Effect of HIV and antiretroviral therapy use on body weight changes in a cohort of U.S. veterans living with and without HIV.

OBJECTIVE: People living with HIV have high rates of obesity and obesity-related comorbidities. Our study sought to evaluate weight trajectory in a retrospective cohort of people living with HIV and matched HIV-negative veterans (controls) and to evaluate risk factors for weight gain. METHODS: This was a retrospective database analysis of data extracted from the VA Corporate Data Warehouse that included people living with HIV (n = 22 421) and age-matched HIV-negative controls (n = 63 072). The main outcomes were baseline body weight and weight change from baseline at 1, 2, and 5 years after diagnosis (baseline visit for controls). RESULTS: Body weight at baseline was lower in people living with HIV than in controls. People living with HIV on antiretroviral therapy (ART) gained more weight than did controls. In a sub-analysis of ART-exposed people living with HIV, age >50 years, African American race, body mass index (BMI) <25, CD4 ≤200, and HIV diagnosis year after 2000 were associated with more weight gain at year 1. Nucleoside reverse transcriptase inhibitors (NRTI) plus non-NRTIs (NNRTIs) were associated with less weight gain than NRTIs plus protease inhibitors, NRTIs plus integrase inhibitors, or NRTIs plus other agents at year 1. CONCLUSIONS: Among US veterans, those living with HIV had lower rates of obesity than age-matched HIV-negative controls; however, primarily in the first 2 years after starting ART, people living with HIV gained more weight than did controls.

Risk and incidence of head and neck cancers in veterans living with HIV and matched HIV-negative veterans.

BACKGROUND: Persons living with HIV/AIDS have a higher incidence of virus-related and tobacco/alcohol-related cancers. This study is the first to estimate the effect of HIV versus HIV-negative veterans on the risk of head and neck squamous cell carcinoma incidence in a large retrospective cohort study. METHODS: The authors constructed a retrospective cohort study using patient data from 1999 to 2016 from the National Veterans Administration Corporate Data Warehouse and the VA Central Cancer Registry. This cohort study included 45,052 veterans living with HIV/AIDS and 162,486 HIV-negative patients matched by age, sex, and index visit (i.e., HIV diagnosis date or clinic visit date). The age-standardized incidence rates and estimated adjusted hazard ratios were calculated with a Cox proportional hazards regression for oropharyngeal and nonoropharyngeal head and neck cancer squamous cell carcinoma (HNSCC). The authors also abstracted human papillomavirus (HPV) status from oropharyngeal HNSCC diagnosed after 2010. RESULTS: Veterans living with HIV/AIDS (VLWH) have 1.71 (95% confidence interval [CI], 1.36, 2.14) times the risk of oropharyngeal cancer and 2.06 (95% CI, 1.76, 2.42) times the hazard of nonoropharyngeal cancer compared with HIV-negative veterans. VLWH with oropharyngeal squamous cell carcinoma (OPSCC) were more likely to be HPV-positive (N = 30 [81.1%]) than the HIV-negative veterans with OPSCC (N = 50 [67.6%]), although this difference was not significant (p = .135). For nonoropharyngeal cancer, the increased risk of oral cavity cancer among VLWH drove the increased risk. CONCLUSIONS: The study results suggest that HIV may play a role in virally mediated and nonvirally mediated HNSCC. As the HIV prevalence rises in the United States due to better survival and the incidence of HPV-positive oropharyngeal HNSCC increases, the interaction between HPV and HIV becomes increasingly relevant.

The association between protease inhibitors and anal cancer outcomes in veterans living with HIV treated with definitive chemoradiation: a retrospective study.

