Evaluating the effect of atorvastatin exposure and vitamin D levels on lipid outcomes in people with HIV-1 with suppressed HIV-1 RNA and LDL cholesterol <130 mg/dL.

INTRODUCTION: Cardiovascular disease (CVD) has become a leading cause of morbidity and mortality among people with HIV. Atorvastatin is known to reduce cardiovascular risk. We (1) compared atorvastatin concentrations between different boosted protease inhibitors (PIs) and with lipid outcomes and (2) compared pre-atorvastatin 25-OH vitamin D levels with atorvastatin concentrations and with lipid outcomes, in people with HIV with suppressed HIV-1 RNA and low-density lipoprotein cholesterol (LDL-C) <130 mg/dL. METHODS: A5275 was a randomized, double-blind, placebo-controlled crossover study of atorvastatin in virally suppressed people with HIV with fasting LDL-C <130 mg/dL. We analyzed results over the 20 weeks of active atorvastatin treatment. Atorvastatin was initiated at 10 mg daily and increased to 20 mg daily after 4 weeks if there were no findings of toxicity. Atorvastatin trough concentrations were measured at week 20. Participants took combination antiretroviral therapy (ART) that included a boosted PI throughout. RESULTS: Overall (n = 67), 70% of participants were male, and the median age was 51 years. There was no apparent association between atorvastatin trough concentrations and pre-atorvastatin vitamin D levels (r = 0.01, p = 0.9) or by boosted PI (p = 0.20). Median pre- to post-atorvastatin change was -39.0 mg/dL in fasting total cholesterol, -40.4 ng/mL in lipoprotein-associated phospholipase A2 (LP-PLA2), and -13.8 U/L in oxidized LDL, with all changes negatively correlated with atorvastatin trough concentrations (r = -0.19, -0.09, -0.21; p ≥ 0.096). CONCLUSIONS: No apparent associations between pre-atorvastatin vitamin D levels and outcomes were observed (all p > 0.70). In virologically suppressed people with HIV, higher atorvastatin concentrations were marginally associated with greater decreases in lipid outcomes.

Effect of high intensity interval training and moderate intensity continuous training on lymphoid, myeloid and inflammatory cells in kidney transplant recipients.

Kidney transplantations are seen to be a double-edge sword. Transplantations help to partially restore renal function, however there are a number of health-related co-morbidities associated with transplantation. Cardiovascular disease (CVD), malignancy and infections all limit patient and graft survival. Immunosuppressive medications alter innate and adaptive immunity and can result in immune dysfunction. Over suppression of the immune system can result in infections whereas under suppression can result in graft rejection. Exercise is a known therapeutic intervention with many physiological benefits. Its effects on immune function are not well characterised and may include both positive and negative influences depending on the type, intensity, and duration of the exercise bout. High intensity interval training (HIIT) has become more popular due to it resulting in improvements to tradional and inflammatory markers of cardiovascular (CV) risk in clinical and non-clinical populations. Though these improvements are similar to those seen with moderate intensity exercise, HIIT requires a shorter overall time commitment, whilst improvements can also be seen even with a reduced exercise volume. The purpose of this study was to explore the physiolocial and immunological impact of 8-weeks of HIIT and moderate intensity continuous training (MICT) in kidney transplan recipients (KTRs). In addition, the natural variations of immune and inflammatory cells in KTRs and non-CKD controls over a longitudinal period are explored. Newly developed multi-colour flow cytometry methods were devised to identify and characterise immune cell populations. Twenty-six KTRs were randomised into one of two HIIT protocols or MICT: HIIT A (n=8; 4-, 2-, and 1-min intervals; 80-90% VO2peak), HIIT B (n=8, 4x4 min intervals; 80-90% VO2peak), or MICT (n=8, ~40 min; 50-60% VO2peak) for 24 supervised sessions on a stationary bike (approx. 3x/week over 8 ± 2 weeks). Blood samples taken pre-training, mid training, post-training and 3 months later. Novel multi-colour flow cytometric panels were developed to characterise lymphoid and myeloid cell population from peripheral blood mononuclear cells. No changes were observed for circulating immune and inflammatory cells over the 8-week interventions. The feasibility study does not suggest that exercise programmes using HIIT and MICT protocols elicit adverse negative effects on immunity in KTRs. Therefore, such protocols may be immunologically safe for these patients. The inability of the participants to achieve the target exercise intensities may be due to physiological abnormalities in this population which warrants further investigation.

