HIV Lipoatrophy Research Articles

Diabetes Drug Improves Lipoatrophy in HIV

Diabetes Drug Improves Lipoatrophy in HIV

Treatment of HIV lipoatrophy and lipoatrophy of aging with poly-L-lactic acid: A prospective 3-year follow-up study

Poly-L-lactic acid (PLLA), marketed as Sculptra (Dermik Laboratories, Bridgewater, NJ), is used for subcutaneous volume restoration. Durability studies are ongoing and longevity data are not yet available. We sought to evaluate the long-term efficacy and safety of PLLA during 3 years of follow-up. We conducted a prospective cohort study. Primary outcome measures were facial lipoatrophy score, complications, and patient satisfaction. In all, 65 patients were initially treated with PLLA; 27 patients were HIV positive and 38 were HIV negative. Of those patients, 12 were lost to follow-up. Both HIV-positive and HIV-negative patients demonstrated statistically significant improvement in facial lipoatrophy score at the end of 3 years; HIV-positive patients had a net improvement of 2.50 points (P < .01) and HIV-negative patients had a net improvement of 1.11 points (P < .01) on the Facial Lipoatrophy Grading Scale. Subgroup analyses revealed no statistically significant difference in facial lipoatrophy score between years 2 and 3 among patients who did not receive treatment during the third year. Complications were rare and included subcutaneous papule formation, which improved spontaneously and partially responded to subcision in one patient. Sample size was limited in this study. In addition, 12 of 65 patients (18%) were lost to follow-up between years 2 and 3. PLLA provides volumetric correction of HIV lipoatrophy and lipoatrophy of aging. Results appear to be long lasting and correction can be maintained for up to 3 years with additional treatment sessions. In a subset of patients, correction is maintained for at least 1 year after their last treatment session. Patient satisfaction with PLLA is high.

Mitochondrial Oxidative Phosphorylation Protein Levels in Peripheral Blood Mononuclear Cells Correlate with Levels in Subcutaneous Adipose Tissue within Samples Differing by HIV and Lipoatrophy Status

Depletion of mitochondrial DNA (mtDNA) and mtDNA-encoded respiratory chain proteins in subcutaneous (SC) fat from patients with HIV lipoatrophy have clearly demonstrated the role of mitochondrial dysfunction in this syndrome. Research in HIV lipoatrophy, however, has been severely hampered by the lack of a suitable surrogate marker in blood or other easily obtained clinical specimens as fat biopsies are invasive and mtDNA levels in peripheral blood mononuclear cells (PBMC) do not consistently correlate with the disease process. We used a simple, rapid, quantitative 2-site dipstick immunoassay to measure OXPHOS enzymes Complex I (CI) and Complex IV (CIV), and rtPCR to measure mtDNA in 26 matched SC fat and PBMC specimens previously banked from individuals on potent antiretroviral (ARV) therapy with HIV lipoatrophy, on similar ARV therapy without lipoatrophy, and in HIV seronegative controls. Significant correlations were found between the respective PBMC and fat levels for both CI (r = 0.442, p = 0.024) and for CIV (r = 0.507, p = 0.008). Both CI and CIV protein levels were also significantly reduced in both PBMCs and fat in lipoatrophic subjects compared to HIV seronegative controls (p < or = 0.05), while a comparative reduction in mtDNA levels in lipoatrophic subjects was observed only in fat. We conclude that CI and CIV levels in PBMCs correlate to their respective levels in fat and may have utility as surrogate markers of mitochondrial dysfunction in lipoatrophy.

P.107 Lipofllling treatment for facial lipoatrophy in HIV

Stereotactic ablative radiotherapy (SABR; or stereotactic body radiotherapy, SBRT) emerges as treatment option for pulmonary oligometastatic disease (OMD), but there are no studies comparing SABR with pulmonary metastasectomy (PME). We analysed consecutive patients referred via a university-hospital based multidisciplinary team.Patients were offered PME as first choice and SABR in case they were considered to be less suitable surgical candidates. Overall survival was the primary endpoint. Secondary endpoints were progression-free-survival, local control of treated metastases, and freedom-from-failure of a local-only treatment strategy without systemic therapy.From 2007 until 2010, 110 patients were treated and analysed (PME, n = 68; SABR, n = 42). Median follow-up time was 43 months (minimally, 25). Estimated overall survival rates at one, three, and five years were 87%, 62%, and 41% for PME, and 98%, 60%, and 49% for SABR, respectively (logrank-test, p = 0.43). Local control at two years was 94% for SABR and 90% for PME. Progression-free survival was 17% at three years, but 43% of the patients still had not failed a local-only treatment strategy.Although SABR was second choice after PME, survival after PME was not better than after SABR. Prospective comparative studies are clearly required to define the role of both, SABR and PME in OMD.

