HIV Lipoatrophy Research Articles

PCSK9 and ANGPTL3 levels correlate with hyperlipidemia in HIV-lipoatrophy, are regulated by fasting and are not affected by leptin administered in physiologic or pharmacologic doses

BackgroundMedications leveraging the leptin, PCSK9, ANGPTL3 and FABP4 pathways are being developed for the treatment of insulin resistance and/or lipid disorders. To evaluate whether these pathways are independent from each other, we assessed the levels of PCSK9, ANGPTL3 and FABP4, in normal subjects and subjects exhibiting HIV and highly active antiretroviral therapy (HAART) induced metabolic syndrome with lipoatrophy and hypoleptinemia. Studies were performed at baseline and during food deprivation for three days with either a placebo or leptin administration at physiological replacement doses to correct fasting induced acute hypoleptinemia and in pharmacological doses. MethodsPCSK9, ANGPTL3, FABP4 levels and their correlations to lipoproteins-metabolites were assessed in randomized placebo controlled cross-over studies: a) in 15 normal-weight individuals undergoing three-day admissions in the fed state, in complete fasting with placebo and in complete fasting with leptin treatment in physiologic replacement doses (study 1), b) in 15 individuals day baseline in a fed and three fasting admissions for three days with leptin administered in physiologic, supraphysiologic and pharmacologic doses (study 2), c) in 7 hypoleptinemic men with HIV and HAART-induced lipoatrophy treated with leptin or placebo for two months in the context of a cross over randomized trial (study 3). ResultsCirculating ANGPTL3, PCSK9 and FABP4 were markedly elevated in HIV-lipoatrophy and not affected by leptin treatment. PCSK9 levels correlated with lipids and markers of lipid utilization and lipolysis. ANGPTL3 levels correlated with HDL particles and their lipid composition. FABP4 levels were negatively associated with HDL diameter (HDL-D) and composition. PCSK9 and ANGPTL3 levels decreased during food deprivation by ~65 % and 30 % respectively. Leptin administration at physiologic, supraphysiologic and pharmacologic doses did not affect PCSK9, ANGPTL3 and FABP4 levels. ConclusionsPCSK9, ANGPTL3 and FABP4 levels are associated with markers of lipid metabolism and are higher in HIV-lipoatrophy. PCSK9 and ANGPTL3 but not FABP4 decrease in response to food deprivation. PCSK9 and ANGPTL3 regulation is leptin-independent, suggesting independent pathways for lipid regulation. Thus, combining treatments of leptin with PCSK9 and/or ANGPTL3 inhibitors for metabolic diseases should have additive effects and merit further investigation. Clinical trial informationClinicalTrials.gov no. NCT00140231, NCT00140205, NCT00140244.

Poly-L-lactic acid for the Improvement of photodamage and rhytids of the décolletage.

Poly-L-lactic acid (PLLA) is a biostimulatory filler approved for use in HIV lipoatrophy as well as cosmetic improvement in facial folds and wrinkles in immunocompetent patients. Similar to the face and hands, the décolletage is commonly subject to photodamage and the resulting appearance of rhytids and crepiness, which could benefit from PLLA treatment. The objective of the study was to assess the safety and efficacy of injected PLLA for the improvement in rhytids and crepiness of the décolletage. In this open-label, prospective, interventional study, 25 healthy female volunteers aged 40-to-70years with moderate-to-severe crepiness and wrinkling of the décolletage were injected with 1 vial of PLLA at each of three treatments. The Fabi-Bolton 5-point chest wrinkling scale was used by both investigators and subjects to assign pretreatment and post-treatment follow-up scores at 1month, 3months, and 6months. Adverse events were reported at each visit. All post-treatment mean scores had statistically significant improvement compared to the pretreatment baseline means as rated by both investigators and subjects. At 1month following the last treatment, compared to baseline, investigators rated 83% of subjects had improved by at least one point on the scale. Subjects rated 74% of subjects improved by at least one point. At 6months, 90% of subjects, as rated by the investigators, and 57% of subjects, as rated by the subjects, had improvement from baseline. PLLA is safe and effective for improvement in the rhytids and skin quality of the photodamaged décolletage.

The Facial Appearance Inventory: Development and Preliminary Evidence for Reliability and Validity in People with HIV and Lipoatrophy.