BACKGROUND: The incidence of anal squamous cell carcinoma has been increasing, particularly in people living with HIV (PLWH). There is concern that radiosensitizing drugs, such as protease inhibitors, commonly used in the management of HIV, may increase toxicities in patients undergoing chemoradiation. This study examines treatment outcomes and toxicities in PLWH managed with and without protease inhibitors who are receiving chemoradiation for anal cancer. METHODS: Patient demographic, HIV management, and cancer treatment information were extracted from multiple Veterans Affairs databases. Patients were also manually chart reviewed. Among PLWH undergoing chemoradiation for anal carcinoma, therapy outcomes and toxicities were compared between those treated with and without protease inhibitors at time of cancer treatment. Statistical analysis was performed using chi-square, Cox regression analysis, and logistic regression. RESULTS: A total of 219 PLWH taking anti-retroviral therapy undergoing chemoradiation for anal cancer were identified and included in the final analysis. The use of protease inhibitors was not associated with any survival outcome including colostomy-free survival, progression-free survival, or overall survival (all adjusted hazard ratio p-values> 0.05). Regarding toxicity, protease inhibitor use was not associated with an increased odds of hospitalizations or non-hematologic toxicities; however, protease inhibitor use was associated with increased hospitalizations for hematologic toxicities, including febrile neutropenia (p < 0.01). CONCLUSION: The use of protease inhibitors during chemoradiation for anal carcinoma was not associated with any clinical outcome or increase in non-hematologic toxicity. Their use was associated with increased hospitalizations for hematologic toxicities. Further prospective research is needed to evaluate the safety and efficacy of protease inhibitors for patients undergoing chemoradiation.

Genotoxic, Metabolic, and Oxidative Stresses Regulate the RNA Repair Operon of Salmonella enterica Serovar Typhimurium.

The σ54 regulon in Salmonella enterica serovar Typhimurium includes a predicted RNA repair operon encoding homologs of the metazoan Ro60 protein (Rsr), Y RNAs (YrlBA), RNA ligase (RtcB), and RNA 3'-phosphate cyclase (RtcA). Transcription from σ54-dependent promoters requires that a cognate bacterial enhancer binding protein (bEBP) be activated by a specific environmental or cellular signal; the cognate bEBP for the σ54-dependent promoter of the rsr-yrlBA-rtcBA operon is RtcR. To identify conditions that generate the signal for RtcR activation in S Typhimurium, transcription of the RNA repair operon was assayed under multiple stress conditions that result in nucleic acid damage. RtcR-dependent transcription was highly induced by the nucleic acid cross-linking agents mitomycin C (MMC) and cisplatin, and this activation was dependent on RecA. Deletion of rtcR or rtcB resulted in decreased cell viability relative to that of the wild type following treatment with MMC. Oxidative stress from peroxide exposure also induced RtcR-dependent transcription of the operon. Nitrogen limitation resulted in RtcR-independent increased expression of the operon; the effect of nitrogen limitation required NtrC. The adjacent toxin-antitoxin module, dinJ-yafQ, was cotranscribed with the RNA repair operon but was not required for RtcR activation, although YafQ endoribonuclease activated RtcR-dependent transcription. Stress conditions shown to induce expression the RNA repair operon of Escherichia coli (rtcBA) did not stimulate expression of the S Typhimurium RNA repair operon. Similarly, MMC did not induce expression of the E. colirtcBA operon, although when expressed in S Typhimurium, E. coli RtcR responds effectively to the unknown signal(s) generated there by MMC exposure.IMPORTANCE Homologs of the metazoan RNA repair enzymes RtcB and RtcA occur widely in eubacteria, suggesting a selective advantage. Although the enzymatic activities of the eubacterial RtcB and RtcA have been well characterized, the physiological roles remain largely unresolved. Here we report stress responses that activate expression of the σ54-dependent RNA repair operon (rsr-yrlBA-rtcBA) of S Typhimurium and demonstrate that expression of the operon impacts cell survival under MMC-induced stress. Characterization of the requirements for activation of this tightly regulated operon provides clues to the possible functions of operon components in vivo, enhancing our understanding of how this human pathogen copes with environmental stressors.

Novel DNA Binding and Regulatory Activities for σ54 (RpoN) in Salmonella enterica Serovar Typhimurium 14028s.

