Home-based aerobic exercise feasibility in oxaliplatin-receiving newly-diagnosed cancer survivors.

PURPOSE: Physical activity (PA) is beneficial but difficult to maintain during chemotherapy. This pilot RCT explored the feasibility of the MI-Walk intervention-an 8-week motivational enhancement therapy- and home-based brisk walking intervention-among gastrointestinal (GI) cancer survivors receiving chemotherapy. METHODS: Sixty stage II-IV GI cancer survivors were recruited from 5 sites at their second infusion visit. Participants were randomized to receive PA education alone or the MI-Walk intervention: motivational enhancement therapy consisting of 3 motivational interviewing and self-efficacy-enhancing counseling sessions, a Fitbit Charge 2, exercise diaries, telephone follow-up, scripted motivational email messages, and optional weekly walking groups. RESULTS: The enrollment and completion rates were 62% and 90%, respectively. The MI-Walk participants (n = 29; mean age = 56.79, SD = 11.72; 97% white; 79% male) reported a baseline moderate-vigorous PA duration of 250.93 (SD = 636.52) min/wk. The mean MI-Walk Intervention acceptability score was 50.32 (SD = 12.02) on a scale of 14-70. Mean Fitbit and counseling helpfulness scores on a 5-point scale were 3.67 (SD = 1.43) and 3.44 (SD = 1.36), respectively. Participants' Fitbit moderate-vigorous PA 8-week averages ranged from 0 to 716.88 min/wk; 64% of participants adhered to ≥127 min/wk. Several characteristics (e.g., age, comorbidity, PA level, employment status, BMI, education level, gender, symptoms) were associated with enrollment, attrition, and intervention acceptability and adherence (p < 0.05). CONCLUSION: Enrollment and retention were adequate. The Fitbit and counseling were the most helpful. Acceptability and adherence varied based on participant characteristics; therefore, intervention tailoring and further research among cancer survivors less physically active at baseline and most in need of complex exercise intervention are needed. CLINICALTRIALS: gov NCT03515356.

Efficacy of the Motivational Interviewing-Walk Intervention for Chemotherapy-Induced Peripheral Neuropathy and Quality of Life During Oxaliplatin Treatment: A Pilot Randomized Controlled Trial.

BACKGROUND: Oxaliplatin-induced peripheral neuropathy (OIPN) is prevalent among gastrointestinal cancer survivors and often impairs quality of life (QOL). OBJECTIVE: This pilot randomized controlled trial aimed to explore the effect of an 8-week home-based brisk walking (the "MI-Walk") intervention on (1) OIPN severity and (2) QOL at 8 weeks, compared with physical activity (PA) education alone in oxaliplatin-receiving adults with gastrointestinal cancer. INTERVENTIONS/METHODS: Participants (N = 57) recruited from 5 infusion sites received PA education at their second oxaliplatin visit, followed by phone assessments of adverse events over 8 weeks. Half (n = 29) received additional MI-Walk intervention motivational supports (eg, a Fitbit Charge 2 and motivational enhancement therapy sessions). Self-reported OIPN, QOL, and PA were measured before and after intervention. RESULTS: The intervention compared with the control condition had no effect on sensory OIPN (mean difference [] = -0.01; P > .99), motor OIPN (=2.39; P = .17), and QOL (= -1.43; P > .99). Eight-week sensory (=11.48 ± 0.38) and motor OIPN severities ( = 7.48 ± 0.36) were mild but higher than baseline (P ≤ .01). Self-reported PA level increased over time in both groups (=44.85; P = .01). Averaging ≥225 moderate to vigorous PA minutes per week led to less sensory OIPN, particularly finger/hand tingling (= -26.35; P = .01). CONCLUSIONS: This study failed to detect beneficial effects of the MI-Walk intervention; however, the findings suggest that aerobic walking may blunt but not completely prevent OIPN. Further research is necessary. IMPLICATIONS FOR PRACTICE: Although the effectiveness of brisk walking in reducing OIPN is unclear, this study supports prior evidence that moderate to vigorous PA is beneficial and safe during chemotherapy treatment.