Facial lipoatrophy is common in people on antiretroviral (ARV) regimens for HIV/AIDS and can impair health-related quality of life. We developed the Facial Appearance Inventory (FAI) to measure the impact of ARV-associated facial lipoatrophy. Qualitative methods were used to identify key concerns of people with facial lipoatrophy. The major concerns were used to identify 24 items for the FAI. The FAI was administered to a cross-sectional sample of 96 people with HIV and facial lipoatrophy and compared to the established Assessment of Body Change Distress (ABCD) and MOS-HIV questionnaires. Mean age was 48.8 years, 87.5% were men, 69.8% were Caucasian, and 60% had some college education. Mean CD4 count was 435 cells/mm(3). There were few missing data, and the summary score showed no floor or ceiling effects, with a mean (SD) of 25.6 (17.9). Cronbach's alpha for the scale was 0.98. FAI items satisfied criteria for convergent and discriminant construct validity. FAI items were more strongly correlated with mental health domains (R = 0.33) than with physical health domains (R = 0.26) on the MOS-HIV. Patients with greater severity of lipoatrophy had significantly worse scores than those with less severity (James 3-4, vs. James 0-2). There were no significant differences for FAI scores by age group, income group, CD4 cell count, or HIV viral load group. Those with less education and those with darker skin types reported less impairment (P < .05). The 24-item FAI shows evidence for reliability, validity, and usefulness as a measure of the impact of facial lipoatrophy.

Adipokines, hormones related to body composition, and insulin resistance in HIV fat redistribution syndrome.

BackgroundLipodystrophies are characterized by adipose tissue redistribution, insulin resistance (IR) and metabolic complications. Adipokines and hormones related to body composition may play an important role linking these alterations. Our aim was to evaluate adipocyte-derived hormones (adiponectin, leptin, resistin, TNF-α, PAI-1) and ghrelin plasma levels and their relationship with IR in HIV-infected patients according to the presence of lipodystrophy and fat redistribution.MethodsAnthropometric and metabolic parameters, HOMA-IR, body composition by DXA and CT, and adipokines were evaluated in 217 HIV-infected patients on cART and 74 controls. Fat mass ratio defined lipodystrophy (L-FMR) was defined as the ratio of the percentage of the trunk fat mass to the percentage of the lower limb fat mass by DXA. Patient’s fat redistribution was classified into 4 different groups according the presence or absence of either clinical lipoatrophy or abdominal prominence: no lipodystrophy, isolated central fat accumulation (ICFA), isolated lipoatrophy and mixed forms (MXF). The associations between adipokines levels and anthropometric, metabolic and body composition were estimated by Spearman correlation.ResultsLeptin levels were lower in patients with FMR-L and isolated lipoatrophy, and higher in those with ICFA and MXF. Positive correlations were found between leptin and body fat (total, trunk, leg, arm fat evaluated by DXA, and total, visceral (VAT), subcutaneous adipose tissue (SAT), and VAT/SAT ratio evaluated by CT) regardless of FMR-L, and with HOMA-IR only in patients with FMR-L. Adiponectin correlated negatively with VAT, and its mean levels were lower in patients with ICFA and higher in those with no lipodystrophy. Resistin was not correlated with adipose tissue but positively correlated with HOMA-IR in FMR-L patients. PAI-1 levels were higher in MXF-patients and their levels were positively correlated with VAT in those with FMR-L. Ghrelin was higher in HIV-infected patients than controls despite BMI-matching.ConclusionThe overall body fat reduction in HIV lipoatrophy was associated with low leptin plasma levels, and visceral fat accumulation was mainly associated with decreased plasma levels of adiponectin.

A new scientific era in biomedicine – regenerative surgery based on lipotransplant. New therapeutic horizons for HIV-positive patients

