scholarly journals 1020. Higher efavirenz mid-dose plasma concentration is associated with less weight gain among virologically suppressed people living with HIV

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S539-S540
Author(s):  
Wei-chieh Huang ◽  
Sung-Hsi Huang ◽  
Chien-Ching Hung
Keyword(s):  
Weight Gain ◽  
Plasma Concentration ◽  
Weight Change ◽  
Panel Member ◽  
Therapeutic Drug ◽  
People Living With Hiv ◽  
Research Support ◽  
Review Panel ◽  
Negative Effect ◽  
Living With Hiv

Abstract Background Recently, an association between CYP2B6 516 G > T polymorphism and weight change was observed among African people living with HIV (PLWH) who were started on efavirenz(EFV)-based antiretroviral therapy (ART). We aimed to investigate the effect of EFV mid-dose plasma concentration on weight change among Taiwanese PLWH. Methods The medical records of adult PLWH who were taking EFV-containing ART and had been enrolled in a EFV therapeutic drug monitoring study between Oct 2009 and May 2014 were accessed. EFV mid-dose plasma concentration (C12) was determined in the previous study and those with serial weight measurements within 48 weeks around the time of EFV C12 measurement were included in the present study. The weight change in the 48 weeks and its associations with mid-dose EFV concentrations and CYP2B6 516 G > T polymorphism were examined by general estimating equations (GEE) after adjusting for age, baseline HIV viremia, baseline weight, and the companion backbone antiretroviral agents. Results One-hundred and fifteen predominantly male (94.8%) PLWH were included in this study (Table 1). The mean CD4 lymphocyte count was 542 cells/μL at the beginning of the observation and 94.8% achieved HIV viral suppression. Forty-four (38.3%) patients had non-wildtype CYP2B6 516 G > T polymorphism. On average, the included PLWH gained 0.8 kilogram at 48 weeks and the weight change did not differ among those with wildtype and non-wildtype CYP2B6 516 G > T(Figure 1). In the GEE models, CYP2B6 516 G > T polymorphism was not associated with weight change (p=0.81), instead, higher EFV C12 was found to be independently associated with less weight gain (p=0.045). Table 1. Baseline characteristics. Figure 1. The absolute weight (A) and weight change from baseline (B) among patients with wildtype and non-wildtype CYP2B6 516G>T polymorphism. Conclusion Our findings support that increased EFV exposure may have a negative effect on weight gain. Disclosures Chien-Ching Hung, MD,PHD, Abbvie (Advisor or Review Panel member, Speaker’s Bureau)Bristol-Myers Squibb (Speaker’s Bureau)Gilead Sciences (Advisor or Review Panel member, Speaker’s Bureau)Janssen (Grant/Research Support, Advisor or Review Panel member)Merck (Grant/Research Support)ViiV (Grant/Research Support, Advisor or Review Panel member, Speaker’s Bureau)

scholarly journals 823. Characteristics, Comorbidities, and Medication Burden among People Living with HIV in the U.S. Medicare Program

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S504-S504
Author(s):  
Pengxiang Li ◽  
Vrushabh P Ladage ◽  
Jianbin Mao ◽  
Girish Prajapati ◽  
Dovie L Watson ◽  
...  
Keyword(s):  
Panel Member ◽  
Administrative Claims ◽  
People Living With Hiv ◽  
Medicare Beneficiaries ◽  
Research Support ◽  
Review Panel ◽  
Material Support ◽  
Medicare Program ◽  
Living With Hiv ◽  
The U.S