Characteristics and patterns of pediatric chemotherapy-induced peripheral neuropathy: A systematic review.

This systematic review provides a high-quality synthesis of the empirical evidence regarding chemotherapy-induced peripheral neuropathy (CIPN) characteristics and patterns described in studies of children who received neurotoxic chemotherapy to treat cancer. PubMed, CINAHL, PsycINFO, and Embase were searched for articles published 2009 - 2019, yielding 861. Forty-two papers met the eligibility criteria, including 31 that described characteristics and patterns of vincristine-induced CIPN. Fifty-seven percent of articles were of low to moderate quality; measurement flaws were the most common limitations. The reported CIPN incidence varies widely (2.8%-100%) depending on risk factors (e.g., race) and the measurement approach. Incidence rates of sensory, motor, autonomic CIPN, and pain were 12-28%, 50-72%, 0.8-83% and 5.7-44%, respectively. The evidence suggests that sensory and motor neuropathy, pain, and functional deficits are common and can persist into adulthood. Caucasian race is a risk factor and, contrary to prior thinking, cumulative chemotherapy dosage alone does not predict CIPN severity. The influence of other risk factors is less clear, and studies to date have not explored potential interactions among race, genetics, age, sex, drug metabolism, and nutritional status, among other factors.

Approaches to measure paediatric chemotherapy-induced peripheral neurotoxicity: a systematic review.

In children who receive neurotoxic chemotherapy, peripheral neurotoxicity occurs frequently, necessitates dose reduction or treatment cessation, and affects function and long-term quality of life. No treatments exist for peripheral neurotoxicity and few assessment measures are specific to children. We did a systematic review to analyse the published literature concerning the evaluation of assessment measures for paediatric chemotherapy-induced peripheral neurotoxicity. We searched PubMed, CINAHL, PsycINFO, and Embase on Nov 7-8, 2018; of 1409 articles, seven met the inclusion criteria. A total of 335 children (excluding ten healthy controls) were enrolled in the seven studies and the sample sizes ranged from 17 to 86 individuals. 276 (82%) of the 335 children were actively undergoing chemotherapy treatment. Most studies did not comprehensively evaluate the psychometric properties of assessment measures for chemotherapy-induced peripheral neurotoxicity. By use of a narrative analysis that combined approaches from the Joanna Briggs Institute (Adelaide, SA, Australia) and the quality of diagnostic accuracy studies assessment method (known as QUADAS), only one study was deemed high quality. We identified two variants of the Total Neuropathy Score, two grading scales, two semi-objective tests, one patient-reported outcome, and several mobility measures. The National Cancer Institute Common Terminology Criteria for Adverse Events and the Balis grading scales showed lower sensitivity and specificity than the items of the Total Neuropathy Score. Although there is insufficient evidence to support the use of most approaches to assess chemotherapy-induced peripheral neurotoxicity in children, two variants of the Total Neuropathy Score, the pediatric-modified Total Neuropathy Score and the Total Neuropathy Score-pediatric vincristine, are promising but require further testing. Other approaches are less sensitive or less feasible. A patient-reported outcome measure for chemotherapy-induced peripheral neurotoxicity in children is needed.

Chemotherapy-Induced Peripheral Neuropathy: Nursing Implications.

Chemotherapy-induced peripheral neuropathy (CIPN) is an unsolved and potentially life-compromising problem for most patients receiving neurotoxic chemotherapy. It manifests with numbness, tingling, and possibly neuropathic pain and motor and autonomic symptoms. This review aims to provide an evidence synthesis that prepares nurses to comprehensively assess, provide supportive care for, and critically evaluate the literature on CIPN. The prevalence, significance, characteristics, mechanisms, and risk factors of CIPN will be discussed, as well as nursing-relevant evidence on the assessment, prevention, and management of CIPN. The importance of critical literature evaluation before clinical implementation to reduce physical and financial harms to patients will also be highlighted.

