Emerging from the Shadows: Trends in HIV Ambulatory Care, Viral Load Testing, and Viral Suppression in a U.S. HIV Cohort, 2019-2022: Impact of COVID-19 Pandemic.

OBJECTIVES: Analyze the acute impact and the longer-term recovery of COVID-19 pandemic effects on clinical encounter types, HIV viral load (VL) testing and suppression (HIV VL<200 copies/mL). DESIGN: Longitudinal cohort study of participants seen during 2019-2022 at eight HIV Outpatient Study (HOPS) sites. METHODS: Generalized linear mixed models (GLMM) estimated monthly rates of all encounters, office and telemedicine visits, and HIV VL tests using 2010-2022 data. We examined factors associated with non-suppressed VL (VL ≥ 200 copies/mL) and not having ambulatory care visits during the pandemic using GLMM for logistic regression with 2017-2022 and 2019-2022 data, respectively. RESULTS: Of 2351 active participants, 76.0% were male, 57.6% aged ≥ 50 years, 40.7% non-Hispanic White, 38.2% non-Hispanic Black, 17.3% Hispanic/Latino, and 51.0% publicly insured. The monthly rates of in-person and telemedicine visits varied during 2020 through mid-year 2022. Multivariable logistic regression showed persons with no encounters were more likely to be male or have VL ≥ 200 copies/mL. For participants with ≥1 VL test, the prevalence rate of HIV VL ≥ 200 copies/mL during 2020 was close to the rates from 2014 to 2019. The change in probability of viral suppression was not associated with participant's age, sex, race/ethnicity or insurance type. CONCLUSION: In thent encounters declined over 2 years during the pandemic with variations in telemedicine and in-person events, with relative maintenance of viral suppression. Ongoing recovery from the impact of COVID-19 on ambulatory care will require continued efforts to improve retention and patient access to medical services.

Incidence of Hyperlipidemia among Adults Initiating Antiretroviral Therapy in the HIV Outpatient Study (HOPS), USA, 2007-2021.

Current U.S. guidelines recommend integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART) as initial treatment for people with HIV (PWH). We assessed long-term effects of INSTI use on lipid profiles in routine HIV care. We analyzed medical record data from the HIV Outpatient Study's participants in care from 2007 to 2021. Hyperlipidemia was defined based on clinical diagnoses, treatments, and laboratory results. We calculated hyperlipidemia incidence rates and rate ratios (RRs) during initial ART and assessed predictors of incident hyperlipidemia by using Poisson regression. Among 349 eligible ART-naïve PWH, 168 were prescribed INSTI-based ART (36 raltegravir (RAL), 51 dolutegravir (DTG), and 81 INSTI-others (elvitegravir and bictegravir)) and 181 non-INSTI-based ART, including 68 protease inhibitor (PI)-based ART. During a median follow-up of 1.4 years, hyperlipidemia rates were 12.8, 22.3, 22.7, 17.4, and 12.6 per 100 person years for RAL-, DTG-, INSTI-others-, non-INSTI-PI-, and non-INSTI-non-PI-based ART, respectively. In multivariable analysis, compared with the RAL group, hyperlipidemia rates were higher in INSTI-others (RR = 2.25; 95% confidence interval (CI): 1.29-3.93) and non-INSTI-PI groups (RR = 1.89; CI: 1.12-3.19) but not statistically higher for the DTG (RR = 1.73; CI: 0.95-3.17) and non-INSTI-non-PI groups (RR = 1.55; CI: 0.92-2.62). Other factors independently associated with hyperlipidemia included older age, non-Hispanic White race/ethnicity, and ART without tenofovir disoproxil fumarate. PWH using RAL-based regimens had lower rates of incident hyperlipidemia than PWH receiving non-INSTI-PI-based ART but had similar rates as those receiving DTG-based ART, supporting federal recommendations for using DTG-based regimens as the initial therapy for ART-naïve PWH.

HoTDAM! An easy-to-use automated assay expands the inducible thermotolerance phenotype in Drosophila melanogaster: Heat hardening reduces motility.

