Doubly Labeled Water Method and Accelerometer for the Measurement of Energy Expenditure in Human Immunodeficiency Virus-Infected Patients.

BACKGROUND: Several studies have reported increased resting energy expenditure (REE) in human immunodeficiency virus (HIV)-infected patients with HIV-associated lipodystrophy syndrome (HALS). However, limited data exist on the total energy expenditure (TEE). This study was aimed at evaluating the REE and TEE of HIV-infected patients with and without HALS by using the doubly labeled water (DLW) technique and the activity monitor based on accelerometry system (AM), and comparing the results obtained using both methods. METHODS: Evaluated total of 45 HIV+ men undergoing antiretroviral therapy, including 18 LIPO- (without lipodystrophy) and 27 LIPO+ (with lipodystrophy) individuals were evaluated. Habitual physical activity patterns were measured by using the ActivPAL™ AM system, REE by indirect calorimetry, and TEE by DLW and AM. RESULTS: No significant differences were found between LIPO- and LIPO+ in REE (1,433 ± 196 vs. 1,510 ± 203 kcal), TEE-DLW (2,691 ± 856 vs. 2,618 ± 415 kcal) and TEE-AM (2,560 ± 458 vs. 2,594 ± 456 kcal), respectively. RQ was a predictor of REE in LIPO+. TEE estimated by the AM had a moderate correlation with DLW, but there was a wide variance in the intra-subject results. CONCLUSIONS: TEE is not increased in HIV-infected patients with HALS. AM should be used with caution for TEE evaluation during clinical practice.

Tesamorelin: a growth hormone-releasing factor analogue for HIV-associated lipodystrophy.

OBJECTIVE: To evaluate the efficacy and safety of tesamorelin, a growth hormone releasing factor analogue approved by the Food and Drug Administration in November 2010 for the treatment of lipodystrophy associated with HIV infection. DATA SOURCES: Literature was obtained through MEDLINE (1948-November 2011) and International Pharmaceutical Abstracts (1970-October 2011) using the search terms tesamorelin, TH9507, growth hormone releasing factor, and HIV-associated lipodystrophy syndrome. Additional publications were obtained through review of references within primary literature publications as well as pertinent Web sites. STUDY SELECTION AND DATA EXTRACTION: All articles published in English identified from the data sources were evaluated and all pertinent information was included. All studies relevant to the evaluation of efficacy and safety of tesamorelin in the management of HIV-associated lipodystrophy were included, with a focus on trials completed in humans. DATA SYNTHESIS: In 2 Phase 3 clinical trials and their pooled analyses, tesamorelin was proven to significantly decrease waist circumference and visceral adipose tissue (VAT) following 26 weeks of treatment. Both trials also demonstrated significant improvements in some subjective body image parameters. Both studies had 26-week extension phases that confirmed maintenance of VAT improvements on treatment without adverse impact on blood glucose and lipid parameters. Limited data support off-label uses of tesamorelin at this time. CONCLUSIONS: Tesamorelin is effective in improving visceral adiposity and body image in patients with HIV-associated lipodystrophy over 26-52 weeks of treatment. Potential limitations for its use include high cost and lack of long-term safety and adherence data. Tesamorelin provides a useful treatment option for management of patients with significant lipodystrophy related to HIV infection.

Sonographic assessment of facial HIV-related lypoatrophy.

OBJECTIVE: To investigate the utility of ultrasonography (US) for assessing and grading facial lypoatrophy (FLA) in patients with HIV. DESIGN: The social effect of FLA is huge and may reduce antiretroviral therapy adherence. Strategies for the early detection of FLA are crucial, because complete correction of FLA in late stages is unlikely. METHODS: Fifty-two HIV-positive patients undergoing highly active antiretroviral therapy underwent US with nasogenian transversal scan using a high-frequency broadband transducer (5-17 MHz) to detect FLA. Intra- and interobserver variability were calculated to assess US reproducibility. Concerning FLA grading, patients were categorized in five clinical classes and four US classes. RESULTS: Our results regarding inter- and intraobserver coefficients of variation permit the validation of US as a reproducible technique (p<.001), and a high correlation between US and clinical classification was obtained, with complete concordance for more advanced FLA classes. CONCLUSIONS: The lack of a reference objective method to quantify subcutaneous fat is a major difficulty in measuring HIV-related FLA. Our results, in accordance with data from the literature, suggest that US is an ideal tool for assessing and grading FLA. Furthermore, US may be suitable for routine evaluation in HIV-infected patients for early detection of FLA and to select its optimal management.

Assessment of ultrasound for use in detecting lipoatrophy in HIV-infected patients taking combination antiretroviral therapy.

