Antimicrobial potential of unstressed and heat stressed Allium sativum.

Garlic (Allium sativum) is generally known to be of medicinal value, possessing potentials that include antimicrobial activity, but are often consumed in foods after subjection to cooking heat. The antimicrobial potential of heat stressed garlic may become decreased or lost when cooked, making its medicinal benefit unavailable to consumers. The potential of uncooked and cooked extracts from garlic imported to Jamaica, to inhibit the growth of eight microbes of clinical significance was investigated. Aqueous extracts of fresh garlic of 15 g/100 ml (fw), and dried and pulverized garlic cloves of 12.5 g/100 ml, 25 g/100 ml, 50 g/100 ml, and 100 g/100 ml (dw), were tested for inhibition of microbial growth. Extracts were tested uncooked, and cooked by boiling for 5, 10, and 15 min respectively. Of all the microbes studied, C. albicans incurred the largest zone of inhibition (57.7 ± 0.6 mm at the 100 g/100 ml of the dried extract, F(3, 8) = 51.778, p < 0.001, ω2 = 0.93). Cooking of garlic extracts resulted in statistically significant decreases in zones of inhibition of microbes, as evident in the linear regression and one-way ANOVA analyses, and/or complete loss of microbial inhibition. C. albicans was the most inhibited microbe, followed by E. coli, and Salmonella sp., respectively. The use of uncooked garlic may be the best route for obtaining the greatest antimicrobial potential of garlic against susceptible bacteria and fungi because cooking heat stress resulted in the decrease and complete loss of the antimicrobial potentials of the garlic.

The Impact of Homelessness, Substance Use, and Mental Illness on Surgical Inpatient Outcomes in Australia.

This study investigated inpatient surgical outcomes for people experiencing homelessness (PEH) in Australia. Retrospective administrative health data of emergency surgical admissions from a single center over five years, 2015 to 2020, was included. Independent associations between factors and outcomes were analyzed with binary logistic and log-linear regression. Of 11 229 admissions, 2% were experiencing homelessness. People experiencing homelessness were on average younger (49 vs 56 years), more likely to be males than females (77% vs 61%), suffer mental illness (10% vs 2%), and substance use disorders (54% vs 10%). People experiencing homelessness were not more likely to suffer surgical complications. However, male sex, older age, mental illness, and substance use were risk factors for poor surgical outcomes. Homelessness predicted greater odds of discharge against medical advice (4.3 times) and longer length of stay (1.25 times). These results highlighted the need for health interventions simultaneously addressing physical, mental health, and substance use issues in the care of PEH.

Differential attainment in higher surgical training: scoping pan-specialty spectra.

INTRODUCTION: This study aimed to evaluate differential attainment during higher surgical training (HST; all specialties) related to three ethnic cohorts: White UK (WUKG), Black and Minority Ethnic UK Graduates (BMEUKG), and International Medical Graduates (IMG). METHOD: Anonymised records of 266 HSTs (126 WUKG, 65 BMEUKG, 75 IMG; 7 years) in a single UK Statutory Education Body were examined. Primary effect measures were Annual Record of Competency Progression Outcome (ARCPO) and Fellowship of the Royal College of Surgeons (FRCS) pass. RESULTS: ARCPOs related to ethnicity and specialty were similar with the exception of general surgery (GS) trainees, four of whom received ARCPO 4 (GS 4.9% (75% BME; p=0.025) vs all other 0%). ARCPO 3 was commoner in women (22/76, (28.9%) than men 27/190 (14.2%), OR 2.46, p=0.006). FRCS pass rates (WUKG vs BMEUKG vs IMG) were 76.9%, 52.9% and 53.9% respectively (p=0.064) but unrelated to gender (M 70.4% vs F 64.3%). On multivariable analyses: ARCPO 3 was associated with Female gender and Maternity Leave (OR 8.05, p=0.001); FRCS pass with ethnicity (OR 0.21, p=0.028) and Hirsch Indices of ≥5 (OR 11.17, p=0.001). CONCLUSION: Differential attainment was plain with BMEUKG FRCS performance almost a third poorer than WUKG, and women twofold more likely to receive adverse ARCPOs, with return from statutory leave independently associated with training extension. Focused counter measures targeted at non-operative technical skills (including academic reach), Keeping in Touch, Return to Work, and re-induction programmed support are urgently needed for trainees at risk.

