A systematic review of filler agents for aesthetic treatment of HIV facial lipoatrophy (FLA).

HIV facial lipoatrophy (FLA) is characterized by facial volume loss. HIV FLA affects the facial contours of the cheeks, temples, and orbits, and is associated with social stigma. Although new highly active antiretroviral therapy medications are associated with less severe FLA, the prevalence of HIV FLA among treated individuals exceeds 50%. The goal of our systematic review is to examine published clinical studies involving the use of filler agents for aesthetic treatment of HIV FLA and to provide evidence-based recommendations based on published efficacy and safety data. A systematic review of the published literature was performed on July 1, 2015, on filler agents for aesthetic treatment of HIV FLA. Based on published studies, poly-L-lactic acid is the only filler agent with grade of recommendation: B. Other reviewed filler agents received grade of recommendation: C or D. Poly-L-lactic acid may be best for treatment over temples and cheeks, whereas calcium hydroxylapatite, with a Food and Drug Administration indication of subdermal implantation, may be best used deeply over bone for focal enhancement. Additional long-term randomized controlled trials are necessary to elucidate the advantages and disadvantages of fillers that have different biophysical properties, in conjunction with cost-effectiveness analysis, for treatment of HIV FLA.

Proposed ratios and cutoffs for the assessment of lipodystrophy in HIV-seropositive individuals.

OBJECTIVES: To propose objective ratios using anthropometry and dual-energy X-ray absorptiometry (DXA) and to suggest cutoff points for them in order to classify lipodystrophy in male patients. METHODS: It is a cross-sectional study. DXA was applied and anthropometric measurements were performed in 100 men on highly active antiretroviral therapy. Receiver operating characteristic curves were used to propose cutoffs. Individuals were divided in without (lipo-) or with (lipo+) lipodystrophy and their metabolic parameters were compared. RESULTS: The following ratios were proposed: fat mass ratio by DXA (FMR), waist thigh ratio (WTR), waist calf ratio (WCR), and arm to trunk ratio (ATR). The best cutoffs observed for FMR, WTR and ATR were 1.26, 1.74 and 2.08, respectively. Using the proposed cutoff for FMR, we observed worse metabolic profile, with increased tryglicerides, fasting serum glucose and more hypercholesterolemia in the lipo+ group. WTR and ATR showed a significant correlation with FMR. CONCLUSIONS: Anthropometric ratios (WTR/ATR) and FMR can be used to aid the diagnosis of lipodystrophy in order to contribute to a more accurate and earlier diagnosis permitting intervention and even preventing metabolic disturbances.

Social isolation in HIV-infected patients according to subjective patient assessment and DEXA-confirmed severity of lipodystrophy.

This study was designed to investigate the persistence of lipodystrophy (LD)-related social distress and isolation in HIV-infected patients in the current era, according to confirmatory dual energy X-ray absorptiometry (DEXA) measurements. Cross-sectional interview data were collected from 168 HIV-positive adult patients taking more than 2 years of antiretroviral therapy (133 cases with LD diagnosed a mean of 7.2 years before; 35 without LD, controls). Mean time of HIV infection was 16.2 years (2.1-27.3), and the mean time of exposure to highly active antiretroviral therapy of 11.7 years (2.1-21.1). The presence and severity of LD, confirmed by DEXA measurements, correlated with social isolation through a validated scale, including avoidance of social relationships, sex, work, or sport activities. In comparison with control patients, social distress was observed for patients having moderate body changes. The significant correlation between LD and social isolation was irrespective of age, CD4+ count, HIV RNA level, AIDS diagnosis, time of HIV infection, anxiety, or depressive symptoms. These results confirm that patient assessment of LD is correlated with whole-body DEXA scan, and they highlight the role of LD as an independent cause of social isolation even after years of the diagnosis.

Epidemiology, assessment, and management of excess abdominal fat in persons with HIV infection.

Metabolic and morphologic abnormalities in persons with HIV remain common contributors to stigma and morbidity. Increased abdominal circumference and visceral adiposity were first recognized in the late 1990s, soon after the advent of effective combination antiretroviral therapy. Visceral adiposity is commonly associated with metabolic abnormalities including low HDL-cholesterol, raised triglycerides, insulin resistance, and hypertension, a constellation of risk factors for cardiovascular disease and diabetes mellitus known as "the metabolic syndrome". Medline and conference abstracts were searched to identify clinical research on factors associated with visceral adiposity and randomized studies of management approaches. Data were critically reviewed by physicians familiar with the field. A range of host and lifestyle factors as well as antiretroviral drug choice were associated with increased visceral adiposity. Management approaches included treatment switching and metformin, both of which have shown benefit for insulin-resistant individuals with isolated fat accumulation. Testosterone supplements may also have benefits in a subset of individuals. Supra-physiological doses of recombinant human growth hormone and the growth hormone releasing hormone analog tesamorelin both significantly and selectively reduce visceral fat over 12-24 weeks; however, the benefits are only maintained if doping is continued. In summary, the prevention and management of visceral adiposity remains a substantial challenge in clinical practice.

Subjective clinical lipoatrophy assessment correlates with DEXA-measured limb fat.

