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An observational cohort study was conducted with data from the Observational Pharmaco-Epidemiology ResearchAnalysis (OPERA) cohort to investigate weight gain among virologically suppressed people with HIV (PWH) switching to regimens containing tenofovir alafenamide/emtricitabine/(TAF/FTC). Virologically suppressed, antiretroviral therapy (ART)-experienced PWH switching to TAF/FTC with darunavir/cobicistat (DRV/c), elvitegravir/cobicistat (EVG/c), dolutegravir (DTG), or bictegravir (BIC) were selected. Cox proportional hazards models were used to assess the risk of excessive weight gain (i.e., ≥5% gain within 28 weeks or ≥10% within 54 weeks), by regimen. A linear mixed effects model with random intercept and restricted cubic splines on time was used to assess continuous changes in weight. Confounding was controlled for with both inverse probability of treatment weighting and traditional covariate adjustment. Among 5,536 PWH, 18% gained ≥5% of their weight within 28 weeks, and 9% gained ≥10% within 54 weeks. There were no differences in the risk of excessive weight gain by regimen, although there was a nonstatistically significant 20% increase in the risk of gaining ≥10% within 54 weeks with all regimens compared to DRV/c. Throughout follow-up, the mean predicted weight remained fairly constant, with no notable differentiation between regimens. Expected weight gains ranged from +0.2 to +0.3 kg at 6 months and from +0.5 to +0.6 kg at 24 months. In conclusion, in this study of virologically suppressed, ART-experienced PWH switching to regimens containing TAF/FTC and DRV/c, EVG/c, DTG, or BIC, up to 18% experienced excessive levels of weight gain. However, no statistically significant difference was observed across regimens.

Deficient skeletal muscle regeneration, which often leads to permanent sequelae, is a common clinical finding in envenomations caused by snakes of the family Viperidae, such as those of Bothrops alternatus and B. diporus in South America. The causes of such poor muscle regenerative outcome are still incompletely understood. Using a murine experimental model of envenomation by the venoms of these two species, we assessed whether traces of venom components that remain in muscle tissue days after envenomation affect myoblasts and myotube formation in culture. The kinetics of drop in venom concentration in the tissue was assessed by ELISA and Western blot, and by the quantification of venom phospholipase A

Background Multi-class resistance, intolerance, and drug–drug interactions can result in unique antiretroviral (ART) combinations for heavily treatment-experienced (HTE) people living with HIV (PLWH). We aimed to compare clinical outcomes between HTE and non-HTE PLWH. Methods Eligible ART-experienced PLWH in care in the OPERA® Cohort were identified in a cross-sectional manner on December 31, 2016 and observed from the date of initiation of the ART regimen taken on December 31, 2016 until loss to follow up, death, study end (December 31, 2018), or becoming HTE (non-HTE group only). In the absence of resistance data, HTE was defined based on the ART regimens used (i.e., exposed to ≥ 3 core agent classes or regimen suggestive of HTE). Time to virologic undetectability, failure, and immunologic preservation were assessed using Kaplan–Meier methods; cumulative probabilities were compared between the two groups. Regimen changes, incident morbidities, and death were described. Results A total of 24,183 PLWH (2277 HTE PLWH, 21,906 non-HTE) were followed for a median of 28 months (IQR 21, 38). Viremic HTE PLWH (viral load [VL] ≥ 50 copies/mL) were less likely to achieve undetectability (VL Conclusions HTE PLWH were at greater risk of unfavorable treatment outcomes than non-HTE PLWH, suggesting additional therapeutic options are needed for this vulnerable population.

Background Paired with other active antiretrovirals (ARVs), fostemsavir (FTR) may offer heavily treatment-experienced (HTE) people with HIV (PWH) options for continuing effective treatment. Durability and effectiveness of FTR-containing regimens in routine clinical care in the United States were assessed. Methods Electronic health record data from the OPERA® cohort were used to identify adults initiating FTR-containing regimens between 2JUL2020 (FDA approval) and 1SEP2021. Eligible PWH were followed from first FTR prescription (baseline) until FTR discontinuation, death, loss to follow up, or study end (28FEB2022). Durability was assessed as frequency of FTR discontinuation. Virologic outcomes assessed at 6 and 12 months (±3 months) included suppression (viral load [VL] < 50 copies/mL), virologic failure (2 consecutive VL ≥200 copies/mL or 1 VL ≥200 copies/mL + FTR discontinuation within 120 days after suppression), and viral blips (1 VL ≥50 copies/mL preceded and followed by VLs < 50 copies/mL). Analyses were stratified by baseline viral load (bVL < 50 copies/mL; bVL ≥50 copies/mL). Results Overall, 86 PWH initiated FTR (bVL < 50: 30; bVL ≥50: 55), with median follow up of 10.8 months (IQR: 6.8, 15.3). Compared to PWH with bVL ≥50, those with bVL < 50 were older and more likely to be white and have lived longer with HIV (Table 1). Over follow up, 20% discontinued FTR (Table 2). Most (82%) FTR discontinuations were switches to alternative regimens; the remaining were ARV interruptions (no ARVs for > 45 days). Among PWH with bVL < 50, most maintained suppression (6 months: 74%; 12 months: 82%; Figure). Among PWH with bVL ≥50 and with follow up VL during the period assessed, 33% were suppressed at 6 months, 36% were suppressed at 12 months, and 48% achieved suppression at any time over the entire follow up (Figure). In either group, ≤5 PWH experienced virologic failure or blip, though the proportion of PWH with multiple follow up VLs was low. Conclusion Despite a heterogenous population and diverse regimens, most HTE PWH remained on FTR at study end. Most PWH with bVL < 50 remained suppressed and half of PWH with bVL ≥50 achieved suppression over the entire study period. Virologic failure and blips were infrequent, although follow up was limited in this early evaluation of real-world FTR use. Disclosures Ricky K. Hsu, MD, Gilead: Honoraria|Merck: Honoraria|ViiV: Advisor/Consultant|ViiV: Grant/Research Support|ViiV: Honoraria Laurence Brunet, PhD, AIDS Healthcare Foundation: Client of my employer|EMD Serono: Client of my employer|Gilead Sciences: Client of my employer|Janssen: Client of my employer|Merck & Co: Client of my employer|TheraTechnologies: Client of my employer|ViiV Healthcare: Client of my employer Jennifer S. Fusco, BS, AIDS Healthcare Foundation: Client of my employer|EMD Serono: Client of my employer|Gilead Sciences: Client of my employer|Janssen: Client of my employer|Merck & Co.: Client of my employer|TheraTechnologies: Client of my employer|ViiV Healthcare: Client of my employer Cassidy Henegar, PhD, MSPH, GlaxoSmithKline: Stocks/Bonds|ViiV Healthcare: full-time employee Vani Vannappagari, MBBS, MPH, PhD, ViiV Healthcare: I am full time employee of ViiV Healthcare and receive GlaxoSmithKline stock as part of my compensation package|ViiV Healthcare: Stocks/Bonds Andrew Clark, MD, ViiV Healthcare: Employee|ViiV Healthcare: Stocks/Bonds Gerald Pierone, Jr., MD, Gilead: Grant/Research Support|GSK-VIIV: Grant/Research Support Gregory P. Fusco, MD, MPH, AIDS Healthcare Foundation: Client of employer|EMD: Grant/Research Support|Gilead Sciences: Client of employer|Janssen: Client of employer|Merck & Co.: Client of employer|Theratechnologies: Client of employer|ViiV Healthcare: Client of employer.