Strategic organisational skills predict surgical training success.

INTRODUCTION: Surgical career progression is determined by examination success and Annual Review of Competence Progression (ARCP) outcome, yet data on organisational skills are sparse. This study aimed to determine whether organisational skills related to Core Surgical Training (CST) outcome. Primary outcome measures include operative experience, publications, examination success (Membership of the Royal College of Surgeons or the Diploma in Otolaryngology-Head and Neck Surgery (MRCS/DO-HNS)) and ARCP outcome. METHODS: The study was conducted prospectively at three consecutive CST induction boot camps (2017-2019) providing clinical and simulation training for 125 trainees. Arrival time at course registration was the selected surrogate for organisational skills. Trainees were advised to arrive promptly at 8:45 for registration and that the course would start at 9:00. Trainee arrival times were grouped as follows: early (before 8:45), on time (8:45-8:59am) or late (after 9:00). Arrival times were compared with primary outcome measures. SETTING: Health Education and Improvement Wales' School of Surgery, UK. RESULTS: Median arrival time was 8:53 (range 7:55-10:03), with 29 trainees (23.2%) arriving early, 63 (50.4%) on-time and 33 (26.4%) late. Arrival time was associated with operative experience (early vs late; 206 vs 164 cases, p=0.012), publication (63.2% vs 18.5%, p=0.005), MRCS/DO-HNS success (44.8% vs 15.2%, p=0.029), ARCP outcome (86.2% vs 60.6% Outcome 1, p=0.053), but not National Training Number success (60.0% vs 53.3%, p=0.772). CONCLUSIONS: Better-prepared trainees achieved 25% more operative experience, were four-fold more likely to publish and pass MRCS, which aligned with consistent desirable ARCP outcome. Timely arrival at training events represents a skills-composite of travel planning and is a useful marker of strategic organisational skills.

Trainee burnout: when does the fire start?

PURPOSE OF THE STUDY: Burnout is an increasingly recognised phenomenon in acute healthcare specialities and associated with depersonalisation, ill health and training programme attrition. This study aimed to quantify contributory physiological variables that may indicate stress in newly qualified doctors. STUDY DESIGN: Post Graduate Year 1 doctors (n=13, 7 f, 6 m) were fitted with a VivaLNK wellness device during four prior induction days, followed by their first 14 days work as qualified doctors. Minute-by-minute Heart Rate (HR), Respiratory Rate (RR), and Stress Index (SI) data were correlated with Maslach Burnout Inventories, Short Grit Scales (SGS) and clinical rota duties: Induction vs Normal Working-Day (NWD) versus On-call shift. RESULTS: In a total 125 recorded shift episodes, on comparing Induction versus NWD versus On-call shift work, no variation was observed in HR above baseline (25.47 vs 27.14 vs 24.34, p=0.240), RR above baseline (2.21 vs 1.86 vs 1.54, p=0.126) or SI (32.98 vs 38.02 vs 35.47, p=0.449). However, analysis of participant-specific temporal SIs correlated with shift-related clinical duties; that is, study participants who were most stressed during a NWD, were also more stressed during Induction (R2 0.442, p=0.026), and also during On-call shifts (R2 0.564, p=0.012). Higher SGS scores were inversely related to lower SIs (coefficient -32.52, 95% CI -45.881 to 19.154, p=0.001). CONCLUSION: Stress and burnout stimulus appear to start on day one of induction for susceptible PGY1 doctors, and continues into front-line clinical work irrespective of shift pattern. Short Grit Scale questionnaires appear an effective tool to facilitate targeted stress countermeasures.

Surgical curriculum concordance: requiem for the educational dream.

This study aimed to analyse the degree of relative variation in speciality-specific competencies required for Certification of Completion of Training (CCT) set by the UK Joint Committee for Surgical Training (JCST) 2021 curriculum. Regulatory body guidance related to operative and non-operative surgical skill competencies required for CCT were analysed and compared. Wide inter-speciality variation was demonstrated in the minimum number of logbook cases (median 815; range 54 to 2100), indexed operations (8; 5 to 24) and procedure-based assessments (35; 6 to 110). Academic competencies related to peer-reviewed publications, communications to learned societies and audits were aligned at zero, zero and three across specialities, respectively. Mandatory courses have been standardised with Advanced Trauma Life Support being the sole pre-requisite CCT for all. JCST certification guidelines have broadly standardised competency domains, yet large discrepancies persist regarding operative indicative numbers and assessments. This article serves as a definitive CCT guide regarding prevailing changes.