Exercise Effects on Chemotherapy-Induced Peripheral Neuropathy: A Comprehensive Integrative Review.

BACKGROUND: No effective cures for chemotherapy-induced peripheral neuropathy (CIPN) are known; however, exercise may be beneficial. OBJECTIVE: The purpose of this review was to synthesize high-quality research publications reporting the effects of exercise on CIPN and related outcomes among people of all age groups who received neurotoxic chemotherapy. METHODS: PubMed, CINAHL, Scopus, PsycINFO, and SPORTDiscus databases were searched first between May and November 2016 and then again in April 2019 for all clinical trials and meta-analyses. Subsequent hand-searching continued through April 2019. Potential scientific bias was rigorously evaluated, using the CONSORT (Consolidated Standards of Reporting Trials) guidelines. RESULTS: Thirteen studies (7 randomized controlled trials, 6 quasi-experiments) were found that reported exercise effects in various adult CIPN populations (ie, mixed cancer types and stages, chemotherapy regimens and status, and CIPN presence and severity). No studies provided high-quality evidence; 2 studies provided moderate-quality evidence. Most studies (76.3%) evaluated combined aerobic, strength, and balance training interventions of varying dosages. The most commonly improved outcomes were CIPN, balance, and fitness. All 7 studies with an aerobic exercise component led to significant-most studies showing moderate to large-CIPN benefits. CONCLUSIONS: Few studies-none of high quality or in child/adolescent populations-have evaluated exercise effects on CIPN. The exercise interventions, dosages, and settings have been too heterogeneous to identify the most beneficial intervention for other CIPN-related outcomes. However, aerobic exercise may be a key component of exercise interventions for CIPN. IMPLICATIONS FOR PRACTICE: Although promising, the empirical evidence is insufficient to definitively conclude that exercise interventions ameliorate CIPN.

Proactive Rehabilitation for Chemotherapy-Induced Peripheral Neuropathy.

OBJECTIVE: To review assessment and management approaches for chemotherapy-induced peripheral neuropathy-related physical function deficits. DATA SOURCES: Peer-reviewed articles from PubMed, Ovid MEDLINE, CINAHL PsycINFO, SPORTDiscus, Scopus, and key studies' reference lists. CONCLUSION: Brief clinical tests (eg, gait, Timed Up and Go) can screen for neuropathy-related physical function deficits. Exercise and physical therapy may be promising treatments, but the efficacy and optimal dose of such treatments for chemotherapy-induced peripheral neuropathy are unclear. IMPLICATIONS FOR NURSING PRACTICE: Screening and assessment of neuropathy-associated physical function deficits should occur throughout neurotoxic chemotherapy treatment. If such deficits are identified, referral for rehabilitation (ie, physical or occupational therapy) and/or exercise interventions is warranted.

Childhood Trauma Predicts Cancer Treatment-Related Pain in Breast Cancer Survivors.

BACKGROUND: Childhood trauma has been linked to neuropathic pain in noncancer populations, but its relationship with cancer treatment-related neuropathic pain is unknown. OBJECTIVE: This secondary data analysis of a prospective, longitudinal, observational study aimed to explore the relationship of childhood trauma experience with pain severity, pain interference, and neuropathic symptom severity (NSS) 12 months after surgery in women receiving treatment for stage 0 to III breast cancer. METHODS: Women (N = 44) recruited from a comprehensive cancer center self-reported childhood trauma experience, pain severity, pain interference, NSS, co-occurring symptoms, and pain beliefs via questionnaires. Descriptive statistics were used to describe childhood trauma experience. Linear regression was used to model childhood trauma and other predictors on pain variables 12 months after surgery. RESULTS: Childhood trauma predicted pain severity and pain interference 12 months after surgery (P < .05), as did baseline pain severities and helplessness-pain catastrophizing. Age predicted only NSS. Together, the best models predicted 31.6% to 40.9% of the variance in pain severities at 12 months (P < .001). CONCLUSIONS: Childhood trauma exposure was a significant predictor of pain 12 months after breast cancer surgery and adjuvant treatment. Younger and helplessness-pain catastrophizing women are also at risk. Research is needed to identify preventive neuropathic pain interventions for high-risk women. IMPLICATIONS FOR PRACTICE: Women receiving breast cancer treatment should proactively be assessed for childhood trauma history, possibly by using discreet previsit questionnaires. Childhood trauma survivors may be at high risk for poor pain outcomes and may benefit from tailored pain interventions.