OBJECTIVES: Although physician- and patient-rated diagnoses of lipoatrophy are currently used as a basis for inclusion into clinical trials, few studies have compared physician- or patient-rated lipoatrophy severity with objective measures. We aim to assess the validity of physician- and patient-rated diagnoses of lipoatrophy by evaluating the correlation between clinical assessments of lipoatrophy and objective fat indices. METHODS: This cross-sectional study evaluated the association between clinical lipoatrophy scores and DEXA-measured limb fat (n = 154) and subcutaneous fat mitochondrial DNA (mtDNA) levels (n = 80) in HIV+ individuals. RESULTS: There was a significant negative correlation between DEXA-measured limb fat and lipoatrophy scores generated by either the patients (r = -0.27, p = .008) or the physician (r = -0.48, p < .0001). Also, a significant positive correlation was found between the patient-generated lipoatrophy score and the physician score (r = 0.68, p < .0001). However, there was no correlation between fat mtDNA levels and DEXA-measured limb fat (r = -0.09, p = .42) or between physician- or patient-generated lipoatrophy scores (r = -0.09, p = .43, and r = 0.04, p = .71, respectively). CONCLUSION: These results suggest that physician- and patient-rated lipoatrophy scores may be useful surrogates for more expensive measures of lipoatrophy, which could be reserved for research studies.

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.

Objective assessment of facial lipoatrophy changes in a cohort of HIV-infected patients taking combination antiretroviral therapy.

BACKGROUND: An objective method is needed for assessing facial fat changes in HIV-infected patients. OBJECTIVE: To measure facial fat changes using three-dimensional laser scans (LS) and examine the relationship with clinically assessed lipoatrophy changes and dual-energy X-ray absorptiometry (DEXA) measured body composition changes in a cohort of patients taking combination antiretroviral therapy (ART). METHOD: Consecutive patients taking ART for at least 12 months were recruited from an outpatient clinic. Clinical lipoatrophy assessment, LS of the face, and whole-body DEXA were performed at baseline and repeated after 12 months. Cheek surface volume (CSV) change and cheek surface point displacement (CPD) change were calculated from the LS using a standardized technique. RESULTS: Baseline and follow-up assessments were obtained in 146 patients. In the 102 patients with stable clinical lipoatrophy grade during follow-up, there was no CSV change (0.0 +/- 1.7 mL). In the 27 patients with clinical lipoatrophy progression, CSV decreased by 1.3 +/- 1.8 mL (p < .001 vs. stable patients); in the 17 patients with clinical facial lipoatrophy recovery, CSV increased by 1.0 +/- 1.7 mL (p = .092 vs. stable patients). CSV change was significantly related to limb fat change in the overall cohort (r = 0.32, p < .001). Multivariate regression analysis showed that stavudine use was a significant independent predictor of CSV (beta = -0.20, p = .038). Similar results were seen with calculation of CPD change. CONCLUSION: LS can detect facial lipoatrophy changes in a cohort of patients over time and can clearly detect the effects of individual drugs. This may be an objective and reliable method to assess facial fat change in future clinical trials.

Mitochondrial DNA assessment in adipocytes and peripheral blood mononuclear cells of HIV-infected patients with lipodystrophy according to a validated case definition.

BACKGROUND: Several studies have compared mitochondrial DNA (mtDNA) content in tissue from HIV-1-infected patients on highly active antiretroviral therapy with and without evidence of lipodystrophy, the diagnosis of which was based on subjective clinical assessment. OBJECTIVES: The aim of this study was to assess the utility of mtDNA quantification as a marker of HIV-associated lipodystrophy as diagnosed using a published validated case definition. METHODS: We assessed mtDNA content in adipocytes from both thigh and lumbar subcutaneous adipose tissue (n=19), and in peripheral blood mononuclear cells (PBMC) (n=26), obtained from 26 HIV-1-infected patients classified as having lipodystrophy (n=17) or not having lipodystrophy (n=9) according to the validated definition derived from the Lipodystrophy Case Definition Study. RESULTS: The adipocyte and PBMC mtDNA contents did not significantly differ between patients with and without lipodystrophy. Lipodystrophy patients had been treated for significantly longer times, especially with dideoxynucleoside analogues. In both groups, the thigh adipocyte mtDNA content was significantly greater than that of the lumbar region. When all patients were considered together, a statistically significant negative correlation was found between thigh adipocyte mtDNA content and stavudine treatment duration. CONCLUSIONS: Longer exposure to dideoxynucleoside analogues was associated with lipodystrophy, and longer exposure to stavudine was correlated with lower mtDNA content in thigh adipocytes. However, a single measurement of adipocyte mtDNA content in this limited sample of patients could not distinguish between patients with and without clinical lipodystrophy. The observed variation in mtDNA content between different subcutaneous adipose tissue depots argues for harmonization of future studies regarding which depot to biopsy.

Laser scanning as a tool for assessment of HIV-related facial lipoatrophy: evaluation of accuracy and reproducibility.

BACKGROUND: Facial lipoatrophy (LA) is a common complication of highly active antiretroviral therapy (HAART). Research into causes and treatment of facial LA is hindered by the lack of an objective measurement tool. OBJECTIVE: To evaluate the accuracy and reproducibility of three-dimensional laser scanning (LS) for estimating cheek volume changes. METHODS: Paired laser scans were performed and the images superimposed using commercial software. The volume difference between images was computed within a circle of radius 25 mm placed in a standardized position over the cheek area. Accuracy was tested by scanning before and after known volumes of plasticine (0.5--5 mL) were applied to the cheek area of a mannequin to simulate volume change. Reproducibility was tested by repeated scanning of the mannequin with and without 2 mL of plasticine, and repeated scanning of 10 healthy subjects over the course of 1 week. RESULTS: The mean difference between actual and estimated volume change was small across the range of volumes tested [mean difference 0.08 mL; 95% confidence interval (CI)-0.36 to 0.20 mL). The coefficient of variation for repeated measurements of 2-mL volume change was 5.8%. The intraclass correlation coefficient for scan-to-scan variability was 0.812 (95% CI 0.515--0.947) and for day-to-day variability it was 0.764 (95% CI 0.332--0.935). Conclusions LS is an accurate and reproducible method for estimating cheek volume changes. It may be useful as an objective tool for assessment of facial LA in clinical research studies.