Impact of inflammatory cytokine and adipokine gene variations in the development of HIV-associated lipodystrophy.

Cytokines affect lipid and glucose metabolism and also alter the body's habitus. They play a role in the development of lipodystrophy syndrome. Adipocytes secrete the pro-inflammatory cytokines IL-1, TNF-α and IL-6. The plasma cytokine concentration is associated with the percentage and distribution of fat tissue in the body. The metabolic disturbances are strongly associated with increased levels of pro-inflammatory cytokines (IL-1, IL-6 and TNF-α). Plasma levels of cytokines such as TNF-α, IL-6 and leptin were found to be increased while plasma resistin levels were found to be variable in patients suffering from obesity and type II diabetes mellitus. Until now, limited information has been available on the polymorphism of cytokine and adipokine genes in patients of HIV-associated lipodystrophy (HIVLD), which can contribute to individual variations in susceptibility to metabolic diseases, especially to HIVLD. Hence, we studied the association of cytokine and adipokine gene polymorphisms in various diseases and their impact on HIVLD. We carry out an extensive search using several databases, including PubMed, EMBASE and Google Scholar. The distribution of cytokine and adipokine gene polymorphisms and their expression levels varied among various populations. We examined the variants of cytokine and adipokine genes, which can contribute to individual variations in susceptibility to metabolic diseases, especially to HIVLD. In the current review, we present a brief account of the risk factors of HIVLD, the pathogenesis of HIVLD and the polymorphism of cytokine and adipokine genes in various diseases with special reference to their impact on HIVLD.

Fat Mass Ratio in Brazilian HIV-infected Patients Under Antiretroviral Therapy and Its Relationship With Anthropometric Measurents.

INTRODUCTION: Human immunodeficiency virus-related lipodystrophy is characterized by a variety of phenotypes and metabolic changes; however, consensus has not yet been reached on its diagnostic criteria. Different cutoff values for fat mass ratio have been proposed for this specific population as an objective diagnostic criterion for lipodystrophy. This study aimed to establish sex-specific reference values for fat mass ratio and to correlate them with anthropometric measurements for the diagnosis of human immunodeficiency virus-related lipodystrophy. METHODOLOGY: A cross-sectional study was performed on 189 human immunodeficiency virus-infected patients under antiretroviral therapy. Anthropometric measurements were evaluated, and body composition was determined using dual-energy X-ray absorptiometry. Fat mass ratio was calculated as the ratio of the percentage of the trunk fat mass and the percentage of the lower limb fat mass. RESULTS: One hundred and thirty-two patients (69%) presented lipodystrophy by objective criteria. In men, the cutoff for the fat mass ratio was 1.55 (area under the receiver operating characteristic curve: 0.73 [95% confidence interval: 0.62-0.83], p = 0.000008), with a sensitivity of 62.5%, a specificity of 70.5%, a positive predictive value of 77.8%, and a negative predictive value of 53.4%. In women, the cutoff for the fat mass ratio was 0.959 (area under the receiver operating characteristic curve: 0.70 [95% confidence interval: 0.56-0.85], p = 0.03), with a sensitivity of 83.60%, a specificity of 61.5%, a positive predictive value of 90.2%, and a negative predictive value of 47.1%. Fat mass ratio was positively correlated with waist circumference (men: r = 0.246, p = 0.019; women: r = 0.302, p = 0.014) and neck circumference (men: r = 0.304, p = 0.004; women: r = 0.366, p = 0.003) in both sexes; and body mass index (r = 0.288, p = 0.006) and waist-hip ratio (r = 0.288, p = 0.006) in men. CONCLUSION: The fat mass ratio evaluated using dual-energy X-ray absorptiometry with the sex-specific cutoffs is an objective tool to define human immunodeficiency virus-related lipodystrophy.

Can Biomarkers Advance HIV Research and Care in the Antiretroviral Therapy Era?

Despite achieving human immunodeficiency virus type 1 (HIV-1) RNA suppression below levels of detection and, for most, improved CD4+ T-cell counts, those aging with HIV experience excess low-level inflammation, hypercoagulability, and immune dysfunction (chronic inflammation), compared with demographically and behaviorally similar uninfected individuals. A host of biomarkers that are linked to chronic inflammation are also associated with HIV-associated non-AIDS-defining events, including cardiovascular disease, many forms of cancer, liver disease, renal disease, neurocognitive decline, and osteoporosis. Furthermore, chronic HIV infection may interact with long-term treatment toxicity and weight gain after ART initiation. These observations suggest that future biomarker-guided discovery and treatment may require attention to multiple biomarkers and, possibly, weighted indices. We are clinical trialists, epidemiologists, pragmatic trialists, and translational scientists. Together, we offer an operational definition of a biomarker and consider how biomarkers might facilitate progress along the translational pathway from therapeutic discovery to intervention trials and clinical management among people aging with or without HIV infection.