Very often the psychological repercussions of lipodystrophy in HIV infected patients are important to a level that can reach reluctance to antiretroviral therapy or lead to depression and anxiety. In some patients' opinion, it is easier to live with HIV than with lipodystrophy. The facial appearance is perceived by the patient and the society as a stigma of this particular condition, with all negative consequences. We know that HIV-related lipodystrophy (first described in '97 and '98) is expressed by peripheral atrophy of the face, limbs and buttocks, simultaneous with central fat accumulation (visceral), as well as in the breasts, neck and dorsocervical area (the so-called “buffalo hump”). These features coexist with subcutaneous lipomas and metabolic disturbances such as insulin resistance, hypercholesterolemia and hypertriglyceridemia. Although the distribution of the adipose tissue is unbalanced (visceral increase and peripheral decrease) with overall fat loss, the mean body mass is preserved. The pathogenesis of HIV lipodystrophy remains unclear. Consistent studies (cohort and in vitro) of adipocytes, skeletal muscle and hepatocytes point toward a complex of factors involving antiretroviral theories, environmental and host-related aspects. The most effective treatment for facial lipodystrophy in HIV positive patients is still to be found; numerous treatment attempts have been made, based on changes in antiretroviral therapy, addition of other drugs (such as growth hormones, insulin, steroids), lipid-lowering drugs, diets or exercising, but these attempts have often proved disappointing. Even the nonresorbable or (slowly) resorbable fillers came with their high rate of complications. In this light, the newly born regenerative plastic surgery seems to be a very promising therapeutic solution. It is important to mention the brilliant scientific and practical contribution of pioneers in this field: S. Coleman, J.M. Serra-Renom, J. Fontdevila, M. Eisenmann-Klein, G. Rigotti, N. Pallua, P. Rubin, W. Futrell, R. Khouri, R. Mazzola, K. Yoshimura. Although facial fat grafting for HIV infected patients began in the late ’90s, the techniques (and instruments) have only recently become more refined, more precise, with a higher degree of predictability. And very importantly – there is more (although still not enough) science behind this approach, leading to a better understanding of the composition and behavior of the various cellular populations and other components generically called “adipose tissue”, which will soon probably be named “adipose organ”. The new researches and applications on adipose tissue revealed a whole fascinating universe of new therapies and scientific paths. “Adipocytes”, “preadipocytes”, “ADSC’s” (adipose-derived stromal cells), “niche”, scaffold, cell-cell interaction, blood circulating factors, paracrine factors, cell-matrix interaction, neurotransmitters, are key terms and, in the same time, key elements involved in regenerative surgery using fat transplant, leading to healing processes in facial HIV lipoatrophy. This novel type of closed surgery requires harvesting of the fat from the excessive deposits, which is then slowly centrifuged and transplanted with very fine instruments. The transplanted fat is stimulated with Fractional CO2 LASER (λ10600 nm) and with diode LASER (λ860 nm) as promising additional therapy due to LLLT (low level laser therapy). The LASER has at least two effects, acting to improve the quality of the skin (which is often very damaged) and optimize the take of the adipose graft. Due to the systemic effect of LLLT (and the derived photoproducts described by Mester and Oshiro), it is possible to record normalizations of remote tissue (cellular) disturbances. To improve skin condition and fat graft survival, one other additional simultaneous therapy can be performed – PRP (platelet-rich plasma), which contains growth factors. The science has still to deepen the good, often remarkable clinical results. The therapies based on self cellular regeneration with autologous products (adipose tissue transplant and stem cells, PRP) acting in synergy with light (LASER) energy and the science behind them, appear as an interesting, vast “station” for treating various conditions including HIV lipoatrophy, until the next scientific challenge, such as gene engineering therapy, becomes available.

Experience with polymethylmethacrylate 30% (PMMA) facial filling in patients with facial HIV lipoatrophy using of local anesthesia dentistry

BackgroundHIV‐associated lipoatrophy in a common and stigmatizing side effect of HIV infection, is aggravated by antiretroviral therapy; its presence causes distress and compromises adherence to therapy. PMMA filling is often associated with pain and discomfort.ObjectiveTo evaluate outpatient intervention using local dentistry anesthesia.MethodsPatients complaining of facial lipoatrophy, from 10/2007 to 11/2011, were offered the filling with PMMA. Cases with bleeding potential, acute or decompensated chronic diseases or use of immunosuppressors or chemotherapy were excluded. Inclusion criteria: perception of distressing malar lipoatrophy and both the assisting physician and the applicant agreeing with potential benefit. After informed consent, patients were infused with 30 mg prilocaine/0.03 IU felypressin in 1.8 ml, using a carpule type syringe aiming to block the posterior superior alveolar nerve. This was followed by PMMA infiltration in different points at the malar region. At first return a simple questionnaire evaluating pain, satisfaction, grading 0 to 10 and if would repeat the procedure.ResultsAll 64 eligible patients were included. Mean age 46 (13 to 73) years, mostly white (71.87%), males (68.75%), 37.5% of them MSM. Arterial hypertension was the most prevalent comorbidity (17%), 78% with viral load &lt;50 c/mL, with a median 585 CD4 cells/mL (95–2063). On a median of 8 years on treatment, 1/3 had been exposed to three classes (NRTI/ NNRTI/PI), one antiretroviral‐naïve. Of the 12 patients who had detectable viral load in the first procedure, seven were suppressed to below 50 copies/mL during follow up. Two of the five patients remaining with detectable viremia died from other causes, 2 transferred and 1 remained naïve. 127 procedures were made in 64 patients, a median of 2 (1–6) per patient. After a mean follow‐up of 33 weeks, no infection or late complications were observed. Mean dispensed volume was 9 mL (1.5 to 22). Pain grade was documented in 105 procedures; grade &lt;4 reported by 46%, 4–6 by 34%; 7–8 by 16%, 9 by 2%. All reported that the pain would not hamper future procedures; 94% refer an overall satisfaction from 8 to 10.ConclusionThe use of local anesthesia in dental facial filling with PMMA in patients with HIV lipoatrophy of the face is safe, decreases pain to tolerable levels and allows high levels of satisfaction with the procedure. The procedure may improve patient adherence to ARV.