Statin usage and cardiovascular risk among people living with HIV in the U.S. Military HIV Natural History Study.

OBJECTIVES: Using the American College of Cardiology/American Heart Association 2013 atherosclerotic cardiovascular disease (ASCVD) management guidelines, we conducted a retrospective cross-sectional analysis of people living with HIV in the US Military HIV Natural History Study to determine whether individuals were receiving statins when indicated. METHODS: Prescription data was taken from Military Health System data. Statin eligibility was defined by ASCVD guidelines. We used the 10-year ASCVD pooled cohorts' equation to evaluate risk for each participant. RESULTS: Across all categories, 31.9% (n = 390) of individuals met criteria for statin use, and when adding these subjects to the number of those already receiving statins (n = 96), 62.1% of all eligible subjects (n = 302/486) were actually receiving statin therapy. In multivariable analysis, individuals of African American race [odds ratio (OR) = 0.48, 95% confidence interval (CI): 0.31-0.73] or Hispanic ethnicity (OR = 0.42, 95% CI: 0.19-0.94) were less likely to receive statin prescriptions than white individuals. Individuals with a higher CD4 count (OR = 1.12, 95% CI: 1.05-1.20 per 100 cells/µL]) were significantly more likely to receive a statin prescription. CONCLUSIONS: These data highlight discrepancies between ASCVD guidelines and primary care management of people living with HIV (PLWH) in the military health system, along with important racial differences. Targeted interventions are critical to identify and treat appropriate candidates for statin therapy among PLWH in the military and other settings.

Prognostic significance of drivers at work and learning styles in surgical training.

PURPOSE OF THE STUDY: Drivers at work (DW) and Learning Styles (LS) refer to contentious theories that aim to account for differential career development yet seldom feature in assessment. This study aimed to quantify the influence of core surgical trainees' (CST) DW and LS on career progress. STUDY DESIGN: DW questionnaires and Kolb LS inventories were distributed to 168 CSTs during five consecutive induction boot camps in a single-statutory education body. Primary outcome measures were membership of the Royal College of Surgeons (MRCS) examination and national training number (NTN) success. RESULTS: Of 108 responses received (response rate 64.3%), 64.8% were male and 35.2% female (p=0.003). DW spectrum was: please people (25.0%), be perfect (21.3%), hurry up (18.5%), be strong (13.9%) and try hard (0%, p<0.001). DW was either equivocal (n=14) or not provided (n=9) by 21.3% of CSTs. LS were: converging (34.3%), accommodating (28.7%), diverging (23.1%) and assimilating (13.9%, p=0.021). Men were more likely to be convergers (29/70, 41.4%), and women divergers (15/38, 39.5%, p=0.018) also preferring team-based LS (accommodating/diverging, 26/38 (68.4%) vs 30/70 (42.9%), p=0.010). MRCS success was not associated with DW (p=0.329) or LS (p=0.459). On multivariable analysis, NTN success was associated with LS (accommodators 64.5%, divergers 32.0%, OR 10.90, p=0.014), scholarly activity (OR 1.71, p=0.001), improving surgical training programme (OR 36.22, p=0.019) and universal ARCP 1 outcome (OR 183.77, p<0.001). CONCLUSIONS: LS are associated with important differences in career progress with accommodator twofold more likely than diverger to achieve NTN.

Trainee perspective of the causes of stress and burnout in surgical training: a qualitative study from Wales.

OBJECTIVES: Stress and burn-out among surgical trainees has been reported most prevalent in core surgical trainees (CST) and female trainees in particular. This study aimed to identify factors perceived by CSTs to be associated with stress and burnout in those at risk. DESIGN: An open-ended questionnaire was distributed to 79 CSTs and two researchers categorised responses independently, according to Michie's model of workplace stress. SETTING: A UK regional postgraduate medical region (Wales). PARTICIPANTS: Sixty-three responses were received; 42 males, 21 females. The response rate was 79.7%. RESULTS: Inter-rater reliability was good (k=0.792 (79.2%), p<0.001). The most common theme of Michie's model related to CST stress and burnout was career development, with most statements associated with curriculum, examination and academic demands required to attain a CST certificate of completion of training, and higher surgical national training number appointment. This was closely followed by those intrinsic to the job with recurrent discussion around the difficulties balancing work perceived to be service provision (ward work and on-calls), outpatient clinic and operative experience. Conversely, the most common themes relevant to stress and burnout among female trainees were associated with relationships at work (primarily the male-dominated nature of surgery), extraorganisational factors (family-work life balance) and individual characteristics (personality and physiological differences). CONCLUSION: CSTs' perceptions regarding the causes of National Health Service related stress and burnout are numerous, and these findings provide a basis for the development of targeted stressor counter-measures to improve training and well-being.

