Excess heart age in adult outpatients in routine HIV care.

OBJECTIVE: Cardiovascular disease (CVD) is a common cause of morbidity and mortality among persons living with HIV (PLWH). We used individual cardiovascular risk factor profiles to estimate heart age for PLWH in medical care in the United States. DESIGN: Cross-sectional analyses of HIV Outpatient Study (HOPS) data METHODS:: Included in this analysis were participants aged 30-74 years, without prior CVD, with at least two HOPS clinic visits during 2010-2017, at least 1-year of follow-up, and available covariate data. We calculated age and race/ethnicity-adjusted heart age and excess heart age (chronological age - heart age), using a Framingham risk score-based model. RESULTS: We analyzed data from 2467 men and 619 women (mean chronologic age 49.3 and 49.1 years, and 23.6% and 54.6% Non-Hispanic/Latino black, respectively). Adjusted excess heart age was 11.5 years (95% confidence interval, 11.1-12.0) among men and 13.1 years (12.0-14.1) among women. Excess heart age was seen among all age groups beginning with persons aged 30-39 years [men, 7.8 (6.9-8.8); women, 7.7 (4.9-10.4)], with the highest excess heart age among participants aged 50-59 years [men, 13.7 years (13.0-14.4); women, 16.4 years (14.8-18.0)]. More than 50% of participants had an excess heart age of at least 10 years. CONCLUSIONS: Excess heart age is common among PLWH, begins in early adulthood, and impacts both women and men. Among PLWH, CVD risk factors should be addressed early and proactively. Routine use of the heart age calculator may help optimize CVD risk stratification and facilitate interventions for aging PLWH.

Cardiovascular Disease Risk Prediction in the HIV Outpatient Study.

BACKGROUND: Cardiovascular disease (CVD) risk prediction tools are often applied to populations beyond those in which they were designed when validated tools for specific subpopulations are unavailable. METHODS: Using data from 2283 human immunodeficiency virus (HIV)-infected adults aged ≥18 years, who were active in the HIV Outpatient Study (HOPS), we assessed performance of 3 commonly used CVD prediction models developed for general populations: Framingham general cardiovascular Risk Score (FRS), American College of Cardiology/American Heart Association Pooled Cohort equations (PCEs), and Systematic COronary Risk Evaluation (SCORE) high-risk equation, and 1 model developed in HIV-infected persons: the Data Collection on Adverse Effects of Anti-HIV Drugs (D:A:D) study equation. C-statistics assessed model discrimination and the ratio of expected to observed events (E/O) and Hosmer-Lemeshow χ2 P value assessed calibration. RESULTS: From January 2002 through September 2013, 195 (8.5%) HOPS participants experienced an incident CVD event in 15 056 person-years. The FRS demonstrated moderate discrimination and was well calibrated (C-statistic: 0.66, E/O: 1.01, P = .89). The PCE and D:A:D risk equations demonstrated good discrimination but were less well calibrated (C-statistics: 0.71 and 0.72 and E/O: 0.88 and 0.80, respectively; P < .001 for both), whereas SCORE performed poorly (C-statistic: 0.59, E/O: 1.72; P = .48). CONCLUSIONS: Only the FRS accurately estimated risk of CVD events, while PCE and D:A:D underestimated risk. Although these models could potentially be used to rank US HIV-infected individuals at higher or lower risk for CVD, the models may fail to identify substantial numbers of HIV-infected persons with elevated CVD risk who could potentially benefit from additional medical treatment.

High Prevalence of Low Bone Mineral Density and Substantial Bone Loss over 4 Years Among HIV-Infected Persons in the Era of Modern Antiretroviral Therapy.

HIV-infected persons are living longer on combination antiretroviral therapy (cART) but experiencing more comorbidities including low bone mineral density (BMD). Using data from the Study to Understand the Natural History of HIV and AIDS in the Era of Effective Therapy (SUN Study), we determined the prevalence of low BMD (T-score below one standard deviation of the reference mean) and compared it with matched controls from the National Health and Nutrition Examination Survey (NHANES). We also assessed 4-year longitudinal BMD changes among participants virologically suppressed on cART. Of 653 participants included in this analysis (77% male, 29% black, median age 41 years, median CD4(+) cell count 464 cells/mm(3), 89% with HIV RNA <400 copies/ml), 51% and 10% had baseline osteopenia and osteoporosis, respectively. Low BMD at the femoral neck was significantly more prevalent than for the NHANES controls (47% versus 29%, p<0.001). Lower body mass index, nonwhite race, longer tenofovir exposure, older age, being unemployed or retired, and lower apolipoprotein E were independently associated with baseline osteoporosis. Among 170 participants virologically suppressed on cART and with longitudinal BMD data, 31% experienced substantial bone loss (≥5% BMD decline from baseline) over 4 years. Female sex, current smoking, and longer stavudine use were more common among participants who had substantial bone loss, although these variables failed to reach statistical significance. Low BMD was highly prevalent among HIV-infected persons. One-third of participants experienced substantial bone loss despite cART, suggesting the need for monitoring and potential clinical interventions.