Mitochondrial Function, Inflammation, Fat and Bone in HIV Lipoatrophy: Randomized Study of Uridine Supplementation or Switch to Tenofovir

Lipoatrophy modestly improves when the thymidine analogue nucleoside reverse transcriptase inhibitor (tNRTI) is removed. In vitro, uridine (NucleomaxX(®); Pharma Nord, Vojens, Denmark) reversed tNRTI mitochondrial toxicity. All patients had lipoatrophy on a tNRTI-containing regimen with HIV RNA<400 copies/ml. A randomized 48-week study switched patients from tNRTI to tenofovir (TDF) or added uridine (continuing tNRTI). End points were changes in limb fat (DEXA), subcutaneous abdominal fat mitochondrial DNA (mtDNA) and mitochondrial RNA (mtRNA), inflammation markers (soluble tumour necrosis factor receptors, high-sensitivity C reactive protein [hsCRP], interleukin-6 [IL-6], soluble vascular cell adhesion molecule 1), bone mineral density (BMD) of the hip and spine, HIV-1 RNA, CD4(+) T-cells and fasting metabolic parameters. Fifty patients were enrolled (n=24 TDF switch; n=26 uridine); median age 48 years; 54% white; 86% male; limb fat 4,494 g. Baseline characteristics were similar between groups. In the NucleomaxX(®) arm, mtRNA increased (all P<0.001), hsCRP and IL-6 increased (both P=0.02), whereas fat mtDNA decreased without changes in limb fat. In the TDF-switch arm, fat mtDNA and inflammation markers did not change; however, significant increases in mtRNAs (P<0.001), limb fat (409 g; IQR -59-1,155) and CD4(+) T-cell count (P=0.03), and decreases in total and hip BMD (median -3.3%; IQR -5.1-0; P=0.005) were observed. Between-group changes were significant for fat mtDNA, hsCRP, IL-6, limb fat and hip BMD. No correlation was found between changes in limb fat and those of fat mtRNA, inflammation markers or protease inhibitor duration. In HIV lipoatrophy, NucleomaxX(®) improved mtRNA, but worsened inflammation markers and fat mtDNA without changes in limb fat. Switching from a tNRTI to TDF for 48 weeks increased limb fat and fat mtRNA. Large decreases in total and hip BMD were seen after TDF switch. ClinicalTrials.gov identifier: NCT00119379.

Association between 25‐OH vitamin D and insulin is independent of lipoatrophy in HIV

Vitamin D deficiency (VDD) is prevalent in HIV, and following antiretroviral therapy (ART), increased rates of lipoatrophy and metabolic abnormalities are described. We investigated the relationships between 25-hydroxyvitamin D [25(OH)D] and other metabolic parameters in a group of HIV patients with and without lipoatrophy to examine whether lipoatrophy could explain the high prevalence of VDD and metabolic abnormalities. Vitamin D receptors are expressed in adipose tissue implicating vitamin D, through paracrine/autocrine mechanism, in exerting effects on fat metabolism. HIV patients frequently suffer from VDD, and those treated with thymidine analogues frequently suffer from lipoatrophy so we investigated whether lipoatrophy could explain these associations. Cross-sectional study of HIV-infected male patients (n = 107; 39 with lipoatrophy) from the West Australian cohort with measurements of 25(OH)D, adiponectin, insulin, lipids and leg fat as a percentage of mass. Reduced 25(OH)D levels were common and significantly associated with higher serum insulin in the entire cohort (P = 0·006), but there was no difference in 25(OH)D between untreated and antiretroviral-treated patients with or without lipoatrophy. Treated patients with lipoatrophy were more likely to take thymidine analogue therapy, were older and on therapy longer than treated patients without lipoatrophy. Adiponectin levels did not correlate with 25(OH)D, but lipoatrophic-treated patients had lower levels of adiponectin compared with nonlipoatrophic-treated patients. Lower 25(OH)D is associated with higher serum insulin but not lipoatrophy or hypoadiponectinemia in HIV-infected patients. The association between VDD and insulin resistance is likely to be mediated by independent mechanisms.