Mechanisms, Predictors, and Challenges in Assessing and Managing Painful Chemotherapy-Induced Peripheral Neuropathy.

OBJECTIVE: To describe the known predictors and pathophysiological mechanisms of chronic painful chemotherapy-induced peripheral neuropathy (CIPN) in cancer survivors and the challenges in assessing and managing it. DATA SOURCES: PubMed/Medline, CINAHL, Scopus, and PsycINFO. CONCLUSION: The research on chronic painful CIPN is limited. Additional research is needed to identify the predictors and pathophysiological mechanisms of chronic painful CIPN to inform the development of assessment tools and management options for this painful and possibly debilitating condition. IMPLICATIONS FOR NURSING PRACTICE: Recognition of the predictors of chronic painful CIPN and proactive CIPN assessment and palliative management are important steps in reducing its impact on physical function and quality of life.

Pressure Pain Phenotypes in Women Before Breast Cancer Treatment.

OBJECTIVES: To explore associations between quantitative sensory testing (QST) and pretreatment pain, physical, and psychological characteristics in women with breast cancer. SAMPLE & SETTING: 41 women with treatment-naive stage 0-III breast cancer at the University of Michigan Comprehensive Cancer Center in Ann Arbor. METHODS & VARIABLES: Participants completed self-report surveys and QST within the month before breast surgery. Pressure pain thresholds (PPTs) were measured bilaterally at each trapezius with a manual QST algometer. PPT values were split, yielding low, moderate, and high pain sensitivity subgroups. Subgroup self-reported characteristics were compared using Spearman's correlation, chi-square, and one-way analysis of variance. RESULTS: Lower PPT (higher sensitivity) was associated with higher levels of pain interference and maladaptive pain cognitions. The high-sensitivity group reported higher pain severities, interference, and catastrophizing and lower belief in internal locus of pain control than the low-sensitivity group. IMPLICATIONS FOR NURSING: Individualized interventions for maladaptive pain cognitions before surgery may reduce pain sensitivity and the severity of chronic pain developed after surgery.

Improved blood pressure control associated with a large-scale hypertension program.

IMPORTANCE: Hypertension control for large populations remains a major challenge. OBJECTIVE: To describe a large-scale hypertension program in Northern California and to compare rates of hypertension control in that program with statewide and national estimates. DESIGN, SETTING, AND PATIENTS: The Kaiser Permanente Northern California (KPNC) hypertension program included a multifaceted approach to blood pressure control. Patients identified as having hypertension within an integrated health care delivery system in Northern California from 2001-2009 were included. The comparison group comprised insured patients in California between 2006-2009 who were included in the Healthcare Effectiveness Data and Information Set (HEDIS) commercial measurement by California health insurance plans participating in the National Committee for Quality Assurance (NCQA) quality measure reporting process. A secondary comparison group was included to obtain the reported national mean NCQA HEDIS commercial rates of hypertension control between 2001-2009 from health plans that participated in the NCQA HEDIS quality measure reporting process. MAIN OUTCOMES AND MEASURES: Hypertension control as defined by NCQA HEDIS. RESULTS: The KPNC hypertension registry included 349,937 patients when established in 2001 and increased to 652,763 by 2009. The NCQA HEDIS commercial measurement for hypertension control within KPNC increased from 43.6% (95% CI, 39.4%-48.6%) to 80.4% (95% CI, 75.6%-84.4%) during the study period (P < .001 for trend). In contrast, the national mean NCQA HEDIS commercial measurement increased from 55.4% to 64.1%. California mean NCQA HEDIS commercial rates of hypertension were similar to those reported nationally from 2006-2009 (63.4% to 69.4%). CONCLUSIONS AND RELEVANCE: Among adults diagnosed with hypertension, implementation of a large-scale hypertension program was associated with a significant increase in hypertension control compared with state and national control rates. Key elements of the program included a comprehensive hypertension registry, development and sharing of performance metrics, evidence-based guidelines, medical assistant visits for blood pressure measurement, and single-pill combination pharmacotherapy.