Abstract Background Among the 1.2 million people living with HIV (PLWH) in the U.S., many are covered by Medicare, a federally funded health insurance program for elderly (≥65 years) and disabled (< 65 years) individuals. Medicare has emerged as a major source of HIV care for PLWH. Given limited research in this population, a better understanding of patient characteristics, comorbidities, and comedication use among PLWH in the Medicare program is needed to help optimize clinical care. Methods A retrospective claims analysis of a national cross-sectional sample of fee-for-service (FFS) Medicare beneficiaries with continuous medical and prescription coverage in 2018 was conducted using 100% Medicare administrative claims. The PLWH group included individuals with ≥1 HIV diagnosis code in medical claims and ≥1 pharmacy claim for an anchor antiretroviral (ARV) drug (i.e., NNRTI, PI or InSTI) in 2018. The comparison group included a random sample of Medicare beneficiaries without HIV (PLWoH). Sociodemographic characteristics, comorbidities, and medication use were compared between PLWH and PLWoH. Results The study sample included 86,856 PLWH and 552,645 PLWoH. PLWH were more likely to be younger (mean age: 57.4 vs 71.1 years and < 65 years: 72% vs 18%), male (75% vs 42%), Black (42% vs 10%), eligible for Medicare due to disability (83% vs 27%) and receiving full low-income subsidies (77% vs 31%); all p< 0.001. Prevalence of >3 comorbidities was high in PLWH (70.2%) and only slightly lower than in PLWoH (71.7% p< 0.001). Prevalence of neuropsychiatric conditions, chronic kidney disease, liver disease, COPD, hepatitis B, and hepatitis C were higher in PLWH (Figure 1). The mean hierarchical condition categories risk score was higher in PLWH vs PLWoH (1.81 vs. 1.32; p< 0.001). On average, polypharmacy was higher among PLWH vs PLWoH (annual number of unique medications: 12.6 vs. 9.4 for all drugs and 10.3 vs. 9.4 for non-ARV drugs, both p< 0.001). Figure 1. Percentage of PLWH and PLWoH with multimorbidity and selected comorbid conditions. Abbreviations: COPD=chronic obstructive pulmonary disease; GI=gastrointestinal; PLWH=people living with HIV; PLWoH=people living without HIV All p-values <0.001 except GI Disorders (p=0.14). Conclusion In the Medicare FFS population, multimorbidity and polypharmacy were highly prevalent in PLWH despite their substantially younger age compared to PLWoH. Our findings highlight the need to consider comorbidities and comedications in HIV management including ARV regimens to minimize medication burden and drug interactions, which might improve clinical outcomes. Disclosures Pengxiang Li, PhD, Avalon Health Economics LLC (Consultant)COVIA Health Solutions (Consultant)Healthstatistics, LLC (Consultant) Jianbin Mao, PhD, Merck (Employee)Merck (Shareholder) Girish Prajapati, M.B.B.S., MPH , Merck & Co., Inc. (Employee, Shareholder) Robert Gross, MD, MSCE, Pfizer (Other Financial or Material Support, Serve on DSMB for drug unrelated to HIV) Jalpa A. Doshi, PhD, Acadia (Consultant, Advisor or Review Panel member)Allergan (Advisor or Review Panel member)Biogen (Grant/Research Support)Boehringer Ingelheim (Other Financial or Material Support, Scientific lecture)Catabasis (Consultant)Humana (Grant/Research Support)Janssen, Inc. (Consultant, Grant/Research Support)MeiraGTX (Consultant)Merck (Grant/Research Support, Advisor or Review Panel member)Novartis (Grant/Research Support)Otsuka (Advisor or Review Panel member)Regeneron (Grant/Research Support)SAGE Therapeutics (Consultant)Sanofi (Grant/Research Support)Shire (Advisor or Review Panel member)The Medicines Company (Advisor or Review Panel member)

scholarly journals 951. Weight Gain Associated With Antiretroviral Therapy

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S508-S508
Author(s):  
Yesha Patel ◽  
Sheila Okere ◽  
Mark Lustberg ◽  
Carlos Malvestutto
Keyword(s):  
Human Immunodeficiency Virus ◽  
Weight Gain ◽  
Antiretroviral Therapy ◽  
Weight Change ◽  
Panel Member ◽  
Male Gender ◽  
Review Panel ◽  
Factors Associated ◽  
Immunodeficiency Virus

Abstract Background Obesity is a global public health crisis with a growing prevalence in persons with human immunodeficiency virus (PWH) population. In this study, we aimed to investigate factors associated with weight gain in the PWH population. Methods This was a single-centered, retrospective cohort study of our clinic patient population from January 1, 2015 to January 1, 2019. Patients with human immunodeficiency virus (HIV) were identified from the electronic health record and a randomized sample of 300 patients who had at least two follow up appointments, were on antiretroviral therapy, and had viral loads less than 200 were evaluated. The primary outcome was weight change over follow up. Cox Proportional Hazards models were used, taking a weight gain > 3 kg as the outcome, and the time on therapy between visits as the time to event. Robust linear regression was used to model mean changes in weight, accounting for influential observations. All analysis were performed in STATA 16.0. Table 1 Results At baseline, 87% were male, 63% were white, and 65% were overweight/obese. 30% were on a protease inhibitor, 46% were on non-nucleoside reverse transcriptase inhibitor, and 37% were on an integrase inhibitor. 64% were on Tenofovir disoproxil (TDF), 8% were on Tenofovir alafenamide (TAF), and 19% were on Abacavir. Mean weight change over follow up was significantly increased at 1.31 kg (95% CI = 0.58 – 2.04 kg, p= 0.0004). TAF use and male gender were significantly associated with risk of weight gain > 3 kg in univariate analysis [respectively, OR = 2.53, 95% CI = 1.30 – 4.92, p = 0.006; OR = 2.60, 95% CI = 1.05 – 6.45, p = 0.04]. In multivariate analysis, TAF use was significantly associated with weight gain > 3 kg, while male gender was of borderline significance [respectively, OR = 2.29, 95% CI = 1.17 – 4.47, p = 0.01; OR = 2.40, 95% CI = 0.96 – 5.97, p=0.060]. Significant factors associated with weight change are noted in Table 1. Conclusion As PWH are living longer on effective ARV therapy, monitoring for weight gain is required as obesity contributes to morbidity and mortality from cardiovascular disease and metabolic diseases. Key factors for weight gain in our clinic population include male gender, baseline diagnosis of hypertension, use of TAF, bictegravir use, and rilpivirine use. Disclosures Carlos Malvestutto, MD, Gilead Sciences (Advisor or Review Panel member)ViiV Healthcare (Advisor or Review Panel member)

scholarly journals 832. Body Mass Index and Quality of Life in People Living With HIV