Egalitarianism in surgical training: let equity prevail.

This study aimed to quantify core surgical trainee (CST) differential attainment (DA) related to three cohorts; white UK graduate (White UKG) versus black and minority ethnic UKG (BME UKG) versus international medical graduates (IMGs). The primary outcome measures were annual review of competence progression (ARCP) outcome, intercollegiate Membership of the Royal College of Surgeons (iMRCS) examination pass and national training number (NTN) selection. Intercollegiate Surgical Curriculum Programme (ISCP) portfolios of 264 consecutive CSTs (2010-2017, 168 white UKG, 66 BME UKG, 30 IMG) from a single UK regional post graduate medical region (Wales) were examined. Data collected prospectively over an 8-year time period was analysed retrospectively. ARCP outcomes were similar irrespective of ethnicity or nationality (ARCP outcome 1, white UKG 60.7% vs BME UKG 62.1% vs IMG 53.3%, p=0.395). iMRCS pass rates for white UKG vs BME UKG vs IMG were 71.4% vs 71.2% vs 50.0% (p=0.042), respectively. NTN success rates for white UKG vs BME UKG vs IMG were 36.9% vs 36.4% vs 6.7% (p=0.023), respectively. On multivariable analysis, operative experience (OR 1.002, 95% CI 1.001 to 1.004, p=0.004), bootcamp attendance (OR 2.615, 95% CI 1.403 to 4.871, p=0.002), and UKG (OR 7.081, 95% CI 1.556 to 32.230, p=0.011), were associated with NTN appointment. Although outcomes related to BME DA were equitable, important DA variation was apparent among IMGs, with iMRCS pass 21.4% lower and NTN success sixfold less likely than UKG. Targeted counter measures are required to let equity prevail in UK CST programmes.

Navigating the Gluten-Free Boom: The Dark Side of Gluten Free Diet.

In gluten dependent conditions the gluten free diet is the cornerstone of therapy, decreasing disease activity, improving health and quality of life and treating or preventing the associated complications. Gluten withdrawal implies strict and lifelong elimination not only of wheat, barley, rye, and wheat-contaminated oats, but also of numerous non-nutritional products where components of wheat are often added. Due to multiple reasons the diet is difficult to follow and the long-term adherence is decreased with time. The present review summarizes the dark side of gluten restriction where nutritional deficiencies, toxicity, morbidity, mortality, and mental health problems are reported. The aim being to increase awareness, avoid, detect and treat the side effects and to promote a healthier nutrition, for the patient's benefits.

The US Military HIV Natural History Study: Informing Military HIV Care and Policy for Over 30 Years.

