiency Virus (PWH)

Abstract Background Weight gain among PWH on ART is a growing clinical concern. We explore factors associated with weight gain at The Ohio State University Wexner Medical Center Infectious Diseases Clinic. Methods This was a single-center, retrospective, cohort study of adult PWH on ART for at least 3 months seen at our clinic from 1/1/2015 to 1/1/2019. Patients with CD4+ T cell count < 200 cells/mm3, viral load >200 copies/mL, history of malignancy, or pregnancy were excluded. 870 patients met criteria. Patient demographics, lifestyle factors, medical co-morbidities, concurrent medications, and ART regimens were documented during the study period. The primary outcome was percent weight change over the follow up period. Secondary outcome was the odds of > 5kg weight gain over the study period. The effects of concurrent medications, medical comorbidities, ART combinations, and self-reported lifestyle behaviors on these outcomes were modeled using mixed effect linear and logistic regression analysis. Results At baseline, 83.6% were male, 29.2% were African American, and 65.6% had a body mass index ≥ 25 kg/m. Over a mean follow up of 1.86 years, the study population gained a mean percent weight of 2.12 ± 0.21% (p< 0.001) with an odds of weight gain >5kg of 0.293 (p< 0.001). Male sex and increasing age were significantly associated with a decrease in percent weight over the study period as reflected in the table below. Diet was also significantly associated with a decrease in percent weight change over the study period of -1.99 ± 0.47 %, p= < 0.001 and a lower odds of > 5kg of weight gain (OR= 0.70, 95% CI= 0.50 – 0.97, p=0.03). In regression models, combination therapy with tenofovir alafenamide (TAF) and integrase strand transfer inhibitor (INSTI) containing regimens were significantly associated with an increase in percent weight over the study period. Other significant factors including demographics and ART regimens are noted in Table 1. Table 1. Multivariable Regression Models* Conclusion Weight gain in PWH is multifactorial. Key factors associated with weight gain include combination therapy with TAF, particularly when combined with an INSTI. This data highlights the influential role of diet in PWH at risk of ART-associated weight gain. Disclosures Carlos Malvestutto, M.D., Lilly (Scientific Research Study Investigator)Regeneron Inc. (Scientific Research Study Investigator)ViiV Healthcare (Advisor or Review Panel member)


Figure 1. BRIGHTE Study Design
Results. 371 subjects [272 Randomized Cohort (RC), 99 Non-Randomized Cohort (NC)] were enrolled; 44% were ≥ 50 years of age and 86% had an AIDS history. Median CD4+ count at study start of was 80 cells/mm 3 ; 30% with ≤ 20 cells/mm 3 . 250 subjects remained in BRIGHTE at pandemic start. By April 2021, 17 subjects (14 RC, 3 NC) had confirmed COVID infection (positive PCR test). Severity was Grade 1-3, all cases resolved with no deaths. Six subjects were hospitalized (Table  1); most recent CD4+ count prior to COVID were 293-1641 cells/mm 3 and 5/6 subjects were virologically suppressed. Treatments often included prophylactic anticoagulants and supplemental oxygen; no cART changes were made. The remaining 11/17 confirmed cases were managed outpatient. Five more subjects had suspect COVID not confirmed by PCR and 2 subjects had negative PCR tests.  Background. Weight gain among PWH on ART is a growing clinical concern. We explore factors associated with weight gain at The Ohio State University Wexner Medical Center Infectious Diseases Clinic.
Methods. This was a single-center, retrospective, cohort study of adult PWH on ART for at least 3 months seen at our clinic from 1/1/2015 to 1/1/2019. Patients with CD4+ T cell count < 200 cells/mm 3 , viral load >200 copies/mL, history of malignancy, or pregnancy were excluded. 870 patients met criteria. Patient demographics, lifestyle factors, medical co-morbidities, concurrent medications, and ART regimens were documented during the study period. The primary outcome was percent weight change over the follow up period. Secondary outcome was the odds of > 5kg weight gain over the study period. The effects of concurrent medications, medical comorbidities, ART combinations, and self-reported lifestyle behaviors on these outcomes were modeled using mixed effect linear and logistic regression analysis.
Results. At baseline, 83.6% were male, 29.2% were African American, and 65.6% had a body mass index ≥ 25 kg/m. Over a mean follow up of 1.86 years, the study population gained a mean percent weight of 2.12 ± 0.21% (p< 0.001) with an odds of weight gain >5kg of 0.293 (p< 0.001). Male sex and increasing age were significantly associated with a decrease in percent weight over the study period as reflected in the table below. Diet was also significantly associated with a decrease in percent weight change over the study period of -1.99 ± 0.47 %, p= < 0.001 and a lower odds of > 5kg of weight gain (OR= 0.70, 95% CI= 0.50 -0.97, p=0.03). In regression models, combination therapy with tenofovir alafenamide (TAF) and integrase strand transfer inhibitor (INSTI) containing regimens were significantly associated with an increase in percent weight over the study period. Other significant factors including demographics and ART regimens are noted in Table 1.  Methods. A retrospective chart review of HIV/HCV co-infected patients treated for HCV with DAA at Detroit VAMC was performed. All patients were on anti-retroviral treatment for HIV with undetectable viral loads. Pre-and post-DAA treatment parameters were compared in patients who completed 12 weeks of treatment. Drug interactions, SVR, CD4+ counts AST, ALT, albumin, INR, platelets, creatinine, alpha-fetoprotein (AFP), HCV RNA, and FIB-4 score were recorded. Pearson correlation coefficient was used for data analysis.
Results. Out of 46 patients, 4 died and 20 were ineligible due to non-compliance, mental illness, or drug use; 22 eligible patients, who had well controlled HIV, received DAAs for 12 weeks. (Genotype was 1a in 14, 1b in 7 and 2b in 1 patient). Compliance rate was 100%, 21 patients were HCV treatment naïve, 1 treated with interferon in the past) and all 22 patients achieved SVR by 12 weeks (in 2 weeks), including patients (n=12) on long term opioids and/or mental health treatment. Among 10/24 patients who showed a significant increase in CD4+ (range > 100 to 400 within 6 months), 8 were cirrhotic and had received DAA + RIB therapy. HIV therapy regimen change to alafenamide combination was required in 7/22 patients, for renal dysfunction. There were decreases in AST/ALT, but no changes in FIB-4 score, platelets, albumin, creatinine, or AFP were noted.