The aim of this study was evaluation of ultrasound (US) as a tool for the assessment of lipoatrophy in a population of HIV-infected patients. We enrolled a convenience sample of 151 HIV-infected Caucasian participants (males, 79%) who were treated for at least 1 year with combination antiretroviral therapy (CART) in Zagreb, Croatia. US measurements of subcutaneous fat thickness were done over the malar, brachial, and crural region. We determined sensitivity and specificity of US as a diagnostic tool for lipoatrophy using receiver-operating curves and concordant patient and clinician assessment as our reference for the presence of lipoatrophy. HIV was acquired through heterosexual contact in 50% of participants and by sex between men in 42%. The mean current CD4 cell count was 503.1 cells=mm3 (standard deviation [SD] = 250.8). Seventy-seven (51%) participants were treated with stavudine and 91 (64%) with a protease inhibitor for at least 6 months. Nineteen (13%)participants had lipoatrophy in at least one anatomic site. Sensitivity of US ranged from 67%-71%, specificity from 65%-71%, positive and negative predictive values ranged from 11%-20% and 96-97%, respectively. US diagnosed lipoatrophy was more frequently found in patients with a history of stavudine treatment and in females. Patients with lipoatrophy had a longer duration of CART than those without lipoatrophy. US is a useful tool in ruling out the presence of clinical lipoatrophy in patients on CART. Using this objective measure of subcutaneous fat may be useful in helping clinicians make decisions about changing therapy.

Quality of life and body image in the assessment of psychological impact of lipodystrophy: validation of the Italian version of assessment of body change and distress questionnaire.

Lipodystrophy (LD) includes morphologic changes that are distressing to patients with HIV. We tested the validity of an Italian version of the Assessment of Body Change and Distress (ABCD) questionnaire and analysed its relationship to physical and mental aspects of Health-Related Quality of Life. Two hundred and fifty-two patients completed the questionnaires. Construct validity of the ABCD was tested against the MOS-HIV Health Survey, body mass-index (BMI) and CD4+ T-lymphocyte counts. Cronbach's alpha for the ABCD total score was 0.94. The ABCD showed the hypothesized moderate correlations to MOS-HIV scales and clinical variables. Preliminary evidence supports the reliability and validity of the Italian version of the ABCD in people with HIV and LD. This questionnaire may be useful to identify people experiencing greater impact of LD, or to evaluate the impact of interventions to treat LD such as plastic surgery.

Assessment of adipokine expression and mitochondrial toxicity in HIV patients with lipoatrophy on stavudine- and zidovudine-containing regimens.

OBJECTIVES: Despite evidence for the role of adipokines such as adiponectin in the metabolic toxicities of protease inhibitor (PI)-treated patients, little is known about their role in nucleoside reverse transcriptase inhibitor (NRTI)-induced lipoatrophy (LA). We analyzed the relations between mitochondrial toxicity, adipokine expression, and clinical LA in peripheral blood mononuclear cells (PBMCs) and adipose samples from individuals treated with stavudine (d4T) or zidovudine (ZDV) in comparison to patients undergoing highly active antiretroviral therapy (HAART) as well as HIV-negative individuals. METHODS: In this cross-sectional analysis, we studied 18 PI-naive HIV-infected patients with LA treated with d4T (d4T+LA+ [n = 12]) or zidovudine (ZDV+LA+ [n = 6]) in comparison to HAART-treated patients with (HAART+LA+ [n = 8]) and without (HAART+LA- [n = 8]) LA as well as HIV-negative controls (n = 12). Adipose samples were assessed for protein and/or messenger RNA (mRNA) levels of adiponectin, tumor necrosis factor-alpha (TNFalpha), interleukin (IL)-6, and sterol regulatory element-binding protein (SREBP) 1a/c in all groups, whereas adipose and PBMC samples from the d4T+LA+, ZDV+LA+, and HIV-negative subgroups were assessed for mitochondrial DNA (mtDNA) depletion and cytochrome c-oxidase (COX) II/COX IV ratios. RESULTS: There was no change in mtDNA levels in adipose or PBMC samples in NRTI-treated patients with LA, although patients treated with d4T had reduced COX II/COX IV ratios in adipose and PBMC samples. Adipose tissue adiponectin mRNA and plasma levels were reduced in the d4T- and ZDV-treated patients regardless of the use of PIs. Tissue SREBP1c mRNA levels were also significantly reduced in both NRTI groups when compared with the HIV-negative controls. Significant reductions in SREBP1c levels were also evident with the HAART+LA+ group when compared with HAART+LA- controls. CONCLUSIONS: Patients with LA on d4T-based regimens show evidence of mitochondrial respiratory chain dysfunction, whereas the d4T- and ZDV-based regimens also demonstrated reduced SREBP1c and adiponectin levels, findings that have previously been shown with PIs.