Background The first long-acting (LA) antiretroviral therapy (ART) regimen, cabotegravir+rilpivirine (CAB+RPV) injection, was approved by the FDA in January 2021 for ART-experienced, people with HIV (PWH) with undetectable viral load (VL< 50 copies/mL). We assessed clinical effectiveness of CAB+RPV LA in the first year of use in the United States (US). Methods Using electronic health record data from the OPERA® cohort, all ART-experienced adults who received ≥1 CAB+RPV LA prescriptions for the first time between 21Jan2021 and 28Feb2022 were followed until 13Mar2022. Discontinuation was defined as an ART switch or > 2 consecutive missed doses. VL were monitored from first injection until end of follow-up or discontinuation. Confirmed virologic failure was defined as 2 consecutive VLs > 200 copies/mL or 1 VL > 200 copies/mL + discontinuation. Results were stratified by VL at first prescription (i.e., suppressed: < 200 copies/mL; viremic: ≥ 200 copies/mL). Results Of 994 PWH prescribed CAB+RPV, all were ART-experienced and 85% had undetectable VL (< 50 copies/mL), 90% were suppressed (< 200 copies/mL), and the remainder had VL ≥200/mL (6%) or missing baseline VL (4%). Of those prescribed, 344 (38%) received CAB+RPV LA injections over a median 53 (IQR: 35, 79) days; 14% were women, 36% were Black, 29% were Hispanic, 25% had a BMI of ≥30, and the median age was 40 (IQR: 32, 53) years (Table 1). At the end of observation, 62% had not yet received CAB+RPV injections as they were in the process of approval, were on oral lead-in, or had been denied. At study end, 310 (90%) of the 344 remained on CAB+RPV LA with median follow-up of 3.4 (2.2, 6.1) months. Among those with VLs after first injection, the last VL was < 200 copies/mL in 99% and < 50 copies/mL in 94% (Table 2); all follow-up VLs were < 200 copies/mL in 97%, and < 50 copies/mL in 88%. Thirty viremic PWH received CAB+RPV LA injections (Table) with a median VL at first prescription of 4.2 (IQR: 3.2, 4.9) log copies/mL. Five or fewer PWH experienced confirmed virologic failure in each of the suppressed and viremic groups. Conclusion In this real-world cohort of PWH who received CAB+RPV LA injections in the US, observations from the first year suggest that this regimen is effective among virologically suppressed individuals. Disclosures Michael G. Sension, MD, Gilead: Advisor/Consultant|Gilead: Honoraria|Viiv: Advisor/Consultant|Viiv: Grant/Research Support|Viiv: Honoraria Ricky K. Hsu, MD, Gilead: Honoraria|Merck: Honoraria|ViiV: Advisor/Consultant|ViiV: Grant/Research Support|ViiV: Honoraria Jennifer S. Fusco, BS, AIDS Healthcare Foundation: Client of my employer|EMD Serono: Client of my employer|Gilead Sciences: Client of my employer|Janssen: Client of my employer|Merck & Co.: Client of my employer|TheraTechnologies: Client of my employer|ViiV Healthcare: Client of my employer Laurence Brunet, PhD, AIDS Healthcare Foundation: Client of my employer|EMD Serono: Client of my employer|Gilead Sciences: Client of my employer|Janssen: Client of my employer|Merck & Co: Client of my employer|TheraTechnologies: Client of my employer|ViiV Healthcare: Client of my employer Gayathri Sridhar, MBBS, MPH, PhD, GlaxoSmithKline: Stocks/Bonds|ViiV Healthcare: Employment Vani Vannappagari, MBBS, MPH, PhD, ViiV Healthcare: I am full time employee of ViiV Healthcare and receive GlaxoSmithKline stock as part of my compensation package|ViiV Healthcare: Stocks/Bonds Andrew Zolopa, MD, ViiV Healthcare: full time employee|ViiV Healthcare: Stocks/Bonds Jean A. van Wyk, MB,ChB; MFPM, ViiV Healthcare Limited: I am an employee of ViiV Healthcare|ViiV Healthcare Limited: Stocks/Bonds Gregory P. Fusco, MD, MPH, AIDS Healthcare Foundation: Client of employer|EMD: Grant/Research Support|Gilead Sciences: Client of employer|Janssen: Client of employer|Merck & Co.: Client of employer|Theratechnologies: Client of employer|ViiV Healthcare: Client of employer.

Background In-vitro neutralizing antibody (Ab) titers correlated with ∼250 IU/mL Spike Ig Ab level for the Delta COVID-19 variant, establishing the 2021 French and Swiss cutoff for booster guidance. In a New York City healthcare clinic where those guidelines were adopted, we aimed to quantify vaccination responses in HIV+ and HIV- individuals to assess the utility of quantifying antibodies to guide booster timing. Methods Adults who were fully vaccinated against SARS-CoV-2 virus (i.e., 2 Pfizer, 2 Moderna or 1 J&J vaccine) were included if >1 Roche SARS-CoV-2 Semi-Quant Spike Ig Ab test was performed >21 days after vaccination and before any booster (through 03DEC2021). Vaccine response was assessed at the first Ab test and considered adequate (>250 IU/mL) or inadequate (low: ≥51 to ≤250 IU/mL; no response: < 51 IU/mL). The rate of Ab decline was estimated with linear regression, using all sequential Ab tests over the first 6 months between vaccination and boosting. Analyses were stratified by vaccine type, HIV status and CD4 count in HIV+ ( >200 cells/µL cutoff). Results Out of 1979 patients, 869 completed their primary vaccinations, of whom 825 (95%) had ≥1 eligible Ab test (HIV+: 512; HIV-: 313; Table). Overall, 83% had an adequate immune response to vaccination (Pfizer: 82%, Moderna: 94%, J&J: 51%), with similar findings regardless of HIV status and CD4 count (Figure 1). In those with ≥2 Ab tests within six months between vaccination and boosting, Ab levels declined at a rate of 91 IU/mL per month (95% CI: -138, -44). While some variation was observed, rates of Ab decay were generally consistent across vaccine, HIV status and CD4 count strata (Figure 2). Only 1/7 breakthrough COVID-19 infections occurred post booster (6 days later). Conclusion In the pre-omicron era, primary COVID immunization with a mRNA vaccine generally yielded adequate Ab responses, although inadequate responses were observed in 19% of Pfizer, 6% of Moderna, and 49% of J&J vaccine recipients. Ab levels decreased at an average rate of 91 IU/mL per month after primary immunization. Variability in vaccine responses and Ab declines show the utility of measuring spike Ig Ab levels rather than using empiric time frames for booster guidance. Omicron-specific quantitative IgG neutralization levels must be established to inform preventative care. Disclosures Ricky K. Hsu, MD, Gilead: Honoraria|Merck: Honoraria|ViiV: Advisor/Consultant|ViiV: Grant/Research Support|ViiV: Honoraria Laurence Brunet, PhD, AIDS Healthcare Foundation: Client of my employer|EMD Serono: Client of my employer|Gilead Sciences: Client of my employer|Janssen: Client of my employer|Merck & Co: Client of my employer|TheraTechnologies: Client of my employer|ViiV Healthcare: Client of my employer Jennifer S. Fusco, BS, AIDS Healthcare Foundation: Client of my employer|EMD Serono: Client of my employer|Gilead Sciences: Client of my employer|Janssen: Client of my employer|Merck & Co.: Client of my employer|TheraTechnologies: Client of my employer|ViiV Healthcare: Client of my employer.

Background HIV-associated wasting (i.e., progressive, involuntary weight loss with both fat and lean tissue loss; HIVAW) is an under-appreciated AIDS-defining illness; the 2012-2018 period prevalence was reported as 18% in a recent claims study in the United States. We aimed to assess the association between incident HIVAW/low weight and all-cause mortality in the era of modern combination antiretroviral therapy (ART). Methods In the Observational Pharmaco-Epidemiology Research & Analysis (OPERA®) cohort, PWH without (a) any prior HIVAW/low weight, (b) malignancy within 3 years, and (c) opportunistic infection within 1 year who were active in care between 2016 and 2020 were followed through death, loss to follow-up, or study end (31OCT2021). HIVAW/low weight included a wasting or low BMI/underweight diagnosis (ICD codes, title search) or BMI < 20 kg/m2. Hazard ratios (HR) and 95% confidence intervals (CI) for the association between time-dependent incident HIVAW/low weight (exposure) and all-cause mortality (outcome) were estimated with extended Cox regression models. The adjusted model included age at baseline, race, ethnicity, and time-dependent covariates (log10 viral load, Veterans Aging Cohort Study [VACS] Mortality Index score). Viral load and VACS score were included as surrogate markers for ART use and comorbidities, respectively. Linear and quadratic terms of continuous variables were included. Results Of 67,119 PWH without prior HIVAW/low weight in OPERA®, 62,314 (93%) PWH had non-missing covariate data and were included in the models; baseline characteristics did not differ between the full and model study populations (Table 1). Over a median follow-up of 45 months (interquartile range: 27, 65), there were 4,755 (8%) cases of incident HIVAW/low weight and 1,354 (2%) deaths. In the adjusted model, PWH who experienced incident HIVAW/low weight had a significantly increased risk of death over follow-up than those who did not experience HIVAW/low weight (HR: 1.96; 95% CI: 1.68, 2.27) (Table 2). Conclusion In this analysis of 62,314 PWH in care, incident HIVAW/low weight was associated with twice the risk for all-cause mortality in the modern ART era. Particular attention needs to be paid to HIVAW/low weight among PWH to restore health and potentially reduce the risk of death. Disclosures Rachel P. Weber, PhD, AIDS Healthcare Foundation: Client of my employer|EMD Serono: Client of my employer|Gilead Sciences: Client of my employer|Janssen: Client of my employer|Merck & Co.: Client of my employer|TheraTechnologies: Client of my employer|ViiV Healthcare: Client of my employer Laurence Brunet, PhD, AIDS Healthcare Foundation: Client of my employer|EMD Serono: Client of my employer|Gilead Sciences: Client of my employer|Janssen: Client of my employer|Merck & Co: Client of my employer|TheraTechnologies: Client of my employer|ViiV Healthcare: Client of my employer Javeed Siddiqui, MD, MPH, Abbvie: Advisor/Consultant|Abbvie: Honoraria|Cumberland pharmaceuticals: Advisor/Consultant|Cumberland pharmaceuticals: Honoraria|EMD serono: Advisor/Consultant|EMD serono: Honoraria|Merck: Advisor/Consultant|Merck: Honoraria Javeed Siddiqui, MD, MPH, Abbvie: Advisor/Consultant|Abbvie: Honoraria|Cumberland pharmaceuticals: Advisor/Consultant|Cumberland pharmaceuticals: Honoraria|EMD serono: Advisor/Consultant|EMD serono: Honoraria|Merck: Advisor/Consultant|Merck: Honoraria Michael Harbour, MD, MPH, FACP, EMD Serono: Employee Amy L. Phillips, PharmD, EMD Serono, Inc.: Employment Brooke Hayward, SM, MBA, EMD Serono, Inc.: Employee Jennifer S. Fusco, BS, AIDS Healthcare Foundation: Client of my employer|EMD Serono: Client of my employer|Gilead Sciences: Client of my employer|Janssen: Client of my employer|Merck & Co.: Client of my employer|TheraTechnologies: Client of my employer|ViiV Healthcare: Client of my employer Ricky K. Hsu, MD, Gilead: Honoraria|Merck: Honoraria|ViiV: Advisor/Consultant|ViiV: Grant/Research Support|ViiV: Honoraria Gregory P. Fusco, MD, MPH, AIDS Healthcare Foundation: Client of employer|EMD: Grant/Research Support|Gilead Sciences: Client of employer|Janssen: Client of employer|Merck & Co.: Client of employer|Theratechnologies: Client of employer|ViiV Healthcare: Client of employer.