A Comparison of Dietary Intake Between Individuals Undergoing Maintenance Hemodialysis in the United Kingdom and China.

OBJECTIVE: Protein-energy wasting is highly prevalent in people with end-stage kidney disease receiving regular hemodialysis. Currently, it is unclear what the optimal nutritional recommendations are, which is further complicated by differences in dietary patterns between countries. The aim of the study was to understand and compare dietary intake between individuals receiving hemodialysis in Leicester, UK and Nantong, China. METHODS: The study assessed 40 UK and 44 Chinese participants' dietary intake over a period of 14 days using 24-hour diet recall interviews. Nutritional blood parameters were obtained from medical records. Food consumed by participants in the UK and China was analyzed using the Nutritics and Nutrition calculator to quantify nutritional intake. RESULTS: Energy and protein intake were comparable between UK and Chinese participants, but with both below the recommended daily intake. Potassium intake was higher in UK participants compared to Chinese participants (2,115 [888] versus 1,159 [861] mg/d; P < .001), as was calcium (618 [257] versus 360 [312] mg/d; P < .001) and phosphate intake (927 [485] versus 697 [434] mg/d; P = .007). Vitamin C intake was lower in UK participants compared to their Chinese counterparts (39 [51] versus 64 [42] mg/d; P = .024). Data are reported here as median (interquartile range). CONCLUSION: Both UK and Chinese hemodialysis participants have insufficient protein and energy in their diet. New strategies are required to increase protein and energy intakes. All participants had inadequate daily intake of vitamins C and D; there may well be a role in the oral supplementation of these vitamins, and further studies are urgently needed.

A Systematic Review of Handgrip Strength Measurement in Clinical and Epidemiological Studies of Kidney Disease: Toward a Standardized Approach.

In chronic kidney disease (CKD), handgrip strength (HGS) is recommended as a surrogate measure of protein-energy status and functional status. However, it is not routinely used because of inconsistencies such as the optimal timing of the HGS measurement and unclear guidance regarding technique. We aimed to determine the extent of variation in the protocols and methods of HGS assessment. We aimed to identify clinical and epidemiological studies conducted on CKD that reported on the use of HGS as an outcome. A systematic literature search identified n = 129 studies with a total participant population of n = 35,192. We identified large variations in all aspects of the methodology including body and arm position, repetitions, rest time, timing, familiarization, and how scores were calculated. The heterogeneous methodologies used reinforce the need to standardize HGS measurement. After reviewing previously employed methodology in the literature, we propose a comprehensive HGS assessment protocol for use in CKD.

Human Immunodeficiency Virus-Experienced Clinician Workforce Capacity: Urban-Rural Disparities in the Southern United States.

BACKGROUND: Human immunodeficiency virus (HIV)-experienced clinicians are critical for positive outcomes along the HIV care continuum. However, access to HIV-experienced clinicians may be limited, particularly in nonmetropolitan areas, where HIV is increasing. We examined HIV clinician workforce capacity, focusing on HIV experience and urban-rural differences, in the Southern United States. METHODS: We used Medicaid claims and clinician characteristics (Medicaid Analytic eXtract [MAX] and MAX Provider Characteristics, 2009-2011), county-level rurality (National Center for Health Statistics, 2013), and diagnosed HIV cases (AIDSVu, 2014) to assess HIV clinician capacity in 14 states. We assumed that clinicians accepting Medicaid approximated the region's HIV workforce, since three-quarters of clinicians accept Medicaid insurance. HIV-experienced clinicians were defined as those providing care to ≥ 10 Medicaid enrollees over 3 years. We assessed HIV workforce capacity with county-level clinician-to-population ratios, using Wilcoxon-Mann-Whitney tests to compare urban-rural differences. RESULTS: We identified 5012 clinicians providing routine HIV management, of whom 28% were HIV-experienced. HIV-experienced clinicians were more likely to specialize in infectious diseases (48% vs 6%, P < .001) and practice in urban areas (96% vs 83%, P < .001) compared to non-HIV-experienced clinicians. The median clinician-to-population ratio for all HIV clinicians was 13.3 (interquartile range, 38.0), with no significant urban-rural differences. When considering HIV experience, 81% of counties had no HIV-experienced clinicians, and rural counties generally had fewer HIV-experienced clinicians per 1000 diagnosed HIV cases (P < .001). CONCLUSIONS: Significant urban-rural disparities exist in HIV-experienced workforce capacity for communities in the Southern United States. Policies to improve equity in access to HIV-experienced clinical care for both urban and rural communities are urgently needed.