To quantify heat tolerance in insects, two manual observation measures are typically implemented: the time to physiological collapse at a static noxious temperature (time to knockdown; TKD) or the temperature at which collapse occurs as temperature increases (critical thermal maximum; CTmax). Both assay modalities focus on physiological collapse, neglecting the prior behavioral processes. In this study, the locomotion response of Drosophila melanogaster to relatively high temperature (39 and 40.5 °C) was quantified using the TriKinetics Drosophila Activity Monitor (DAM2 system). The absence of locomotion was defined as the state of physiological collapse resulting from extended exposure to high temperature. An easy-to-use executable application that allows the user to automatically extract individual TKD from the activity data was developed. For validation, manual TKD assays were performed in parallel to automated assays across multiple factors, including sex, hardening, recovery time after hardening, and assay temperature, which gave similar results. In terms of behavioral aspects, heat hardening consistently led to reduced activity during a subsequent heat stress, irrespective of assay temperature, sex, or recovery time after hardening. Our automated heat tolerance assay utilizing the DAM2 system is one way to expand the scope of the heat tolerance phenotype to include a behavioral component in conjunction with the traditional TKD measure.

Weight Gain and Metabolic Effects in Persons With HIV Who Switch to ART Regimens Containing Integrase Inhibitors or Tenofovir Alafenamide.

BACKGROUND: The timing and magnitude of antiretroviral therapy-associated weight change attributions are unclear. SETTING: HIV Outpatient Study participants. METHODS: We analyzed 2007-2018 records of virally suppressed (VS) persons without integrase inhibitor (INSTI) experience who switched to either INSTI-based or another non-INSTI-based ART, and remained VS. We analyzed BMI changes using linear mixed models, INSTI- and tenofovir alafenamide (TAF) contributions to BMI change by linear mixed models-estimated slopes, and BMI inflection points. RESULTS: Among 736 participants (5316 person-years), 441 (60%) switched to INSTI-based ART; the remainder to non-INSTI-based ART. The mean follow-up was 7.15 years for INSTI recipients and 7.35 years for non-INSTI. Preswitch, INSTI and non-INSTI groups had similar median BMI (26.3 versus 25.9 kg/m 2 , P = 0.41). INSTI regimens included raltegravir (178), elvitegravir (112), and dolutegravir (143). Monthly BMI increases postswitch were greater with INSTI than non-INSTI (0.0525 versus 0.006, P < 0.001). A BMI inflection point occurred 8 months after switch among INSTI users; slopes were similar regardless of TAF use immediately postswitch. Among INSTI + TAF users, during 8 months postswitch, 87% of BMI slope change was associated with INSTI use, 13% with TAF use; after 8 months, estimated contributions were 27% and 73%, respectively. For non-INSTI+TAF, 84% of BMI gain was TAF-associated consistently postswitch. Persons switching from TDF to TAF had greater BMI increases than others ( P < 0.001). CONCLUSION: Among VS persons who switched ART, INSTI and TAF use were independently associated with BMI increases. During 8 months postswitch, BMI changes were greatest and most associated with INSTI use; afterward, gradual BMI gain was largely TAF-associated.

Edaphic controls of soil organic carbon in tropical agricultural landscapes.

Predicting soil organic carbon (SOC) is problematic in tropical soils because mechanisms of SOC (de)stabilization are not resolved. We aimed to identify such storage mechanisms in a tropical soil landscape constrained by 100 years of similar soil inputs and agricultural disturbance under the production of sugarcane, a C4 grass and bioenergy feedstock. We measured soil physicochemical parameters, SOC concentration, and SOC dynamics by soil horizon to one meter to identify soil parameters that can predict SOC outcomes. Applying correlative analyses, linear mixed model (LMM) regression, model selection by AICc, and hierarchical clustering we found that slow moving SOC was related to many soil parameters, while the fastest moving SOC was only related to soil surface charge. Our models explained 78-79%, 51-57%, 7-8% of variance in SOC concentration, slow pool decay, and fast pool decay, respectively. Top SOC predictors were roots, the ratio of organo-complexed iron (Fe) to aluminum (Al), water stable aggregates (WSagg), and cation exchange capacity (CEC). Using hierarchical clustering we also assessed SOC predictors across gradients of depth and rainfall with strong reductions in Roots, SOC, and slow pool decay associated with increasing depth, while increased rainfall was associated with increased Clay and WSagg and reduced CEC in surface soils. Increased negative surface charge, water stable aggregation, organo-Fe complexation, and root inputs were key SOC protection mechanisms despite high soil disturbance. Further development of these relationships is expected to improve understanding of SOC storage mechanisms and outcomes in similar tropical agricultural soils globally.