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S508-S508
Author(s):  
Jennifer Ken-Opurum ◽  
Girish Prajapati ◽  
Joana E Matos ◽  
Swarnali Goswami ◽  
Princy N Kumar
Keyword(s):  
Quality Of Life ◽  
Body Mass Index ◽  
Weight Gain ◽  
People Living With Hiv ◽  
Research Support ◽  
Material Support ◽  
Vas Scores ◽  
Living With Hiv ◽  
Eq Vas

Abstract Background Weight gain among people living with HIV (PLWH) on antiretroviral therapy (ART) may lead to obesity. This study evaluated association between body mass index (BMI) and health-related quality of life (HRQoL) from the patient’s perspective. Methods A cross-sectional study using self-reported data from the 2018 and 2019 US National Health and Wellness Survey (NHWS), a nationally representative online survey of ~75,000 adults was conducted. Respondents self-reporting a physician diagnosis of and prescription use for treatment of HIV were included. HRQoL was assessed using Short-Form 36-Item Health Survey Version 2 [Mental and Physical Component Summary scores (MCS and PCS)] and EQ-5D-5L [dimension responses: “no” vs “any problems”/“yes”); EQ-Visual Analogue Scale (VAS) score]. Bivariate analyses (chi-square tests for categorical and ANOVA for continuous variables) compared patient characteristics and HRQoL outcomes across BMI (kg/m2) categories: normal weight (NW; 18.5-< 25), overweight (OW; 25-< 30) and obese (OB; ≥30). Multivariable models analyzed each outcome as a function of BMI, controlling for age, sex, race, and Charlson Comorbidity Index (CCI; excluding HIV/AIDS). Results A total of 566 respondents were analyzed. Majority were aged ≥50 years (58%) and male (87%). The OB (vs NW) group had higher proportion of respondents who were female (22% vs 10%), Black (37% vs 24%), residing in the South (46% vs 33%), and higher mean CCI score (1.28 vs. 0.97) (Table 1). A higher proportion of OB (vs NW) respondents reported having pain/discomfort and problems with mobility and usual activities but not self-care. Anxiety/depression was reported less in OB vs NW groups (Table 1) However, self-reported use of prescription medications for anxiety (19% vs 20%) and depression (34% vs 25%) was similar in OB and NW groups. PCS and EQ-VAS scores were lower in OB vs OW and NW, but no difference in MCS score was observed (Table 1). Lower PCS and EQ-VAS scores were associated with higher BMI (both p=0.01) but not MCS (p=0.68) in multivariate models. Conclusion PLWH with higher BMI have poorer physical and general HRQoL. Impact of potential adverse weight gain and transition to higher BMI on humanistic and clinical outcomes should be considered when selecting ART regimens. Table 1. Comorbidity Burden and Quality of Life in People Living with HIV by BMI Categories. Disclosures Jennifer Ken-Opurum, PhD, Kantar Health (Employee) Girish Prajapati, M.B.B.S., MPH , Merck & Co., Inc. (Employee, Shareholder) Joana E. Matos, PhD, Kantar Health (Employee) Princy N. Kumar, MD, AMGEN (Other Financial or Material Support, Honoraria)Eli Lilly (Grant/Research Support)Gilead (Grant/Research Support, Shareholder, Other Financial or Material Support, Honoraria)GSK (Grant/Research Support, Shareholder, Other Financial or Material Support, Honoraria)Merck & Co., Inc. (Grant/Research Support, Shareholder, Other Financial or Material Support, Honoraria)

scholarly journals 900. Switching to DTG/3TC Fixed-Dose Combination (FDC) Is Non-inferior to Continuing a TAF-Based Regimen (TBR) in Maintaining Virologic Suppression Through 144 Weeks (TANGO Study)

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S541-S541
Author(s):  
Olayemi Osiyemi ◽  
Faïza Ajana ◽  
Fiona Bisshop ◽  
Stéphane De Wit ◽  
Joaquín Portilla ◽  
...  
Keyword(s):  
Virologic Failure ◽  
Panel Member ◽  
Drug Regimen ◽  
Fixed Dose ◽  
People Living With Hiv ◽  
Virologic Suppression ◽  
Research Support ◽  
Review Panel ◽  
Good Tolerability ◽  
Material Support