Prevalence and correlates of physical activity across kidney disease stages: an observational multicentre study.

BACKGROUND: People with chronic kidney disease (CKD) report high levels of physical inactivity, a major modifiable risk factor for morbidity and mortality. Understanding the biological, psychosocial and demographic causes of physical activity behaviour is essential for the development and improvement of potential health interventions and promotional initiatives. This study investigated the prevalence of physical inactivity and determined individual correlates of this behaviour in a large sample of patients across the spectrum of kidney disease. METHODS: A total of 5656 people across all stages of CKD (1-2, 3, 4-5, haemodialysis, peritoneal dialysis and renal transplant recipients) were recruited from 17 sites in England from July 2012 to October 2018. Physical activity was evaluated using the General Practice Physical Activity Questionnaire. Self-reported cardiorespiratory fitness, self-efficacy and stage of change were also assessed. Binominal generalized linear mutually adjusted models were conducted to explore the associations between physical activity and correlate variables. This cross-sectional observational multi-centre study was registered retrospectively as ISRCTN87066351 (October 2015). RESULTS: The prevalence of physical activity (6-34%) was low and worsened with disease progression. Being older, female and having a greater number of comorbidities were associated with greater odds of being physically inactive. Higher haemoglobin, cardiorespiratory fitness and self-efficacy levels were associated with increased odds of being active. Neither ethnicity nor smoking history had any effect on physical activity. CONCLUSIONS: Levels of physical inactivity are high across all stages of CKD. The identification of stage-specific correlates of physical activity may help to prioritize factors in target groups of kidney patients and improve the development and improvement of public health interventions.

Differences in physical symptoms between those with and without kidney disease: a comparative study across disease stages in a UK population.

BACKGROUND: Those living with kidney disease (KD) report extensive symptom burden. However, research into how symptoms change across stages is limited. The aims of this study were to 1) describe symptom burden across disease trajectory, and 2) to explore whether symptom burden is unique to KD when compared to a non-KD population. METHODS: Participants aged > 18 years with a known diagnosis of KD (including haemodialysis (HD) and peritoneal dialysis (PD)) and with a kidney transplant) completed the Leicester Kidney Symptom Questionnaire (KSQ). A non-KD group was recruited as a comparative group. Multinominal logistic regression modelling was used to test the difference in likelihood of those with KD reporting each symptom. RESULTS: In total, 2279 participants were included in the final analysis (age 56.0 (17.8) years, 48% male). The main findings can be summarised as: 1) the number of symptoms increases as KD severity progresses; 2) those with early stage KD have a comparable number of symptoms to those without KD; 3) apart from those receiving PD, the most frequently reported symptom across every other group, including the non-KD group, was 'feeling tired'; and 4) being female independently increased the likelihood of reporting more symptoms. CONCLUSIONS: Our findings have important implications for patients with KD. We have shown that high symptom burden is prevalent across the spectrum of disease, and present novel data on symptoms experienced in those without KD. Symptoms requiring the most immediate attention given their high prevalence may include pain and fatigue. TRIAL REGISTRATION: The study was registered prospectively as ISRCTN11596292 .

Utility of Ultrasound as a Valid and Accurate Diagnostic Tool for Sarcopenia: Sex-Specific Cutoff Values in Chronic Kidney Disease.