Clinical correlates of atypical femoral fracture.

BACKGROUND: Reports of atypical femur fracture in bisphosphonate-exposed women have prompted interest in characterizing the clinical profiles of these patients. METHODS: Among women age ≥60 years with hip or femur fracture during 2007-2008, we identified 79 with low-trauma subtrochanteric or femoral shaft fracture. Radiographic images were reviewed to assign fracture pattern and distinguish atypical femur fracture from non-atypical femur fracture. Differences in clinical characteristics and pharmacologic exposures were compared. RESULTS: Among 79 women (38 subtrochanteric and 41 femoral shaft fracture), 38 had an atypical femur fracture. Compared to those with a non-atypical femur fracture, women with atypical femur fracture were significantly younger (74.0 vs 81.0 years), more likely to be Asian (50.0 vs 2.4%) and to have received bisphosphonate therapy (97.4 vs 41.5%). Similarly, the contralateral femur showed a stress or complete fracture in 39.5% of atypical femur fractures vs 2.4% non-atypical femur fracture, and focal cortical hypertrophy of the contralateral femur in an additional 21.1% of atypical cases. CONCLUSIONS: Women suffering atypical femur fractures have a markedly different clinical profile from those sustaining typical fractures. Women with atypical femur fracture tend to be younger, Asian, and bisphosphonate-exposed. The high frequency of contralateral femur findings suggests a generalized process.

Boosting dose ritonavir does not alter peripheral insulin sensitivity in healthy HIV-seronegative volunteers.

BACKGROUND: Some HIV protease inhibitors (PIs), including full-dose ritonavir (800 mg) and ritonavir-boosted lopinavir, acutely induce insulin resistance in the absence of HIV infection and changes in body composition. Boosting dose ritonavir (100-200 mg) is the most commonly prescribed PI, yet its effects on glucose metabolism have not been described in the absence of another PI. METHODS: In this randomized, double-blind, cross-over study, a single dose of ritonavir 200 mg or placebo was given to healthy HIV-seronegative volunteers before assessment of insulin sensitivity by euglycemic hyperinsulinemic clamp. RESULTS: Boosting dose ritonavir had no effect on insulin-mediated glucose disposal (M/I, placebo: 8.59 ± 0.83 vs. ritonavir: 8.51 ± 0.64 mg/kg per minute per µU/mL insulin, P = 0.89). CONCLUSIONS: A single boosting dose of ritonavir does not alter insulin sensitivity, suggesting lopinavir is likely responsible for the induction of insulin resistance demonstrated in prior short-term studies of lopinavir/ritonavir. There is a dose-dependent effect of ritonavir on insulin sensitivity.

The protease inhibitor combination lopinavir/ritonavir does not decrease insulin secretion in healthy, HIV-seronegative volunteers.