Background Real-world effectiveness of fixed dose dolutegravir/lamivudine (DTG/3TC) two-drug regimens (2DR) during the first 24 months of availability in the US was compared to common three-drug regimens (3DRs) among suppressed antiretroviral therapy (ART)-experienced people living with HIV (PLWH). Methods Suppressed (viral load [VL] < 200 copies/mL) PLWH initiating DTG/3TC 2DR, bictegravir (BIC)-3DR, or DTG-3DR between 01MAY2019 and 31OCT2020 in the OPERA® Cohort were followed until 30APR2021 (potential for ≥6 months of follow-up). Univariate Poisson regression (incidence rates) and Cox proportional hazards marginal structural models were employed to assess confirmed virologic failure (2 viral loads [VLs] ≥200 copies/mL) or regimen discontinuation. Results Overall, 8037 PLWH were included in the analysis (Table). Virologic failure incidence rates were low, ranging from 0.66 (DTG/3TC) to 1.78 (DTG 3DR) per 100 person-years. Compared to DTG/3TC, only DTG 3DR was associated with an increase in the hazard of virologic failure. Discontinuation incidence rates ranged from 8.30 (BIC 3DR) to 24.9 (DTG 3DR) per 100 person-years. The discontinuation hazard was 69% greater with DTG 3DRs and 49% lower with BIC 3DRs compared to DTG/3TC. Regardless of regimen, most discontinuers were suppressed (VL< 200 copies/mL) at the time of discontinuation (DTG/3TC 2DR: 96%, BIC 3DR: 94%, DTG 3DR: 93%; all p >0.05). Discontinuations following an adverse diagnosis/side effect were uncommon with DTG/3TC 2DR (3%) and DTG 3DR (4%, p=0.5), and higher with BIC 3DR discontinuation (7%, p=0.02). The most common reason for DTG 3DR discontinuations was regimen simplification (21%); no reason was given for >50% of the discontinuations in each group. Conclusion Among ART-experienced, virologically suppressed PLWH, virologic failure was rare after switching to DTG/3TC 2DR, BIC 3DR or DTG 3DR. Most discontinuations were not attributed to the treatment (i.e., loss of suppression, adverse diagnosis, side effects), suggesting other reasons for discontinuation despite high levels of suppression and tolerability. Disclosures Gerald Pierone, Jr., MD, Gilead: Grant/Research Support|GSK-VIIV: Grant/Research Support Jennifer S. Fusco, BS, AIDS Healthcare Foundation: Client of my employer|EMD Serono: Client of my employer|Gilead Sciences: Client of my employer|Janssen: Client of my employer|Merck & Co.: Client of my employer|TheraTechnologies: Client of my employer|ViiV Healthcare: Client of my employer Laurence Brunet, PhD, AIDS Healthcare Foundation: Client of my employer|EMD Serono: Client of my employer|Gilead Sciences: Client of my employer|Janssen: Client of my employer|Merck & Co: Client of my employer|TheraTechnologies: Client of my employer|ViiV Healthcare: Client of my employer Vani Vannappagari, MBBS, MPH, PhD, ViiV Healthcare: I am full time employee of ViiV Healthcare and receive GlaxoSmithKline stock as part of my compensation package|ViiV Healthcare: Stocks/Bonds Supriya Sarkar, PhD, MPH, ViiV Healthcare: Salary|ViiV Healthcare: Stocks/Bonds Cassidy Henegar, PhD, MSPH, GlaxoSmithKline: Stocks/Bonds|ViiV Healthcare: full-time employee Andrew Zolopa, MD, ViiV Healthcare: full time employee|ViiV Healthcare: Stocks/Bonds Gregory P. Fusco, MD, MPH, AIDS Healthcare Foundation: Client of employer|EMD: Grant/Research Support|Gilead Sciences: Client of employer|Janssen: Client of employer|Merck & Co.: Client of employer|Theratechnologies: Client of employer|ViiV Healthcare: Client of employer.

With obesity on the rise among people living with HIV (PLWH), there is growing concern that weight gain may result as an undesired effect of antiretroviral therapy (ART). This analysis sought to assess the association between ART regimens and changes in body mass index (BMI) among ART-experienced, virologically suppressed PLWH. ART-experienced, virologically suppressed PLWH ≥18 years of age in the Observational Pharmacoepidemiology Research and Analysis (OPERA) cohort were included for analysis if prescribed a new regimen containing one of the following core agents: dolutegravir (DTG), elvitegravir/cobicistat (EVG/c), raltegravir (RAL), rilpivirine (RPV), or boosted darunavir (bDRV), for the first time between August 1, 2013 and December 31, 2017. Multivariable linear regression was used to assess the association between regimen and mean changes in BMI at 6, 12, and 24 months after switch. In unadjusted analyses, BMI increases ranged from 0.30 kg/m

Background and Objective Many people living with HIV (PLWH) on stable tenofovir disoproxil fumarate (TDF)-containing regimens have switched to tenofovir alafenamide (TAF), despite the potential lipid-lowering effect of TDF. We aimed to assess the impact of switching from TDF to TAF on lipids in real-world clinical practice. Methods PLWH prescribed TDF for ≥ 4 weeks who switched to TAF were identified in the OPERA cohort. Patterns of dyslipidemia were compared before and after switch based on NCEP ATPIII guidelines. Elevated 10-year risk of atherosclerotic cardiovascular disease (ASCVD ≥ 7.5%) and statin use were assessed. Results Among 6423 PLWH switched from TDF to TAF, the proportion with dyslipidemia/severe dyslipidemia observed after switch from TDF to TAF increased statistically significantly (p < 0.0001) with total cholesterol (5–10%), low-density lipoprotein cholesterol (16–23%), and triglycerides (21–27%), but decreased statistically significantly with high-density lipoprotein cholesterol (35–30%, p < 0.0001). These patterns of dyslipidemia persisted in sensitivity analyses restricted to PLWH who maintained all other antiretrovirals (N = 4328) or stratified by pharmaco-enhancer use before and after switch. An elevated ASCVD risk was detected in 29% before and 31% after switch. As many as 59% of PLWH with an elevated ASCVD risk were not prescribed a statin after switch from TDF to TAF. Conclusions In this large, diverse population of PLWH in the USA, the switch from TDF to TAF was associated with development of less favorable lipid profiles, regardless of pharmaco-enhancers or third-agent use. Statins remained underutilized after a switch from TDF to TAF.