Changes in Inflammation, Oxidative Stress, Mitochondrial DNA Content after Rosiglitazone in HIV Lipoatrophy

OBJECTIVE: We aim to evaluate the mechanisms of rosiglitazone-induced fat recovery in HIV+ patients with lipoatrophy on thymidine Nucleoside Reverse Transcriptase Inhibitors (NRTI) sparing regimens. METHOD: Measures of limb fat (DXA), oxidative stress (F2 isoprostanes) and inflammation [High-sensitivity C-reactive protein (hsCRP), soluble Tumor Necrosis Factor Receptors (sTNFR)-I, sTNFR-II, and interleukin (IL)-6] were performed. Gluteal fat mitochondrial DNA (mtDNA) and peroxisome proliferator-activated receptor (PPAR)-γ RNA [expressed as PPAR-γ/Glyceraldehyde 6-Phosphate Dehydrogenase (GAPDH) RNA ratio] were measured by quantitative PCR. RESULT: 71 patients on thymidine NRTI-sparing regimens were randomized to rosiglitazone vs. placebo for 48 weeks. Duration off thymidine NRTIs was similar between groups. From week 0-48, limb fat increased significantly (p=0.02) more in the rosiglitazone than in the placebo group. Within both groups, F2-isoprostanes, sTNFR-I and sTNFR-II increased significantly (p ≤ 0.003), hsCRP decreased significantly (≤ 0.02), and IL-6 did not change. No differences were seen between groups in any of the inflammation markers. Fat mtDNA (copies/cell) increased nonsignificantly: +41(p=0.08) and +29(p=0.38) within rosiglitazone and placebo group; respectively. PPAR-γ/GAPDH ratio did not change within or between groups. CONCLUSION: Limb fat improvements seen after rosiglitazone were not associated with changes in mtDNA, oxidative or inflammation markers, or PPAR-γ expression. F2 isoprostanes and some of the inflammation markers worsened over time in these subjects on stable ART, regardless of the rosiglitazone assignment. Thus, lipoatrophy can be in part overcome by a separate pathway independent of mitochondrial DNA depletion, such as PPAR-γ.

Psychological morbidity and facial volume in HIV lipodystrophy: Quantification of treatment outcome

HIV lipoatrophy is a stigmatizing condition associated with significant psychological morbidity. The aim of this study was to evaluate change in facial volume and psychological morbidity following treatment with autologous fat, Sculptra and Bio-alcamid. HIV LD patients were treated based on a clinical assessment in a prospective, observational study. 3-D images were obtained pre-operatively then at 2, 6 and 12 months post-operatively using the DI3D system. Volume changes were measured using DI3D software. The DAS-24 and HADS were used to assess psychological morbidity at similar time intervals. Forty-eight patients with HIV LD were treated: 16 patients had Bio-alcamid, 20 patients received Sculptra and 12 patients underwent fat transfer. The mean injected volume of Bio-alcamid was 25.5 cc which was comparable to the measured volume change at follow-up. The mean injected volume of fat was 20.1 cc, which did not differ from the measured volumes at 2 months. There was a mean reduction in measured volume change to11.2 cc at 6 months and 10 cc at 12 months. For Sculptra, the mean volume change compared to baseline was 8.7 cc at 2 months, increasing to 12.6 cc at 6 months and 12.3 cc at 12 months. ANOVA tests demonstrated no difference in psychological outcomes between groups. There was a significant improvement in DAS-24 scores compared to baseline for all 3 groups. No correlation between change in facial volume and psychological measures was demonstrated. Change in 3-D measured facial volume for all 3 groups was seen. Treatment was associated with improved body image perception.

Surgical correction of HIV-associated facial lipoatrophy

Surgical correction of HIV-associated facial lipoatrophy

Uridine supplementation in the treatment of HIV lipoatrophy: results of ACTG 5229