Characterization of Cross-Species Transmission of Drosophila melanogaster Nora Virus.

Drosophila melanogaster Nora virus (DmNV) is a novel picorna-like virus first characterized in 2006. Since then, Nora virus has been detected in several non-Drosophila species, including insects in the Orders Hymenoptera, Lepidoptera, Coleoptera, and Orthoptera. The objective of this study was to determine if DmNV could infect individuals of other species of invertebrates besides D. melanogaster. The presence of DmNV in native invertebrates and commercially available stocks was determined. Laboratory-reared D. yakuba, D. mercatorum, Gryllodes sigillatus, Tenebrio molitor, Galleria mellonella, and Musca domestica were intentionally infected with DmNV. In addition, native invertebrates were collected and D. melanogaster stocks were purchased and screened for DmNV presence using reverse transcription-polymerase chain reaction (RT-PCR) before being intentionally infected for study. All Drosophila species and other invertebrates, except M. domestica, that were intentionally infected with DmNV ended up scoring positive for the virus via RT-PCR. DmNV infection was also detected in three native invertebrates (Spilosoma virginica, Diplopoda, and Odontotaenius disjunctus) and all commercially available stocks tested. These findings suggest that DmNV readily infects individuals of other species of invertebrates, while also appearing to be an endemic virus in both wild and laboratory D. melanogaster populations. The detection of DmNV in commercially available stocks presents a cautionary message for scientists using these stocks in studies of virology and immunology.

Leakage does not fully offset soy supply-chain efforts to reduce deforestation in Brazil.

Zero-deforestation supply chain policies that leverage the market power of commodity buyers to change agricultural producer behavior can reduce forest clearing in regions with rapid commodity expansion and weak forest governance. Yet leakage-when deforestation is pushed to other regions-may dilute the global effectiveness of regionally successful policies. Here we show that domestic leakage offsets 43-50% of the avoided deforestation induced by existing and proposed zero-deforestation supply chain policies in Brazil's soy sector. However, cross-border leakage is insignificant (<3%) because soybean production is displaced to existing U.S. farmland. Eliminating deforestation from the supply chains of all firms exporting Brazilian soy to the EU or China from 2011-2016 could have reduced net global deforestation by 2% and Brazilian deforestation by 9%. Thus, if major tropical commodity importers (e.g., the EU) require traders to eliminate deforestation from their supply chains, it could help bend the curve on global forest loss.

Cerner real-world data (CRWD) - A de-identified multicenter electronic health records database.

Cerner Real-World Data TM (CRWD) is a de-identified big data source of multicenter electronic health records. Cerner Corporation secured appropriate data use agreements and permissions from more than 100 health systems in the United States contributing to the database as of March 2022. A subset of the database was extracted to include data from only patients with SARS-CoV-2 infections and is referred to as the Cerner COVID-19 Dataset. The December 2021 version of CRWD consists of 100 million patients and 1.5 billion encounters across all care settings. There are 2.3 billion, 2.9 billion, 486 million, and 11.5 billion records in the condition, medication, procedure, and lab (laboratory test) tables respectively. The 2021 Q3 COVID-19 Dataset consists of 130.1 million encounters from 3.8 million patients. The size and longitudinal nature of CRWD can be leveraged for advanced analytics and artificial intelligence in medical research across all specialties and is a rich source of novel discoveries on a wide range of conditions including but not limited to COVID-19.

A Heavy Burden: Preexisting Physical and Psychiatric Comorbidities and Differential Increases Among Male and Female Participants After Initiating Antiretroviral Therapy in the HIV Outpatient Study, 2008-2018.