Statin Use Is Associated With Incident Diabetes Mellitus Among Patients in the HIV Outpatient Study.

INTRODUCTION: Statin therapy is effective in the prevention of cardiovascular disease in the general population but has been shown to modestly increase the risk for incident diabetes mellitus (DM). METHODS: We analyzed incident DM in HIV Outpatient Study (HOPS) participants followed at 8 HIV clinic sites during 2002-2011, comparing rates among those who initiated statin therapy during that period with those who did not. Using Cox proportional hazards models, we examined the association between cumulative years of statin exposure and the risk of developing DM, after controlling for age, sex, race/ethnicity, antiretroviral history, prevalent hepatitis C, body mass index, and cumulative exposure to protease inhibitor therapy. We also adjusted for propensity scores to account for residual confounding by indication. RESULTS: Of 4692 patients analyzed, 590 (12.6%) initiated statin therapy and 355 (7.2%) developed DM. Incident DM was independently associated with statin therapy (adjusted hazard ratio, 1.14 per year of statin use), as well as older age, Hispanic/Latino ethnicity, non-Hispanic/Latino black race, antiretroviral-naive status, prevalent hepatitis C, and body mass index ≥30 kg/m² (P < 0.05 for all). The association of statin use with incident DM was similar in the model adjusted for propensity score. CONCLUSIONS: Statin use was associated with a modestly increased risk of incident DM in an HIV-infected population, similar to existing data for the general population. HIV-infected patients should be monitored for glucose intolerance, but statins should not be withheld if clinically indicated for cardiovascular disease risk reduction.

Provider compliance with guidelines for management of cardiovascular risk in HIV-infected patients.

INTRODUCTION: Compliance with National Cholesterol Education Program Adult Treatment Panel III (NCEP) guidelines has been shown to significantly reduce incident cardiovascular events. We investigated physicians' compliance with NCEP guidelines to reduce cardiovascular disease (CVD) risk in a population infected with HIV. METHODS: We analyzed HIV Outpatient Study (HOPS) data, following eligible patients from January 1, 2002, or first HOPS visit thereafter to calculate 10-year cardiovascular risk (10yCVR), until September 30, 2009, death, or last office visit. We categorized participants into four 10yCVR strata, according to guidelines determined by NCEP, the Infectious Disease Society of America, and the Adult AIDS Clinical Trials Group. We calculated percentages of patients treated for dyslipidemia and hypertension, calculated percentages of patients who achieved recommended goals, and categorized them by 10yCVR stratum. RESULTS: Of 2,005 patients analyzed, 33.7% had fewer than 2 CVD risk factors. For patients who had 2 or more risk factors, 10yCVR was less than 10% for 28.2%, 10% to 20% for 18.2%, and higher than 20% for 20.0% of patients. Of patients eligible for treatment, 81% to 87% were treated for elevated low-density lipoprotein cholesterol/non-high-density lipoprotein cholesterol (LDL-C/non-HDL-C), 2% to 11% were treated for low HDL-C, 56% to 91% were treated for high triglycerides, and 46% to 69% were treated for hypertension. Patients in higher 10yCVR categories were less likely to meet treatment goals than patients in lower 10yCVR categories. CONCLUSION: At least one-fifth of contemporary HOPS patients have a 10yCVR higher than 20%, yet a large percentage of at-risk patients who were eligible for pharmacologic treatment did not receive recommended interventions and did not reach recommended treatment goals. Opportunities exist for CVD prevention in the HIV-infected population.

Disparities in prevalence of key chronic diseases by gender and race/ethnicity among antiretroviral-treated HIV-infected adults in the US.