Abstract Background DTG/3TC is a complete 2-drug regimen (2DR) for the treatment of HIV-1 infection. Non-inferior virologic efficacy has been proven over 3 years in treatment-naive people living with HIV (PLWH) and 2 years in a stable switch setting. Methods TANGO, a randomized, open-label, non-inferiority study, evaluates efficacy and safety of switching to DTG/3TC in PLWH who are virologically suppressed ( > 6 months, no prior virologic failure [VF], no major NRTI/INSTI resistance) vs remaining on a 3- or 4-drug TAF-based regimen (TBR), stratified by baseline 3rd agent class. Week 144 analyses assessed non-inferiority (NI) with a 4% NI margin for Snapshot virologic failure (VF) and 8% for virologic success (VS; FDA Snapshot algorithm, intention-to-treat–exposed [ITT-E] population). Results Of 741 randomized/exposed pts (DTG/3TC: 369; TBR: 372), most pts entered the study on EVG/c (66%). For Week 144 Snapshot VF, switching to DTG/3TC was non-inferior to continuing TBR in the ITT-E analysis: 0.3% vs 1.3%; adjusted difference (95% CI): −1.1% (−2.4%, 0.2%) and superior to TBR in the per-protocol analysis: 0% vs 1.1%; adjusted difference: −1.1% (−2.3, −0.0); P=0.044 (2-sided). Snapshot VS was high in both arms and demonstrated non-inferiority (Table). Zero pts on DTG/3TC and 3 (0.8%) on TBR met confirmed virologic withdrawal criteria with no resistance observed. Zero pts on DTG/3TC and 6 (1.6%) on TBR discontinued for lack of efficacy. Overall AE rates were similar between arms (Table). TC, LDL-C, and triglycerides improved with DTG/3TC, HDL-C improved with TBR, with no difference in TC/HDL-C ratio between arms. Changes in eGFR (cystatin C) and proximal tubular function marker were similar across arms. Adjusted mean change from BL in weight was 2.2 and 1.7 kg in the DTG/3TC and TBR arms, respectively, and proportion of pts with > 10% weight increase was similar across arms (13% and 12%, respectively). Table. Efficacy and Key Safety Results for the ITT-E and Safety Population Conclusion Switching to the 2-drug regimen of DTG/3TC from a TAF-based 3- or 4-drug regimen resulted in high, non-inferior efficacy with zero confirmed virologic withdrawals and good tolerability over 3 years of treatment. DTG/3TC 2DR is a robust switch option with durable efficacy, good safety and tolerability, and a high barrier to resistance. Disclosures Olayemi Osiyemi, M.D, Gilead (Advisor or Review Panel member, Speaker’s Bureau)Merck (Advisor or Review Panel member)ViiV Healthcare (Advisor or Review Panel member, Speaker’s Bureau) Fiona Bisshop, MBBBS, Gilead (Grant/Research Support)ViiV Healthcare (Grant/Research Support) Stéphane De Wit, MD, Gilead (Grant/Research Support)Janssen (Grant/Research Support)Merck Sharpe & Dohme (Grant/Research Support)ViiV Healthcare (Grant/Research Support) Joaquín Portilla, MD, AbbVie (Other Financial or Material Support)Gilead (Grant/Research Support, Other Financial or Material Support)Janssen (Grant/Research Support, Other Financial or Material Support)Merck Sharpe & Dohme (Other Financial or Material Support)ViiV Healthcare (Grant/Research Support, Other Financial or Material Support) Jean-Pierre Routy, MD, FRCPC, ViiV Healthcare (Grant/Research Support) Mounir Ait-Khaled, PhD, ViiV Healthcare (Employee) Keith Pappa, PharmD, Glaxo Smith Kline (Shareholder)ViiV Healthcare (Employee) Ruolan Wang, Master of Science, ViiV Healthcare (Employee) Peter Leone, MD, viiv healthcare (Employee) Jonathan Wright, MSc, GlaxoSmithKline (Employee, Shareholder) Brian Wynne, MD, ViiV Healthcare (Employee, Shareholder, I have shares in GSK, the part owner of ViiV) Jean A. van Wyk, MB,ChB, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Michael Aboud, MBChB, MRCP, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Kimberly Smith, MD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee)

scholarly journals LB-7. Weight Change in Suppressed People with HIV (PWH) Switched from Either Tenofovir Disoproxil Fumarate (TDF) or Abacavir (ABC) to Tenofovir Alafenamide (TAF)

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S846-S847
Author(s):  
Paul Sax ◽  
Keri N Althoff ◽  
Keri N Althoff ◽  
Todd T Brown ◽  
Janna Radtchenko ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Reverse Transcriptase ◽  
Weight Change ◽  
Negative Binomial ◽  
Panel Member ◽  
Review Panel ◽  
Adjusted Risk ◽  
Weight Suppression ◽  
Research Grant