Attention to non-AIDS comorbidities is increasingly important in the HIV care and management in the United States. We sought to assess comorbidities before and after antiretroviral therapy (ART) initiation among persons with HIV (PWH). Using the 2008-2018 HIV Outpatient Study (HOPS) data, we assessed changes in prevalence of physical and psychiatric comorbidities, by sex, among participants initiating ART. Cox proportional hazards models were fit to investigate factors associated with the first documented occurrence of key comorbidities, adjusting for demographics and other covariates, including insurance type, CD4+ cell count, ART regimen, and smoking status. Among 1,236 participants who initiated ART (median age 36 years, CD4 cell count 375 cells/mm3), 79% were male, 66% non-white, 44% publicly insured, 53% ever smoked, 33% had substance use history, and 22% had body mass index ≥30 kg/m2. Among females, the percentages with at least one condition were: at ART start, 72% had a physical and 42% a psychiatric comorbidity, and after a median of 6.1 years of follow-up, these were 87% and 63%, respectively. Among males, the percentages with at least one condition were: at ART start, 61% had a physical and 32% a psychiatric comorbidity, and after a median of 4.6 years of follow-up, these were 82% and 53%, respectively. In multivariable Cox proportional hazards analyses, increasing age and higher viral loads (VL) were associated with most physical comorbidities, and being a current/former smoker and higher VL were associated with all psychiatric comorbidities analyzed. HOPS participants already had a substantial burden of physical and psychiatric comorbidities at the time of ART initiation. With advancing age, PWH who initiate ART experience a clinically significant increase in the burden of chronic non-HIV comorbidities that warrants continued surveillance, prevention, and treatment.

Longitudinal Changes in, and Factors Associated with, the Frequency of Condomless Sex Among People in Care for HIV Infection, HIV Outpatient Study USA, 2007-2019.

During 2007-2019, the percentage of HIV Outpatient Study participants reporting anal or vaginal condomless sex in the past 6 months ranged from a low of 17% among heterosexual males to 59% for men who have sex with men (MSM). MSM reported having had condomless sex more frequently than heterosexual males and females and were the only group in which an increase in condomless sex was observed during the study period (from 39 to 59%). Although persons with undetectable HIV viral load have effectively no risk of transmitting HIV sexually (U = U), there is still the potential risk of transmission or acquisition of other sexually transmitted infections (STIs) when engaging in condomless sex. Continuing education about risks of HIV and STI transmission as well as ongoing screening for and treatment of STIs, retention in HIV treatment, and support for sexual health are critical components of care for people living with HIV.

Effect of Pulsed Low-Intensity Ultrasonography on Symptom Relief and Tibiofemoral Articular Cartilage Thickness Among Veterans Affairs Enrollees With Knee Osteoarthritis: A Randomized Clinical Trial.

