Abstract Background We evaluated utilization of emtricitabine/tenofovir disoproxil fumarate or tenofovir alafenamide (F/TDF, F/TAF) among PN after the approval of F/TAF for PrEP in the US. Methods EMR and dispensing data from Trio Health HIV Research Network were used for this retrospective observational study. The study included HIV-negative PN ≥ 18 years with first dispense of daily oral PrEP (≥30-day supply) between 10/19-5/21 followed for ≥6 mo; individuals with hepatitis B or post-exposure prophylaxis were excluded. Prescription adherence, measured as proportion of days covered (PDC; mean and proportion with PDC ≥50, 70, and 80%) and time to regimen discontinuation (no drug >3 mo) or switch (TRD; Kaplan-Meier analysis) were compared between regimens. Characteristics associated with PDC and time to first regimen stop (switch/discontinuation) were evaluated using generalized linear regression and Cox proportional hazard models, respectively. Results Of 1330 PrEP starts, 86% (1144) were dispensed F/TAF vs 14% F/TDF (186). Baseline characteristics differed by regimen [Table 1]. While PDC was similar for both regimens, F/TAF had higher number of dispenses and mean days supplied vs F/TDF; mean days of follow-up were similar [Table 1]. F/TAF users had longer TRD (mean 20.2 vs 8.5 mo, Log-rank p< .001); median TRD was 3.9 mo for F/TDF and not reached for F/TAF [Figure 1]. A higher proportion of PN on F/TDF discontinued (46% vs 24% F/TAF) and switched (26% vs 2% F/TAF) their regimen (both p< .001). After accounting for gender, race, payer, age, high-risk behavior, F/TDF had a higher risk of discontinuation or switch (HR=4.9 CI 3.9-6.2); Black race was also associated with higher risk of discontinuation or switch [Table 2]. Results were similar when considering only discontinuation (censoring at time of switch or loss to follow up). Older age was identified as the primary driver of PDC controlling for other factors [Table 2]. Table 1.Characteristics of PN Individuals Dispensed Oral PrEP After October 2019 and PDC on First PrEP RegimenFigure 1.Time to PrEP Regimen Discontinuation or Switch (TRD, months)Table 2.Risk of First Oral PrEP Regimen Discontinuation or Switch and Characteristics Associated with Higher PDC Conclusion In this study PN adults dispensed F/TAF had greater number of dispenses, mean days supplied, and were less likely to discontinue or switch from F/TAF compared to F/TDF. Older age was the primary driver of increased PDC when considering other factors, including demographics, insurance and regimen. Disclosures Rick A. Elion, MD, Gilead Sciences: Advisor/Consultant|Trio Health: Employee|ViiV: Advisor/Consultant Joshua Gruber, PhD, Gilead Sciences: Employee Janna Radtchenko, MBA, Trio Health: Employee Megan Dunbar, PhD, Gilead Sciences: Employee Kenneth H. Mayer, MD, Gilead: Advisor/Consultant|Merck: Advisor/Consultant|ViiV: Advisor/Consultant Gregory Huhn, MD, MPHTM, Eli Lilly: Advisor/Consultant|Eli Lilly: Grant/Research Support|Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Jannsen: Advisor/Consultant|Jannsen: Grant/Research Support|Merck: Advisor/Consultant|Viiv: Advisor/Consultant|Viiv: Grant/Research Support Karam Mounzer, MD, Epividian: Advisor/Consultant|Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|Trio Health: Advisor/Consultant|ViiV: Advisor/Consultant|ViiV: Grant/Research Support Anthony Mills, MD, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|ViiV: Advisor/Consultant|ViiV: Grant/Research Support.