INTRODUCTION: In October 1985, 4 years after the initial descriptions of the acquired immunodeficiency syndrome (AIDS), the U.S. Department of Defense (DoD) began routine screening for human immunodeficiency virus (HIV) infection to prevent infected recruits from exposure to live virus vaccines, implemented routine active-duty force screening to ensure timely care and help protect the walking blood bank, and initiated the U.S. Military HIV Natural History Study (NHS) to develop epidemiologic, clinical, and basic science evidence to inform military HIV policy and establish a repository of data and specimens for future research. Here, we have reviewed accomplishments of the NHS over the past 30 years and sought to describe relevant trends among NHS subjects over this time, with emphasis on combination antiretroviral therapy (cART) use and non-AIDS comorbidities. METHODS: Subjects who were prospectively enrolled in the NHS from 1986 through 2015 were included in this analysis. Time periods were classified by decade of study conduct, 1986-1995, 1996-2005, and 2006-2015, which also correlate approximately with pre-, early-, and late-combination ART (cART) eras. Analyses included descriptive statistics and comparisons among decades. We also evaluated mean community log10 HIV viral load (CVL) and CD4 counts for each year. RESULTS: A total of 5,758 subjects were enrolled between 1986 and 2015, of whom 92% were male with a median age of 28 years, and 45% were African-American, 42% Caucasian, and 13% Hispanic/other. The proportion of African-Americans remained stable over the decades (45%, 47%, and 42%, respectively), while the proportion of Hispanic/other increased (10%, 13%, and 24%, respectively). The CD4 count at HIV diagnosis has remained high (median 496 cells/uL), while the occurrence of AIDS-defining conditions (excluding low CD4 count) has decreased by decade (36.7%, 5.4%, and 2.9%, respectively). Following the introduction of effective cART in 1996, CVL declined through 2000 as use increased and then plateaued until guidelines changed. After 2004, cART use again increased and CVL declined further until 2012-15 when the vast majority of subjects achieved viral suppression. Non-AIDS comorbidities have remained common, with approximately half of subjects experiencing one or more new diagnoses overall and nearly half of subjects diagnosed between 2006 and 2015, in spite of their relatively young age, shorter median follow-up, and wide use of cART. CONCLUSIONS: The US Military HIV NHS has been critical to understanding the impact of HIV infection among active-duty service members and military beneficiaries, as well as producing insights that are broadly relevant. In addition, the rich repository of NHS data and specimens serves as a resource to investigators in the DoD, NIH, and academic community, markedly increasing scientific yield and identifying novel associations. Looking forward, the NHS remains relevant to understanding host factor correlates of virologic and immunologic control, biologic pathways of HIV pathogenesis, causes and consequences of residual inflammation in spite of effective cART, identifying predictors of and potential approaches to mitigation of excess non-AIDS comorbidities, and helping to understand the latent reservoir.

A Computational Model for Assessing the Population Health Impact of Introducing a Modified Risk Claim on an Existing Smokeless Tobacco Product.

Computational models are valuable tools for predicting the population effects prior to Food and Drug Administration (FDA) authorization of a modified risk claim on a tobacco product. We have developed and validated a population model using best modeling practices. Our model consists of a Markov compartmental model based on cohorts starting at a defined age and followed up to a specific age accounting for 29 tobacco-use states based on a cohort members transition pathway. The Markov model is coupled with statistical mortality models and excess relative risk ratio estimates to determine survival probabilities from use of smokeless tobacco. Our model estimates the difference in premature deaths prevented by comparing Base Case ("world-as-is") and Modified Case (the most likely outcome given that a modified risk claim is authorized) scenarios. Nationally representative transition probabilities were used for the Base Case. Probabilities of key transitions for the Modified Case were estimated based on a behavioral intentions study in users and nonusers. Our model predicts an estimated 93,000 premature deaths would be avoided over a 60-year period upon authorization of a modified risk claim. Our sensitivity analyses using various reasonable ranges of input parameters do not indicate any scenario under which the net benefit could be offset entirely.

Assessment of Perfusion and Oxygenation of the Human Renal Cortex and Medulla by Quantitative MRI during Handgrip Exercise.

BACKGROUND: Renal flow abnormalities are believed to play a central role in the pathogenesis of nephropathy and in primary and secondary hypertension, but are difficult to measure in humans. Handgrip exercise is known to reduce renal arterial flow (RAF) by means of increased renal sympathetic nerve activity. METHODS: To monitor medullary and cortical oxygenation under handgrip exercise-reduced perfusion, we used contrast- and radiation-free magnetic resonance imaging (MRI) to measure regional changes in renal perfusion and blood oxygenation in ten healthy normotensive individuals during handgrip exercise. We used phase-contrast MRI to measure RAF, arterial spin labeling to measure perfusion, and both changes in transverse relaxation time (T2*) and dynamic blood oxygenation level-dependent imaging to measure blood oxygenation. RESULTS: Handgrip exercise induced a significant decrease in RAF. In the renal medulla, this was accompanied by an increase of oxygenation (reflected by an increase in T2*) despite a significant drop in medullary perfusion; the renal cortex showed a significant decrease in both perfusion and oxygenation. We also found a significant correlation (R2=0.8) between resting systolic BP and the decrease in RAF during handgrip exercise. CONCLUSIONS: Renal MRI measurements in response to handgrip exercise were consistent with a sympathetically mediated decrease in RAF. In the renal medulla, oxygenation increased despite a reduction in perfusion, which we interpreted as the result of decreased GFR and a subsequently reduced reabsorptive workload. Our results further indicate that the renal flow response's sensitivity to sympathetic activation is correlated with resting BP, even within a normotensive range.