BACKGROUND: Certain sociodemographic subgroups of HIV-infected patients may experience more chronic disease than others due to behavioural risk factors, advanced HIV disease or complications from extended use of combination antiretroviral therapy (cART), but recent comparative data are limited. METHODS: We studied HIV-infected adult patients in care during 2006-2010 who had been prescribed ≥ 6 months of cART. We analysed the prevalence of selected key chronic conditions and polymorbidity (having 2 or more out of 10 key conditions) by gender and race/ethnicity. RESULTS: Of the 3,166 HIV-infected patients (median age 47 years, CD4⁺ T-cell count 496 cells/mm³, duration of cART use 6.8 years), 21% were female, 57% were non-Hispanic White and over half were current or former tobacco smokers. The five most frequent conditions among women (median age 45 years) were dyslipidaemia (67.3%), hypertension (57.4%), obesity (31.7%), viral hepatitis B or C coinfection (29.0%) and low high-density lipoprotein cholesterol (HDLc; 27.3%). The five most frequent conditions in men (median age 47 years) were dyslipidaemia (81.2%), hypertension (54.4%), low HDLc (41.1%), elevated triglycerides (32.3%) and elevated non-HDLc (26.8%). In multivariable analyses, Hispanic patients had higher prevalence of obesity and diabetes than White patients; Black patients had higher prevalence of obesity and hypertension but lower rates of lipid abnormalities. Of all patients, 73.7% of women and 66.8% of men had polymorbidity, with no evidence of disparities by race/ethnicity. CONCLUSIONS: Among contemporary cART-treated HIV-infected adults, chronic conditions and polymorbidity were common, underscoring the importance of chronic disease prevention and management among ageing HIV-infected patients.

A pilot study to assess inflammatory biomarker changes when raltegravir is added to a virologically suppressive HAART regimen in HIV-1-infected patients with limited immunological responses.

BACKGROUND: Despite successful suppression of HIV-1 with HAART, some patients do not have robust immunological recovery. Chronic inflammation from persistent immune activation could contribute to this poor response, resulting in HIV-1 disease progression and the development of some non-HIV-1 comorbidities. METHODS: We conducted a pilot study of 30 HIV-1-infected patients with undetectable viral loads and poor CD4(+) T-cell responses on long-term stable HAART to assess whether the addition of raltegravir would have an effect on biomarkers of chronic inflammation. A total of 26 patients were followed for 1 year on the intensified regimen. In addition to T-cell responses, we evaluated changes in activated CD4(+) and CD8(+) T-cells, several pro-inflammatory cytokines and chemokines and memory cell responses to HIV-1-associated peptides. RESULTS: Although there was no improvement in CD4(+) T-cell counts, the percentage change in CD4(+)%, CD4(+)/CD8(+) ratios and RANTES (regulated on activation normal T-cells expressed and secreted) increased significantly while the percentage change in CD8(+) T-cell counts and CD8(+)%, activated CD4(+) T-cells and several pro-inflammatory chemokines and cytokines decreased significantly. The percentage change in HIV-1-specific nef, pol set 1, gag and env memory T-cells also declined. CONCLUSIONS: The addition of raltegravir to a virologically suppressive HAART regimen in patients with poor immunological responses resulted in the reduction of several pro-inflammatory biomarkers; increases were seen in RANTES levels and CD4(+)/CD8(+) T-cell ratios. The clinical relevance of these observations is beyond the scope of this study.

Low CD4+ T cell count is a risk factor for cardiovascular disease events in the HIV outpatient study.

BACKGROUND: Traditional cardiovascular disease (CVD) risk factors, human immunodeficiency virus (HIV) infection, and antiretroviral (ARV) agents have been associated with CVD events in HIV-infected patients. We investigated the association of low CD4(+) T lymphocyte cell count with incident CVD in a cohort of outpatients treated in 10 HIV specialty clinics in the United States. METHODS: We studied patients who were under observation from 1 January 2002 (baseline), categorized them according to National Cholesterol Education Program guidelines into 10-year cardiovascular risk score (10-y CVR) groups , and observed them until CVD event, death, last HIV Outpatient Study contact, or 30 September 2009. We calculated rates of incident CVD events and identified associated baseline risk factors using Cox proportional hazard models. We also performed a nested case-control study to examine the association of latest CD4(+) cell count with CVD events. RESULTS: Among 2005 patients, 148 experienced incident CVD events. CVD incidence increased steadily from 0.4 to 3.0 events per 100 person-years from lowest to highest 10-y CVR group (P < .001). In multivariable Cox analyses adjusted for 10-y CVR, CD4(+) cell count <350 cells/mm(3) was associated with incident CVD events (hazard ratio, 1.58 [95% confidence interval, 1.09-2.30], compared with >500 cells/mm(3)), suggesting an attributable risk of approximately 20%. In the multivariable case-control analyses, traditional CVD risk factors and latest CD4(+) cell count <500 cells/mm(3), but not cumulative use of ARV class or individual drugs, were associated with higher odds of experiencing CVD events. CONCLUSION: CD4(+) count <500 cells/mm(3) is an independent risk factor for incident CVD, comparable in attributable risk to several traditional CVD risk factors in the HIV Outpatient Study cohort.