Abstract Background Weight gain in PWH occurred in both naïve and switch studies and is linked to use of integrase inhibitors (INSTIs) with varying associations with nucleoside reverse transcriptase inhibitors (NRTIs). One hypothesis is that gain associated with TAF when switching from TDF is a result of cessation of TDF-induced weight suppression. Methods The study evaluated weight change in suppressed PWH on INSTI+NRTIs switched from ABC or TDF to TAF. Eligible pts had HIV, were ≥ 18 yrs at index (date of switch), treatment-experienced with known prior regimen, suppressed at index (-12 to +1 mo) and 1 yr, ≥ 6 mo pre-index history, with weight measures at index and 1 yr, no current or pre-index use of protease inhibitor or non-nucleoside reverse transcriptase inhibitor. Univariate comparisons were performed using Χ2 for categorical and t-test for continuous variables; negative binomial model with log link function evaluated risk of gain ≥ 3% of body weight between groups accounting for age, gender, race, body mass index (BMI), CD4. Linear mixed effects model was used to estimate mean weight at index and 1 yr post switch. Results Of 970 pts, 828 (85%) switched from TDF to TAF and 142 (15%) from ABC to TAF. Groups were balanced by race, gender, index BMI [Table 1]. Figures 1a-b describe pre- and post-switch INSTI use. At 1 yr, mean unadjusted weight change was 1.4 kg in TDF and 0.2 in ABC group p=0.039. TDF to TAF had higher proportion of PWH with gain ≥ 3% vs ABC to TAF (40% vs 27% p=0.003); differences in gain ≥ 5% and ≥ 10% were not statistically significant (26% vs 22% p=0.323 and 10% vs 6% p=0.220). Pts who gained ≥ 3% were younger, with greater proportion of females, non-obese, with 1 prior regimen, and prior elvitegravir (EVG) use. In adjusted analysis TDF to TAF had higher risk of gain ≥ 3% vs ABC to TAF [Figure 2]. In sensitivity analysis accounting for EVG or dolutegravir (DTG) use, TDF to TAF also had higher risk of ≥ 3% gain vs ABC to TAF: adjusted risk ratio (aRR)= 1.38 [1.01–1.89] and aRR= 1.42 [1.02–1.97]. Table 1. Baseline (index) characteristics. Figures 1a-b. Distribution of pre switch and post switch INSTI use. Figure 2. Risk of weight gain ≥ 3% of body weight at 1 year post switch accounting for age, gender, race, index BMI, and CD4. Conclusion Switching from TDF to TAF in INSTI-based regimens had a greater risk of weight gain vs ABC to TAF. This difference persisted when accounting for impact of the INSTI agent in the current regimen. These data suggest that differences in weight gain between TAF and TDF are driven by removal of TDF-associated weight suppression. Disclosures Paul Sax, MD, Gilead (Consultant, Research Grant or Support)Janssen (Consultant)Merck (Consultant, Research Grant or Support)ViiV Healthcare (Consultant, Research Grant or Support) Keri N. Althoff, PhD, MPH, Gilead (Advisor or Review Panel member) Keri N. Althoff, PhD, MPH, All of Us Study (NIH) (Individual(s) Involved: Self): Consultant; MedIQ (Individual(s) Involved: Self): Consultant; TrioHealth (Individual(s) Involved: Self): Advisor or Review Panel member Todd T. Brown, MD, PhD, Gilead (Consultant)Merck (Consultant)Theratechnologies (Consultant)ViiV Healthcare (Consultant) Janna Radtchenko, MBA, Trio Health (Employee) Helena Diaz Cuervo, PhD, Gilead Sciences (Employee) Steven Santiago, MD, Gilead (Advisor or Review Panel member, Speaker's Bureau)Janssen (Speaker's Bureau) Graeme Moyle, MD, Theratechnologies (Consultant) Karam Mounzer, MD, Epividian (Advisor or Review Panel member)Gilead (Advisor or Review Panel member, Research Grant or Support, Speaker's Bureau)Janssen (Advisor or Review Panel member, Research Grant or Support, Speaker's Bureau)Merck (Advisor or Review Panel member, Research Grant or Support, Speaker's Bureau)ViiV Healthcare (Advisor or Review Panel member, Research Grant or Support, Speaker's Bureau) Richard Elion, MD, Gilead (Advisor or Review Panel member, Research Grant or Support, Speaker's Bureau)Janssen (Speaker's Bureau)Proteus (Research Grant or Support)ViiV Healthcare (Advisor or Review Panel member, Research Grant or Support)

Impact of efavirenz mid-dose plasma concentration on long-term weight change among virologically suppressed people living with HIV

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Sung-Hsi Huang ◽  
Wei-Chieh Huang ◽  
Shu-Wen Lin ◽  
Yu-Chung Chuang ◽  
Hsin-Yun Sun ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Weight Change ◽  
People Living With Hiv ◽  
Living With Hiv

scholarly journals 1012. Efficacy, safety and tolerability of switching to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in HIV-1 infected virologically-suppressed older adults in a real-world setting