OBJECTIVES: Patients with chronic kidney disease (CKD) have aberrant changes in body composition, including low skeletal muscle mass, a feature of "sarcopenia." The measurement of the (quadriceps) rectus femoris (RF) cross-sectional area (CSA) is widely used as a marker of muscle size. Cutoff values are needed to help discriminate the condition of an individual's muscle (eg, presence of sarcopenia) quickly and accurately. This could help distinguish those at greater risk and aid in targeted treatment programs. METHODS: Transverse images of the RF were obtained by B-mode 2-dimensional ultrasound imaging. Sarcopenic levels of muscle mass were defined by established criteria (1, appendicular skeletal muscle mass [ASM]; 2, ASM/height2 ; and 3, ASM/body mass index) based on the ASM and total muscle mass measured by a bioelectrical impedance analysis. The discriminative power of RF-CSA was assessed by receiver operating characteristic curves, and optimal cutoffs were determined by the maximum Youden index (J). RESULTS: One hundred thirteen patients with CKD (mean age [SD], 62.0 [14.1] years; 48% male; estimated glomerular filtration rate, 38.0 [21.5] mL/min/1.73m2 ) were included. The RF-CSA was a moderate predictor of ASM (R2 = 0.426; P < .001) and total muscle mass (R2 = 0.438; P < .001). With a maximum J of 0.47, in male patients, an RF-CSA cutoff of less than 8.9 cm2 was deemed an appropriate cutoff for detecting sarcopenic muscle mass. In female patients, an RF-CSA cutoff of less than 5.7 cm2 was calculated on the basis of ASM/height2 (J = 0.71). CONCLUSIONS: Ultrasound may provide a low-cost and simple means to diagnose sarcopenia in patients with CKD. This would allow for early management and timely intervention to help mitigate the effects in this group.

Influence of acute moderate- to high-intensity aerobic exercise on markers of immune function and microparticles in renal transplant recipients.

Renal transplant recipients (RTRs) and patients with nondialysis chronic kidney disease display elevated circulating microparticle (MP) counts, while RTRs display immunosuppression-induced infection susceptibility. The impact of aerobic exercise on circulating immune cells and MPs is unknown in RTRs. Fifteen RTRs [age: 52.8 ± 14.5 yr, estimated glomerular filtration rate (eGFR): 51.7 ± 19.8 mL·min-1·1.73 m-2 (mean ± SD)] and 16 patients with nondialysis chronic kidney disease (age: 54.8 ± 16.3 yr, eGFR: 61.9 ± 21.0 mL·min-1·1.73 m-2, acting as a uremic control group), and 16 healthy control participants (age: 52.2 ± 16.2 yr, eGFR: 85.6 ± 6.1 mL·min-1·1.73 m-2) completed 20 min of walking at 60-70% peak O2 consumption. Venous blood samples were taken preexercise, postexercise, and 1 h postexercise. Leukocytes and MPs were assessed using flow cytometry. Exercise increased classical (P = 0.001) and nonclassical (P = 0.002) monocyte subset proportions but decreased the intermediate subset (P < 0.001) in all groups. Exercise also decreased the percentage of platelet-derived MPs that expressed tissue factor in all groups (P = 0.01), although no other exercise-dependent effects were observed. The exercise-induced reduction in intermediate monocyte percentage suggests an anti-inflammatory effect, although this requires further investigation. The reduction in the percentage of tissue factor-positive platelet-derived MPs suggests reduced prothrombotic potential, although further functional assays are required. Exercise did not cause aberrant immune cell activation, suggesting its safety from an immunological standpoint (ISRCTN38935454).

Identification of the most clinically useful skeletal muscle mass indices pertinent to sarcopenia and physical performance in chronic kidney disease.