AIDS-defining opportunistic illnesses in US patients, 1994-2007: a cohort study.

OBJECTIVES: To assess the incidence and spectrum of AIDS-defining opportunistic illnesses in the highly active antiretroviral therapy (cART) era. DESIGN: A prospective cohort study of 8070 participants in the HIV Outpatient Study at 12 U.S. HIV clinics. METHODS: We calculated incidence rates per 1000 person-years of observation for the first opportunistic infection, first opportunistic malignancy, and first occurrence of each individual opportunistic illness during 1994-2007. Using stratified Poisson regression models, and adjusting for sex, race, and HIV risk category, we modeled annual percentage changes in opportunistic illness incidence rates by calendar period. RESULTS: Eight thousand and seventy patients (baseline median age 38 years; median CD4 cell count 298 cells/microl) experienced 2027 incident opportunistic illnesses during a median of 2.9 years of observation. During 1994-1997, 1998-2002, and 2003-2007, respectively, rates of opportunistic infections (per 1000 person-years) were 89.0, 25.2 and 13.3 and rates of opportunistic malignancies were 23.4, 5.8 and 3.0 (P for trend <0.001 for both). Opportunistic illness rate decreases were similar for the subset of patients receiving cART. During 2003-2007, there were no significant changes in annual rates of opportunistic infections or opportunistic malignancies; the leading opportunistic illnesses (rate per 1000 person-years) were esophageal candidiasis (5.2), Pneumocystis pneumonia (3.9), cervical cancer (3.5), Mycobacterium avium complex infection (2.5), and cytomegalovirus disease (1.8); 36% opportunistic illness events occurred at CD4 cell counts at least 200 cells/microl. CONCLUSIONS: Opportunistic illness rates declined precipitously after introduction of cART and stabilized at low levels during 2003-2007. In this contemporary cART era, a third of opportunistic illnesses were diagnosed at CD4 cell counts at least 200 cells/microl.

Antiretroviral treatment interruptions and risk of non-opportunistic diseases.

Structured treatment interruptions have been studied as a strategy to reduce antiretroviral toxicities and expenditures in the treatment of HIV-infected individuals. Paradoxically, in addition to the increased incidence of death and opportunistic infections, these interruptions in therapy have resulted in the development of a number of non-opportunistic diseases, including cardiovascular events, renal insufficiency, hepatic failure, and non-AIDS-defining malignancies. Hypotheses regarding these findings suggest that the augmented stimulation of the host response to unabated viral replication may contribute to these comorbidities. Increased expression of chemokine receptor 5 and proinflammatory cytokines, disruption of immune cell function, and reduction in key inflammatory cells have been studied as potential mechanisms. Additionally, the increased inflammatory response has been shown to increase intracellular levels of nucleoside and nucleotide reverse transcriptase inhibitors, resulting in increased toxic manifestations. Structured treatment interruptions should be avoided in the management of HIV-infected individuals.

Initiation of antiretroviral therapy at CD4 cell counts >/=350 cells/mm3 does not increase incidence or risk of peripheral neuropathy, anemia, or renal insufficiency.