Importance: Osteoarthritis (OA) is a major cause of disability in the US, with no approved treatments to slow progression, but animal models suggest that pulsed low-intensity ultrasonography (PLIUS) may promote cartilage growth. Objective: To evaluate the efficacy of PLIUS in providing symptom reduction and decreased loss of tibiofemoral cartilage thickness in patients with knee OA. Design, Setting, and Participants: A phase 2A, sham-controlled, parallel, double-blind randomized clinical trial was conducted at 2 Veterans Affairs hospitals in Salt Lake City, Utah, and San Diego, California, from May 22, 2015, to January 31, 2019. Data were analyzed from June 27, 2020, to October 20, 2020. Participants recruited through the US Department of Veterans Affairs (N = 132) with clinical and radiographic evidence of early knee OA were randomly assigned to receive PLIUS or a sham device, self-administered for 20 minutes daily over the medial compartment of the knee. All enrollees participated in a 4-week prerandomization sham run-in period, followed by a 48-week treatment period. Randomization was stratified by study site and Kellgren-Lawrence grades 1 (n = 15), 2 (n = 51), and 3 (n = 66). Intervention: Participants either received 48 weeks of PLIUS or sham ultrasonography. Main Outcomes and Measures: The trial incorporated 2 coprimary outcomes: symptomatic improvement assessed by Outcome Measures in Rheumatology Clinical Trials-Osteoarthritis Research Society International Responder Criteria (ie, met if either >50% improvement in pain and function with at least a 20% absolute improvement of at least 2 of the following 3 factors: improvement by at least 20% [pain, function, and patient global assessment] with at least a 10-mm absolute improvement), and cartilage preservation assessed as change in central medial femoral condyle cartilage thickness by magnetic resonance imaging. Intention-to-treat analysis was used. Results: The mean (SD) participant age was 63.6 (10.7) years and 119 were men (90.2%). The mean (SD) duration of OA symptoms was 13.4 (12.3) years. In the PLIUS group, 70.4% (95% CI, 58.2%-82.6%) of the participants experienced symptomatic improvement, compared with 67.3% (95% CI, 54.9%-79.7%) of participants in the sham group (P = .84); there was no statistically significant difference in response rates between the treatment groups, and the between-group rate difference of 3.1% (95% CI, -14.3% to 20.5%) did not meet the predefined 10% threshold for clinically significant symptomatic improvement from application of PLIUS. At 48 weeks of treatment, central medial femoral condyle cartilage thickness decreased by a mean (SD) of 73.8 (168.1) µm in the PLIUS group and by 42.2 (297.0) µm in the sham group. This 48-week mean change between the 2 groups did not reach statistical significance (P = .44), and the between-group 48-week difference of -31.7 µm (95% CI, -129.0 µm to 65.7 µm) did not meet the predefined threshold. There were 99 nonserious adverse events in the PLIUS group and 89 in the sham group during the trial. No serious adverse events were deemed related to the study device. Conclusions and Relevance: PLIUS, as implemented in this study, demonstrated neither symptomatic benefit nor a decrease in loss of tibiofemoral cartilage thickness in knee OA. Trial Registration: ClinicalTrials.gov Identifier: NCT02034409.

Aging, trends in CD4+/CD8+ cell ratio, and clinical outcomes with persistent HIV suppression in a dynamic cohort of ambulatory HIV patients.

BACKGROUND: Age blunts CD4+ lymphocyte cell count/µl (CD4+) improvements observed with antiretroviral therapy (ART)-induced viral suppression among people with HIV (PWH). Prolonged viral suppression reduces immune dysregulation, reflected by rising CD4+/CD8+ ratios (CD4+/CD8+). We studied CD4+/CD8+ over time to determine whether it predicts risk for select comorbidities and mortality among aging PWH with viral suppression. METHODS: We studied HIV Outpatient Study (HOPS) participants prescribed ART during 2000-2018 who achieved a viral load less than 200 copies/ml on or after 1 January 2000, and remained virally suppressed at least 1 year thereafter. We modeled associations of CD4+/CD8+ with select incident comorbidities and all-cause mortality using Cox regression and controlling for demographic and clinical factors. RESULTS: Of 2480 eligible participants,1145 (46%) were aged less than 40 years, 835 (34%) 40-49 years, and 500 (20%) ≥ 50 years. At baseline, median CD4+/CD8+ was 0.53 (interquartile range: 0.30-0.84) and similar among all age groups (P = 0.18). CD4+/CD8+ values and percentage of participants with CD4+/CD8+ at least 0.70 increased within each age group (P < 0.001 for all). CD4+/CD8+ increase was greatest for PWH aged less than 40 years at baseline. In adjusted models, most recent CD4+/CD8+less than 1.00 and less than 0.70 were independently associated with higher risk of non-AIDS cancer and mortality, respectively. CONCLUSION: Pretreatment immune dysregulation may persist as indicated by CD4+/CD8+ less than 0.70. Persistent viral suppression can improve immune dysregulation over time, reducing comorbidity, and mortality risk. Monitoring CD4+/CD8+ among ART-treated PWH with lower values provide a means to assess for mortality and comorbidity risk.

Barriers and Challenges to Making Referrals for Treatment and Services for Opioid Misuse in Family Planning Settings.