Mitochondrial RNA and DNA alterations in HIV lipoatrophy are linked to antiretroviral therapy and not to HIV infection

The aim of this study was to assess the effect of antiretroviral therapy (ART) versus HIV on mitochondria in fat. Subcutaneous fat was collected from 45 HIV-infected patients on ART with lipoatrophy, 11 HIV-infected ART-naive patients and nine healthy controls. Three mitochondrial transcripts: NADH dehydrogenase subunit 1 (ND1), cytochrome B (CYTB) and NADH dehydrogenase subunit 6 (ND6) genes were quantitated using TaqMan probes and normalized to nuclear-encoded ribosomal L13. ND1/L13 and CYTB/L13 were lower in HIV-positive patients on ART with lipoatrophy versus ART-naive patients (3.4 versus 7.2 [P=0.017] and 2.5 versus 4.6 [P=0.006], respectively). No difference was found between ART-naive patients and controls (P>0.70). ND6/L13 was similar between all groups. Dual-energy X-ray absorptiometry-measured limb fat and mitochondrial DNA in fat were also lower in HIV-positive patients on ART with lipoatrophy versus HIV-infected, ART-naive patients (4,382 versus 7,662 g [P=0.02] and 726 versus 1,372 copies/cell [P=0.03], respectively), but no difference was found between ART-naive and controls. In a multiple regression analysis, limb fat correlated with all three mitochrondrial RNA, whereas mitochondrial DNA did not correlate with mitochondrial RNA or limb fat. In contrast to ART-naive patients, HIV-positive patients on ART with lipoatrophy had significant depletion in mitochondrial DNA in fat and mitochondrial RNAs. This suggests that mitochondrial toxicity in lipoatrophy could be driven by ART and not by HIV itself. In addition, mitochondrial RNA abnormalities, and not mitochondrial DNA depletion, could be a key driving force behind lipoatrophy.

Early changes in adipokine levels and baseline limb fat may predict HIV lipoatrophy over 2 years following initiation of antiretroviral therapy*

No biological marker has been identified that predicts the development of lipodystrophy (LD). We investigated whether metabolic and body composition parameters could predict the development of LD over 2 years in adults initiating antiretroviral therapy (ART). We used stored plasma collected at baseline and weeks 12, 24 and 48 from adults initiating combination ART. Adipocytokine, inflammatory cytokine, lipid and glycaemic parameters were measured and related to subsequent lipoatrophy (loss of limb fat mass of at least 2 kg from weeks 24 to 96 by dual-energy X-ray absorptiometry) and an increase in visceral adipose tissue (VAT; an increase of at least 18 cm(2) from baseline to week 48 by abdominal computed tomography). Risk factors associated with limb fat loss and VAT gain were analysed by logistic regression. Fifty-four HIV-infected, treatment-naïve adults were included in the study: 53 (98%) of them were men, and they had a median age of 39 years [interquartile range (IQR) 34-48 years] and a median body mass index of 22.6 kg/m(2) (IQR 20-24.8 kg/m(2)). In multivariate analysis, a higher baseline limb fat percentage, and a 1 mmol/L increase in plasma leptin levels during the first 6 months of ART, independently predicted a peripheral fat loss of > or = 2 kg [odds ratio (OR) 2.58, 95% confidence interval (CI) 1.04-6.41; OR 3.15, 95% CI 1.34-7.35, respectively). VAT changes showed a borderline association with high baseline tumour necrosis factor-alpha levels and hip circumference (OR 1.04, 95% CI 1.00-1.07; OR 1.44, 95% CI 1.07-1.95, respectively). In ART-naïve men, higher baseline limb fat and an early increase in leptin concentrations may predict the subsequent development of lipoatrophy. We did not find the same risk factors in the two different groups of patients with peripheral fat loss and central fat gain, suggesting a partially independent pathogenesis.

Effect of Pioglitazone on HIV-1-Related Lipodystrophy: A Randomized Double-Blind Placebo-Controlled Trial (ANRS 113)