The variable sigma (σ) subunit of the bacterial RNA polymerase (RNAP) holoenzyme, which is responsible for promoter specificity and open complex formation, plays a strategic role in the response to environmental changes. Salmonella enterica serovar Typhimurium utilizes the housekeeping σ70 and five alternative sigma factors, including σ54 The σ54-RNAP differs from other σ-RNAP holoenzymes in that it forms a stable closed complex with the promoter and requires ATP hydrolysis by an activated cognate bacterial enhancer binding protein (bEBP) to transition to an open complex and initiate transcription. In S. Typhimurium, σ54-dependent promoters normally respond to one of 13 different bEBPs, each of which is activated under a specific growth condition. Here, we utilized a constitutively active, promiscuous bEBP to perform a genome-wide identification of σ54-RNAP DNA binding sites and the transcriptome of the σ54 regulon of S. Typhimurium. The position and context of many of the identified σ54 RNAP DNA binding sites suggest regulatory roles for σ54-RNAP that connect the σ54 regulon to regulons of other σ factors to provide a dynamic response to rapidly changing environmental conditions.IMPORTANCE The alternative sigma factor σ54 (RpoN) is required for expression of genes involved in processes with significance in agriculture, bioenergy production, bioremediation, and host-microbe interactions. The characterization of the σ54 regulon of the versatile pathogen S. Typhimurium has expanded our understanding of the scope of the σ54 regulon and how it links to other σ regulons within the complex regulatory network for gene expression in bacteria.

A Randomized Trial to Test a Peer Mentor Intervention to Improve Outcomes in Persons Hospitalized With HIV Infection.

BACKGROUND: Few interventions have been shown to improve retention in human immunodeficiency virus (HIV) care, and none have targeted the hospitalized patient. Peer mentoring has not been rigorously tested. METHODS: We conducted a randomized, controlled clinical trial of a peer mentoring intervention. Eligible adults were hospitalized and were either newly diagnosed with HIV infection or out of care. The intervention included 2 in-person sessions with a volunteer peer mentor while hospitalized, followed by 5 phone calls in the 10 weeks after discharge. The control intervention provided didactic sessions on avoiding HIV transmission on the same schedule. The primary outcome was a composite of retention in care (completed HIV primary care visits within 30 days and between 31 and 180 days after discharge) and viral load (VL) improvement (≥1 log10 decline) 6 months after discharge. RESULTS: We enrolled 460 participants in 3 years; 417 were in the modified intent-to-treat analysis. The median age was 42 years; 74% were male; and 67% were non-Hispanic black. Baseline characteristics did not differ between the randomized groups. Twenty-eight percent of the participants in both arms met the primary outcome (P = .94). There were no differences in prespecified secondary outcomes, including retention in care and VL change. Post hoc analyses indicated interactions between the intervention and length of hospitalization and between the intervention and receipt of linkage services before discharge. CONCLUSIONS: Peer mentoring did not increase reengagement in outpatient HIV care among hospitalized, out-of-care persons. More intense and system-focused interventions warrant further study. CLINICAL TRIALS REGISTRATION: NCT01103856.

Retaining HIV Patients in Care: The Role of Initial Patient Care Experiences.

Cross-sectional studies have shown an association between better patient experiences and health outcomes. However, the direction of causality remains unclear. Our prospective study seeks to determine whether better initial patient experiences predict subsequent retention in HIV care. We enrolled patients new to an HIV clinic in Houston, Texas, from August 26, 2013 to November 18, 2013. The patients' overall experience with the HIV provider was based on six items; overall experience with the HIV clinic was based on five items. We measured subsequent retention over the first 6 months and entire first year of HIV care. Analyses included 140 patients. Sixty-one percent were non-Hispanic black, 41 % were diagnosed with HIV within the last 3 months, and 36 % had a CD4 cell count <200. Thirty three percent were totally satisfied with their initial HIV provider experience and 32 % were totally satisfied with their initial HIV clinic experience. Retention was 68 % over the first 6 months and 51 % over the first year. Satisfaction with the HIV provider at the initial visit significantly predicted 6-month retention in care (aOR = 3.56, p = 0.006). Similar results were found for satisfaction with the HIV clinic (aOR = 4.67, p = 0.002). Neither of the patient experience measures at the initial visit predicted 12-month retention. Patients with better initial care experiences have significantly greater retention in HIV care. The effect of better initial care experiences was limited in duration. Consistently improving patient care experiences, not only at baseline but also on subsequent visits, may be a way to increase retention in HIV care.

Increased thyroid cancer incidence corresponds to increased use of thyroid ultrasound and fine-needle aspiration: a study of the Veterans Affairs health care system.