AIM: Patients with chronic kidney disease (CKD) are characterised by low skeletal muscle mass that negatively impacts physical performance. Operational definitions of 'low muscle mass' are inconsistent, and it is unknown how different skeletal muscle mass indices affect the relationship between muscle mass and physical function. METHODS: Appendicular skeletal muscle mass (ASM) was measured by dual-energy X-ray absorptiometry in 72 CKD patients. Along with crude ASM, alternative muscle indices were calculated adjusting for height, height-squared, body mass, and BMI. Physical performance was assessed by handgrip strength, sit-to-stand tests, gait speed, the incremental shuttle walk test and 'Short Physical Performance Battery'. RESULTS: Prevalence of 'low muscle mass' ranged from 26% to 35% of patients depending on the criteria used. The relationship between muscle mass indices and physical function differed for each criteria. Using average coefficients, the association with overall physical function and muscle indices were as follows: crude ASM (r = .258), ASM/height (r = .249), ASM/height-squared (r = .332), ASM/body mass (r = .249) and ASM/BMI (r = .206). Muscle adjusted for markers of adiposity (ASM/body fat %, r = .266; ASM/fat mass, r = .338) provided the best overall associations with physical function. CONCLUSION: The use of alternative muscle mass indices provide different estimates of 'low muscle mass' prevalence, and the strongest (and most useful definition in regard to functional status) involves adjustment for either total or relative body fat. ASM adjusted for adiposity may be physiologically and clinically more relevant in patients with renal disease.

Quality over quantity? Association of skeletal muscle myosteatosis and myofibrosis on physical function in chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is characterized by adverse changes in body composition, which are associated with poor clinical outcome and physical functioning. Whilst size is the key for muscle functioning, changes in muscle quality specifically increase in intramuscular fat infiltration (myosteatosis) and fibrosis (myofibrosis) may be important. We investigated the role of muscle quality and size on physical performance in non-dialysis CKD patients. METHODS: Ultrasound (US) images of the rectus femoris (RF) were obtained. Muscle quality was assessed using echo intensity (EI), and qualitatively using Heckmatt's visual rating scale. Muscle size was obtained from RF cross-sectional area (RF-CSA). Physical function was measured by the sit-to-stand-60s (STS-60) test, incremental (ISWT) and endurance shuttle walk tests, lower limb and handgrip strength, exercise capacity (VO2peak) and gait speed. RESULTS: A total of 61 patients (58.5 ± 14.9 years, 46% female, estimated glomerular filtration rate 31.1 ± 20.2 mL/min/1.73 m2) were recruited. Lower EI (i.e. higher muscle quality) was significantly associated with better physical performance [STS-60 (r = 0.363) and ISWT (r = 0.320)], and greater VO2peak (r = 0.439). The qualitative rating was closely associated with EI values, and significant differences in function were seen between the ratings. RF-CSA was a better predictor of performance than muscle quality. CONCLUSIONS: In CKD, increased US-derived EI was negatively correlated with physical performance; however, muscle size remains the largest predictor of physical function. Therefore, in addition to the loss of muscle size, muscle quality should be considered an important factor that may contribute to deficits in mobility and function in CKD. Interventions such as exercise could improve both of these factors.

Characterising skeletal muscle haemoglobin saturation during exercise using near-infrared spectroscopy in chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) patients have reduced exercise capacity. Possible contributing factors may include impaired muscle O2 utilisation through reduced mitochondria number and/or function slowing the restoration of muscle ATP concentrations via oxidative phosphorylation. Using near-infrared spectroscopy (NIRS), we explored changes in skeletal muscle haemoglobin/myoglobin O2 saturation (SMO2%) during exercise. METHODS: 24 CKD patients [58.3 (± 16.5) years, eGFR 56.4 (± 22.3) ml/min/1.73 m2] completed the incremental shuttle walk test (ISWT) as a marker of exercise capacity. Using NIRS, SMO2% was measured continuously before, during, and after (recovery) exercise. Exploratory differences were investigated between exercise capacity tertiles in CKD, and compared with six healthy controls. RESULTS: We identified two discrete phases; a decline in SMO2% during incremental exercise, followed by rapid increase upon cessation (recovery). Compared to patients with low exercise capacity [distance walked during ISWT, 269.0 (± 35.9) m], patients with a higher exercise capacity [727.1 (± 38.1) m] took 45% longer to reach their minimum SMO2% (P = .038) and recovered (half-time recovery) 79% faster (P = .046). Compared to controls, CKD patients took significantly 56% longer to recover (i.e., restore SMO2% to baseline, full recovery) (P = .014). CONCLUSIONS: Using NIRS, we have determined for the first time in CKD, that favourable SMO2% kinetics (slower deoxygenation rate, quicker recovery) are associated with greater exercise capacity. These dysfunctional kinetics may indicate reduced mitochondria capacity to perform oxidative phosphorylation-a process essential for carrying out even simple activities of daily living. Accordingly, NIRS may provide a simple, low cost, and non-invasive means to evaluate muscle O2 kinetics in CKD.