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S534-S535
Author(s):  
Charlotte-Paige M Rolle ◽  
Vu Nguyen ◽  
Kiran Patel ◽  
Dan Cruz ◽  
Federico Hinestrosa ◽  
...  
Keyword(s):  
Older Adults ◽  
Drug Interactions ◽  
Real World ◽  
Research Study ◽  
Panel Member ◽  
Median Number ◽  
Research Support ◽  
Review Panel ◽  
Study Investigator ◽  
Hiv 1

Abstract Background Approximately 50% of people living with HIV (PLWH) in the United States are ≥50 years old. Efforts are ongoing to identify antiretrovirals associated with fewer drug-drug interactions (DDIs) and long-term side effects in this group. Clinical trials of B/F/TAF demonstrated favorable efficacy and safety in older adults, however, data from real-word settings are needed to validate these results. Methods This retrospective analysis evaluated records from PLWH aged ≥ 50 years at the Orlando Immunology Center who were switched to B/F/TAF between 2/7/2018 and 5/31/2019. Eligible patients had baseline HIV-1 RNA< 50 copies/mL and were followed for 48 weeks post-switch. The primary endpoint was maintenance of HIV-1 RNA< 50 copies/mL at week 48. The impact of switching to B/F/TAF on DDIs, adverse events (AEs) and safety parameters were analyzed throughout the study. Results 306 patients met inclusion criteria. 62 (20%) were female, 126 (41%) were non-white, median age was 58 years (range [r] 50-81), median duration of HIV infection was 19.5 years (r 2-40), median number of chronic co-morbid conditions was 5 (r 0-20), and median number of baseline concomitant medications was 4 (r 0-23). 159 (52%) patients were switched from regimens containing ritonavir or cobicistat. The most commonly documented reason for switch was simplification (Table 1). At Week 48, 287 (94%) patients maintained an HIV-1 RNA< 50 copies/ml and 19 (6%) had an HIV-1 RNA between 50-200 copies/mL (Figure 1). 1 patient discontinued due to lack of efficacy. A total of 123 potential DDIs were identified in 104 (34%) patients taking a boosting agent or rilpivirine at baseline (Table 2). At Week 48, there was a significant median decline in total cholesterol (15.5 mg/dL, 95% confidence interval [CI]: 9.5; 21.5), LDL cholesterol (9.5 mg/dL, 95% CI: 4; 15.5) and triglycerides (20 mg/dL, 95% CI: 9.5; 32.5), and median weight increased by 2.5 pounds (95% CI: 1.5; 3.5). Treatment-related AEs occurred in 33 (11%) patients (all Grade 1-2) and led to 7 (2%) discontinuations. Table 1-Baseline demographic and clinical characteristics Table 2-Avoidance of Drug-Drug Interactions (DDIs) following switch to B/F/TAF Figure 1-Subgroup analysis of virologic outcomes at Week 48 Conclusion In this real-world cohort, switching to B/F/TAF was associated with maintenance of virologic control, improvement in lipid parameters, and avoidance of DDIs in a large proportion of patients. These data support use of B/F/TAF as a treatment option in older PLWH. Disclosures Charlotte-Paige M. Rolle, MD MPH, Gilead Sciences (Grant/Research Support, Scientific Research Study Investigator, Speaker’s Bureau)Janssen Infectious Disease (Grant/Research Support)ViiV Healthcare (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member, Speaker’s Bureau) Kiran Patel, PharmD, Gilead Sciences (Employee) Federico Hinestrosa, MD, AbbVie (Speaker’s Bureau)Gilead Sciences (Speaker’s Bureau)Merck (Speaker’s Bureau)Theratechnologies (Speaker’s Bureau) Edwin DeJesus, MD, Gilead Sciences (Advisor or Review Panel member)

scholarly journals 1104. Risk Factors and Outcomes of Refractory and/or Resistant Cytomegalovirus (CMV) Infection after Allogeneic Hematopoietic Stem Cell Transplantation

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S582-S583
Author(s):  
Eleni Karantoni ◽  
Yiqi Su ◽  
Anat Stern ◽  
Phaedon D Zavras ◽  
Sergio Giralt ◽  
...  
Keyword(s):  
Risk Factors ◽  
Overall Survival ◽  
T Cell ◽  
Panel Member ◽  
Multivariable Model ◽  
Research Support ◽  
Review Panel ◽  
Material Support ◽  
Advisory Boards ◽  
Research Grant