Hyaluronic Acid Filler in HIV-Associated Facial Lipoatrophy: Evaluation of Tissue Distribution and Morphology with MRI.

OBJECTIVE: This prospective observational study evaluated magnetic resonance imaging (MRI) findings of hyaluronic acid (HA) injections used for the correction of HIV-associated facial lipoatrophy. METHODS: Ten consecutive males underwent subdermal HA injection (mean 1.3 ± 0.6 ml per side) and MRI examinations prior to and then 1, 6 and 12 months after injection. Two radiologists blinded to the clinical data assessed morphologic and quantitative changes. RESULTS: MRI revealed HA deposition in the subdermal and deep fat compartments. A significant HA volume increase was observed 1 month after injection (mean increase 331%, p < 0.0001) as compared to the injected amount. No volume reduction occurred at 12 months (p = 0.9961). The measured bound water content did not change (p > 0.9991), whereas skin thickness and tissue vascularization increased during the first 6 months (p = 0.01). CONCLUSION: Our data show that the cosmetic results of HA injections are caused by water binding in the deep facial fat and by a transient increase in vascularization and skin thickness.

Carotid intima media thickness is associated with body fat abnormalities in HIV-infected patients.

BACKGROUND: HIV-infected patients may be at increased risk of cardiovascular (CV) events, and lipodystrophy is generally associated with proatherogenic metabolic disturbances. Carotid intima-media thickness (cIMT) has been used as a surrogate marker for atherosclerosis and it has been shown to be an independent risk factor for CV disease. Our objective was to evaluate cIMT in HIV-infected patients on combined anti-retroviral therapy (cART) with and without lipodystrophy defined by fat mass ratio (L-FMR), and to determine the association of lipodystrophy and visceral obesity [(visceral (VAT), subcutaneous adipose tissue (SAT) volume and VAT/SAT ratio, objectively evaluated by CT scan] with cIMT. METHODS: Cross-sectional study of 199 HIV-infected patients. Body composition by DXA and abdominal CT, lipids, blood pressure, inflammatory markers, and cIMT by ultrasonography were performed. L-FMR was defined as the ratio of the percentage of trunk fat mass to the percentage of lower limb fat mass by DXA. Categorical variables were compared using the chi-square or Fisher's exact test. Spearman correlation coefficients were estimated to study the association between cIMT and clinical and metabolic characteristics. Means of cIMT, adjusted for age, were calculated, using generalized linear models. RESULTS: L-FMR was present in 41.2% of patients and cIMT was higher in these patients [0.81 (0.24) vs. 0.76 (0.25); p=0.037)]. Lipodystrophic patients had higher VAT and VAT/SAT ratio and lower SAT. cIMT was associated with lipodystrophy evaluated by FMR, trunk fat, total abdominal fat, VAT and VAT/SAT ratio. No association was observed between cIMT and leg fat mass. Using generalized linear models, cIMT means were adjusted for age and no significant differences remained after this adjustment. The adjusted mean of cIMT was 0.787 (95%CI: 0.751-0.823) in patients without lipodystrophy, and 0.775 (95%CI: 0.732-0.817) in those with lipodystrophy (p=0.671). CONCLUSIONS: HIV-infected patients on cART with lipodystrophy defined by FMR, had a significantly higher cIMT. Carotid IMT was also associated with classical cardiovascular risk factors. In these patients, visceral adipose tissue had a significant impact on cIMT, although age was the strongest associated factor.

The "smile-and-fill" injection technique: a dynamic approach to midface volumization.