BACKGROUND: Thyroid cancer incidence has increased in the last several decades and may represent either a true increase in the number of cases or increased screening. The objective of this study was to examine thyroid cancer incidence and the use of thyroid ultrasound and fine-needle aspiration (FNA) screening in the Veterans Affairs (VA) health care system. The authors hypothesized that the incidence of thyroid cancer would correspond to increases in the use of these diagnostic modalities. METHODS: This was a multiyear, cross-sectional study using VA administrative data from 2000 to 2012. Joinpoint regression analysis was used to identify trends in thyroid cancer incidence and the use of thyroid ultrasound and FNA. RESULTS: An increase in thyroid cancer incidence occurred from 10.3 per 100,000 individuals in 2000 to 21.5 per 100,000 individuals in 2012. The rate of thyroid ultrasound use increased from 125.6 per 100,000 individuals in 2001 to 572.1 per 100,000 individuals in 2012, and the rate of thyroid FNA use increased from 7.0 per 100,000 individuals in 2000 to 46.2 per 100,000 individuals in 2012. A statistically significant increase in thyroid cancer incidence between 2000 and 2008 (annual percent change [APC], 3.81; P < .05) was followed by a more pronounced increase between 2008 and 2012 (APC, 10.32; P < .05). A simultaneous increase in the use of thyroid ultrasound occurred between 2002 and 2012 (APC, 15.48; P < .05) and the use of thyroid FNA between 2000 and 2012 (APC, 18.36; P < .05). CONCLUSIONS: Although the incidence of thyroid cancer doubled, a nearly 5-fold increase in the use of thyroid ultrasound and a nearly 7-fold increase in the use of thyroid FNA occurred between 2000 and 2012. These findings suggest that the increase in thyroid cancer incidence may be related to increases in the use of thyroid ultrasound and FNA.

Risk of lower and upper gastrointestinal bleeding, transfusions, and hospitalizations with complex antithrombotic therapy in elderly patients.

BACKGROUND: Complex antithrombotic therapy (CAT) prescribed to elderly patients increases the risk of gastrointestinal bleeding. We quantified upper (UGIE) and lower gastrointestinal (LGIE) events, transfusions, and hospitalizations in a national cohort of elderly veterans prescribed CAT. METHODS AND RESULTS: Veterans ≥60 years of age prescribed anticoagulant-antiplatelet, aspirin (ASA)-antiplatelet, ASA-anticoagulant, or triple therapy (ie, TRIP, anticoagulant-antiplatelet-ASA) were identified from the national pharmacy database (October 1, 2002 to September 30, 2008). Prescription-fill data were linked to Veteran Affairs and Medicare encounter files, each person-day of follow-up was assessed for CAT exposure, and outcomes were defined by using diagnostic code algorithms derived following chart abstraction. Incidence density ratios (compared with the reference category of no CAT) and survival analysis was conducted. Among 78,133 veterans (98.6% white; mean age, 72.3 [standard deviation 7.7]), 64% were prescribed ASA-antiplatelet and anticoagulant-antiplatelet and 6% were prescribed TRIP. The incidence of UGIE was 20.1/1000 patient-years, and the incidence of LGIE was 70.1/1000 patient-years. ASA-anticoagulant and TRIP were associated with the highest incidence of transfusion and hospitalization. A 40% to 60% increased risk of UGIE was observed with all strategies. LGIE was 30% higher with anticoagulant-antiplatelet, and transfusion increased with ASA-anticoagulant (hazard ratio, 6.1; 95% confidence interval, 5.2-7.1) and TRIP (hazard ratio, 5.0; 95% confidence interval, 4.2-5.8). Increased risk of hospitalization was noted with all strategies. The number needed to harm for UGIE or LGIE ranged from 52 to 65 and 15 to 23, respectively. The number needed to harm for hospitalization was 39 (anticoagulant-antiplatelet), 34 (ASA-anticoagulant), 67 (ASA-antiplatelet), and 45 (TRIP) patients. CONCLUSIONS: Among elderly patients, CAT-related LGIE and UGIE are clinically relevant risks resulting in increased hospitalizations and transfusions.

Risk and predictors of penile cancer in US Veterans with HIV.