Conclusion.
HIV/HCV Co-infected patients who received DAA + RIB had a significant increase in CD4+ lymphocyte counts (p< 0.05) (unlike interferon-based regimen). Chronic opioid use and mental health treatment were not a hindrance to successful therapy. The clinical impact of our findings on long-term complications including cirrhosis, hepatocellular carcinoma, and extra-hepatic manifestations of HCV remain to be seen. Recognition of positive predictive markers will delineate the cohort of co-infected veterans who would benefit from DAA therapy beyond HCV eradication.
Disclosures. All Authors: No reported disclosures Background. The gold standard for diagnosis of Pneumocystis jirovecii pneumonia (PCP) is direct visualization of the microorganism in respiratory samples, usually obtained via bronchoalveolar lavage (BAL). Blood β-D-glucan (BDG) is used as a non-invasive adjunctive diagnostic test for PCP, but specificity is only modest, in part because other opportunistic fungal infections cause high BDG. We previously showed BDG-positivity in 94% of people with AIDS (PWA), progressive disseminated histoplasmosis (PDH), and respiratory symptoms in our hospital. In this study, we aim to assess the performance of BDG as a diagnostic test for PCP in PWA who have respiratory symptoms.

Performance of Blood (1->3)-β-D-Glucan in People with AIDS Presenting with Respiratory Symptoms
Methods. We retrospectively identified PWA who had a BDG result between 2014 and 2019. AIDS was defined as past or current absolute CD4 count < 200 cells/ µL, or a past or current AIDS-defining condition. Positive cytological or histological evidence of P. jirovecii in bronchoalveolar lavage (BAL) fluid or lung biopsy, or positive Pneumocystis PCR on sputum or BAL confirmed PCP. The Fungitell Assay (Associates of Cape Cod, East Falmouth, MA) determined BDG levels as follows: negative, < 60 pg/mL; indeterminate, 60-79 pg/mL, and positive, ≥ 80 pg/mL. Values < 31 pg/mL and those >500 pg/mL were censored at 30 pg/mL and 500 pg/mL, respectively. Respiratory symptoms were defined as cough, dyspnea, chest pain, or hypoxia. We compared BDG results for participants with proven PCP and participants without proven PCP.
Results. We identified 260 PWA with a BDG result, of whom 183 had at least one respiratory symptom. 84 (45.9%) of these participants had a positive BDG. BDG results among participants with and without PCP are shown in Table 1. Of the 44 participants with a positive BDG who did not have PCP, 29 (65.9%) had PDH. Other diagnoses included cryptococcosis and candidemia. The test performance of BDG for the diagnosis of PCP is shown in Table 2. Exclusion of participants with PDH increased the specificity of BDG for PCP to 86.4%. Table 1. Results of (1->3)-β-D-glucan Testing by Pneumocystis jirovecii Pneumonia Diagnosis Among Participants with AIDS and Respiratory Symptoms Table 2. Test Performance of (1->3)-β-D-glucan for the Diagnosis of Pneumocystis jirovecii Pneumonia* Conclusion. At our center where histoplasmosis is endemic, a positive BDG should not be attributed to PCP among PWA with respiratory symptoms because of