Abstract Background The epidemiology of CMV end-organ disease (EOD) after Hematopoietic Cell Transplant (HCT) in the era of preemptive therapy (PET) is defined. In contrast, less data exists on refractory and/or resistant (R/R) CMV. We report on 1) the incidence; 2) risk factors and outcomes of R/R CMV by 1-year post HCT. Methods Retrospective review of 167 CMV seropositive (R+) recipients of first marrow or peripheral blood HCT from 1/2014 - 12/2017 managed by PET. Refractory CMV was defined as failure to achieve >1 log10 decrease in CMV viral load (VL) and having VL >1,000 IU/mL after ≥14 day of PET. Resistant CMV required genotypic confirmation of resistance mutation(s) in UL54 and/or UL97 genes. End organ disease (EOD) was defined by standard criteria. Patients (pts) were followed through 1-year post HCT and were categorized in two mutually exclusive groups as R/R and no R/R. Demographics, clinical characteristics and outcomes were extracted from medical records and hospital databases. Univariable and multivariable logistic models were used to identify risk factors for R/R CMV. Results Of 167 PET recipients, 91 (54.5%) received ex vivo T cell depleted (TCD) HCT; 40 (24.0%) had mismatched donor; and 26 (15.6%) had multiple myeloma. 66/167 (39.5%) pts developed refractory CMV (6 pts also had resistant CMV). Time from HCT to CMV viremia was shorter in R/R group: median (IQR) 21.5 (17.2-27.8) days compared to no R/R group: 26 (19-32) days (p=0.031). Maximum VL was higher for R/R compared to no R/R: median (IQR) 9,118 (2,849-18,456) and 868 (474-1,908), respectively (p< 0.001). In multivariable model, risk factors for R/R included TCD HCT (p< 0.0001) and higher VL at PET initiation (p=0.0002). In contrast, CMV seropositive donor (p=0.035) was protective (Figure 1). CMV EOD developed in 28.2% of R/R and 16.2% of no R/R groups (p=0.085) (Figure 2). Overall survival at 1 year was 59.1% for R/R compared to 83.1% for no R/R group (p=0.00027) (Figure 3). Figure 1. Adjusted odds ratio (OR) and 95% confidence interval (CI) from multivariable model evaluating risk factors of refractory/resistant (R/R) CMV. Figure 2. Cumulative incidence curves of CMV end-organ disease (EOD) at 1-year post HCT Figure 3. Kaplan-Meier survival curves of overall survival (OS) at 1-year post HCT Conclusion 1) Refractory and/or resistant CMV occurred in 39,5% of PET recipients. 2) T-cell depletion and higher CMV VL at PET initiation were risk factors for R/R CMV in multivariable models. 3) R/R CMV was associated with more EOD and worse overall survival. Disclosures Sergio Giralt, MD, Amgen (Advisor or Review Panel member, Research Grant or Support, Served an advisory board for Amgen, Actinuum, Celgene, Johnson & Johnson, JAZZ pharmaceutical, Takeda, Novartis, KITE, and Spectrum pharma and has received research support from Amgen, Actinuum, Celgene, Johnson & Johnson, and Miltenyi, Takeda.) Miguel-Angel Perales, MD, Abbvie (Other Financial or Material Support, Honoraria from Abbvie, Bellicum, Celgene, Bristol-Myers Squibb, Incyte, Merck, Novartis, Nektar Therapeutics, Omeros, and Takeda.)ASTCT (Other Financial or Material Support, Volunteer member of the Board of Directors of American Society for Transplantation and Cellular Therapy (ASTCT), Be The Match (National Marrow Donor Program, NMDP), and the CIBMTR Cellular Immunotherapy Data Resource (CIDR) Committee)Cidara Therapeutics (Advisor or Review Panel member, Other Financial or Material Support, Serve on DSMBs for Cidara Therapeutics, Servier and Medigene, and the scientific advisory boards of MolMed and NexImmune.)Kite/Gilead (Research Grant or Support, Other Financial or Material Support, Received research support for clinical trials from Incyte, Kite/Gilead and Miltenyi Biotec.) Genovefa Papanicolaou, MD, Chimerix (Research Grant or Support)Merck&Co (Research Grant or Support, Investigator and received funding and consulting fees from Merck, Chimerix, Shire and Astellas)

scholarly journals 652. Comparison of fosfomycin (FOF) activity and prevalence of subpopulations between Escherichia coli (EC) and Klebsiella pneumoniae (KP) during susceptibility testing

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S384-S384
Author(s):  
Jadyn C Anderson ◽  
Amanda R Krueger ◽  
Elizabeth C Smith ◽  
Morgan L Bixby ◽  
Hunter V Brigman ◽  
...  
Keyword(s):  
Clinical Efficacy ◽  
Inhibitory Concentration ◽  
Panel Member ◽  
Colony Growth ◽  
The United States ◽  
Research Support ◽  
Review Panel ◽  
Agreement Rate ◽  
Future Studies ◽  
Agar Dilution