OBJECTIVES: People with HIV (PWH) may have an increased burden of penile cancer. We aimed to evaluate the risk of penile cancer in PWH compared with that of the general population. DESIGN: We conducted a nationwide retrospective matched cohort study of penile cancer incidence among veterans with HIV (VWH) compared with veterans without HIV. METHODS: We compared penile cancer incidence rates in 44 173 VWH to those of veterans without HIV ( N  = 159 443; 4 : 1 matched in age). We used Cox regression models to estimate hazard ratios and 95% confidence intervals (CIs) for associations with HIV infection and for penile cancer risk factors. RESULTS: HIV positivity was associated with an increased risk of penile cancer, with adjusted hazard ratios of 2.63 (95% CI 1.64-4.23) when adjusting for age, race/ethnicity, baseline BMI, smoking and alcohol use, economic means test, and history of condyloma. The risk increased to hazard ratio = 4.25 (95% CI 2.75-6.57) when adjusting for all factors except history of condyloma. Risk factors for penile cancer in VWH included lower nadir CD4 + count, less than 50% of follow-up time with undetectable HIV viral load, and history of condyloma. CONCLUSION: VWH - particularly those with low CD4 + counts, detectable HIV viral loads, or history of condyloma - are at increased risk of penile cancer, suggesting the penile cancer prevention activities are needed in this population.

Area deprivation index and segregation on the risk of HIV: a U.S. Veteran case-control study.

Background: Preventing HIV infection remains a critically important tool in the continuing fight against HIV/AIDS. The primary aim is to evaluate the effect and interactions between a composite area-level social determinants of health measure and an area-level measure of residential segregation on the risk of HIV/AIDS in U.S. Veterans. Methods: Using the individual-level patient data from the U.S. Department of Veterans Affairs, we constructed a case-control study of veterans living with HIV/AIDS (VLWH) and age-, sex assigned at birth- and index date-matched controls. We geocoded patient's residential address to ascertain their neighborhood and linked their information to two measures of neighborhood-level disadvantage: area deprivation index (ADI) and isolation index (ISOL). We used logistic regression to estimate the odds ratio (OR) and 95% confidence interval (CI) for comparing VLWH with matched controls. We performed analyses for the entire U.S. and separately for each U.S. Census division. Findings: Overall, living in minority-segregated neighborhoods was associated with a higher risk of HIV (OR: 1.88 (95% CI: 1.79-1.97) while living in higher ADI neighborhoods was associated with a lower risk of HIV (OR: 0.88; 95% CI: 0.84-0.92). The association between living in a higher ADI neighborhood and HIV was inconsistent across divisions, while living in minority-segregated neighborhoods was consistently associated with increased risk across all divisions. In the interaction model, individuals from low ADI and high ISOL neighborhoods had a higher risk of HIV in three divisions: East South Central; West South Central, and Pacific. Interpretation: Our results suggest that residential segregation may prevent people in disadvantaged neighborhoods from protecting themselves from HIV independent from access to health care. There is the need to advance knowledge about the neighborhood-level social-structural factors that influence HIV vulnerability toward developing interventions needed to achieve the goal of ending the HIV epidemic. Funding: US National Cancer Institute.

Validity of self-report measures in assessing antiretroviral adherence of newly diagnosed, HAART-naïve, HIV patients.