BACKGROUND Patients with underlying medical conditions are at increased risk for severe coronavirus disease 2019 (Covid-19). Whereas vaccine-derived immunity develops over time, neutralizing monoclonal-antibody treatment provides immediate, passive immunity and may limit disease progression and complications. METHODS In this phase 3 trial, we randomly assigned, in a 1:1 ratio, a cohort of ambulatory patients with mild or moderate Covid-19 who were at high risk for progression to severe disease to receive a single intravenous infusion of either a neutralizing monoclonal-antibody combination agent (2800 mg of bamlanivimab and 2800 mg of etesevimab, administered together) or placebo within 3 days after a laboratory diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The primary outcome was the overall clinical status of the patients, defined as Covid-19-related hospitalization or death from any cause by day 29. RESULTS A total of 1035 patients underwent randomization and received an infusion of bamlanivimab-etesevimab or placebo. The mean (+/- SD) age of the patients was 53.8 +/- 16.8 years, and 52.0% were adolescent girls or women. By day 29, a total of 11 of 518 patients (2.1%) in the bamlanivimab-etesevimab group had a Covid-19-related hospitalization or death from any cause, as compared with 36 of 517 patients (7.0%) in the placebo group (absolute risk difference, -4.8 percentage points; 95% confidence interval [CI], -7.4 to -2.3; relative risk difference, 70%; P<0.001). No deaths occurred in the bamlanivimab-etesevimab group; in the placebo group, 10 deaths occurred, 9 of which were designated by the trial investigators as Covid-19-related. At day 7, a greater reduction from baseline in the log viral load was observed among patients who received bamlanivimab plus etesevimab than among those who received placebo (difference from placebo in the change from baseline, -1.20; 95% CI, -1.46 to -0.94; P<0.001). CONCLUSIONS Among high-risk ambulatory patients, bamlanivimab plus etesevimab led to a lower incidence of Covid-19-related hospitalization and death than did placebo and accelerated the decline in the SARS-CoV-2 viral load.

Background: Older adults (≥50 y) living with HIV (OALWH) may experience elevated levels of depression, anxiety, and loneliness. Online mindfulness lessons have the potential to ameliorate these problems and enhance access, especially during the COVID-19 pandemic. The objective of this randomized controlled trial was to determine the effectiveness of online mindfulness lessons in reducing feelings of depression, anxiety, and loneliness among OALWH. Methods: The study was conducted between May and August 2020. Individuals with any degree of self-reported loneliness at baseline were eligible to participate. Outcomes of interest included depression, measured using the Center for Epidemiologic Studies Depression Scale (CES-D-10), anxiety measured using the Generalized Anxiety Disorder (GAD-7), and loneliness measured using both the Three-item Loneliness Scale (3IL) and a Daily Diary that asked “How lonely do you feel today?” Two sample t-tests were used to compare group scores at follow-up. Results: Of 214 participants who were randomized, the mean (SD) age was 60.4 (5.9) years, 89% were male, 69% were white, and 74% were gay or lesbian. At the end of the 25-day intervention, the intervention group demonstrated reduced levels of depression (2.6 point improvement;p<0.01), and reduced levels of anxiety (1.5 point improvement;p=0.03) compared to the control group (Table 1). Among the subset of participants with elevated baseline depression scores (defined as CES-D-10 ≥ 8), the between-group improvement in depression scores was greater (4.2 point improvement;p<0.01). Similarly, among the subset of participants with elevated baseline anxiety scores (defined as GAD-7 ≥ 5), the between-group improvement in anxiety scores was greater (2.4 point improvement;p<0.01). Loneliness improved significantly, as indicated by the Daily Diary, for those with at least moderate loneliness at baseline (0.7 point improvement;p<0.01). Conclusion: This randomized controlled trial is the first to show that a series of brief, online mindfulness audio lessons improves mental health outcomes among OALWH who report some degree of loneliness. For many patients, this intervention may offer emotional relief, particularly with regard to depression and anxiety, even in the face of the COVID-19 pandemic.