Anthropometry-based Equations to Estimate Body Composition: A Suitable Alternative in Renal Transplant Recipients and Patients With Nondialysis Dependent Kidney Disease?

OBJECTIVE: Chronic kidney disease (CKD) patients and renal transplant recipients (RTRs) are characterized by aberrant body composition such as muscle wasting and obesity. It is still unknown which is the most accurate method to estimate body composition in CKD. We investigated the validity of the Hume equation and bioelectrical impedance analysis (BIA) as an estimate of body composition against dual-energy X-ray absorptiometry (DXA) in a cohort of nondialysis dependent (NDD)-CKD and RTRs. DESIGN AND METHODS: This was a cross-sectional study with agreement analysis of different assessments of body composition conducted in 61 patients (35 RTRs and 26 NDD-CKD) in a secondary care hospital setting in the UK. Body composition (lean mass [LM], fat mass [FM], and body fat% [BF%]) was assessed using multifrequency BIA and DXA, and estimated using the Hume formula. Method agreement was assessed by intraclass correlation coefficient (ICC), regression, and plotted by Bland and Altman analysis. RESULTS: Both BIA and the Hume formula were able to accurately estimate body composition against DXA. In both groups, the BIA overestimated LM (1.7-2.1 kg, ICC .980-.984) and underestimated FM (1.3-2.1 kg, ICC .967-.972) and BF% (3.1-3.8%, ICC .927-.954). The Hume formula also overestimated LM (3.5-3.6 kg, ICC .950-.960) and underestimated BF% (1.9-2.1%, ICC .808-.859). Hume-derived FM was almost identical to DXA in both groups (-0.3 to 0.1 kg, ICC .947-.960). CONCLUSION: Our results demonstrate, in RTR and NDD-CKD patients, that the Hume formula, whose estimation of body composition is based only upon height, body mass, age, and sex, may reliably predict the same parameters obtained by DXA. In addition, BIA also provided similar estimates versus DXA. Thus, the Hume formula and BIA could provide simple and inexpensive means to estimate body composition in renal disease.

Do stiffness and asymmetries predict change of direction performance?

Change of direction speed (CODS) underpins performance in a wide range of sports but little is known about how stiffness and asymmetries affect CODS. Eighteen healthy males performed unilateral drop jumps to determine vertical, ankle, knee and hip stiffness, and a CODS test to evaluate left and right leg cutting performance during which ground reaction force data were sampled. A step-wise regression analysis was performed to ascertain the determinants of CODS time. A two-variable regression model explained 63% (R2 = 0.63; P = 0.001) of CODS performance. The model included the mean vertical stiffness and jump height asymmetry determined during the drop jump. Faster athletes (n = 9) exhibited greater vertical stiffness (F = 12.40; P = 0.001) and less asymmetry in drop jump height (F = 6.02; P = 0.026) than slower athletes (n  = 9); effect sizes were both "large" in magnitude. Results suggest that overall vertical stiffness and drop jump height asymmetry are the strongest predictors of CODS in a healthy, non-athletic population.

A Phase 1 Study of 4 Live, Recombinant Human Cytomegalovirus Towne/Toledo Chimera Vaccines in Cytomegalovirus-Seronegative Men.