Brief Report: Racial Comparison of D-Dimer Levels in US Male Military Personnel Before and After HIV Infection and Viral Suppression.

BACKGROUND: D-dimer blood levels in persons with HIV infection are associated with risk of serious non-AIDS conditions and death. Black race has been correlated with higher D-dimer levels in several studies. We examined the effects of race and HIV on D-dimer over time and the impact of viral load suppression by longitudinally comparing changes in levels among healthy young adult male African Americans and whites before HIV seroconversion and before and after initiation of antiretroviral therapy (ART). METHODS: We analyzed D-dimer levels and clinical and laboratory data of 192 participants enrolled in the US Military HIV Natural History Study, a 30-year cohort of military personnel infected with HIV. D-dimer levels were measured on stored sera from each participant at 3 time points: (1) before HIV seroconversion (Pre-SC), (2) ≥6 months after HIV seroconversion but before ART initiation (Post-SC), and (3) ≥6 months after ART with documented viral suppression (Post-ART). Levels were compared at each time point using nonparametric and logistic regression analysis. RESULTS: Compared with whites (n = 106), African Americans (n = 86) had higher D-dimer levels post-SC (P = 0.007), but in the same individuals, pre-SC baseline and post-ART levels were similar (P = 0.40 and P = 0.99, respectively). There were no racial differences in CD4 cell counts, HIV RNA viral load, time from estimated seroconversion to ART initiation, and duration on ART. CONCLUSIONS: Observed longitudinally, racial differences in D-dimer levels were seen only during HIV viremia. Higher levels of D-dimer commonly observed in African Americans are likely due to factors in addition to race.

Mindfulness and Climate Change Action: A Feasibility Study.

Pro-environmental behaviors and the cultural shifts that can accompany these may offer solutions to the consequences of a changing climate. Mindfulness has been proposed as a strategy to initiate these types of behaviors. In 2017, we pilot-tested Mindful Climate Action (MCA), an eight-week adult education program that delivers energy use, climate change, and sustainability content in combination with training in mindfulness meditation, to 16 individuals living in Madison, WI. At baseline and at different times across the study period, we collected data regarding participants, household energy use, transportation, diet, and health and happiness. This pilot study aimed to evaluate the feasibility of the various MCA study practices including measurement tools, outcome assessment, curriculum and related educational materials, and especially the mindfulness-based climate action trainings. MCA was well-received by participants as evidenced by high adherence rate, high measures of participant satisfaction, and high participant response rate for surveys. In addition, we successfully demonstrated feasibility of the MCA program, and have estimated participant's individual carbon footprints related to diet, transportation, and household energy.

Factors associated with 10 years of continuous viral load suppression on HAART.

BACKGROUND: The principal goal of HAART is sustained viral load (VL) suppression resulting in immune reconstitution and improved HIV outcomes. We studied the factors associated with 10 years of continuous VL suppression on HAART in the US Military HIV Natural History Study. METHODS: Participants with continuous VL suppression (CS, n = 149) were compared to those who did not have continuous viral load suppression (NCS, n = 127) for ≥10 years on HAART. Factors associated with >10 years of VL suppression were evaluated by multivariate logistic regression. Additionally, association between CS and CD4 reconstitution was analyzed with a mixed effects model. RESULTS: Compared to NCS participants, a lower proportion of CS participants started HAART in the early HAART era (66 vs 90 %, for years 1996-1999; p < 0.001) and had less antiretroviral use prior to HAART (37 vs 83 %; p < 0.001). At initial HAART, the median CD4 cell count was higher and VL was lower for CS compared to NCS participants (375 cells/uL [256, 499] vs 261 cells/uL [146, 400]; p < 0.001 and 4.4 log10 copies/mL [3.5, 4.9] vs 4.5 log10 copies/mL [3.8, 5.0]; p = 0.048, respectively). New AIDS events were lower during HAART (5 vs 13 %; p = 0.032) and post-HAART CD4 trajectories were greater for the CS compared to NCS group. Factors negatively associated with ≥10 years of VL suppression included log10 VL at first HAART (OR 0.61, 95 % CI 0.4, 0.92; p = 0.020) and antiretroviral use prior to HAART (OR 0.16, 95 % CI 0.06, 0.38; p < .001). CONCLUSIONS: Sustained VL suppression is a key to long-term health in HIV-infected patients, as demonstrated by the lower proportion of AIDS events observed 10 years after HAART initiation. The current use of more potent and well-tolerated regimens may mitigate the negative factors of pre-HAART VL and prior ARV use encountered by treatment initiated in the early HAART era.