BACKGROUND: HIV protease inhibitors have been shown to worsen glucose and lipid metabolism. Recent studies have suggested that protease inhibitors can impair insulin secretion in HIV-infected patients. We studied the effects of the protease inhibitor combination lopinavir and ritonavir on insulin secretion, insulin sensitivity, and lipid metabolism in HIV-negative persons. METHODS: A combination dose of lopinavir 400 mg and ritonavir 100 mg was given twice daily to eight HIV-seronegative men for 4 weeks. Fasting glucose, insulin, lipid, and lipoprotein profiles; oral glucose tolerance; insulin secretion and insulin-mediated glucose disposal by hyperglycemic clamp; and body composition by dual energy X-ray absorptiometry were determined before and after lopinavir/ritonavir administration. RESULTS: There was no change in first-phase insulin secretion (2.82 +/- 0.30 versus 2.71 +/- 0.31 nmol/l; P = 0.60), as well as fasting insulin and glucose levels, oral glucose tolerance, or insulin-mediated glucose disposal after 4 weeks administration of lopinavir/ritonavir. However, there were significant increases in fasting triglycerides (1.02 +/- 0.13 versus 2.20 +/- 0.31 mmol/l; P = 0.001), total cholesterol (4.42 +/- 0.30 versus 5.70 +/- 0.60 mmol/l; P = 0.007), and apo B-100 levels (0.86 +/- 0.07 versus 1.07 +/- 0.11 g/l; P = 0.0009). High-density lipoprotein cholesterol decreased (0.99 +/- 0.11 versus 0.82 +/- 0.10 mmol/l; P = 0.005). There were no changes in body composition, weight, or body fat. CONCLUSION: Although administration of lopinavir/ritonavir to healthy, HIV-seronegative volunteers for 4 weeks resulted in increased triglyceride and decreased high-density lipoprotein cholesterol levels, there was no change in first-phase insulin secretion during the hyperglycemic clamp. The reported effects of protease inhibitor on insulin secretion in HIV-infected individuals may be due to changes in HIV-related factors and not a direct drug effect.

The acute effects of HIV protease inhibitors on insulin suppression of glucose production in healthy HIV-negative men.

BACKGROUND: The effects of different HIV protease inhibitors (PIs) on peripheral insulin resistance have been described, but less is known about their effects on insulin suppression of endogenous glucose production (EGP). METHODS: We tested the acute effects of 3 PIs, indinavir, ritonavir, and amprenavir, on EGP quantified by stable isotope techniques during the hyperinsulinemic, euglycemic clamp in 3 similar placebo-controlled protocols. RESULTS: EGP was higher with indinavir in the hyperinsulinemic state than with placebo (4.1 +/- 1.3 vs. 2.2 +/- 0.8 microg x kg(-1) x min(-1), P = 0.04). A trend toward higher EGP was seen with ritonavir (3.6 +/- 0.3 vs. 3.0 +/- 0.5 microg x kg(-1) x min(-1), P = 0.08). There was no evidence that amprenavir blunted insulin suppression of EGP compared with placebo (2.9 +/- 0.04 vs. 3.2 +/- 0.7 microg x kg(-1) x min(-1), P = 0.63). CONCLUSIONS: Some PIs can acutely blunt the ability of insulin to suppress EGP, but, as with insulin resistance, the effects of PIs on EGP are drug-specific, not class-specific.

The effects of recombinant human leptin on visceral fat, dyslipidemia, and insulin resistance in patients with human immunodeficiency virus-associated lipoatrophy and hypoleptinemia.

CONTEXT: Leptin deficiency is associated with dyslipidemia and insulin resistance in animals and humans with lipoatrophy; leptin replacement ameliorates these abnormalities. OBJECTIVE: The objective of the study was to evaluate the effects of leptin therapy in lipoatrophic HIV-infected patients with dyslipidemia and hypoleptinemia. DESIGN: This was a 6-month, open-label, proof-of-principle pilot study. SETTING: Metabolic ward studies were performed before and 3 and 6 months after leptin treatment. PARTICIPANTS: Participants included eight HIV-infected men with lipoatrophy, fasting triglycerides greater than 300 mg/dl, and serum leptin less than 3 ng/ml. INTERVENTION: Recombinant human leptin was given by sc injection (0.01 mg/kg and 0.03 mg/kg twice daily for successive 3 month periods). OUTCOME MEASURES: Measures included fat distribution by magnetic resonance imaging and dual-energy X-ray absorptiometry; fasting lipids; insulin sensitivity by euglycemic hyperinsulinemic clamp; endogenous glucose production, gluconeogenesis, glycogenolysis, and whole-body lipolysis by stable isotope tracer studies; oral glucose tolerance testing; liver fat by proton magnetic resonance spectroscopy; and safety. RESULTS: Visceral fat decreased by 32% (P = 0.001) with no changes in peripheral fat. There were significant decreases in fasting total (15%, P = 0.012), direct low-density lipoprotein (20%, P = 0.002), and non-high-density lipoprotein (19%, P = 0.005) cholesterol. High-density lipoprotein cholesterol increased. Triglycerides, whole-body lipolysis, and free fatty acids decreased during fasting and hyperinsulinemia. Fasting insulin decreased. Endogenous glucose production decreased during fasting and hyperinsulinemia, providing evidence of improved hepatic insulin sensitivity. Leptin was well tolerated but decreased lean mass. CONCLUSIONS: Leptin treatment was associated with marked improvement in dyslipidemia. Hepatic insulin sensitivity improved and lipolysis decreased. Visceral fat decreased with no exacerbation of peripheral lipoatrophy. Results from this pilot study suggest that leptin warrants further study in patients with HIV-associated lipoatrophy.