Lipoatrophy is prevalent on thymidine nucleoside reverse transcriptase inhibitors (tNRTIs). A pilot trial showed that uridine (NucleomaxX) increased limb fat. A5229 was a multicenter trial in which HIV-infected individuals with lipoatrophy on tNRTI regimens were randomized to NucleomaxX or placebo. Primary endpoint was change in limb fat from baseline to week 48. The study was powered to detect 400-g difference between arms at week 48. A stratified Wilcoxon rank-sum test was used to assess between-arm differences. The 165 participants were 91% men, 62% white; median age 49 years, CD4 cell count 506 cells/μl, and limb fat 3037 g; 81% had HIV-1 RNA 50 copies/ml or less; 76% were on zidovudine (ZDV). Baseline characteristics were similar between groups. Only 59% completed 48 weeks of treatment; however, only three participants (one on uridine) discontinued due to toxicity (diarrhea). In intent to treat, there was no difference for changes in limb fat between treatments at week 24 or week 48. On as-treated analysis, uridine resulted in an increase in %limb fat vs. placebo (3.4 vs. -0.8%, P = 0.01) at week 24 but not at week 48 (1.8 vs. 3.8%, P = 0.93). Similar results were seen when limiting the analysis to patients with at least 80% adherence. The results were not related to severity of lipoatrophy or type of tNRTI. No changes were found in facial anthropometrics, fasting lipids, trunk fat, CD4 cell count, or HIV RNA. We found a modest transient improvement in limb fat after 24 weeks of uridine. The lack of sustained efficacy at week 48 was not due to changes in adherence or reduction in sample size. Uridine was well tolerated and did not impair virologic control.

No significant effect of uridine or pravastatin treatment for HIV lipoatrophy in men who have ceased thymidine analogue nucleoside reverse transcriptase inhibitor therapy: a randomized trial*

Lipoatrophy can complicate thymidine analogue nucleoside reverse transcriptase inhibitor (tNRTI)-based antiretroviral therapy (ART). Lipoatrophy may be less likely with ART including ritonavir-boosted lopinavir (LPV/r). Small, placebo-controlled studies found that uridine (in tNRTI recipients) and pravastatin improved HIV lipoatrophy over 12 weeks. Today, most patients with lipoatrophy receive non-tNRTI-based ART; the effect of uridine in such patients is unknown. We performed a prospective, randomized trial in lipoatrophic adults with plasma HIV RNA<50 HIV-1 RNA copies/mL on tNRTI-sparing ART including LPV/r. Patients received uridine [36 g three times a day (tid) on 10 consecutive days per month; n=10], pravastatin [40 mg every night (nocte); n=12], uridine plus pravastatin (n=11) or neither (n=12) for 24 weeks. The primary endpoint was mean change in limb fat mass as assessed by dual-energy X-ray absorptiometry (DEXA). With 20 patients per intervention, the study had 80% power to detect a mean difference between a treatment and the control of 0.5 kg, assuming a standard deviation of 0.9 and an alpha threshold equal to 5% (two-sided). Of 45 participants (all men, with median age 49.5 years and median limb fat 2.6 kg), two discontinued pravastatin and one participant stopped both pravastatin and uridine. The difference between the mean changes in limb fat mass for uridine vs. no uridine was 0.03 kg [95% confidence interval (CI) -0.35, +0.28; P=0.79]. The respective difference for pravastatin was -0.03 kg (95% CI -0.29, +0.34; P=0.84). Pravastatin slightly decreased total cholesterol (0.44 mmol/L; P=0.099). Visceral adipose tissue measured by computed tomography did not change significantly. In this population and at the doses used, neither uridine nor pravastatin for 24 weeks significantly increased limb fat mass.

Estimation of Total-Body and Regional Soft Tissue Composition From DXA Bone Densitometry of the Lumbar Spine and Hip

The percent fat in soft tissues adjacent to the lumbar spine and proximal femur, which are required parameters in the calculation of bone mineral by conventional dual-energy X-ray absorptiometry (DXA) of the spine and hip, were analyzed for their relationship with the total-body soft tissue–scanning derivatives. The cohort (N = 149), consisting of stable actively treated male human immunodeficiency virus HIV-positive patients, was split in half to obtain prediction equations with one half to be validated by the other half. Prediction equations for the dependent variables total-body fat, total-body lean mass, trunk fat, total arm + leg fat, and leg fat were derived by step-down multiple regression. A Bland-Altman comparison of the predicted and observed values showed that the limits of agreement were too large to be clinically helpful. The correlations of the ratio of adjacent spine/hip fat with ratios of trunk/arm + leg fat and trunk/leg fat, markers of peripheral lipoatrophy in HIV, were 0.725 and 0.780, respectively. The 3 ratios were compared with the clinical diagnosis of the presence or absence of peripheral lipoatrophy by receiver operating characteristic analysis. The area under the curve was 0.720 for adjacent spine/hip fat ratio and 0.655 and 0.699 for trunk/arm + leg fat and trunk/leg fat, respectively; they were not significantly different. In conclusion, for male HIV-positive patients, the difference between predicted values and actual values rendered limits of agreement that were too wide to be clinically acceptable. The ratio of percent fat in the lumbar spine region to percent fat in the proximal femur region reflected the presence of peripheral lipoatrophy as effectively as the trunk/peripheral fat ratio that was derived from the total-body scan.