OBJECTIVES To assess the risk of adverse diagnoses and laboratory abnormalities associated with a 300 or 150 mg daily dose of lamivudine (3TC) initiated by people with HIV (PWH) with an estimated glomerular filtration rate (eGFR) between at least 30 and 49 ml/min per 1.73 m2 or less. DESIGN Longitudinal study based on electronic health records of 539 PWH with eGFR between at least 30 and 49 ml/min per 1.73 m2 or less from the Observational Pharmaco-Epidemiology Research and Analysis (OPERA) cohort. METHODS Common unintended effects of 3TC were evaluated as composite outcomes. We estimated the incidence (univariate Poisson regression) and association between dose and incident composite outcomes (multivariate Poisson regression) among PWH without the relevant diagnoses or laboratory abnormalities at 3TC initiation. RESULTS PWH initiating 150 mg 3TC had higher HIV RNA, lower eGFR, and more comorbidities than those initiating 300 mg 3TC. The prevalence of relevant diagnoses and laboratory abnormalities was similar in both groups. The most common lab abnormality was low hemoglobin. There was no statistically significant difference in incident adverse diagnoses/severe lab abnormalities with 300 mg versus 150 mg [incidence rate ratio (IRR): 1.51; 95% confidence interval (CI) 0.59--3.92). However, a statistically significant association was observed when gastrointestinal symptoms/moderate lab abnormalities were included in the outcome (IRR: 3.07, 95% CI 1.12--8.40). CONCLUSION As 3TC is a well tolerated drug with a wide therapeutic window, dose adjustment may be unnecessary among PWH with eGFR between at least 30 and 49 ml/min per 1.73 m2 or less. Clinical judgement is key when weighing the risks and benefits of 3TC dose adjustment for PWH experiencing gastrointestinal symptoms or moderate lab abnormalities.

Background Sustained, routine care is vital to the health of people with HIV (PWH) and decreasing transmission of HIV. We evaluated whether the identification of PWH at-risk of falling out of care and prompts for outreach were effective in retaining PWH in care in the United States. Methods In this cluster randomized controlled trial, 20 AIDS Healthcare Foundation Healthcare Centers (HCCs) were randomized to the intervention (n = 10) or control (n = 10) arm; all maintained existing retention efforts. The intervention included daily automated flags in CHORUS™, a mobile app and web-based reporting solution utilizing electronic health record data, that identified PWH at-risk of falling out of care to clinic staff. Among flagged PWH, the association between the intervention and visits after a flag was assessed using logistic regression models fit with generalized estimating equations (independent correlation structure) to account for clustering. To adjust for differences between HCCs, models included geographic region, number of PWH at HCC, and proportions of PWH who self-identified as Hispanic or had the Ryan White Program as a payer. Results Of 15,875 PWH in care, 56% were flagged; 76% (intervention) and 75% (control) resulted in a visit, of which 76% were within 2 months of the flag. In adjusted analyses, flags had higher odds of being followed by a visit (odds ratio [OR]: 1.08, 95% confidence interval [CI]: 0.97, 1.21) or a visit within 2 months (OR: 1.07, 95% CI: 0.97, 1.17) at intervention than control HCCs. Among at-risk PWH with viral loads at baseline and study end, the proportion with Conclusion Despite challenges of the COVID-19 pandemic, adding an intervention to existing retention efforts, and the reality that behavior change takes time, PWH flagged as at-risk of falling out of care were marginally more likely to return for care at intervention than control HCCs and a greater proportion achieved undetectability. Sustained use of the retention module in CHORUS™ has the potential to streamline retention efforts, retain more PWH in care, and ultimately decrease transmission of HIV. Trial Registration The study was first registered at Clinical Trials.gov (NCT04147832, https://clinicaltrials.gov/show/NCT04147832) on 01/11/2019.

Objectives To describe the prevalence and incidence of prediabetes and type 2 diabetes mellitus (T2DM) among people living with HIV (PLHIV) and evaluate the association between antiretroviral therapy (ART) initiation with dolutegravir (DTG), elvitegravir/cobicistat (EVG/c), raltegravir (RAL), or boosted darunavir (bDRV) and incident T2DM. Design Longitudinal study based on electronic health records of 29,674 PLHIV from the Observational Pharmaco-Epidemiology Research and Analysis (OPERA®) cohort. Methods Calculate prevalence of prediabetes and T2DM at regimen initiation. Among PLHIV without prevalent disease, estimate prediabetes and T2DM incidence (Poisson regression) and association between regimen and incident T2DM (multivariate Cox proportional hazards regression). Analyses stratified by ART-experience. Results Among ART-naive and ART-experienced/suppressed PLHIV, the estimated prevalence of prediabetes was 8% and 11%; that of T2DM was 4% and 10%, respectively. The T2DM incidence rate was 9 per 1,000 person-years (95% confidence interval [CI]: 8, 11) among ART-naive and 13 per 1,000 person-years (95% CI: 12, 15) among ART-experienced/suppressed PLHIV, with no statistically significant differences between regimens. Compared to DTG, no statistically significant association between T2DM risk and regimen was observed among ART-naive on EVG/c (adjusted hazard ratios: 0.70 [95% CI: 0.47, 1.05]) or bDRV (0.53 [0.26, 1.04]) and ART-experienced/suppressed on EVG/c (0.96 [0.70, 1.33]), RAL (1.17 [0.70, 1.96]) or bDRV (0.90 [0.57, 1.42]). Conclusions No increased risk of T2DM was observed with EVG/c, RAL or bDRV compared to DTG in ART-naive and experienced PLHIV. However, despite a large cohort, there was a small number of events and differential risk cannot be excluded.

Background Increases in lipids have been observed in people with HIV (PWH) switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF). We assessed changes in low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) following a switch from TDF to TAF. Methods Adults with ≥1 lipid measure before and after switch from TDF to TAF were identified in the OPERA cohort. Multivariable linear regression using generalized estimating equations was used to estimate predicted changes in lipids over time on TAF, modeled flexibly with linear splines. Results A total of 6451 PWH switched from TDF to TAF, of whom 4328 maintained all other agents. LDL-C increased significantly by 1.40 mg/dL/mo over the first 3 months on TAF, by 0.33 mg/dL/mo between 3 and 9 months and then plateauing beyond 9 months. TG increased significantly by 3.52 mg/dL/mo over the first 3 months of TAF, by 0.91 mg/mL/mo between 3 and 9 months and by 0.72 mg/mL/mo between 9 and 16 months, but decreased thereafter. Similar patterns were observed in analyses restricted to PWH who switched from TDF to TAF but maintained all other agents. Conclusions TDF-to-TAF switch was associated with LDL-C and TG increases over the first 9 to 16 months on TAF. The dynamic patterns observed cannot be attributed to changes in other agents.

Objective: Sensory deficits are important risk factors for delirium but have been investigated in single-center studies and single clinical settings. This multicenter study aims to evaluate the association between hearing and visual impairment or bi-sensory impairment (visual and hearing impairment) and delirium. Design: Cross-sectional study nested in the 2017 "Delirium Day" project. Setting and participants: Patients 65 years and older admitted to acute hospital medical wards, emergency departments, rehabilitation wards, nursing homes, and hospices in Italy. Methods: Delirium was assessed with the 4AT (a short tool for delirium assessment) and sensory deficits with a clinical evaluation. We assessed the association between delirium, hearing and visual impairment in multivariable logistic regression models, adjusting for: Model 1, we included predisposing factors for delirium (ie, dementia, weight loss and autonomy in the activities of daily living); Model 2, we added to Model 1 variables, which could be considered precipitating factors for delirium (ie, psychoactive drugs and urinary catheters). Results: A total of 3038 patients were included; delirium prevalence was 25%. Patients with delirium had a higher prevalence of hearing impairment (30.5% vs 18%; P < .001), visual impairment (24.2% vs 15.7%; P < .01) and bi-sensory impairment (16.2% vs 7.5%) compared with those without delirium. In the multivariable logistic regression analysis, the presence of bi-sensory impairment was associated with delirium in Model 1 [odds ratio (OR) 1.5, confidence interval (CI) 1.2-2.1; P = .00] and in Model 2 (OR 1.4; CI 1.1-1.9; P = .02), whereas the presence of visual and hearing impairment alone was not associated with delirium either in Model 1 (OR 0.8; CI 0.6-1.2, P = .36; OR 1.1; CI 0.8-1.4; P = .42) or in Model 2 (OR 0.8, CI 0.6-1.2, P = .27; OR 1.1, CI 0.8-1.4, P = .63). Conclusions and implications: Our findings support the importance of routine screening and specific interventions by a multidisciplinary team to implement optimal management of sensory impairments and hence prevention and the management of the patients with delirium.

Preventing HIV transmission is a crucial step in ending the HIV epidemic. Safe and effective pre-exposure prophylaxis (PrEP) has been available in the United States since 2012. We set out to determine if persons at greatest risk for HIV acquisition were receiving HIV PrEP. HIV-negative individuals from the Observational Pharmaco-Epidemiology ResearchAnalysis (OPERA) cohort who were prescribed daily PrEP were contrasted with newly diagnosed HIV persons without PrEP use between July 16, 2012 and October 31, 2020 to determine if the PrEP prescriptions reached the populations who were seroconverting. Poisson regression was used to estimate incidence rates of seroconversion to HIV among PrEP initiators, as well as new diagnoses of sexually transmitted infections among both the PrEP group and the newly HIV+ group. Out of the 14,598 PrEP users and 3558 persons newly diagnosed with HIV in OPERA, demographics varied widely. Older individuals, those of non-Black race, men, nonintravenous (IV) drug users, and those with commercial insurance were proportionally overrepresented among those prescribed PrEP compared to persons newly diagnosed with HIV during the same time period. Over 82% of new HIV+ individuals received care in the southern United States compared to only 45% of PrEP users. Seroconversion to HIV among PrEP users was generally uncommon, although more frequent among those who identified as Black individuals, especially in the 13-25 years old age range. In conclusion, providers need innovative programs to better identify, educate, and link those at greatest risk of HIV acquisition, especially young people, women, Black individuals, and IV drug users, to PrEP.