Although thiazolidinediones have been shown to increase subcutaneous fat in congenital lipodystrophy, rosiglitazone did not show convincing results in HIV lipoatrophy. We assess a potential specific effect of pioglitazone in this setting. One-hundred and thirty HIV-1-infected adults with self-reported lipoatrophy confirmed by physical examination were randomized to receive pioglitazone 30 mg once daily (n=64) or placebo (n=66) for 48 weeks. Changes in limb fat between weeks 0 and 48 were measured using dual-energy Xray absorptiometry. Subcutaneous and visceral fat was measured by single-slice computed tomography; fasting plasma measurements of glucose, insulin and lipids levels were recorded. Limb fat increased by 0.38 kg in the pioglitazone group and 0.05 kg in the placebo group at week 48 (mean difference 0.33 kg, 95% confidence interval [CI] 0.10-0.56; P=0.051) by intention-to-treat analysis. In patients not receiving stavudine, an increase of 0.45 kg versus 0.04 kg was observed (mean difference, 0.40 kg, 95% CI 0.12-0.69; P=0.013), but this was not seen in patients on stavudine (n=36; P=0.404). Overall, there was no significant difference in subcutaneous abdominal fat or in visceral fat areas on computed tomography at L4 vertebra. The lipid profile was not significantly different at week 48 except for levels of high-density lipoprotein cholesterol, which was improved in the pioglitazone group (+0.08 mmol/l versus -0.08; P=0.005). Pioglitazone 30 mg once daily for 48 weeks improved limb fat atrophy in antiretroviral-treated HIV-1-infected patients, although clinical benefits were not perceived by the patients. Treatment did lead to a favourable lipid profile, however, suggesting that this thiazolidinedione should be considered in the context of HIV-related lipoatrophy.

Safety and Efficacy of Poly-L-Lactic Acid in HIV Lipoatrophy and Lipoatrophy of Aging

Safety and Efficacy of Poly-L-Lactic Acid in HIV Lipoatrophy and Lipoatrophy of Aging

Economic modeling of the combined effects of HIV disease, heart disease and lipoatrophy based on ACTG 5142 trial data

Purpose of the study Antiretroviral (ARV) regimens may be statistically noninferior in clinical trials, but have very different economic outcomes due to differences in costs and adverse event profiles. Given the heavy cost burden of HIV disease, it is important to consider economic issues when selecting an ARV regimen. This study examines the cost and consequences of initiating an ARV regimen including LPV/r or EFV, using data from a recent clinical trial in a previously published model of HIV-disease.

Uridine supplementation in HIV lipoatrophy: pilot trial on safety and effect on mitochondrial indices

Uridine abrogates mitochondrial toxicities of nucleoside reverse transcriptase inhibitor in adipocyte cell culture. We aim to study the effect of uridine supplementation on human adipocyte mitochondrial DNA (mtDNA) levels in subjects with human immunodeficiency (HIV) lipoatrophy. Sixteen patients with lipoatrophy on stavudine-containing antiretroviral therapy were enrolled, and received NucleomaxX, a dietary supplement with a high bioavailability of uridine (36 g TID every other day for 16 weeks). Patients were then followed off-uridine for another 16 weeks. Highly active antiretroviral therapy remained unchanged during the trial. Fourteen patients completed the study. Two subjects dropped out before week 4 for study-unrelated reasons. No adverse events were noted throughout the study. HIV-1 RNA, CD4 counts, liver enzymes and hemoglobin remained unchanged. Body mass index, lactate, lipids, insulin and homeostasis model assessment of insulin resistance were unaltered. Fat and peripheral blood and mononuclear cell mtDNA levels did not correlate with each other and exhibited no changes throughout the study. Lipoatrophy scores by patients and physician improved significantly at weeks 16 and 32 compared to study entry. In this pilot study, NucleomaxX was safe, well tolerated without apparent deleterious effect on HIV indices. In contrast to in vitro data, NucleomaxX did not lead to changes in fat or blood mtDNA levels.

Persistent Granulomatous Inflammatory Response Induced by Injectable Poly-l-lactic Acid for HIV Lipoatrophy

Persistent Granulomatous Inflammatory Response Induced by Injectable Poly-l-lactic Acid for HIV Lipoatrophy

Persistent Granulomatous Inflammatory Response Induced by Injectable Poly-L-lactic Acid for HIV Lipoatrophy

Persistent Granulomatous Inflammatory Response Induced by Injectable Poly-L-lactic Acid for HIV Lipoatrophy

Poly-L-lactic Acid for Facial Lipoatrophy in HIV

To review the clinical data for poly-L-lactic acid, a synthetic polymer used as an intradermal injection for the treatment of HIV associated facial fat loss (lipoatrophy). A literature search was performed using MEDLINE (1966-August 2006). The search was limited to articles published in English and used the key words polylactic acid, polylactides, degradation, lipodystrophy, lipoatrophy, and HIV/AIDS. Dermik Laboratories was contacted to obtain unpublished information. Additional articles were retrieved from citations of selected references. Relevant information on the pharmacology, pharmacokinetics, safety, and efficacy of poly-L-lactic acid from clinical trials were selected. Poly-L-lactic acid (Sculptra) is a biocompatible, biodegradable, synthetic polymer able to be tailored into various desired morphologic features. It is approved by the Food and Drug Administration for the correction of facial lipoatrophy in people with HIV. Six clinical trials have evaluated the use of intradermal injections of poly-L-lactic acid. Results showed that cutaneous thickness is improved in patients receiving poly-L-lactic acid. Adverse effects included nodule and hematoma formation, as well as pain at the injection site. Poly-L-lactic acid offers a treatment alternative for patients with HIV-associated lipoatrophy. Further research is required in nonwhite populations.