Background: Patients with underlying medical conditions have a greater risk of developing severe COVID-19. Unlike vaccine-derived immunity which develops over time, administration of neutralizing monoclonal antibodies is an immediate, passive humoral immunotherapy, with the potential to reduce disease progression, emergency room visits, hospitalizations, and death. Methods: In this phase 3 portion of the BLAZE-1 trial, a high-risk ambulatory cohort of 1035 patients with mild-to-moderate COVID-19 were randomly assigned 1:1 to receive a single intravenous infusion of a neutralizing monoclonal antibody combination treatment consisting of 2800mg bamlanivimab+2800mg etesevimab together, or placebo, within 3 days of laboratory diagnosis. The primary outcome was overall patient clinical status, measured by the proportion of patients who experienced COVID-19-related hospitalization or death by any cause by Day 29. Results: 1035 patients were randomized and infused (mean age [SD];53.8 years [16.8], female (52%)). A 70% reduction in COVID-19-related hospitalization and death by any cause by Day 29 was observed in patients who received the bamlanivimab+etesevimab combination treatment (11/518 arm total) compared to those who received placebo (36/517 arm total) (Δ[95% CI]=-4.8[-7.4,-2.3])(p=0.0004). No deaths were observed among patients who received the combination treatment, 10 deaths were reported in the placebo group, at least 8 designated COVID-19-related. A significantly greater reduction in log10(viral load) from baseline at Day 7 was observed amongst patients who received bamlanivimab+etesevimab compared to placebo (Δ[95% CI]=-1.20[-1.46,-0.94])(p<0.00000001). The median time to sustained symptom resolution was shorter for those who received the combination treatment (days [95% CI]=8[7.0,8.0]) compared to those who received placebo (days [95% CI]=9[8.0,10.0])(p=0.007). Similar rates of adverse events were observed between placebo (60/517,11.6%) and combination treatment groups (69/518,13.3%). Conclusion: 2800mg bamlanivimab+2800mg etesevimab neutralizing monoclonal antibody combination therapy significantly reduced COVID-19- related hospitalizations and deaths amongst high-risk ambulatory patients and accelerated the decline in viral load and disease symptoms over time. This study confirms that early intervention with bamlanivimab + etesevimab greatly improves the clinical outcomes for high-risk ambulatory patients, and links reduction in nasopharyngeal viral load to clinically meaningful benefits.

Background Loneliness is a concern among older people living with HIV (PLWH), especially given the ongoing COVID-19 pandemic. Currently, there is little research characterizing loneliness and race. To investigate how HIV impacts older (age 50+) PLWH in the US, a study called Aging with Dignity, Health, Optimism and Community (ADHOC) was launched at ten sites to collect self-reported data. This study uses ADHOC data to compare loneliness between older Black and White PLWH. Methods A cross-sectional analysis was performed to compare loneliness between older Black and White PLWH. Loneliness was assessed using the Three-item Loneliness Scale, a validated patient-reported outcome measure (range 3–9), with higher scores indicating greater loneliness. Student’s t-test was used to compare loneliness between White and Black people. Control variables for loneliness were identified a priori and included in a multivariable linear regression model. Results Of 868 participants, the average age was 60 (SD 6.2) years, 77% (N=671) were White and 23% (N=197) were Black, 85% were male, and 82% were gay or lesbian. In bivariate analyses, Black participants were less lonely than White participants (5.2 vs 5.6, P=.02). In the multivariable linear regression analysis, Black participants were again less lonely than Whites (coef. -0.45, P=0.01) while controlling for age, education, depression, anxiety, number of co-morbid conditions, being single, income, gender, sexual orientation, and spirituality (Adjusted R2=0.38; P<.01). Conclusion Among PLWH over age 50 in ADHOC, Black participants experienced less loneliness than White participants, even after controlling for a variety of factors. Additional research is needed to better understand the causes of these racial differences, so that programs designed to decrease loneliness among PLWH can consider the unique characteristics of each group.