PURPOSE: To compare the performance of self-report instruments assessing adherence to antiretroviral therapy (ART) in patients starting ART for the first time and in a predominately Hispanic population. METHODS: Of 184 patients in a prospective observational cohort study of newly diagnosed, minority patients of low socioeconomic status, 54 were given Medication Event Monitoring System (MEMS) caps for their boosted protease inhibitor (PI) or non-nucleoside reverse transcriptase inhibitor (NNRTI). They completed a 4-week recall visual analogue scale (VAS), the Adult AIDS Clinical Trial Group (AACTG) 4-day recall instrument, and a 1-month recall qualitative single-item measure every 3 months for up to 18 months in English or Spanish. Electronic pharmacy records recorded refill dates. Spearman correlation coefficients were calculated to compare self-report measures with MEMS data and pharmacy data. RESULTS: Of 46 patients with MEMS data, mean adherence was 84.7% (SD 35.6) by MEMS, 84.5% (SD 15.1) by pharmacy, 95.4% (SD 11.9) by VAS, 95.8% (SD 17.2) by AACTG, and 87.6% (SD 28.2) by qualitative single item. The correlation coefficient (CC) of VAS with MEMS was 0.37 (P < .01), and with pharmacy it was 0.34 (P < .01). The CC of the AACTG with MEMS was 0.32 (P < .01), and with pharmacy it was 0.28 (P < .01). The qualitative single item had a CC with MEMS of 0.24 (P < .01) and with pharmacy of 0.32 (P < .01). Spanish-speaking patients' VAS adherence had a CC of 0.40 (P < .01) with MEMS. CONCLUSIONS: The VAS, AACTG, and qualitative single-item measures correlated significantly with MEMS and pharmacy data. Our data support self-administration of the VAS, even in Span-ish speakers.

Persons newly diagnosed with HIV infection are at high risk for depression and poor linkage to care: results from the Steps Study.

Little is known about the prevalence and impact of depression in persons newly diagnosed with HIV infection. The Steps Study is a prospective, observational cohort study of persons newly diagnosed with HIV infection. Participants were administered a battery of instruments, including the CES-D. Linkage to care was defined as attending at least one clinic appointment in each of the first two 90-day intervals following diagnosis. Of 180 participants, 67% screened positive for depression. In multivariate analysis, depression was associated with female sex, income <$25,000, recent substance abuse, baseline poor access to medical care, and low self-efficacy. Fifty-six and sixty-eight percent of depressed and not depressed participants linked to care, respectively. In multivariate analysis, depression was a borderline significant predictor of poor linkage. Depression is very prevalent in persons newly diagnosed with HIV infection. Interventions targeting linkage to care should address depression, substance abuse, and barriers to care.

National trends in oropharyngeal cancer incidence and survival within the Veterans Affairs Health Care System.

BACKGROUND: Oropharyngeal squamous cell carcinoma (OPSCC) epidemiology has not been examined previously in the nationwide Veterans Affairs (VA) population. METHODS: Joinpoint regression analysis was applied to OPSCC cases identified from VA administrative data from 2000 to 2012. RESULTS: We identified 12 125 OPSCC cases (incidence: 12.2 of 100 000 persons). OPSCC incidence declined between 2000 and 2006 (annual percent change [APC] = -4.27, P < .05), then increased between 2006 and 2012 (APC = 7.02, P < .05). Significant incidence increases occurred among white (APC = 7.19, P < .05) and African American (APC = 4.87, P < .05) Veterans and across all age cohorts. The percentage of never-smokers increased from 8% in 2000 to 15.7% in 2012 (P < .001), and 2-year overall survival improved from 31.2% (95% confidence interval (CI) [30-33.4]) to 55.7% (95% CI [54.4-57.1]). CONCLUSIONS: OPSCC incidence is increasing across all racial and age cohorts in the VA population. Smoking rates remain high among Veterans with OPSCC and gains in survival lag those reported in the general population.

Reduced hospitalization cost for upper gastrointestinal events that occur among elderly veterans who are gastroprotected.

BACKGROUND & AIMS: Despite prescription of gastroprotection among elderly nonsteroidal anti-inflammatory drug (NSAID) users, residual bleeding can still occur. We sought to determine the effect of proton pump inhibitors (PPI) on hospitalization and resource use among veterans in whom an upper gastrointestinal event (UGIE) occurred. METHODS: We identified from national pharmacy records veterans > or =65 years prescribed an NSAID, cyclooxygenase-2 selective NSAID (coxib), or salicylate (>325 mg/day) at any Veterans Affairs (VA) facility (01/01/00-12/31/04). Prescription fill data were linked longitudinally to a Veterans Affairs-Medicare dataset of inpatient, outpatient, and death files, and demographic and provider data. Among veterans in whom a UGIE occurred, we assessed the effect of prescription strategy on hospitalization, using a multivariate logistic regression model. RESULTS: A total of 3566 UGIEs occurred among a cohort that was predominantly male (97.5%), white (77%), with a mean age of 73.5 (SD, 5.7). Hospitalization occurred in 47.5%, and gastroprotection was associated with a 30% reduction in hospitalization compared with no PPI. Five-year pharmacy costs associated with the PPI strategy exceeded the no-PPI strategy ($742,406 vs $184,282); however, a substantial reduction in medical costs was observed with PPI ($9,948,738 vs $18,686,081). CONCLUSIONS: Even if an NSAID-UGIE occurs in the PPI-protected older veteran, the reduction in need for hospitalization results in a cost saving to the Department of Veterans Affairs.