Background: In this opioid overdose epidemic, women are an overlooked group seeing increasing rates of overdose death. Implementation challenges have prevented evidence-based interventions from effectively reaching women who misuse opioids, with gaps in access to effective treatment and services. Family planning clinics could serve as important points of contact for referral to needed treatments and services. The study explores how family planning staff knowledge and attitudes related to opioid misuse serve as potential barriers and challenges in making referrals for evidence-based services and treatments. Methods: In 2018, we conducted a national online survey of family planning staff, assessing knowledge and attitudes of treatments and services for opioid misuse. Results: A total of 691 family planning staff completed the survey. Most respondents agreed that opioid misuse was a major problem in their community (86.0%) and identified challenges in responding to it, including a lack of treatment access (70.3%), the absence of in-house behavioral health staff (67.2%), and unfamiliarity with local treatment providers (54.1%). Respondents reported low levels of acceptability for syringe services programs (46.0%), medications such as methadone and buprenorphine (55.4%), and naloxone to reverse opioid overdose (60.1%). Controlling for other factors, race/ethnicity, urbanicity, workplace role, and substance use training were associated with differences in acceptability. Conclusions: Family planning settings could play a critical role in connecting women who misuse opioids to treatment and services. Strategies are needed to increase the acceptability of evidence-based interventions and the feasibility of having family planning staff play a linkage role.

Female mentors positively contribute to undergraduate STEM research experiences.

The positive influence of undergraduate research and mentoring on student success in STEM fields has been well-established. However, the role that the gender of a research mentor may play in the undergraduate research experience warrants further investigation. This is an especially critical issue to address, since the lack of female role models in STEM fields is acknowledged as an impediment to the success and progress of women pursuing STEM-careers. To evaluate how the gender of undergraduate research mentors influences the research experience of students, we collected and analyzed surveys from undergraduates and alumni who had completed undergraduate research at the University of Nebraska at Kearney. We found that even though students did not select mentors based on gender, there were differences in how students perceived their mentors, depending on the gender of their mentors. Interestingly, students with female mentors were more likely than students with male mentors to report that their research experience had prepared them for a career in science. Further, our gender-pairing analyses revealed that students who expressed that the gender of their mentor had contributed to their relationship with their mentor were more likely to have a female mentor. Our data indicate that female mentors favorably influence the undergraduate research experience of both male and female students. Finally, our study reinforces the conclusions of previous studies demonstrating that undergraduate research and mentoring are beneficial for students. Overall, our findings support that, for students to fully benefit from their undergraduate research experience, undergraduate research opportunities for students should include an equitable representation of female mentors.

In vitro assembly and evaluation of Nora virus VLPs.

Nora virus is a RNA picorna-like virus that produces a persistent infection in Drosophila melanogaster. The genome is approximately 12,300 bases and is divided into four open reading frames (ORFs). Structurally, there are four important viral proteins: VP3, VP4A, VP4B, and VP4C. Three proteins (VP4A, VP4B, and VP4C) that form the virion's capsid are encoded by ORF 4, which produces a polyprotein that is post-translationally cleaved. The fourth protein (VP3) is encoded by ORF 3 and it is hypothesized to play a role in virion stability. The genes for these proteins were individually cloned into Escherichia coli, expressed, and the proteins were purified. Virus-like particles (VLPs) were assembled in vitro by mixing the proteins together in different combinations and measured via electron microscopy. Assemblies that contained VP4A and/or VP3 created VLPs with similar sizes to purified empty Nora virus capsids, potentially indicating that VP4A and/or VP3 are vital for Nora virus capsid structure, assembly, and/or stability. Not only does this study provide insight into the role of Nora virus proteins, but it may also lead to a deeper understanding of how Nora virus or other picorna-like viruses undergo assembly.  Keywords: RNA viruses; Nora virus; picorna-like virus; virus-like particles; capsid assembly.

Mapping and Monitoring Zero-Deforestation Commitments.