Background Approximately 20% of newly diagnosed people with HIV (PWH) in the United States have advanced HIV infection, yet the literature on current antiretroviral therapy (ART) options is limited. The discontinuation/modification and effectiveness of common regimens were compared among ART-naïve people with advanced HIV infection (CD4 cell count Methods ART-naïve adults with advanced HIV infection initiating bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) or a boosted darunavir (bDRV)-, dolutegravir (DTG)-, or elvitegravir/cobicistat (EVG/c)-based 3-drug regimen between January 1, 2018, and July 31, 2019, in the OPERA cohort were included. The association between regimen and discontinuation or viral suppression ( Results Overall, 961 PWH were included (416 B/F/TAF, 106 bDRV, 271 DTG, 168 EVG/c); 70% achieved a CD4 cell count ≥200 cells/μL over a 16-month median follow-up. All regimens were associated with a statistically higher likelihood of discontinuation than B/F/TAF (bDRV: adjusted hazard ratio [aHR], 2.65; 95% CI, 1.75–4.02; DTG: aHR, 2.42; 95% CI, 1.75–3.35; EVG/c: aHR, 3.52; 95% CI, 2.44–5.07). Compared with B/F/TAF, bDRV initiators were statistically less likely to suppress to Conclusions Among people with advanced HIV infection, those initiating B/F/TAF were less likely to discontinue/modify their regimen than those on any other regimen, and more likely to achieve viral suppression compared with those on bDRV but not compared with those on other integrase inhibitors.

Background:Women face unique complexities in HIV treatment yet are underrepresented in antiretroviral therapy (ART) studies.Objective:This analysis assessed the one-year durability of the first integrase strand transfer inhibitor (INSTI)-based regimens prescribed to women in a large cohort of patients living with HIV in care.Methods:Women with HIV who initiated their first INSTI-containing regimen between 08/12/2013 and 11/30/2015 were identified in the OPERA cohort, a collaboration of 79 US outpatient clinics. Discontinuation within the first year of treatment with an INSTI was compared between dolutegravir (DTG), raltegravir (RAL) and elvitegravir (EVG), using multivariable Cox regression and Kaplan- Meier estimates. Virologic response and regimen modifications were described and compared across INSTIs.Results:A total of 537 treatment-naïve (DTG: 39%, EVG: 48%, RAL: 13%) and 878 treatmentexperienced (DTG: 57%, EVG: 29%, RAL: 13%) women were analyzed. In the first twelve months after initiation, women taking EVG or RAL were more likely to discontinue their initial INSTI than those taking DTG among both treatment-naïve (adjusted hazard ratio EVG vs. DTG: 1.59 (95% CI: 1.09, 2.39); RAL vs. DTG: 2.46 (1.49, 4.05)) and treatment-experienced women (EVG vs. DTG: 1.39 (1.02, 1.88); RAL vs. DTG: 2.17 (1.51, 3.12)). Following discontinuation of the initial INSTI, women commonly switched to a regimen containing a different drug from the INSTI class (treatment-naïve DTG: 34%, RAL: 33% EVG: 41%; treatment-experienced DTG: 23%, RAL: 19% EVG: 41%).Conclusion:In treatment-naïve and treatment-experienced women living with HIV, women taking DTG had the lowest risk for early (≤1 year) discontinuation.

Background Researchers must often rely on creatinine measurements to assess kidney function because direct glomerular filtration rates (GFR) and cystatin-c are rarely measured in routine clinical settings. However, HIV treatments often include dolutegravir, raltegravir, rilpivirine or cobicistat, which inhibit the proximal tubular secretion of creatinine without impairing kidney function, thus leading to measurement bias when using creatinine-based estimated GFR (eGFR). We developed eGFR correction factors to account for this potential bias. Methods 11,359 treatment-naive HIV-positive individuals in OPERA were included if they initiated dolutegravir, elvitegravir/cobicistat, darunavir/cobicistat, raltegravir, rilpivirine or efavirenz (control) with an eGFR >60 ml/min/1.73 m2. The eGFR was corrected by adding the median decrease reported in the literature to the calculated eGFR; correction factors were not validated. Incidence rates of eGFR 2 (Poisson regression) and the relationship between regimens and eGFR 2 (multivariate Cox proportional hazards models) were estimated with and without eGFR correction. Results Without eGFR correction, dolutegravir, elvite-gravir/cobicistat, darunavir/cobicistat, raltegravir and rilpivirine based regimens were statistically significantly associated with a higher likelihood of eGFR 2 than efavirenz. With eGFR correction, each of these regimens was associated with a statistically significantly lower likelihood of eGFR 2 compared with efavirenz. Conclusions With increasing use of agents that inhibit tubular creatinine secretion, artificially low eGFR values could lead to erroneous conclusions in studies of HIV treatment and kidney outcomes measured with creatinine-based eGFR equations. Sensitivity analyses assessing the potential magnitude of bias arising from creatinine secretion inhibition should be performed.

Background People living with human immunodeficiency virus (PLWH) initiating antiretroviral therapy (ART) with viral loads (VLs) ≥100 000 copies/mL are less likely to achieve virologic success, but few studies have characterized real-world treatment outcomes. Methods ART-naive PLWH with VLs ≥100 000 copies/mL initiating dolutegravir (DTG), elvitegravir (EVG), raltegravir (RAL), or darunavir (DRV) between 12 August 2013 and 31 July 2017 were identified from the OPERA database. Virologic failure was defined as (i) 2 consecutive VLs ≥200 copies/mL after 36 weeks of ART; (ii) 1 VL ≥200 copies/mL with core agent discontinuation after 36 weeks; (iii) 2 consecutive VLs ≥200 copies/mL after suppression (≤50 copies/mL) before 36 weeks; or (iv) 1 VL ≥200 copies/mL with discontinuation after suppression before 36 weeks. Cox modeling estimated the association between regimen and virologic failure. Results There were 2038 ART-naive patients with high VL who initiated DTG (36%), EVG (46%), DRV (16%), or RAL (2%). Median follow-up was 18.1 (interquartile range, 12.4–28.9) months. EVG and DTG initiators were similar at baseline, but RAL initiators were older and more likely to be female with low CD4 cell counts while DRV initiators differed notably on factors associated with treatment failure. Virologic failure was experienced by 9.2% DTG, 13.2% EVG, 18.4% RAL, and 18.8% DRV initiators. Compared to DTG, the adjusted hazard ratio (95% confidence interval) was 1.46 (1.05–2.03) for EVG, 2.24 (1.50–3.34) for DRV, and 4.13 (1.85–9.24) for RAL. Conclusions ART-naive PLWH with high VLs initiating on DTG were significantly less likely to experience virologic failure compared to EVG, RAL, and DRV initiators. Antiretroviral therapy-naïve people living with HIV (PLWH) initiating therapy with viral loads ≥100,000 copies/mL varied markedly at baseline. In adjusted models, PLWH initiating dolutegravir-based regimens were less likely to experience virologic failure as compared to elvitegravir, raltegravir and darunavir initiators., Baseline characteristics of antiretroviral therapy–naive people living with HIV (PLWH) initiating 4 commonly prescribed core agents with high viral load varied markedly. In adjusted models, PLWH initiating dolutegravir-based regimens were significantly less likely to experience virologic failure as compared to elvitegravir, raltegravir, and darunavir initiators.

Introduction Although weight gain has been reported with the use of integrase strand transfer inhibitors (InSTI), concurrent use of tenofovir alafenamide (TAF) has been implicated in recent studies. This study examined weight changes in people living with HIV (PLWH) who switched from tenofovir disoproxil fumarate (TDF) to TAF, to clarify the relative contribution to weight gain of core agents versus TDF to TAF switch. Methods Antiretroviral‐experienced, virologically suppressed PLWH in the U.S. OPERA cohort were included if they switched from TDF to TAF (5NOV2015‐28FEB2019) and either maintained all other antiretrovirals or switched from a non‐InSTI to an InSTI. Linear mixed models were used to assess weight changes before/after the switch to TAF (restricted cubic splines on time) and rates of change over time (linear splines on time, based on the shape of the weight change curves). Changes in weight on TDF or TAF were assessed among those who maintained other antiretrovirals (overall, by core class), and those who maintained an InSTI or switched to an InSTI (by core agent). All models were adjusted for age, sex, race, (age‐sex, race‐sex interactions), BMI, CD4 cell count, endocrine disorders and concurrent medications that could affect weight. Results A total of 6908 PLWH were included, with 5479 maintaining all other antiretrovirals (boosted protease inhibitor: 746, non‐nucleoside reverse transcriptase inhibitor: 1452, InSTI: 3281) and 1429 switching from a non‐InSTI to an InSTI (elvitegravir/cobicistat: 1120, dolutegravir: 174, bictegravir: 129). In adjusted models, modest weight gain was observed over time on TDF for most (0.24 to 0.71 kg/year); raltegravir was the exception with weight loss. Switching to TAF was associated with early, pronounced weight gain for all (1.80 to 4.47 kg/year). This effect with TAF switch was observed both in PLWH maintaining other antiretrovirals and those switching to an InSTI, regardless of which InSTI agent was used. Weight gain tended to slow down or plateau approximately nine months after switch to TAF. Conclusions In this large, diverse U.S. cohort of PLWH, switching from TDF to TAF was associated with pronounced weight gain immediately after switch, regardless of the core class or core agent, suggesting an independent effect of TAF on weight gain.

A decrease in the infection rates in the operating room (OR) is attributable to advances in sterile technique; heating, ventilation, and air-conditioning (HVAC) filtration; and limiting the number of people entering and leaving the OR. However, some infection complications after open heart procedures have been linked to the discharge fans of surgical equipment, most notably from the LivaNova 3T. We believe that surgical infection within the OR may also be due to other devices with internal fans. The purpose of this study was to 1) identify surgical equipment with an internal fan and see how they affect the airflow in an OR, 2) use the equipment to positively affect airflow to possibly reduce the risk of surgical site infections, and 3) bring attention to the HVAC system ability to exchange air throughout the OR. By using a fog machine and multiple camera angles, we identified the devices that have an effect on the airflow. We saw that the direction of the intake vent of specific devices can change the direction of airflow and possibly help to remove air. Last, we showed how the current HVAC air exchange rate might not be enough to remove contaminated air within the OR. Understanding intake and discharge vents for all equipment is important because sterile contamination and wound infection may be minimized or mitigated completely by simply repositioning a few devices.

Background HLA-B*57:01 screening was added to clinical care guidelines in 2008 to reduce the risk of hypersensitivity reaction from abacavir. The uptake of HLA-B*57:01 screening and incidence of hypersensitivity reaction were assessed in a prospective clinical cohort in the United States to evaluate the effectiveness of this intervention. Methods We included all patients initiating an abacavir-containing regimen for the first time in the pre-HLA-B*57:01 screening period (January 1, 1999 to June 14, 2008) or the post-HLA-B*57:01 screening period (June 15, 2008 to January 1, 2016). Yearly incidence of both HLA-B*57:01 screening and physician panel-adjudicated hypersensitivity reactions were calculated and compared. Results Of the 9619 patients eligible for the study, 33% initiated abacavir in the pre-screening period and 67% in the post-screening period. Incidence of HLA-B*57:01 screening prior to abacavir initiation increased from 43% in 2009 to 84% in 2015. The incidence of definite or probable hypersensitivity reactions decreased from 1.3% in the pre-screening period to 0.8% in 2009 and further to 0.2% in 2015 in the post-screening period. Conclusions Frequency of HLA-B*57:01 screening increased steadily since its first inclusion in treatment guidelines in the United States. This increase in screening was accompanied by a decreasing incidence of definite or probable hypersensitivity reactions over the same period. However, a considerable proportion of patients initiating abacavir were not screened, representing a failed opportunity to prevent hypersensitivity reactions. Where HLA-B*57:01 screening is standard of care, patients should be confirmed negative for this allele before starting abacavir treatment.

Background This study compared the effectiveness and durability of DTG/RPV with commonly prescribed 3-drug regimens (3-DR) in people living with HIV (PLWH) in a real-world setting. Methods Antiretroviral therapy (ART)-experienced, virologically suppressed PLWH who initiated DTG/RPV or a 3-DR in 2018 were identified in the OPERA® database and followed through 6/30/2019. Virologic failure (two consecutive viral loads (VL) ≥ 200 copies/mL or single VL ≥ 200 copies/mL with regimen modification/discontinuation) and maintained virologic suppression (last VL test < 50 or < 200 copies/mL) were described. Kaplan–Meier methods were used to estimate time to virologic failure and treatment discontinuation. Risk of virologic failure was adjusted for age, sex, race/ethnicity, risk of infection, region, baseline CD4 cell count, history of substance abuse or syphilis, and mortality risk score at baseline in a Cox model. Results PLWH initiating DTG/RPV were older and more likely to be Hispanic or have comorbidities than 3-DR initiators. DTG/RPV users experienced fewer discontinuations (15%) and were more likely to be suppressed at study end (98%) than 3-DR users (28% and 96%, respectively). Virologic failure was uncommon; rates per 100 person-years did not differ between the DTG/RPV (1.45, 95% CI: 0.69, 3.03) and 3-DR (2.63, 95% CI: 2.21, 3.14) groups. The risk of virologic failure did not differ significantly between the groups in adjusted Cox models (adjusted hazard ratio 1.32, 95% CI: 0.61, 2.89). Conclusions The findings of this real-world OPERA® study suggest that DTG/RPV can be a viable alternative to standard 3-DRs for ART-experienced, virologically suppressed PLWH.

Supplemental Digital Content is Available in the Text., Introduction: Psychiatric symptoms (PSs) are reported to occur frequently in people living with HIV and may be associated with specific antiretrovirals. We analyzed PSs observed with dolutegravir (DTG) and other frequently prescribed anchor drugs. Methods: Selected PSs (insomnia, anxiety, depression, and suicidality) occurring in HIV-positive patients during DTG treatment across 5 randomized clinical trials (3 double-blind), in the Observational Pharmaco-Epidemiology Research & Analysis (OPERA) cohort, and among cases spontaneously reported to ViiV Healthcare were analyzed. Results: In clinical trials, PSs were reported at low and similar rates in patients receiving DTG or comparators [atazanavir, darunavir, efavirenz, or raltegravir (RAL)]. Insomnia was most commonly reported. The highest rates were observed in SINGLE (DTG 17%, efavirenz 12%), with consistently lower rates in the other trials (DTG: 3%–8% versus comparator: 3%–7%). More efavirenz-treated patients withdrew because of PSs than patients treated with other anchor drugs. In OPERA, history of PSs at baseline was lowest in efavirenz-treated patients compared with patients treated with DTG, RAL, or darunavir. Despite baseline differences, prevalence and incidence during treatment were similar across the 4 anchor drugs. Withdrawal rates for PSs were lowest for DTG (0%–0.6%) and highest for RAL (0%–2.5%). Spontaneously reported events were similar in nature to clinical trial data. Conclusions: Analysis of 3 different data sources shows that, similar to other frequently prescribed anchor drugs to treat HIV infection, PSs are also reported in DTG-treated patients. These events are reported with low frequency and rarely necessitate DTG discontinuation.

Background Clinical decision support system (CDSS) alerts may help retain people living with HIV (PLWH) in care. A system of CDSS alerts utilizing the CHORUS™ portal was developed to identify PLWH at risk of being lost to care. To evaluate feasibility for a larger scale study, a before and after implementation research pilot study was implemented in the OPERA Cohort at three clinic sites in a southeastern US city. Methods Periods without intervention (before) or with CDSS alerts (after) were followed by 3 months of follow up. The study population consisted of PLWH with ≥ 1 electronic health record entry in the 2 years prior to, or during, the before or after period (Fig 1). To support clinicians through a discrete implementation strategy, alerts warning of suboptimal patient attendance were generated daily for the eligible PLWH at each site; providers or other clinic staff could respond to the alerts (Fig 2). Alerts, responses, and visits (i.e., meeting with provider or HIV lab measurement) were characterized. The proportion of PLWH with ≥ 1 visit in the before and after periods were compared at each site by Pearson’s Chi-square. Figure 1. Pilot study timeline Figure 2. CDSS alert criteria and response options Results A total of 12,230 PLWH were eligible (sites A: 11,271; B: 733; C: 1,344 PLWH), with > 75% in both the before and after periods. The ratio of alerts to responses was 11.9 at site A (2,245 alerts to 189 responses in 309 days; Fig 3A), and comparatively lower at sites B (756 alerts to 334 responses in 352 days, ratio=2.2; Fig 3B) and C (1,305 alerts to 896 responses in 246 days, ratio=1.5; Fig 3C). Responses to alerts were sporadic at sites A and B and consistent at site C. After the intervention, the proportion of PLWH with ≥ 1 visit stayed the same at site A (46% in both periods; p=0.47), decreased at site B (91% to 80%; p< 0.01), and increased at site C (72% to 81%; p< 0.01). Figure 3. Alerts and responses over time in (A) Site A, (B) Site B, and (C) Site C Conclusion This pilot study was ecological by design: measures of retention in care were compared over two calendar periods, without accounting for changes in study populations, clinic characteristics, and policies in place over time (which could have impacted clinic attendance). Though engagement with the CDSS was suboptimal at some sites, this implementation pilot study has demonstrated the ability to implement a CDSS aimed at identifying at-risk PLWH, while highlighting areas for improvement in future larger scale studies. Disclosures Joel Wesley Thompson, MHS, PA-C, AAHIVS, DFAAPA, MHS, PA-C, AAHIVS, DFAAPA, Gilead (Shareholder, Speaker’s Bureau)Janssen (Speaker’s Bureau)Theratechnologies (Speaker’s Bureau)ViiV (Speaker’s Bureau) Tammeka Evans, MoP, ViiV Healthcare (Employee)

INTRODUCTION Two-drug regimens (2-DR) have the potential to be a viable solution to the challenges of treatment complexity, cost, adverse effects and contraindications. We sought to describe the real-world use and effectiveness of 2-DR among persons living with HIV (PLHIV) in the United States. METHODS We analysed data for 10,190 treatment-experienced patients from the OPERA® Observational Database initiating a new 2-DR or three-drug regimen (3-DR) between 1 January 2010 and 30 June 2016. Multivariate Cox Proportional Hazards models were used to estimate the association among 2-DR or 3-DR initiation and virologic suppression (viral load (VL) 200 copies/mL or 1 VL > 200 copies/mL + discontinuation) or regimen discontinuation. RESULTS Patients initiating a 2-DR (n = 1337, 13%) were older, and more likely to have a lower CD4 count, a history of AIDS and comorbid conditions than patients initiating a 3-DR. There was no difference between groups in time to virologic suppression (aHR: 1.00 (95% CI: 0.88, 1.13)) among viraemic patients (baseline VL ≥ 50 copies/mL, n = 4180), or time to virologic failure (aHR: 1.15 (95% CI: 0.90, 1.48)) among virologically stable patients (baseline VL

OBJECTIVES The aim of the study was to assess the validity of an easy-to-calculate chronic kidney disease (CKD) risk score developed by the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) group in a longitudinal observational study of people living with HIV (PLWH) in the USA. METHODS PLWH (2002-2016) without prior exposure to potentially nephrotoxic antiretroviral agents and with at least three estimated glomerular filtration rate (eGFR) test results were identified in the Observational Pharmaco-Epidemiology Research and Analysis (OPERA® ) cohort. Three samples were drawn independently using the same eligibility criteria but each using a different eGFR equation, specifically the Cockcroft-Gault (C-G), Modification of Diet in Renal Disease (MDRD) or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFR estimation method. Full and short D:A:D risk scores were applied. CKD was defined as a confirmed decrease in eGFR to < 60 mL/min/1.73 m2 (stages 3-5). Poisson models estimated the association between CKD incidence and a one-point increase in the continuous risk score. The incidence rate ratio (IRR), adjusted IRR (aIRR), and Harrell's discrimination statistic were used to assess validity. RESULTS There were 19 444, 22 727 and 22 748 PLWH in the OPERA C-G, CKD-EPI and MDRD samples, respectively. The median (minimum-maximum) follow-up duration was 6.1 (0.3-9.1) years in the D:A:D cohort and ranged from 3.2 to 3.5 (0.2-15.5) years in the OPERA validation samples. The observation time for the majority of PLWH in the D:A:D cohort began prior to 2006, in stark contrast to the OPERA validation samples, where the majority of PLWH were observed after 2011. The CKD incidence ranged from 7.3 per 1000 person-years [95% confidence interval (CI) 6.8, 7.9 per 1000 person-years] in OPERA C-G to 11.0 (95% CI 10.4, 11.6 per 1000 person-years) in OPERA MDRD. In OPERA samples, IRRs by risk group and adjusted IRRs (full risk score) were similar to those in the D:A:D derivation cohort (adjusted IRR 1.3; 95% CI 1.3, 1.3). Harrell's c-statistic ranged from 0.87 to 0.92 in the OPERA samples, comparable to that in the derivation cohort (0.92). Results for short scores were similar. CONCLUSIONS The findings support the validity of the D:A:D risk scoring method for assessing CKD (stages 3-5) probability in an exclusively USA-based sample regardless of eGFR method.

Background and Objectives The standard of care for HIV treatment is a three-drug regimen consisting of two nucleoside reverse transcriptase inhibitors (NRTIs) and either a non-nucleoside reverse transcriptase inhibitor, a protease inhibitor (PI) or an integrase strand transfer inhibitor. Darunavir boosted with ritonavir (DRV/r) is the only preferred PI in the US Department of Health and Human Services (DHHS) HIV treatment guidelines for antiretroviral-naïve patients, recommended in combination with tenofovir/emtricitabine for antiretroviral-naïve patients. For treatment-experienced and certain antiretroviral-naïve patients, abacavir and lamivudine (ABC/3TC) in combination with DRV/r is considered an effective and tolerable alternative, despite limited research on the effectiveness of this particular combination. This study evaluated virologic outcomes in treatment-experienced patients taking ABC/3TC + DRV/r compared to treatment-experienced patients taking ABC/3TC with any other PI. Methods Treatment-experienced HIV-infected patients initiating their first regimen containing ABC/3TC in combination with any PI in the year 2005 or later were selected from the Observational Pharmaco-Epidemiology Research and Analysis (OPERA®) cohort, a prospective observational cohort reflecting routine medical care. Viral load measurements taken during follow-up were compared between patients taking ABC/3TC + DRV/r and ABC/3TC with a PI other than DRV/r. Logistic regression models were fit to assess the association between regimen exposure and viral load suppression. Results A total of 151 patients initiating ABC/3TC + DRV/r and 525 patients initiating ABC/3TC + a non-darunavir PI were included. Patients in both treatment groups had comparable clinical indicators (viral load, CD4) at baseline. A regimen of ABC/3TC + DRV/r was more likely to be prescribed in the later years of the study period, leading to a shorter median follow-up in the DRV/r treatment group (as-treated analysis: 14 vs. 17 months, p = 0.04; intent-to-treat analysis: 33 vs. 68 months, p

Background HLA-B*57:01 screening was added to clinical care guidelines in 2008 to reduce the risk of hypersensitivity reaction from abacavir. The uptake of HLA-B*57:01 screening and incidence of hypersensitivity reaction were assessed in a prospective clinical cohort in the United States to evaluate the effectiveness of this intervention. Methods We included all patients initiating an abacavir-containing regimen for the first time in the pre-HLA-B*57:01 screening period (January 1, 1999 to June 14, 2008) or the post-HLA-B*57:01 screening period (June 15, 2008 to January 1, 2016). Yearly incidence of both HLA-B*57:01 screening and physician panel-adjudicated hypersensitivity reactions were calculated and compared. Results Of the 9619 patients eligible for the study, 33% initiated abacavir in the pre-screening period and 67% in the post-screening period. Incidence of HLA-B*57:01 screening prior to abacavir initiation increased from 43% in 2009 to 84% in 2015. The incidence of definite or probable hypersensitivity reactions decreased from 1.3% in the pre-screening period to 0.8% in 2009 and further to 0.2% in 2015 in the post-screening period. Conclusions Frequency of HLA-B*57:01 screening increased steadily since its first inclusion in treatment guidelines in the United States. This increase in screening was accompanied by a decreasing incidence of definite or probable hypersensitivity reactions over the same period. However, a considerable proportion of patients initiating abacavir were not screened, representing a failed opportunity to prevent hypersensitivity reactions. Where HLA-B*57:01 screening is standard of care, patients should be confirmed negative for this allele before starting abacavir treatment.

Background: Psychiatric outcomes are common among people living with HIV and may be associated with specific antiretroviral use. We evaluated the occurrence of psychiatric outcomes in patients taking dolutegravir (DTG)-containing regimens compared with five other core agents. Methods: Patients in the OPERA database prescribed regimens based on DTG, efavirenz (EFV), raltegravir (RAL), darunavir (DRV), rilpivirine (RPV), or elvitegravir (EVG) for the first time between 1 January 2013 and 31 December 2015 were analyzed. Psychiatric outcomes included diagnoses of anxiety, depression, insomnia, or suicidality during core agent exposure. Multivariable Cox analysis models were used to assess time to psychiatric outcomes between core agents stratified by psychiatric history, with DTG as the referent. Results: A total of 13,261 patients initiated a regimen of interest (DTG: 2783; RAL: 979; EVG: 3895, EFV: 1746, RPV: 1921, DRV: 1937). Psychiatric history was common, with varied prevalence across groups (DTG 38%, EFV 24%, RAL 40%, DRV 34%, RPV 29%, EVG 31%). Among patients without a psychiatric history, the likelihood of a psychiatric outcome during follow up did not differ between DTG and the other core agents. Among patients with a psychiatric history, risk during follow up for patients taking DTG was equivalent ( versus RPV), marginally reduced ( versus RAL and EFV), or reduced ( versus EVG and DRV). Conclusions: In a large cohort of HIV+ patients in care, patients with a psychiatric history appeared channeled towards drugs with known favorable psychiatric safety profiles, including DTG. Despite this, DTG exposure was not associated with an increased risk of psychiatric outcomes during follow up in patients with or without a psychiatric history.

Background A potential association between integrase inhibitor (INSTI) use and weight gain has been reported in people living with HIV (PLWH). We examined body mass index (BMI) increases after a switch to dolutegravir (DTG), elvitegravir/cobicistat (EVG/c), raltegravir (RAL), rilpivirine (RPV), or boosted darunavir (bDRV) among virologically suppressed ART-experienced PLWH. Methods ART-experienced, suppressed (ART-ES; baseline viral load < 200 copies/mL) PLWH ≥ 18 years of age initiating DTG, EVG/c, RAL, RPV, or bDRV for the first time were identified in the OPERA® cohort. The association between core agents and mean increases in BMI at 6, 12, and 24 months was estimated with multivariable linear regression. Inverse probability-of-censoring weights (IPCW) were used to account for censoring (regimen discontinuation, loss to follow-up, death, pregnancy, or no BMI measured). Analyses were stratified by baseline BMI categories (underweight: Results At baseline, endocrine disorders were reported in >40% of PLWH receiving DTG and RAL; >60% were overweight/obese in all groups (Figure 1). Mean BMI (unadjusted) increased for all ARVs over time, with changes at 24 months ranging from 0.30 (DRV) to 0.83 (RPV, Figure 2). At 6 months, the adjusted mean BMI increase was statistically smaller with EVG/c, RAL, and bDRV (range –0.15 to –0.30) than with DTG (Figure 3); these differences only remained significantly different for bDRV at 12 (–0.29) and 24 months (–0.29, Figure 3). Among those with a normal baseline BMI, the adjusted mean change in BMI at 12 months was smaller with EVG/c, bDRV, and RAL than DTG (range –0.26 to –0.27). Among overweight PLWH, the adjusted mean BMI increase was statistically smaller with bDRV than DTG (–0.32, Figure 4). Results were consistent in IPCW estimates. Conclusion The majority of PLWH on stable ART in this US-based cohort were overweight/obese at the time of switch to the regimens of interest. Small mean increases in BMI for all regimens were noted over time, for which the clinical significance is not yet known. Apparent differences in BMI changes favoring EVG/c, RAL, and bDRV vs. DTG over the short term were largely attenuated with longer follow-up, with significant differences mainly observed in those with a normal BMI at baseline. Disclosures All Authors: No reported Disclosures.

Background Robust pharmacoeconomic modeling is dependent on high quality inputs, preferably from randomized clinical trials (RCT), but not all needed head to head comparisons occur in RCTs. We compared virologic outcomes in an antiretroviral (ART) naïve population initiating a dolutegravir (DTG) or elvitegravir (EVG)-based regimen using clinical trial-like criteria. Methods ART-naïve adults, initiating a DTG- or EVG-based regimen and meeting all study eligibility criteria (Figure 1) were identified in the OPERA® Observational Database, a collaboration of HIV caregivers following 100,000+ people living with HIV (PLWH) through electronic medical records. PLWH were followed from the date of first prescription until DTG- or EVG discontinuation, death, or study end (July 31, 2018). The primary outcome was verified (2 consecutive viral load (VL) ≥200 copies/mL or 1 VL ≥200 copies + discontinuation) virologic failure (VF), defined as either failure to achieve suppression ( Results A total of 1,688 (DTG) and 2,537 (EVG) met all eligibility criteria. Median (IQR) length of follow-up in the DTG users was 21 months (14–30), in the EVG users was 20 (14–32) months. Figure 2 characterizes baseline demographic/clinical characteristics. Figures 3 and 4 depict Kaplan–Meier curves and Cox model results, respectively. VF was experienced by 8.2% DTG and 10.9% EVG initiators at a rate (95% CI) per 1,000 person-years of 40.2 (33.8, 47.8) and 51.3 (45.3, 58.1), respectively. Younger age (18–25), being African American, having a baseline CD4 count ≤ 200, or having a government-based payer (ADAP, Ryan White, Medicaid, or Medicare) at baseline were associated with a significant (P < 0.05), increased hazard of VF. Initiating on DTG or initiating therapy with a lower baseline VL was associated with a significant, reduced hazard of VF. Compared with DTG, the adjusted hazard ratio for VF was 1.29 (95% CI: 1.02, 1.63) for EVG. Conclusion Among ART-naïve patients, DTG users were significantly less likely to experience virologic failure than EVG users after adjustment for important baseline covariates. Disclosures All authors: No reported disclosures.

Background In 2017, the first complete antiretroviral regimen (ART) containing only two drugs, dolutegravir/rilpivirine (DTG/RPV), was approved for treatment of HIV-1 in virologically suppressed ( Methods HIV-1+ individuals initiating DTG/RPV from January 1, 2018 to December 31, 2018 were identified in the OPERA Database. Outcomes were evaluated among the virologically suppressed subgroup who initiated in the first 6 months. Discontinuation (d/c) was defined as cessation of DTG/RPV. Virologic failure (VF) was defined as either 2 consecutive HIV viral loads (VL) ≥ 200 copies/mL OR 1 VL ≥200 copies/mL + d/c. Population was observed from DTG/RPV start (index) until the first of: (a) d/c, (b) death, or (c) study end (December 31, 2018). Demographic and clinical characteristics were described at index. Kaplan–Meier methods were used to describe d/c and VF. Results A total of 880 patients were prescribed DTG/RPV in the first 12 months; demographic and clinical characteristics are described in Figures 1 and 2. Most (76%) DTG/RPV users were virologically suppressed at initiation (n = 671). Among the 197 (22%) ART experienced, viremic initiators, a third had a baseline VL ≥ 50 but Conclusion While DTG/RPV initiators were primarily ART-experienced, virologically suppressed individuals older than 50 years of age challenged by significant comorbid conditions, the frequency of d/c or VF in the first 12 months was low. Disclosures All authors: No reported disclosures.

Background Limited data exist on the risk of type 2 diabetes mellitus (T2DM) with the use of integrase inhibitors. We assessed the risk of incident T2DM with antiretroviral therapy (ART). Methods ART-naïve (ART-N) and -experienced, suppressed (ART-ES; baseline viral load 13 years of age initiating dolutegravir (DTG), elvitegravir/cobicistat (EVG/c), raltegravir (RAL) or boosted darunavir (bDRV) in the OPERA® cohort. After excluding prevalent prediabetes/T2DM and missing baseline covariates, incidence rates of T2DM (i.e., diagnosis, antidiabetic drug, and/orHbA1C >6.5%) were estimated with Poisson regression. The association between core agents and incident T2DM was estimated with multivariate Cox proportional hazards regression adjusted for age, sex, race, HCV co-infection and BMI at baseline. Median (IQR) absolute BMI change from baseline was evaluated at 6, 12, 18, and 24 months in those who developed incident T2DM and those who did not. All analyses were stratified by ART experience. Results Individuals prescribed these ART regimens varied significantly (Figure 1). Overall, incidence rate per 1,000 person-years was low for T2DM (ART-N IR: 9.1; 95% CI: 7.5, 10.9; ART-ES IR: 13.3; 95% CI: 11.6, 15.2; Figure 2). Among ART-N initiators, no statistical difference was observed in the risk of progression to T2DM between DTG and EVG/c (aHR: 0.70; 95% CI: 0.47, 1.05) or bDRV (aHR: 0.53; 95% CI: 0.26, 1.04); RAL could not be evaluated due to the small number of T2DM events. Among ART-ES initiators; no difference was observed between DTG and EVG/c (aHR: 0.96; 95% CI: 0.70, 1.33), RAL (aHR: 1.17; 95% CI: 0.70, 1.96) or bDRV (aHR: 0.90; 95% CI: 0.57, 1.42) (Figure 3). A greater absolute change in BMI was observed for ART-N initiators developing T2DM at all timepoints; reaching statistical significance at 12 and 18 months (Figure 4). No differences were observed for ART-ES initiators. Conclusion Incident T2DM was uncommon among ART-N and ART-ES persons initiating DTG, EVG/c, RAL or bDRV in this large clinical population. None of the comparisons between DTG and other core agents showed a statistically significant increased risk of T2DM. However, due to the small number of events in the ART-N population differential risk cannot be excluded and monitoring HbA1c remains prudent. Disclosures All authors: No reported disclosures.