HIV therapy, metabolic syndrome, and cardiovascular risk.

People with HIV infection have metabolic abnormalities that resemble metabolic syndrome (hypertriglyceridemia, low high-density lipoprotein cholesterol, and insulin resistance), which is known to predict increased risk of cardiovascular disease (CVD). However, there is not one underlying cause for these abnormalities and they are not linked to each other. Rather, individual abnormalities can be affected by the host response to HIV itself, specific HIV drugs, classes of HIV drugs, HIV-associated lipoatrophy, or restoration to health. Furthermore, one component of metabolic syndrome, increased waist circumference, occurs less frequently in HIV infection. Thus, HIV infection supports the concept that metabolic syndrome does not represent a syndrome based on a common underlying pathophysiology. As might be predicted from these findings, the prevalence of CVD is higher in people with HIV infection. It remains to be determined whether CVD rates in HIV infection are higher than might be predicted from traditional risk factors, including smoking.

Effects of ritonavir and amprenavir on insulin sensitivity in healthy volunteers.

BACKGROUND: Some HIV protease inhibitors (PIs) have been shown to induce insulin resistance in vitro but the degree to which specific PIs affect insulin sensitivity in humans is less well understood. METHODS: In two separate double-blind, randomized, cross-over studies, we assessed the effects of a single dose of ritonavir (800 mg) and amprenavir (1200 mg) on insulin sensitivity (euglycemic hyperglycemic clamp) in healthy normal volunteers. RESULTS: Ritonavir decreased insulin sensitivity (-15%; P = 0.008 versus placebo) and non-oxidative glucose disposal (-30%; P = 0.0004), whereas neither were affected by amprenavir administration. CONCLUSION: Compared to previously performed studies of identical design using single doses of indinavir and lopinavir/ritonavir, a hierarchy of insulin resistance was observed with the greatest effect seen with indinavir followed by ritonavir and lopinavir/ritonavir, with little effect of amprenavir.

Single-dose lopinavir-ritonavir acutely inhibits insulin-mediated glucose disposal in healthy volunteers.

Previously, we found that 4 weeks of treatment with lopinavir-ritonavir did not decrease insulin sensitivity but did increase adiponectin levels. In the present study, a single dose of lopinavir-ritonavir decreases insulin sensitivity but does not alter adiponectin levels. Insulin resistance from protease inhibitors may decrease with prolonged use; an increase in adiponectin levels may mediate this effect.

Metabolic Abnormalities Associated with the Use of Protease Inhibitors and Non-nucleoside Reverse Transcriptase Inhibitors.

The use of protease inhibitors and non-nucleoside reverse transcriptase inhibitors for the treatment of HIV infection and AIDS has been associated with multiple abnormalities in glucose and lipid metabolism. Specifically, these abnormalities include insulin resistance, increased triglycerides and increased LDL cholesterol levels. The metabolic disturbances are due to a combination of factors, including the direct effect of medications, restoration to health and HIV disease, as well as individual genetic predisposition. Of the available anti-retroviral medications, indinavir has been associated with causing the most insulin resistance and ritonavir with causing the most hypertriglyceridemia.