Incidence and survival for oropharynx and non-oropharynx head and neck cancers among veterans living with HIV.

BACKGROUND: People living with HIV/AIDS (PLWH) have an excess risk for head and neck squamous cell carcinoma (HNSCC) compared to the general U.S. population, but little is known about HIV-specific risk factors associated with the incidence and outcomes HNSCC. We aim to identify clinical and HIV-specific risk factors associated with oropharyngeal and non-oropharyngeal HNSCC incidence and outcomes separately. METHODS: We constructed a retrospective cohort study of 45,052 PLWH aged 18 or above from the national Veteran Affairs (VA) Corporate Data from 1999 to 2015. We extracted demographic data and risk factor information, including history of alcohol abuse, smoking, CD4 count (cells/µl), and percent of follow-up time with undetectable HIV viral load as time-updated variables. We calculated the age-standardized incidence rates of oropharyngeal and non-oropharyngeal HNSCC and estimated adjusted hazard ratios (HR). We also examined overall survival using Kaplan-Meier curves and adjusted HR. RESULTS: The standardized incidence rate of oropharyngeal and non-oropharyngeal HNSCC in this veteran cohort of PLWH is 23.0 (95% confidence intervals (CIs): 17.1-28.9) and 55.4 (95% CI: 46.5-64.3) per 100,000 person-years, respectively. Nadir CD4 count ≤200 was associated with an increased risk of non-oropharyngeal HNSCC (HR: 1.78; 95% CI: 1.31-2.30 vs >200). Five-year overall survival of OPSCC (37.0%) was significantly lower than non-oropharyngeal HNSCC (49.1%). CONCLUSIONS: PLWH who receive care in the VA had higher age-adjusted HNSCC incidence rates than reported in the general population, suggesting that HIV and immunosuppression play a role. Additional studies should be conducted to study the interaction between HPV and HIV.

Effect of Body Weight and Other Metabolic Factors on Risk of Non-Small Cell Lung Cancer among Veterans with HIV and a History of Smoking.

Among people living with HIV (PWH), there has been an increasing incidence of non-small cell lung cancer (NSCLC) and metabolic abnormalities, including dyslipidemia, which can modulate NSCLC risk. In this article, we evaluate which metabolic risk factors are associated with incident risk among PWH who smoke. This is done through a retrospective cohort study, using data of HIV+ veterans who smoke from the nationwide Veterans Affairs (VA) healthcare system. Data on diagnostic codes, medication, and laboratory values of 33,351 veterans were obtained using the VA's Corporate Data Warehouse and Central Cancer Registry. We calculated NSCLC incidence and utilized Cox regression to determine metabolic factors associated with NSCLC risk. HIV+ cohort was 97.4% male; median age = 47 years and 20,050 (60.1%) well-controlled (≥80% follow-up time undetectable viral load). Crude incidence rates were lower in well-controlled PWH (1.46 vs. 2.06/1000 PY). Metabolic factors associated with incident NSCLC risk included lower BMI at HIV diagnosis and cachexia history in both groups, while HDL and triglycerides were significant in non-well-controlled smokers only. Our findings that lower BMI at HIV diagnosis, history of cachexia among individuals with well-controlled HIV, and cachexia presence at diagnosis are associated with increased risk of developing NSCLC in PWH with a history of smoking have important implications.

Predictors of retention in HIV care among a national cohort of US veterans.