Calcium Hydroxylapatite for Facial Rejuvenation

Porous calcium hydroxylapatite has been used in otolaryngology, dentistry and radiology for many years. Currently, calcium hydroxylapatite is gaining popularity for facial esthetics in the form of the product Radiesse (San Mateo, CA). Although Radiesse is not yet approved in the United States for cosmetic use, it is being used off-label by an increasing number of dermatologists and plastic surgeons for facial soft-tissue augmentation. Preliminary clinical and histologic studies have shown safety, efficacy and durability in various esthetic applications including the nasolabial folds and HIV lipoatrophy.

Treatment of human immunodeficiency virus-associated facial lipoatrophy with lipofilling and submalar silicone implants

In the absence of a current therapy to prevent facial lipoatrophy in HIV+ patients treated with HAART, surgical correction of the defect still remains the best option. We evaluate two different surgical techniques for facial contour enhancing and suggest the right choice related to the lipodystrophy severity. Twelve HIV+ patients underwent surgical submalar correction: eight were treated with lipofilling following Coleman's technique and four had bilateral malar silicone implants inserted after determining their positioning with the aid of a new software. Both techniques gave long lasting results in facial contour reshaping ranging from good to very good. No complication was observed. In the mean follow-up period of 2 years no patient felt uncomfortable with his/her image. Both techniques, lipofilling and silicone implant positioning, for managing facial lipoatrophy in HIV+ patients treated with HAART had good results, but the right choice has to be related to the severity of the lipodystrophy in the patient.

Drug Changes Can Reverse Lipoatrophy in HIV

Drug Changes Can Reverse Lipoatrophy in HIV

Drug Changes May Reverse Lipoatrophy in HIV

Drug Changes May Reverse Lipoatrophy in HIV

No effect of rosiglitazone for treatment of HIV-1 lipoatrophy: randomised, double-blind, placebo-controlled trial

Lipodystrophy commonly complicates antiretroviral therapy of HIV-1 infection. Thiazolidinediones such as rosiglitazone promote subcutaneous fat growth in type 2 diabetics and adults with congenital lipodystrophy, and can prevent HIV-1 protease inhibitor toxicity to adipocytes in vitro. We postulated that rosiglitazone would improve HIV lipoatrophy. 108 HIV-1-infected lipoatrophic adults on antiretroviral therapy were randomised to rosiglitazone 4 mg twice daily (n=53) or matching placebo (n=55) for 48 weeks. The study had 80% power to detect a 0.5 kg difference in changes in limb fat (using dual-energy X-ray absorptiometry) between groups at week 48 by intention-to-treat analysis, and a 0.7 kg difference within each protease inhibitor stratum. Limb fat increased by 0.14 kg in the rosiglitazone group and 0.18 kg in the placebo group (mean difference -0.04 kg [95%CI -0.29 to 0.21]; p=0.74 by t test), with three participants (one on rosiglitazone and two controls), lost to follow-up. Rosiglitazone had no significant benefit on any other measure of lipodystrophy, despite large relative increases in plasma adiponectin (4.2 mmol/L [102%]; p<0.0001) and in three markers of insulin sensitivity (p=0.01 to 0.02). Six participants ceased study drug in each group, four participants (three on rosiglitazone and one control) for related adverse events. The main adverse effects, which seem to be almost unique to this population, were asymptomatic hypertriglyceridaemia (mean relative increase 0.9 mmol/L at week 48; p=0.04) and hypercholesterolaemia (1.5 mmol/L; p=0.001). Rosiglitazone for 48 weeks did not improve lipoatrophy in HIV-1-infected adults receiving antiretroviral therapy. Use of less toxic antiretroviral treatment is necessary to prevent lipoatrophy.

Managing HIV lipoatrophy

Treatment with multidrug antiretroviral regimens dramatically reduces HIV-associated morbidity and mortality. However, prolonged therapy can be complicated by a range of adverse effects, including the metabolic syndrome (dyslipidaemia, insulin resistance, visceral adiposity) and subcutaneous lipoatrophy—collectively called lipodystrophy. The morphological changes of lipodystrophy are highly stigmatising and can cause discomfort, disability, psychological morbidity, and reduced adherence or discontinuation of otherwise effective antiretroviral therapy. The metabolic changes contribute to an increased risk of cardiovascular events. No effect of rosiglitazone for treatment of HIV-1 lipoatrophy: randomised, double-blind, placebo-controlled trialRosiglitazone for 48 weeks did not improve lipoatrophy in HIV-1-infected adults receiving antiretroviral therapy. Use of less toxic antiretroviral treatment is necessary to prevent lipoatrophy. Full-Text PDF