Rosiglitazone improves lipoatrophy in patients receiving thymidine-sparing regimens.

Thymidine reverse transcriptase inhibitors (tNRTI) are strong inhibitors of PPAR-gamma and clearly implicated as a cause of lipoatrophy. Thiazolidenediaones (TZD), potent PPAR-gamma agonists, would be expected to be beneficial in HIV lipoatrophy, but prior studies have been conflicting. None specifically excluded the use of tNRTIs. We report the first study in individuals treated with tNRTI-sparing regimens using a TZD for treatment of HIV lipoatrophy. This double-blind, placebo-controlled study evaluated limb fat in HIV-infected individuals with lipoatrophy who discontinued tNRTI at least 24 weeks prior to enrollment. Individuals were randomized to rosiglitazone vs. placebo for 48 weeks. Dual energy X-ray absorptiometry (DEXA)-scans and fasting metabolic assessments were serially performed. We enrolled 71 individuals, 17% were female and 51% white. Baseline characteristics were similar between groups except for higher total cholesterol in the placebo group (P = 0.04). At 48 weeks, limb fat (grams) increased significantly (P = 0.02) more in the rosiglitazone than in the placebo group: median (IQR) 448 (138, 1670) vs. 153 (-100, 682), respectively. Of lipids parameters, only total cholesterol increased significantly more in the rosiglitazone group (P = 0.008). Prevalence of metabolic syndrome and total bone mineral density did not change between or within groups. In the absence of tNRTI, rosiglitazone significantly improves lipoatrophy without deleterious effect on bone mineral density. Total cholesterol, but not triglycerides, significantly increased in the rosiglitazone arm. The glitazones may be a promising addition for accelerating fat recovery in individuals who had switched off tNRTI and remain with significant lipoatrophy.

Orbitofacial Rejuvenation of Temple Hollowing With Perlane Injectable Filler

Temple hollowing with soft tissue volume loss is well recognized in HIV lipoatrophy. Similar changes occur as part of aging, with skeletalization of the orbital rim and clipping of the eyebrow tail. The authors report their initial experience treating temple volume loss and orbitofacial asymmetry with nonanimal stabilized hyaluronic acid (NASHA). This study was a retrospective, interventional case series with a patient satisfaction questionnaire and independent physician grading of results. Patients initially received approximately 1 mL of Perlane (Q-Med, Uppsala, Sweden; Medicis, Inc., Scottsdale, Arizona) injected into the superficial fascia of each temple. The filler was placed behind the frontozygomatic process to soften the bony contour of the lateral orbital rim. Outcome measures included satisfaction with injection procedure, fulfillment of expectations, satisfaction with appearance, change in self-confidence, the need for retreatment, and complications. Twenty patients were treated, for a total of 39 temples. Mean follow-up was nine months (range, four to 14 months). Patients were primarily female (90%), all were Caucasian, and their ages ranged from 20 to 60 years. Eighteen patients had age-related temple hollowing, one had dysthyroid volume loss, and one had hollowing due to orbitotemporal neurofibromatosis. The majority had 1-mL injections to each side (range, 0.3-3 mL). One patient received 3 mL to correct asymmetry. The procedure was well tolerated with ice pack cooling and no local anesthesia. Of 16 patients who replied to the questionnaire, 13 were very or moderately satisfied and requested repeat treatment, whereas three were only mildly satisfied or ambivalent. Side effects included transient mild or moderate discomfort, superficial vein prominence, and localized bruising. This series suggests the effective and safe application of Perlane in temple hollow rejuvenation and correction of asymmetry. It offers tolerability, high patient satisfaction, few complications, and the option of reversibility.