BACKGROUND: Poor retention in HIV care leads to poor survival. The predictors of poor retention in HIV care are not well understood, especially from US nationwide datasets. We determined the predictors of poor retention in HIV care among a group of US veterans and examined whether poor retention was confounded by other predictors of survival. METHODS: We conducted a retrospective cohort study of 2,619 male US veterans who started antiretroviral therapy after January 1, 1998. Poor retention in HIV care was defined as having had at least 1 quarter-year without any primary care visit in the year after starting antiretroviral therapy. Survival was assessed through 2002. Logistic regression and Cox models were constructed. RESULTS: Thirty-six percent of patients had poor retention in care. In multivariable analysis, younger age, Black race/ethnicity, CD4 cell count >350 x10(6)/L, hepatitis C infection, and illicit drug use were predictive of poor retention in care. Having a chronic medical comorbidity and being identified as a man having sex with men (MSM) were associated with improved retention in care. In multivariable survival analyses, poor retention in care was not a confounder or moderator for other variables that predicted survival. CONCLUSIONS: Retention in HIV care is an independent predictor of survival. As routine HIV screening increases, more people with the characteristics predictive of poor retention in care will be identified. Interventions to improve retention in care are needed.

Risk and Predictors of Esophageal and Stomach Cancers in HIV-Infected Veterans: A Matched Cohort Study.

BACKGROUND: To evaluate the risks of esophageal and stomach carcinomas in people living with HIV (PLWH) compared with the general population and risk factors for these cancers in PLWH. SETTING: Retrospective cohort study in the Veterans Health Administration. METHODS: We compared incidence rates for esophageal and stomach cancers in 44,075 HIV-infected male veterans with those in a matched HIV-uninfected cohort (N = 157,705; 4:1 matched on age and HIV-index date). We used Cox regression models to estimate Hazard ratios (HRs) and 95% confidence intervals (CIs) for associations with HIV infection and for cancer risk factors in PLWH. RESULTS: In unadjusted models, HIV infection was associated with increased risks of esophageal squamous cell carcinoma (ESCC; HR, 2.21; 95% CI: 1.47 to 3.13) and gastric cardia cancer (HR, 1.69; 95% CI: 1.00 to 2.85) but associated with lower risk of esophageal adenocarcinoma (EAC; HR, 0.48; 95% CI: 0.31 to 0.74). After adjusting for age, race/ethnicity, smoking and alcohol use, HIV infection remained statistically significantly associated with elevated risk for ESCC [adjusted hazard ratio (aHR), 1.58; 95% CI: 1.02 to 2.47], especially among HIV-infected patients with CD4 count ≤200 (aHR, 2.20; 95% CI: 1.35 to 3.60). HIV infection was not associated with risks of EAC (aHR, 0.82; 95% CI: 0.53 to 1.26), gastric cardia (aHR, 0.80; 95% CI: 0.33 to 1.94), or noncardia (aHR, 1.06; 95% CI: 0.61 to 1.84) cancers. Risk factors for these cancers in HIV-infected patients were otherwise similar to those in general population (eg, Helicobacter pylori for gastric noncardia cancer). CONCLUSION: HIV-infected individuals with low CD4 count are at highest risk for ESCC, but HIV infection was not independently associated with EAC or gastric cancer after adjusting for confounders.

Are Injection Site Reactions in Monoclonal Antibody Therapies Caused by Polysorbate Excipient Degradants?

Injection site reactions (ISRs) and other adverse side effects are commonly observed during therapy with biologics. These hypersensitivity-related side effects can vary from simple rash to life-threatening anaphylactic reaction and may be linked to the immunogenicity of the drug including formation of antidrug antibodies. Reactions can also occur as a consequence of excipients in the product. We report the case of a patient who developed erythematous ISRs to both commercial PCSK9i formulations and had to go off therapy even though efficacy was not impacted. Skin testing showed that the patient was reacting to the polysorbates. Polysorbates are added to stabilize the biotherapeutic. Polysorbates can also activate complement and lead to a range of acute hypersensitivity and systemic immunostimulation reactions. Oxidative degradation products can function as haptens by reacting with proteins at the injection site. Reactive degradation products may even form adducts with the biologic itself, creating a potential neoantigen. Further research is needed to understand the fundamental causes of ISRs. It is critical that only the highest quality raw material is used, and proper storage conditions are employed to minimize degradation of polysorbates in the product. Although complete elimination of ISRs is unlikely, all efforts must be made to minimize them.