BACKGROUND: US guidelines recommend deferring initiation of highly active antiretroviral therapy (HAART) for most patients with CD4 counts >350 cells/mm in part because of concerns about antiretroviral toxicity. METHODS: Incidence rates of peripheral neuropathy, anemia, and renal insufficiency in a cohort of 2165 patients followed more than 3 years (mean) were analyzed in multivariate Cox proportional hazards models by CD4 cell counts at initiation of HAART. A nested cohort of 895 patients restricted to study participants who did or did not start HAART within a CD4 cell count stratum were also compared. RESULTS: Incidence and risks of all 3 comorbidities decreased with initiation of HAART at CD4 counts >200 cells/mm versus <200 cells/mm. Incidence and risks of renal insufficiency were similar with HAART initiation at CD4 counts >/=350 cells/mm versus 200 to 349 cells/mm, but risk of peripheral neuropathy and anemia were further decreased in persons starting HAART at a CD4 count >/=350 cells/mm. The incidence of these conditions was highest during the first 6 months of treatment at any CD4 cell count and declined up to 19-fold with further therapy. DISCUSSION: Initiating HAART at CD4 cell counts >/=200 cells/mm reduced the incidence and risk of the 3 comorbid conditions and for anemia and peripheral neuropathy as well by starting at CD4 counts >/=350 cells/mm. The incidence of each condition decreased rapidly and remained low with increasing time on HAART.

Effects of esomeprazole on the pharmacokinetics of atazanavir and fosamprenavir in a patient with human immunodeficiency virus infection.

The effects of proton pump inhibitors on the pharmacokinetics of atazanavir and amprenavir (administered as fosamprenavir) were rigorously evaluated in healthy volunteers in two studies, but formal studies in persons infected with human immunodeficiency virus (HIV) are lacking. We describe a 65-year-old man with HIV who underwent a 12-hour intensive pharmacokinetic study while receiving esomeprazole with atazanavir-ritonavir and subsequently, an 8-hour study while receiving esomeprazole with fosamprenavir-ritonavir. Consistent with the data in healthy volunteers, a major interaction between esomeprazole and atazanavir-ritonavir was observed in this patient-marked reductions in atazanavir trough plasma concentration and in the area under the concentration-time curve from 0-24 hours-whereas an interaction between esomeprazole and fosamprenavir-ritonavir was not apparent in this patient.

Redefining lipodystrophy syndrome: risks and impact on clinical decision making.

Lipodystrophy syndrome comprises several conditions (lipoatrophy; lipohypertrophy; mixed syndrome, often associated with dyslipidemia; and insulin resistance). These conditions, though sometimes occurring together, may occur independently, suggesting a complex, multifactorial cause. To elucidate the relative contribution of risk factors of drug, disease, and host to fat redistribution, large epidemiologic studies using multivariate analysis were reviewed. In studies assessing lipoatrophy, the most common statistically significant risk factors were use of specific nucleoside analogues, increasing age, presence of markers of disease severity (CD4/HIV RNA), duration of therapy, and white race. In studies assessing lipohypertrophy, the most common statistically significant risk factors were duration of therapy, markers of disease severity, and protease inhibitor use. The pathogenesis of these disorders is complex, but recent hypotheses and evidence suggest that impairment to adipocyte differentiation, impairment of adipokine regulation, unopposed production of proinflammatory cytokines, dysregulation of 11-beta-hydroxysteroid dehydrogenase, and mitochondrial toxicity may play a role.

Modification of the incidence of drug-associated symmetrical peripheral neuropathy by host and disease factors in the HIV outpatient study cohort.

BACKGROUND: We sought to identify factors associated with the clinical diagnosis of symmetrical peripheral neuropathy (SPN) during the era of highly active antiretroviral therapy (HAART) in a retrospective, longitudinal cohort analysis. METHODS: Patients infected with human immunodeficiency virus type 1 were evaluated for clinical signs of SPN and its association with immunologic, virologic, clinical, and drug treatment factors by means of univariate and multivariate logistic regression analyses. RESULTS: Of 2515 patients, 329 (13.1%) received a diagnosis of SPN. In the logistic regression analysis, statistically significant non-drug-based risk factors for SPN were age >40 years (adjusted odds ratio [aOR], 1.17), diabetes mellitus (aOR, 1.79), white race (aOR, 1.33), nadir CD4(+) T lymphocyte count <50 cells/mm(3) (aOR, 1.64), CD4(+) T lymphocyte count 50-199 cells/mm(3) (aOR, 1.40), and viral load >10,000 copies/mL at first measurement (aOR, 1.44). Although initial use of didanosine, stavudine (40 mg b.i.d.), nevirapine, or 4 protease inhibitors was associated with SPN (ORs for all 4 treatments, >1.41), the strength of association decreased with continued use of all medications studied. CONCLUSION: Since HAART was introduced, the incidence of SPN has decreased. Host factors and signs of increased disease severity were associated with an increased risk of developing SPN during the initial period of exposure to drug therapy. Immunity improved and the risk of SPN decreased with continued use of HAART. Delaying the initiation of therapy may select those individuals who will be more likely to develop SPN, and earlier initiation of HAART may decrease the risk of developing this common problem, as well as increase the therapeutic effects and decrease the toxic effects of the drugs.