A Meta-Analysis of Six Placebo-Controlled Trials of Thiazolidinedione Therapy for HIV Lipoatrophy

Objective: To determine the impact of thiazolidinediones (TZD) on changes in limb fat mass in HIV-infected individuals, particularly in those not receiving a thymidine analogue.Methods: Individual patient data from placebo-controlled, randomized trials of rosiglitazone (n = 5) or pioglitazone (n = 1) were combined. Generalized estimating equation (GEE) models were used to estimate the treatment effect on changes in limb fat mass.Results: In the combined dataset of 427 patients, the baseline median age was 45 years, 86% were male, 80% were Caucasian, 63% were receiving stavudine (d4T) or zidovudine (AZT), 66% were on protease inhibitors, and median body mass index was 23 kg/m2. In a univariate GEE model, TZD was associated with an increase in limb fat mass (coeff = 0.14 kg vs placebo,P = .04). In a multivariable GEE model, patients receiving pioglitazone had significantly higher limb fat mass gains (coeff = 0.35 kg,P δ .01) compared to patients receiving placebo, while patients on rosiglitazone did not (coeff = 0.05 kg,P = .48). Interactions between thymidine analogue use and rosiglitazone and pioglitazone were not significant.Conclusions: In this meta-analysis, pioglitazone therapy was more effective than placebo to increase limb fat mass whereas rosiglitazone was not significantly better than placebo. The effectiveness of these drugs did not vary according to whether the patients were receiving thymidine analogues.

P02-132 - Evaluation of psychological impact of facial lipoatrophy in HIV: the “assessment of face & body change and distress” questionnaire

ObjectivesTo construct and test the validity of a new psychometric questionnaire to assess psychological impact of facial lipoatrophy (ABCD-F), that is the most stigmatizing feature of HIV-related lipodystrophy.MethodsConstruction: The development went through Focus groups and Content Validity, Item reduction and Exploratory Factor Analysis.Validation: ABCD-F questionnaire was administered together with ABCD and MOS HIV questionnaires. The Cronbach's Alfa was used to test internal consistency, while convergent validity and divergent validity were analyzed by the correlations with MOS, ABCD items and BMI and CD4 counts respectively.Results42 HIV+ people participated to focus groups. In the EFA the 17 Items were aggregated around psychological distress and role functioning domains.ABCD-F showed high internal consistency (Chronbach's alpha = 0.95). Both convergent and divergent validity were confirmed. ABCD-F scores were highly correlated to Physical Health Summary (B 0.59; 95% [CI] 0.35; 0.84; p&lt; 0.0001), Mental Health Summary (B-1.54; 95% [CI] 1.15; 1.93; p&lt; 0.0001), and weakly correlated to CD4 count (B-0.02; 95% [CI] -0.01; 0.06; p=0.54) and HIV viral load (B-0.004; 95% [CI] -2.69; 2.69; p=1.00).ConclusionsABCD-F is a valid and reliable questionnaire to assess psychological impact of facial lipoatrophy (FLA).ABCD-F may result as a useful tool both in clinical and research settings: it's able to identify people experiencing greater psychological impact due to FLA. It may become an objective instrument to evaluate priority and efficacy of plastic surgery to treat lipodystrophy. In research setting may be used to compare different populations or different treatments of FLA.

A Meta-Analysis of Six Placebo-Controlled Trials of Thiazolidinedione Therapy for HIV Lipoatrophy

A Meta-Analysis of Six Placebo-Controlled Trials of Thiazolidinedione Therapy for HIV Lipoatrophy

Dual-energy X-ray absorptiometry modeling to explain the increased resting energy expenditure associated with the HIV lipoatrophy syndrome

BackgroundThe HIV lipoatrophy syndrome is characterized by loss of subcutaneous fat and is associated with increased resting energy expenditure (REE). Recently, dual-energy X-ray absorptiometry (DXA) modeling of organ-tissue mass combined with specific organ-tissue metabolic rates has been used to gain further insight into the relation of the lean body mass to REE and to better understand differences in REE between groups. ObjectiveThis study examined the organ-tissue basis of the increased REE shown in HIV lipoatrophy. DesignREE was measured in 29 HIV-infected patients with lipoatrophy and in 29 HIV-infected and 19 healthy control subjects. Five organ-tissue mass components (brain, bone, skeletal muscle, adipose tissue, and residual mass) were calculated with the use of DXA modeling and body weight. ResultsDXA modeling showed no significant differences in predicted REE between the 3 groups. However, measured REE was significantly greater in subjects with lipoatrophy than in control subjects. Measured REE remained significantly greater in lipoatrophy subjects after routine adjustment for lean body mass and after adjustment for each organ-tissue mass component. Finally, DXA and regression modeling of REE suggests that increased energy expenditure in skeletal muscle may account for the resting hypermetabolism of patients with HIV lipoatrophy. ConclusionsIncreased REE in subjects with HIV lipoatrophy cannot be explained by differences in organ-tissue mass as modeled by DXA. Instead, DXA and regression modeling of REE suggests that skeletal muscle is hypermetabolic in patients with HIV lipoatrophy. This may be a form of adaptive thermogenesis in response to an inability to store triglyceride fuel in a normal manner.