D-Dimer Levels before HIV Seroconversion Remain Elevated Even after Viral Suppression and Are Associated with an Increased Risk of Non-AIDS Events.

The mechanism underlying the excess risk of non-AIDS diseases among HIV infected people is unclear. HIV associated inflammation/hypercoagulability likely plays a role. While antiretroviral therapy (ART) may return this process to pre-HIV levels, this has not been directly demonstrated. We analyzed data/specimens on 249 HIV+ participants from the US Military HIV Natural History Study, a prospective, multicenter observational cohort of >5600 active duty military personnel and beneficiaries living with HIV. We used stored blood specimens to measure D-dimer and Interleukin-6 (IL-6) at three time points: pre-HIV seroconversion, ≥6 months post-HIV seroconversion but prior to ART initiation, and ≥6 months post-ART with documented HIV viral suppression on two successive evaluations. We evaluated the changes in biomarker levels between time points, and the association between these biomarker changes and future non-AIDS events. During a median follow-up of 3.7 years, there were 28 incident non-AIDS diseases. At ART initiation, the median CD4 count was 361cells/mm3; median duration of documented HIV infection 392 days; median time on ART was 354 days. Adjusted mean percent increase in D-dimer levels from pre-seroconversion to post-ART was 75.1% (95% confidence interval 24.6-148.0, p = 0.002). This increase in D-dimer was associated with a significant 22% increase risk of future non-AIDS events (p = 0.03). Changes in IL-6 levels across time points were small and not associated with future non-AIDS events. In conclusion, ART initiation and HIV viral suppression does not eliminate HIV associated elevation in D-dimer levels. This residual pathology is associated with an increased risk of future non-AIDS diseases.

Factors associated with HIV viral load "blips" and the relationship between self-reported adherence and efavirenz blood levels on blip occurrence: a case-control study.

BACKGROUND: The uncertain etiology of HIV viral load (VL) blips may lead to increased use of clinical resources. We evaluated the association of self-reported adherence (SRA) and antiretroviral (ART) drug levels on blip occurrence in US Military HIV Natural History Study (NHS) participants who initiated the single-tablet regimen efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF). METHODS: ART-naïve NHS participants started on EFV/FTC/TDF between 2006 and 2013 who achieved VL suppression (<50 copies/mL) within 12 months and had available SRA and stored plasma samples were included. Participants with viral blips were compared with those who maintained VL suppression without blips. Untimed EFV plasma levels were evaluated on consecutive blip and non-blip dates by high performance liquid chromatography, with a level ≥1 mcg/mL considered therapeutic. SRA was categorized as ≥85 or <85 %. Descriptive statistics were performed for baseline characteristics and univariate and multivariate Cox proportional hazard models were used to assess the relationship between covariates and blip occurrence. RESULTS: A total of 772 individuals met inclusion criteria, including 99 (13 %) blip and 673 (87 %) control participants. African-American was the predominant ethnicity and the mean age was 29 years for both groups. SRA ≥ 85 % was associated with therapeutic EFV levels at both blip and non-blip time points (P = 0.0026); however no association was observed between blips and SRA or EFV levels among cases. On univariate analysis of cases versus controls, blips were associated with higher mean pre-treatment VL (HR 1.45, 95 % CI 1.11-1.89) and pre-treatment CD4 count <350 cells/µL (68.1 vs 49.7 %). Multivariate analysis also showed that blips were associated with a higher mean VL (HR 1.42, 95 % CI 1.08-1.88; P = 0.0123) and lower CD4 count at ART initiation, with CD4 ≥500 cells/µL having a protective effect (HR 0.45, 95 % CI 0.22-0.95; P = 0.0365). No association was observed for demographic characteristics or SRA. CONCLUSION: Blips are commonly encountered in the clinical management of HIV-infected patients. Although blip occurrence was not associated with SRA or EFV blood levels in our study, blips were associated with HIV-related factors of pre-ART high VL and low CD4 count. Additional studies are needed to determine the etiology of blips in HIV-infected patients.