BACKGROUND: Human cytomegalovirus (HCMV) infection causes disease in newborns and transplant recipients. A HCMV vaccine (Towne) protects transplant recipients. METHODS: The genomes of Towne and the nonattenuated Toledo strain were recombined, yielding 4 Towne/Toledo chimera vaccines. Each of 36 HCMV-seronegative men received 1 subcutaneous dose of 10, 100, or 1000 plaque-forming units (PFU) in cohorts of 3. Safety and immunogenicity were evaluated over 12 weeks after immunization and for 52 weeks for those who seroconverted. RESULTS: There were no serious local or systemic reactions. No subject had HCMV in urine or saliva. For chimera 3, none of 9 subjects seroconverted. For chimera 1, 1 of 9 seroconverted (the seroconverter received 100 PFU). For chimera 2, 3 subjects seroconverted (1 received 100 PFU, and 2 received 1000 PFU). For chimera 4, 7 subjects seroconverted (1 received 10 PFU, 3 received 100 PFU, and 3 received 1000 PFU). All 11 seroconverters developed low but detectable levels of neutralizing activity. CD4+ T-cell responses were detectable in 1 subject (who received 100 PFU of chimera 4). Seven subjects receiving chimera 2 or 4 had detectable CD8+ T-cell responses to IE1; 3 responded to 1-2 additional antigens. CONCLUSIONS: The Towne/Toledo chimera vaccine candidates were well tolerated and were not excreted. Additional human trials of chimeras 2 and 4 are appropriate. CLINICAL TRIALS REGISTRATION: NCT01195571.

The use of unboosted darunavir in the setting of ritonavir intolerance: three case reports.

OBJECTIVE: To describe three patients with human immunodeficiency virus (HIV) who were successfully managed with unboosted darunavir (uDRV). CASE SUMMARIES: The three cases included one woman and two men aged 58, 54, and 51 years, respectively. All patients were HIV positive and unable to tolerate ritonavir-boosted protease inhibitors secondary to significant gastrointestinal intolerance. Unboosted darunavir was tolerated without any further issues when prescribed with an optimized antiretroviral (ARV) background regimen. Despite low darunavir (DRV) concentrations, all three patients achieved a virologic response. DISCUSSION: Darunavir is a relatively well-tolerated ARV, but concurrent ritonavir administration has several disadvantages (e.g., dose-related hyperlipidemia, gastrointestinal intolerance, drug-drug interactions) which may decrease patient adherence. The use of uDRV may be particularly useful in patients with limited therapy options who are unable to tolerate ritonavir-boosted protease inhibitors. Therapeutic drug monitoring (TDM) was performed as unboosted DRV has a bioavailability of 37% and the virologic and immunologic response has only been demonstrated with ritonavirboosted DRV. CONCLUSION: Successful use of uDRV may be an acceptable ARV option in carefully selected patients with limited treatment options, particularly when an optimized background regimen is included. Darunavir TDM should be strongly considered if uDRV is initiated.

The economic costs and cost-effectiveness of HIV self-testing among truck drivers in Kenya.

HIV status awareness is critical for ending the HIV epidemic but remains low in high-HIV-risk and hard-to-reach sub-populations. Targeted, efficient interventions are needed to improve HIV test-uptake. We examined the incremental cost-effectiveness of offering the choice of self-administered oral HIV-testing (HIVST-Choice) compared with provider-administered testing only [standard-of-care (SOC)] among long-distance truck drivers. Effectiveness data came from a randomized-controlled trial conducted at two roadside wellness clinics in Kenya (HIVST-Choice arm, n = 150; SOC arm, n = 155). Economic cost data came from the literature, reflected a societal perspective and were reported in 2020 international dollars (I$), a hypothetical currency with equivalent purchasing power as the US dollar. Generalized Poisson and linear gamma regression models were used to estimate effectiveness and incremental costs, respectively; incremental effectiveness was reported as the number of long-distance truck drivers needing to receive HIVST-Choice for an additional HIV test-uptake. We calculated the incremental cost-effectiveness ratio (ICER) of HIVST-Choice compared with SOC and estimated 95% confidence intervals (CIs) using non-parametric bootstrapping. Uncertainty was assessed using deterministic sensitivity analysis and the cost-effectiveness acceptability curve. HIV test-uptake was 23% more likely for HIVST-Choice, with six individuals needing to be offered HIVST-Choice for an additional HIV test-uptake. The mean per-patient cost was nearly 4-fold higher in HIVST-Choice (I$39.28) versus SOC (I$10.80), with an ICER of I$174.51, 95% CI [165.72, 194.59] for each additional test-uptake. HIV self-test kit and cell phone service costs were the main drivers of the ICER, although findings were robust even at highest possible costs. The probability of cost-effectiveness approached 1 at a willingness-to-pay of I$200 for each additional HIV test-uptake. HIVST-Choice improves HIV-test-uptake among truck drivers at low willingness-to-pay thresholds, suggesting that HIV self-testing is an efficient use of resources. Policies supporting HIV self-testing in similar high risk, hard-to-reach sub-populations may expedite achievement of international targets.