Background Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg was investigated in AMBER (treatment-naïve adults; NCT02431247) and EMERALD (treatment-experienced, virologically-suppressed adults; NCT02269917). Objective To describe a Week 96 pre-planned subgroup analysis of D/C/F/TAF arms by demographic characteristics (age ≤/>50 years, gender, black/non-black race), and baseline clinical characteristics (AMBER: viral load [VL], CD4+ count, WHO clinical stage, HIV-1 subtype and antiretroviral resistance; EMERALD: prior virologic failure [VF], antiretroviral experience, screening boosted protease inhibitor [PI], and boosting agent). Methods Patients in D/C/F/TAF and control arms could continue on/switch to D/C/F/TAF in a single-arm, open-label extension phase after Week 48 until Week 96. Efficacy endpoints were percentage cumulative confirmed VL ≥50 copies/mL (virologic rebound; EMERALD), and VL <50 (virologic response), or ≥50 copies/mL (VF) (FDA snapshot; both trials). Results D/C/F/TAF demonstrated high Week 96 virologic responses (AMBER: 85% [308/362]; EMERALD: 91% [692/763]) and low VF rates (AMBER: 6% [20/362]; EMERALD: 1% [9/763]). In EMERALD, D/C/F/TAF showed low virologic rebound cumulative through Week 96 (3% [24/763]). Results were consistent across subgroups, including prior antiretroviral experience in EMERALD. No darunavir, primary PI, or tenofovir resistance-associated mutations were observed post-baseline. Study-drug-related serious adverse events (AEs) and AE-related discontinuations were <1% and 2%, respectively (both D/C/F/TAF arms), and similar across subgroups. eGFRcyst and bone mineral density improved or were stable and lipids increased through Week 96 across demographic subgroups, with small changes in total-cholesterol/HDL-cholesterol ratio. Conclusions D/C/F/TAF was effective with a high barrier to resistance and bone/renal safety benefits, regardless of demographic or clinical characteristics for treatment-naïve and treatment-experienced, virologically-suppressed adults.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg was investigated through 96 weeks in EMERALD (NCT02269917). Virologically-suppressed, HIV-1-positive treatment-experienced adults (previous non-darunavir virologic failure [VF] allowed) were randomized (2:1) to D/C/F/TAF or boosted protease inhibitor (PI) plus emtricitabine/tenofovir-disoproxil-fumarate (F/TDF) over 48 weeks. At week 52 participants in the boosted PI arm were offered switch to D/C/F/TAF (late-switch, 44 weeks D/C/F/TAF exposure). All participants were followed on D/C/F/TAF until week 96. Efficacy endpoints were percentage cumulative protocol-defined virologic rebound (PDVR; confirmed viral load [VL] >= 50 copies/mL) and VL < 50 copies/mL (virologic suppression) and >= 50 copies/mL (VF) (FDA-snapshot analysis). Of 1141 randomized patients, 1080 continued in the extension phase. Few patients had PDVR (D/C/F/TAF: 3.1%, 24/763 cumulative through week 96; late-switch: 2.3%, 8/352 week 52-96). Week 96 virologic suppression was 90.7% (692/763) (D/C/F/TAF) and 93.8% (330/352) (late-switch). VF was 1.2% and 1.7%, respectively. No darunavir, primary PI, tenofovir or emtricitabine resistance-associated mutations were observed post-baseline. No patients discontinued for efficacy-related reasons. Few discontinued due to adverse events (2% D/C/F/TAF arm). Improved renal and bone parameters were maintained in the D/C/F/TAF arm and observed in the late-switch arm, with small increases in total cholesterol/high-density-lipoprotein-cholesterol ratio. A study limitation was the lack of a control arm in the week 96 analysis. Through 96 weeks, D/C/F/TAF resulted in low PDVR rates, high virologic suppression rates, very few VFs, and no resistance development. Late-switch results were consistent with D/C/F/TAF week 48 results. EMERALD week 96 results confirm the efficacy, high genetic barrier to resistance and safety benefits of D/C/F/TAF.

s (20%). No serious adverse events attributed to study medication were reported.Conclusions: Results in over 450 NS5A inhibitor-experienced patients enrolled in Phase 2 or Phase 3 trials demonstrate that the 3-DAA combination of SOF, VEL and VOX for 12 weeks is a safe, well tolerated and effective treatment for patients who previously failed an NS5A inhibitor-containing DAA-containing regimen, irrespective of the other drugs in the prior treatment regimen.

Summary Identification of perceptions about herpes zoster (HZ) disease, vaccine effectiveness and safety, and vaccine recommendations may impact immunization practices of physicians for HIV-infected patients. A survey was used to quantify knowledge of HZ as well as determine physician immunization perceptions and practices. There were 272/1700 respondents (16%). Correct answers for the incidence of varicella zoster virus (VZV) infection in adults and incidence of HZ in HIV-infected patients were recorded by 14% and 10% of providers, respectively. Providers reported poor knowledge of the incidence of disease recurrence in HIV-infected patients (41% correct), potency of HZ vaccine (47.5% correct) and mechanism of protection against reactivation of VZV (66% correct). Most (88%) agreed that HZ was a serious disease, and 73% believed that the burden of disease made vaccination important. A majority (75%) did not vaccinate HIV patients with HZ vaccine regardless of antiretroviral therapy status. Barriers to administration included safety concerns, concern that vaccine would not prevent HZ, risk of HZ dissemination, reimbursement issues and lack of Infectious Diseases Society of America (IDSA) guidelines. Only 38% of providers agreed that CDC guidelines were clear and 50% believed that clinical trials were needed prior to use of HZ vaccine in HIV-infected patients. Education about HZ is needed among HIV providers. Providers perceived vaccination as important, but data on vaccine safety and clear guidance from the CDC on this issue are lacking.

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK