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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.

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: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.

Introduction Dolutegravir (DTG), Elvitegravir (EVG), Raltegravir (RAL) and Darunavir (DRV) are commonly prescribed core agents for antiretroviral therapy (ART), and a need exists to compare their clinical effectiveness, as defined by virologic failure risks in real-world settings. Methods This observational analysis of a US clinical cohort consisted of ART-naïve people living with HIV (PLWH) in the OPERA database initiating DTG-, EVG-, RAL- or DRV-based regimens between August 2013 and July 2016, with follow-up to July 2017. PLWH were observed from first core agent initiation until core agent discontinuation, clinical activity cessation, death, or study end. Key outcomes included viral suppression (HIV RNA 200 copies/mL or a viral load > 200 copies/mL followed by discontinuation). Association between core agent and time to virologic failure was assessed with multivariate Cox proportional hazards models. Results Overall, 4049 ART-naïve PLWH initiated EVG (47.4%), DTG (34.7%), DRV (14.6%), or RAL (3.2%). DTG and EVG initiators had generally similar baseline demographics and clinical characteristics, including race, risk of infection, baseline viral load, and baseline CD4 levels. RAL and DRV initiators were older and generally sicker than DTG initiators. During follow-up, more DTG initiators achieved virologic suppression (78.7%) compared with EVG (73.6%; p

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.

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.

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 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 People living with HIV (PLWH) have been observed to have twice the risk for atherosclerotic cardiovascular disease (ASCVD) as the general population. Increases in total and low-density lipoprotein cholesterol have been observed in PLWH switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF). Changes in regimens represent an opportunity for healthcare providers to assess health markers and address clinical concerns. Current guidelines recommend initiating statin therapy in individuals with an elevated ASCVD risk. Failure to initiate statins in PLWH with an ASCVD ≥ 7.5% at switch represents a missed opportunity for statin initiation. We aimed to assess missed opportunities for statin therapy in PLWH switching from TDF to TAF-containing antiretroviral therapy. Methods Adults switching from TDF to TAF with ≥1 lipid measure on TDF ≤6 months prior to switch and ≥1 lipid measure ≥7 days after switch to TAF were identified in the OPERA® cohort (84 clinics in 18 US states/territories). The proportion of PLWH prescribed statins pre- and post-switch was stratified by ASCVD risk (recommended threshold: ASCVD ≥ 7.5%). The ASCVD score was imputed using the limit value for components out of the pre-specified range. Results 6,451 PLWH switched from TDF to TAF (Figure 1); over 90% had ASCVD scores available pre- (n = 5801) and post-switch (n = 5881). High ASCVD risk (≥7.5%) was more likely post-switch (34.1) than pre-switch (32.1%, P = 0.02; Figure 2). Of those with high ASCVD risk, only 31% and 41% were prescribed statins pre- vs. post-switch, respectively (Figure 3), representing a considerable missed opportunity for ASCVD prevention, with 59% of PLWH with an elevated risk of ASCVD not prescribed statins after switch from TDF to TAF. ASCVD scores were imputed for those outside the range of the score (e.g., patients < 40 years of age) to evaluate the entire population. Comparable results were obtained when the analysis was limited to PLWH who did not require ASCVD score imputation. Conclusion Despite a switch from TDF to TAF being associated with higher numbers of PLWH with elevated ASCVD risk, most did not receive a statin, representing considerable missed opportunities to reduce risk of cardiovascular disease in this at-risk population. Disclosures All authors: No reported disclosures.

Background Raltegravir (RAL) 400 mg twice-daily (RAL BID) has been an integral part of antiretroviral therapy (ART) in both ART naïve and experienced HIV-1 infected patients for the last decade. In 2017, RAL 1,200 mg (2 × 600 mg), a once-daily formulation (RAL QD) was approved. The objective of this study was to characterize the early utilization of RAL QD in the United States. Methods This is an ongoing cohort study of HIV-1 infected adults with ≥1 prescription for RAL QD in the OPERA® Observational Database, the product of a collaboration of HIV caregivers in 84 clinics across 17 states following over 80,000 people living with HIV through their prospectively collected electronic medical records. Baseline demographic, clinical and laboratory characteristics of patients who initiated RAL QD between July 1 and December 31, 2017 (study window) were analyzed using descriptive statistics. Results A total of 175 patients were prescribed RAL QD during the study window; 57.1% of whom were ≥50 years of age, 80.6% male, 41.1% African American, and 20.0% Hispanic (Figure 1). RAL QD was most often given with emtricitabine/tenofovir (TDF or TAF): 56.0%, abacavir/lamivudine: 8.0%, and darunavir/cobicistat: 4.6%. Twelve patients (7%) were ART naïve, 45 (26%) switched from non-RAL-based regimens, and 118 patients (67%) were previously on RAL BID, most of whom (86%) had no other regimen changes other than switching to RAL QD. A majority (80%) of patients initiated RAL QD with a viral load 350 cells/mm3; 64.0% >500 cells/mm3. Overall, a third of patients had a history of an AIDS-defining illness. Eighty-one percent of patients had at least one of the comorbidities depicted in Figure 2; 45.7% with hypertension, 42.9% hyperlipidemia, 26.7% anxiety disorders, 26.3% anemia and 19.4% with diabetes. The median number of prescriptions for concomitant medications prescribed with RAL QD regimens was 5 (IQR: 4–8). Conclusion Early initiators of RAL QD are primarily treatment-experienced individuals, older than 50 years of age with virologic and immunologic control, significant comorbid conditions and the burden of medications that treat those conditions. Disclosures J. Fusco, Epividian, Inc.: Employee, Salary. Merck & Co.: Merck contracted research with my employer, Epividian, Inc., Employer received funding for research. J. M. Arduino, Merck Sharp & Dohme Corp: Employee and Shareholder, Salary. G. Prajapati, Merck & Co., Inc.: Employee and Shareholder, Salary. G. Fusco, Epividian, Inc.: Employee, Salary. Merck & Co.: Merck research contract with Epividian, employer received funding to perform analysis.

Background. Highly active antiretroviral therapy (HAART) is recommended when the absolute CD4 + T lymphocyte count is

Although highly active antiretroviral therapy has been shown to lower plasma HIV-1 RNA in HIV infection, many patients do not reach the target goal of undetectable viremia. We evaluated whether risk of clinical progression varies by level of viral suppression achieved.Patients in the Collaborations in HIV Outcomes Research/United States cohort who maintained stable HIV-1 RNA levels of either400, 400 to 20,000, or20,000 copies/mL during a run-in period of at least 6 months were studied. Baseline was the first day after this period.Proportional hazards models were used to quantify the relation between baseline HIV-1 RNA levels and risk of a new AIDS-defining diagnosis or death after adjusting for CD4 count, age, gender, ethnicity, study site, prior AIDS-defining diagnosis, and antiretroviral therapy history.Patients (N = 3010) were followed for up to 4.3 years after the 6-month run-in period, with 343 deaths or AIDS-defining diagnoses reported. The risk of a new AIDS-defining diagnosis or death was not significantly different in the 400 to 20,000- and400-copies/mL groups (6% vs. 7%, hazard ratio [HR] = 1.0, 95% confidence interval [CI]: 0.7-1.4; P = 0.9) but was significantly higher in the20,000-copies/mL group (26%, HR = 3.3, 95% CI: 2.5-4.4; P0.001 vs. the400-copies/mL group). Median CD4 count changes during the first year of follow-up showed increases of 75 and 13 cells/mm for the400- and 400 to 20,000-copies/mL groups, respectively, whereas the20,000-copies/mL group had a decrease of 23 cells/mm.Patients who maintained baseline HIV-1 RNA levels of 400 to 20,000 copies/mL for at least 6 months preserved immunologic status and were no more likely to die or develop a new AIDS-defining diagnosis in the time frame studied than those with baseline levels400 copies/mL. Patients with HIV-1 RNA levels20,000 copies/mL at baseline had greater clinical and immunologic deterioration. These data suggest that maintenance of moderate viremia may confer clinical benefit not seen when viremia exceeds 20,000 copies/mL, and this should be taken into account when considering the risks and benefits of continuing failing therapy.

Background and Objectives This prospective, observational study compared disease progression and death in HIV-1 patients treated with stavudine vs. zidovudine in the Collaborations in HIV Outcomes Research/U.S. (CHORUS) cohort. Methods Patients with a first occurrence of CD4 count n =3301) were grouped as: no nucleoside reverse transcriptase inhibitor (NRTI) use; other NRTI without stavudine or zidovudine; stavudine with no zidovudine, with or without other NRTIs; and zidovudine with no stavudine, with or without other NRTIs. The risk for death or disease progression was evaluated in unadjusted analyses and using a Cox proportional hazards model, adjusting for: study site, age, gender, race, route of HIV infection, previous AIDS-defining conditions, number of previous antiretroviral regiments, CD4 count, HIV-1 RNA, and treatment variables. Sensitivity analyses were conducted to determine the sensitivity of the results to major modeling assumptions. A landmark analysis was conducted to determine the absolute difference in time to event. Results During a median follow-up of 2.4 years, there were 57 deaths and 348 AIDS-defining conditions in 405 patients. Stavudine treatment compared with zidovudine resulted in a greater percentage of patients with AIDS-defining events (14.5 vs. 10.9%; P =.013), and an increased risk of disease progression (HR=1.30; 95% CI: 1.01,1.7; P =.04). This result was not sensitive to modeling assumptions. Landmark analysis demonstrated an absolute difference in time to 95% event-free survival of 2.7 months for those with a CD4⩽200 cells/μL and 11 months for those 6 months after model entry. Conclusions In unadjusted and adjusted analyses of 3301 HIV-1 infected patients, stavudine containing combination therapy was associated with an increased risk of disease progression or death compared to therapy containing zidovudine. Most of the difference was attributable to new cases of wasting.

Background Optimal sequencing of zidovudine and stavudine in antiretroviral therapy has not been elucidated. Objective To examine the impact of the sequence of therapeutic regimens containing zidovudine and stavudine on HIV-1 RNA and CD4 lymphocyte counts over 12 months. Design Observational, multicenter, longitudinal cohort study. Setting Four large outpatient, HIV practices participating in the community-based Collaborations in HIV Outcomes Research-U.S. (CHORUS) cohort study. Participants 940 HIV-infected patients. Methods Comparison of HIV-1 RNA and CD4 lymphocyte responses in patients sequenced from zidovudine to stavudine or from stavudine to zidovudine using repeated measures regression models fit to outcomes by application of generalized estimating equation (GEE) methodology. Results Patients treated with zidovudine prior to stavudine (n = 834) achieved a greater mean drop from baseline HIV-1 RNA (p = .01) and higher proportion of undetectable HIV-1 RNA results (p = .05) over 12 months than those sequenced from stavudine to zidovudine (n = 106). CD4+ lymphocyte increases did not differ between the groups (p = .6). Conclusions Prior zidovudine therapy was not associated with long-term attenuation of HIV-1 RNA or CD4 response to subsequent stavudine-containing regimens. Zidovudine before stavudine may have benefit in a strategic long-term therapeutic plan.

BACKGROUND To estimate the clinical benefit of highly active antiretroviral therapy (HAART) initiation vs deferral in a given month in patients with CD4 cell counts less than 800/μL. METHODS In this observational cohort study of human immunodeficiency virus type 1 seroconverters from CASCADE (Concerted Action on SeroConversion to AIDS and Death in Europe), we constructed monthly sequential nested subcohorts between January 1996 and May 2009, including all eligible HAART-naive, AIDS-free individuals with a CD4 cell count less than 800/μL. The primary outcome was time to AIDS or death in those who initiated HAART in the baseline month compared with those who did not, pooled across subcohorts and stratified by CD4 cell count. Using inverse probability-of-treatment weighted survival curves and Cox proportional hazards regression models, we estimated the absolute and relative effects of treatment with robust 95% confidence intervals (CIs). RESULTS Of 9455 patients with 52,268 person-years of follow-up, 812 (8.6%) developed AIDS and 544 (5.8%) died. In CD4 cell count strata of 200 to 349, 350 to 499, and 500 to 799/μL, HAART initiation was associated with adjusted hazard ratios (95% CIs) for AIDS/death of 0.59 (0.43-0.81), 0.75 (0.49-1.14), and 1.10 (0.67-1.79), respectively. In the analysis of all-cause mortality, HAART initiation was associated with adjusted hazard ratios (95% CIs) of 0.71 (0.44-1.15), 0.51 (0.33-0.80), and 1.02 (0.49-2.12), respectively. Numbers needed to treat (95% CIs) to prevent 1 AIDS event or death within 3 years were 21 (14-38) and 34 (20-115) in CD4 cell count strata of 200 to 349 and 350 to 499/μL, respectively. CONCLUSION Compared with deferring in a given month, HAART initiation at CD4 cell counts less than 500/μL (but not 500-799/μL) was associated with slower disease progression.

We noted clinically that patients with aortic root aneurysms and dissections seemed to have little systemic atherosclerosis. It is our objective to determine whether there is a negative association between ascending thoracic aneurysms and systemic atherosclerosis.Atherosclerosis was quantified by evaluating non-contrast CT images of the chest and scoring the degree of calcifications as a marker for atherosclerosis in the coronary arteries and aorta.The degree of calcification was compared in 64 patients with aortic root aneurysm (annuloaortic ectasia, 31 patients; type A dissection, 33 patients) vs 86 control subjects. Multivariable analysis was applied to test for an association between aortic root aneurysms and systemic calcification independent of risk factors for atherosclerosis.Multivariable analysis revealed that patients with ascending aortic aneurysms of the annuloaortic ectasia type and patients with type A dissections had significantly lower overall calcification scores in their arterial vessels compared to patients in the control group (p = 0.03 and p0.0001, respectively). These results were independent of all other risk factors for atherosclerosis. Smoking, dyslipidemia, diabetes, and age were all found to increase the degree of atherosclerosis (p0.01 to 0.05).Aortic root pathology (annuloaortic ectasia or type A dissection) is associated with decreased systemic atherosclerosis. It is possible that a mechanism exists whereby the same genetic mutations predisposing patients to ascending aortic aneurysms also exert a protective effect against systemic atherosclerosis.

The prevalence and predisposing factors of thrombotic microangiopathy (TMA) in the era of highly active antiretroviral therapy (HAART) were evaluated among patients in the Collaborations in Human Immunodeficiency Virus (HIV) Outcomes Research/US cohort. Of 6022 patients, 17 (0.3%) had TMA, with unadjusted incidences per 100 person-years of 0.079 for TMA, 0.009 for thrombotic thrombocytopenic purpura, and 0.069 for hemolytic-uremic syndrome. Compared with patients without TMA, patients with TMA had lower mean CD4(+) cell counts (197 vs. 439 cells/mm(3); P=.0009) and higher mean log(10) HIV-1 RNA levels (4.6 vs. 3.3 copies/mL; P=.0001) at last follow-up and a significantly greater incidence of acquired immune deficiency syndrome (82.4% vs. 55.3%; P=.025), Mycobacterium avium complex infection (17.6% vs. 3.3%; P=.018), hepatitis C (29.4% vs. 11.3%; P=.001), and death (41.2% vs. 7.4%; P

Purpose Effective antiretroviral therapies have improved the prognosis for patients infected with the human immunodeficiency virus (HIV). We aimed to estimate the likelihood that HIV-infected patients would die of comorbid disease. Methods A probabilistic simulation of antiretroviral-naive HIV-infected patients in the United States was calibrated with data from an observational cohort (N = 3545) and validated with data from a separate patient cohort (N = 12574). The simulation explicitly represents the 2 main determinants of treatment failure and subsequent death from HIV-related causes: nonadherence to combination therapy and accumulation of phenotypic resistance to combination therapy. The likelihood of deaths not directly attributable to HIV was estimated from the Collaborations in HIV Outcomes Research-US (CHORUS) cohort. Results For patients with newly diagnosed HIV infections, CD4 counts of 500 cells/mm 3 , and viral loads of 10000 copies/mL, the median estimated survival was 26.8 years for 30-year-olds, 24.4 years for 40-year-olds and 14.6 years for 50-year-olds. The proportion of deaths not directly attributable to HIV was 36% for 30-year-olds, 53% for 40-year-olds, and 72% for 50-year-olds. For patients with characteristics similar to CHORUS participants, the median estimated survival approached 20.4 years, the mean age at death approached 60.4 years, and 41% died of illnesses not directly attributable to HIV. These estimates of non-HIV mortality were likely conservative. Conclusion As HIV-infected patients live longer, our results suggest they will experience increasing mortality from causes not directly attributable to HIV. The projected risk from comorbid disease has clinical and policy implications for future delivery of care to HIV-infected patients.

Introduction Delirium and sarcopenia are common, although underdiagnosed, geriatric syndromes. Several pathological mechanisms can link delirium and low skeletal muscle mass, but few studies have investigated their association. We aimed to investigate (1) the association between delirium and low skeletal muscle mass and (2) the possible role of calf circumference mass in finding cases with delirium. Methods The analyses were conducted employing the cross-sectional “Delirium Day” initiative, on patient 65 years and older admitted to acute hospital medical wards, emergency departments, rehabilitation wards, nursing homes and hospices in Italy in 2017. Delirium was diagnosed as a 4 + score at the 4-AT scale. Low skeletal muscle mass was operationally defined as calf circumference ≤ 34 cm in males and ≤ 33 cm in females. Logistic regression models were used to investigate the association between low skeletal muscle mass and delirium. The discriminative ability of calf circumference was evaluated using non-parametric ROC analyses. Results A sample of 1675 patients was analyzed. In total, 73.6% of participants had low skeletal muscle mass and 24.1% exhibited delirium. Low skeletal muscle mass and delirium showed an independent association (OR: 1.50; 95% CI 1.09–2.08). In the subsample of patients without a diagnosis of dementia, the inclusion of calf circumference in a model based on age and sex significantly improved its discriminative accuracy [area under the curve (AUC) 0.69 vs 0.57, p Discussion and conclusion Low muscle mass is independently associated with delirium. In patients without a previous diagnosis of dementia, calf circumference may help to better identify those who develop delirium.