Abstract Background In the United States, interpretive criteria for FOF are established only for EC, yet those criteria are often extrapolated to KP. Recent studies have highlighted both inferior clinical outcomes after FOF treatment and difficulties in interpretation of inner colony subpopulations, the presence of which may affect clinical efficacy. We sought to compare FOF activity against EC and KP and to determine the prevalence of inner colony subpopulations following disk diffusion (DD) testing of the two species. Methods A convenience collection of 73 KP and 42 EC isolates from 3 U.S. institutions were included. Minimal inhibitory concentration (MIC) testing was performed in duplicate on separate days using agar dilution (AD) and DD as recommended by the Clinical and Laboratory Standards Institute guidelines, with application of EC susceptibility (≤ 64mg/L) breakpoints. The frequency and counts of inner colonies observed during DD testing was calculated, and colonies were subcultured for use in future studies. Results MIC50/90 values were 1/16 mg/L and 32/256 mg/L for EC and KP respectively. All EC isolates were considered susceptible and therefore categorical agreement was 100%. The majority of KP isolates were considered susceptible (83.6% with AD and 86.3% with DD) and categorical agreement between the methods was 84.9%. Inner colonies were observed during DD testing in 88.1% of EC isolates and 80.8% of KP isolates during at least one replicate, with 47.6% of EC isolates and 39.7% of KP isolates showing inner colony growth during both DD test replicates. More than 10 inner colonies were observed in 50% of EC isolates compared to 12.3% of KP isolates. Conclusion KP isolates demonstrated considerably higher FOF MIC values compared to EC, as evidenced by MIC50/90 values 4-5 dilutions higher than those for EC. The categorical agreement rate was higher among EC than KP, highlighting concerns regarding the practice of extrapolating FOF susceptibility breakpoints for EC to KP. The high frequency of inner colonies observed in DD for both species necessitates further studies to determine best practices for interpreting their relevance, fitness, and resistance in order to identify potential impacts to clinical efficacy of FOF. Disclosures Elizabeth B. Hirsch, PharmD, Merck (Grant/Research Support)Nabriva Therapeutics (Advisor or Review Panel member)

scholarly journals 108. Selective Decay of Intact HIV-1 Proviral DNA on Antiretroviral Therapy

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S183-S183
Author(s):  
Rajesh Gandhi ◽  
Joshua Cyktor ◽  
Ronald Bosch ◽  
Hanna Mar ◽  
Gregory Laird ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Panel Member ◽  
Plasma Viremia ◽  
Research Support ◽  
Review Panel ◽  
Proviral Dna ◽  
Hiv 1 ◽  
Over Time ◽  
Residual Plasma Viremia ◽  
Research Grant

Abstract Background HIV-1 proviruses persist in people on antiretroviral therapy (ART) but most are defective and do not constitute a replication-competent reservoir. The decay of infected cells carrying intact compared with defective HIV-1 proviruses has not been well-defined in people on ART. Methods We separately quantified intact and defective proviruses (using an intact proviral DNA assay), residual plasma viremia, and markers of inflammation and activation in people on long-term ART. Longitudinal measurements were done at three timepoints: timepoint 1 was a median of 7.1 years on ART; timepoint 2 was a median of 3.7 years later; timepoint 3 was a median of 5.5 years after timepoint 1 and a median 12 years after starting ART (Figure 1). Figure 1: Study timepoints Results Among 40 participants tested longitudinally from a median of 7.1 years to 12 years after ART initiation, intact provirus levels declined significantly over time (median half-life 7.1 years; 95% confidence interval [CI], 3.9, 18), whereas defective provirus levels did not decrease. The median half-life of total HIV-1 DNA was 41.6 years (95% CI, 13.6, 75). When we evaluated the change in proviral DNA per year, intact proviral DNA declined significantly more (p< 0.001) than defective proviral DNA (the latter did not change) (Figure 2). The proportion of all proviruses that were intact diminished over time on ART, from about 10% at the first on-ART timepoint to about 5% at the last timepoint (Figure 3). At timepoint 1, intact provirus levels on ART correlated with total HIV-1 DNA and residual plasma viremia, but there was no evidence for associations between intact provirus levels and inflammation or immune activation. Figure 2: Percent change in HIV-1 proviral DNA per year Figure 3: Total HIV-1 proviruses (grey bars) and the percentage of intact proviruses (red lines, displaying median, Q1, Q3) by timepoint. Conclusion Cells containing intact, replication-competent proviruses are selectively lost during suppressive ART. Defining the mechanisms involved should inform strategies to accelerate HIV-1 reservoir depletion. Disclosures Rajesh Gandhi, MD, Merck (Advisor or Review Panel member) Gregory Laird, PhD, Accelevir Diagnostics (Shareholder, Other Financial or Material Support, Employee) Albine Martin, PhD, Accelevir Diagnostics (Shareholder, Other Financial or Material Support, Employee) Bernard Macatangay, MD, Gilead (Grant/Research Support) Joseph J. Eron, MD, Gilead Sciences (Consultant, Research Grant or Support)Janssen (Consultant, Research Grant or Support)Merck (Consultant)ViiV Healthcare (Consultant, Research Grant or Support) Janet Siliciano, PhD, Gilead (Advisor or Review Panel member)US Military HIV Research Program (Advisor or Review Panel member) John Mellors, MD, Abound Bio (Shareholder)Accelevir Diagnostics (Consultant)Co-Crystal Pharmaceuticals (Shareholder)Gilead (Consultant, Grant/Research Support)Merck (Consultant)

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