The case for earlier treatment of HIV infection.

Current US guidelines advise that antiretroviral therapy for asymptomatic HIV patients should definitely be started for those who have CD4(+) cell counts of >200 cells/ microL, but antiretroviral therapy is often not started at CD4(+) cell counts much above that level. Guidelines advocating later therapy for HIV infection have been based mainly on sparse and limited cross-sectional data and have been predicated on avoiding drug-related toxicity and viral drug resistance. However, emerging data about factors that contribute to survival and the availability of newer, less toxic drugs are eroding this position. Earlier initiation of antiretroviral therapy--namely, for patients with CD4(+) cell counts of >350 cells/ microL--may, in fact, be associated with lower mortality, better immune improvement, and less drug-related toxicity. These findings coincide with the introduction of antiretroviral drugs that have become more effective and less difficult to take. Earlier initiation of therapy may also reduce HIV transmission, an important public health consideration, and may be beneficial in terms of overall therapeutic cost-effectiveness. Given these accumulating data, we believe reconsideration of the "when-to-start" question is timely and justified.

The cellular pharmacology of nucleoside- and nucleotide-analogue reverse-transcriptase inhibitors and its relationship to clinical toxicities.

Nucleoside- and nucleotide-analogue reverse-transcriptase inhibitors (NRTIs) require intracellular phosphorylation for anti-human immunodeficiency virus (HIV) activity and toxicity. Long-term toxicities associated with NRTIs may be related to overactivation of this process. In vitro experiments have shown increased rates of NRTI and endogenous nucleoside phosphorylation to be associated with cellular activation. Patients with advanced HIV disease often have overexpression of cytokines, which corresponds to an elevated cellular activation state. These patients also have higher rates of NRTI phosphorylation and NRTI toxicity, suggesting an interaction between a proinflammatory biological state, NRTI phosphorylation, and toxicity. Studies suggest that women may have higher rates of NRTI phosphorylation than do men, as well as increased risk for NRTI-induced toxicity. Future research is needed to understand the NRTI activation process and improve the long-term toxicity profile of NRTIs. Such research should include comparisons of NRTI phosphorylation according to sex and cellular activation state (i.e., elevated vs. low).

Total energy expenditure and carbohydrate oxidation are increased in the human immunodeficiency virus lipodystrophy syndrome.

To determine whether total energy expenditure (TEE) is increased in the human immunodeficiency virus (HIV) lipodystrophy syndrome, we compared energy expenditure (EE) and substrate oxidation rates in 12 HIV-infected men with lipodystrophy, 7 HIV-infected men without lipodystrophy, and 14 healthy controls. TEE and nutrient oxidation rates were assessed by whole-room indirect calorimetry. Resting energy expenditure (REE) was measured by indirect calorimetry using the open-circuit technique. Body composition was assessed by dual-energy x-ray absorptiometry (DEXA). Insulin sensitivity was measured using the insulin-modified frequently sampled intravenous glucose tolerance test. TEE adjusted for lean body mass (LBM) was significantly higher in the HIV-infected group with lipodystrophy compared to HIV-infected patients without lipodystrophy (2,873.3 +/- 69 v 2,573.9 +/- 92 kcal/d, P =.02) and compared to healthy controls (2,873.3 +/- 69 v 2,404.0 +/- 64 kcal/d, P <.001). REE and sleeping metabolic rate (SMR) adjusted for LBM were also significantly higher in the HIV-infected group with lipodystrophy compared to both HIV-infected and healthy controls. Carbohydrate oxidation rates adjusted for LBM were higher in men with HIV lipodystrophy as compared to healthy controls (362.5 +/- 23 v 250.0 +/- 22 g/d, P = <.01) and tended to be higher as compared to HIV-infected controls (362.5 +/- 23.6 v 297.3 +/- 31 g/d, P =.1). In conclusion, TEE and carbohydrate oxidation are increased in the HIV lipodystrophy syndrome. The increase in TEE appears to be due to increases in REE. The pathogenesis of elevated EE in HIV lipodystrophy and other forms of lipodystrophy remains to be determined.