A growing number of companies have announced zero-deforestation commitments (ZDCs) to eliminate commodities produced at the expense of forests from their supply chains. Translating these aspirational goals into forest conservation requires forest mapping and monitoring (M&M) systems that are technically adequate and therefore credible, salient so that they address the needs of decision makers, legitimate in that they are fair and unbiased, and scalable over space and time. We identify 12 attributes of M&M that contribute to these goals and assess how two prominent ZDC programs, the Amazon Soy Moratorium and the High Carbon Stock Approach, integrate these attributes into their M&M systems. These programs prioritize different attributes, highlighting fundamental trade-offs in M&M design. Rather than prescribe a one-size-fits-all solution, we provide policymakers and practitioners with guidance on the design of ZDC M&M systems that fit their specific use case and that may contribute to more effective implementation of ZDCs.

Disparities in Treatment with Direct-Acting Hepatitis C Virus Antivirals Persist Among Adults Coinfected with HIV and Hepatitis C Virus in US Clinics, 2010-2018.

Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfection carries substantial risk for all-cause mortality and liver-related morbidity and mortality, yet many persons coinfected with HIV/HCV remain untreated for HCV. We explored demographic, clinical, and sociodemographic factors among participants in routine HIV care associated with prescription of direct-acting antivirals (DAAs). The HIV Outpatient Study (HOPS) is an ongoing longitudinal cohort study of persons with HIV in care at participating clinics since 1993. There are currently eight study sites in six US cities. We analyzed medical records data of HOPS participants diagnosed with HCV since June 2010. Sustained virological response (SVR) was documented with first undetectable HCV viral load (VL). We assessed factors associated with being prescribed DAAs by multi-variable logistic regression and described the cumulative rate of SVR. Among 306 eligible participants, 131 (43%) were prescribed DAA therapy. Factors associated with greater odds of being prescribed DAA were older age, private health insurance, higher CD4 cell count, being a person who injects drugs, and receiving care at publicly funded sites (p < 0.05). Of 127 (97%) participants with at least 1 follow-up HCV VL, 110 (87%) achieved SVR at 12 weeks. Of the total 131 participants, 123 (94%) eventually achieved SVR. Less than half of HIV/HCV coinfected patients in HOPS have been prescribed DAAs. Interventions are needed to address deficits in DAA prescription, including among patients with public or no health insurance, younger age, and lower CD4 cell count.

Incident bone fracture and mortality in a large HIV cohort outpatient study, 2000-2017, USA.

We evaluated the association of bone fracture with mortality among persons with HIV, controlling for sociodemographic, behavioral, and clinical factors. Incident fracture was associated with 48% greater risk of all-cause mortality, underscoring the need for bone mineral density screening and fracture prevention. PURPOSE/INTRODUCTION: Low bone mineral density (BMD) and fracture are more common among persons with HIV (PWH) than those without HIV infection. We evaluated the association of bone fracture with mortality among PWH, controlling for sociodemographic, behavioral, and clinical factors. METHODS: We analyzed data from HIV Outpatient Study (HOPS) participants seen at nine US HIV clinics during January 1, 2000, through September 30, 2017. Incident fracture rates and post-fracture mortality were compared across four calendar periods. Cox proportional hazards analyses determined factors associated with all-cause mortality among all participants and those with incident fracture. RESULTS: Among 6763 HOPS participants, 504 (7.5%) had incident fracture (median age = 47 years) and 719 (10.6%) died. Of fractures, 135 (26.8%) were major osteoporotic (hip/pelvis, wrist, spine, arm/shoulder). During observation, 27 participants with major osteoporotic fractures died (crude mortality 2.97/100 person-years [PY]), and 48 with other site fractures died (crude mortality 2.51/100 PY). Post-fracture, age- and sex-adjusted all-cause mortality rates per 100 PY decreased from 8.5 during 2000-2004 to 1.9 during 2013-2017 (P<0.001 for trend). In multivariable analysis, incident fracture was significantly associated with all-cause mortality (Hazard Ratio 1.48, 95% confidence interval 1.15-1.91). Among 504 participants followed post-fracture, pulmonary, kidney, and cardiovascular disease, hepatitis C virus co-infection, and non-AIDS cancer, remained independently associated with all-cause mortality. CONCLUSIONS: Incident fracture was associated with 48% greater risk of all-cause mortality among US PWH in care, underscoring the need for BMD screening and fracture prevention. Although fracture rates among PWH increased during follow-up, post-fracture death rates decreased, likely reflecting advances in HIV care.