Brief Report: Physician Reimbursement and Retention in HIV Care: Racial Disparities in the US South.

BACKGROUND: Retention in HIV care remains a national challenge. Addressing structural barriers to care may improve retention. We examined the association between physician reimbursement and retention in HIV care, including racial differences. METHODS: We integrated person-level administrative claims (Medicaid Analytic eXtract, 2008-2012), state Medicaid-to-Medicare physician fee ratios (Urban Institute, 2008, 2012), and county characteristics for 15 Southern states plus District of Columbia. The fee ratio is a standardized measure of physician reimbursement capturing Medicaid relative to Medicare physician reimbursement across states. Generalized estimating equations assessed the association between the fee ratio and retention (≥2 care markers ≥90 days apart in a calendar year). Stratified analyses assessed racial differences. We varied definitions of retention, subsamples, and definitions of the fee ratio, including the fee ratio at parity. RESULTS: The sample included 55,237 adult Medicaid enrollees with HIV (179,002 enrollee years). Enrollees were retained in HIV care for 76.6% of their enrollment years, with retention lower among non-Hispanic Black (76.1%) versus non-Hispanic White enrollees (81.3%, P < 0.001). A 10-percentage point increase in physician reimbursement was associated with 4% increased odds of retention (adjusted odds ratio 1.04, 95% confidence interval: 1.01 to 1.07). In stratified analyses, the positive, significant association occurred among non-Hispanic Black (1.08, 1.05-1.12) but not non-Hispanic White enrollees (0.87, 0.74-1.02). Findings were robust across sensitivity analyses. When the fee ratio reached parity, predicted retention increased significantly overall and for non-Hispanic Black enrollees. CONCLUSION: Higher physician reimbursement may improve retention in HIV care, particularly among non-Hispanic Black individuals, and could be a mechanism to promote health equity.

Plasma levels of soluble CD14 independently predict mortality in HIV infection.

BACKGROUND: Chronic human immunodeficiency virus (HIV) infection is associated with intestinal permeability and microbial translocation that contributes to systemic immune activation, which is an independent predictor of HIV disease progression. The association of microbial translocation with clinical outcome remains unknown. METHODS: This nested case-control study included 74 subjects who died, 120 of whom developed cardiovascular disease and 81 of whom developed AIDS during the Strategies for Management of Anti-Retroviral Therapy (SMART) study with matched control subjects. Intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), soluble CD14 (sCD14), endotoxin core antibody (EndoCAb), and 16S ribosomal DNA (rDNA) were measured in baseline plasma samples. RESULTS: Subjects with the highest quartile of sCD14 levels had a 6-fold higher risk of death than did those in the lowest quartile (95% confidence interval, 2.2-16.1; P<.001), with minimal change after adjustment for inflammatory markers, CD4(+) T cell count, and HIV RNA level. No other marker was significantly associated with clinical outcomes. I-FABP, LPS, and sCD14 were increased and EndoCAb was decreased in study subjects, compared with healthy volunteers. sCD14 level correlated with levels of IL-6, C-reactive protein, serum amyloid A and D-dimer. CONCLUSIONS: sCD14, a marker of monocyte response to LPS, is an independent predictor of mortality in HIV infection. Therapeutic attenuation of innate immune activation may improve survival in patients with HIV infection.