Injectable poly-L-lactic acid (PLLA) is a biodegradable, biocompatible, synthetic polymer that acts as a scaffold to promote collagen formation and is FDA-approved for the correction of facial lipoatrophy in patients with human immunodeficiency virus (HIV) infection. The safety and efficacy of injectable PLLA for the treatment of HIV-associated facial lipoatrophy has been demonstrated in clinical studies and is accompanied by improvement in patient quality of life. Volumization of the mid-face is regarded as complex. The importance of respecting patient mid-face differences at rest and in motion was highlighted in a study that demonstrated effectiveness of silicone microdroplets (0.01 mL) in a depot manner to treat HIV patients with facial lipoatrophy. One of the challenges of facial volume rejuvenation with these techniques is preserving and enhancing dynamic facial movements after treatment. To address this challenge, we developed an injection technique termed "smile-and-fill." In this case series, we describe three patients treated by this technique to restore the malar aspect of the mid-face with improvement several months post-treatment.

An adipocitolitic aqueous micro-gelatinous solution for buffalo hump deformity reduction.

Buffalo hump is a manifestation of HIV related lipodistrophy, it is characterized by an enlargment of dorsocervical fat pad and is distressing for patients. Surgical correction until a few years ago was the only option for treatment, however in last years non surgical corrections was carried out with minimally invasive techniques. Authors report this case that describe a longer follow up of an already published study were this deformity was treated with the injection of an adipocitolitic aqueous micro-gelatinous solution and during all the follow up no relapse was observed.

Kager's fat pad inflammation associated with HIV infection and AIDS: MRI findings.

OBJECTIVE: To describe magnetic resonance imaging (MRI) features of Kager's fat pad inflammation in HIV-positive patients with lipodystrophy due to protease inhibitor treatment and posterior ankle pain. METHODS: A case-control, cross-sectional study; group 1 included 14 HIV-positive patients using protease inhibitors, presenting lipodystrophy syndrome and having posterior ankle pain; group 2 (CGHIV-) included 112 HIV-negative patients without lipodystrophy syndrome who were being evaluated for posterior ankle pain; group 3 (CGHIV + 1) included 23 HIV-positive patients not using a protease inhibitor, without lipodystrophy syndrome and with posterior ankle pain; group 4 (CGHIV + 2) comprised 18 HIV-positive patients who were being treated with a protease inhibitor and had lipodystrophy syndrome but did not have posterior ankle pain. Images were evaluated for the presence of edema by two radiologists who were blinded to clinical features. Fisher's exact test was used to evaluate differences among the groups. Interobserver variation was tested using Cohen's kappa (κ) statistic. RESULTS: The presence of edema within Kager's fat pad was strongly associated with symptoms in HIV-positive patients who had lipodystrophy (p ≤ 0.0001). Concordance between observers was excellent (κ > 0.9). CONCLUSION: MRI findings of Kager's fat pad inflammation related to HIV/AIDS is a source of symptoms in HIV patients with posterior ankle pain using protease inhibitors and having lipodystrophy syndrome.

Impact of switching from zidovudine/lamivudine to tenofovir/emtricitabine on lipoatrophy: the RECOMB study.

OBJECTIVES: Lipoatrophy is a long-term adverse effect of some antiretrovirals that affects quality of life, compromises adherence and may limit the clinical impact of HIV treatments. This paper explores the effect of tenofovir/emtricitabine (TDF/FTC) on the amount of limb fat in patients with virological suppression. METHODS: A randomized, prospective clinical trial was performed to compare continuation on a zidovudine/lamivudine (ZDV/3TC)-based regimen with switching to a TDF/FTC-based regimen in terms of the effect on limb fat mass as assessed by DEXA over a 72-week period. RESULTS: Eighty patients were included (39 in the TDF/FTC arm and 41 in the ZDV/3TC arm) and 73 completed the study (37 and 36, respectively). In the switch arm, limb fat increased by a median of 540 g from baseline (P = 0.022), while in the ZDV/3TC arm it decreased by a median of 379 g (P = 0.112; p between groups = 0.007). Subjects with baseline limb fat ≤ 7200 g, previous time on ZDV > 5 years or a body mass index > 25 kg/m(2) experienced higher limb fat gains than other subjects, and these differences were statistically significant. Haemoglobin increased by a median of 1.0 g/dL in the TDF/FTC arm (P < 0.001) and remained unchanged in the ZDV/3TC arm (p between groups = 0.0002). There were no significant differences between groups in other secondary endpoints (body weight, total body and trunk fat content, total body bone mineral density, laboratory parameters, CD4 cell count and viral load). CONCLUSIONS: Switching from a ZDV/3TC-based to a TDF/FTC-based regimen led to a statistically significant improvement in limb fat, in contrast to the progressive loss of limb fat in subjects continuing ZDV/3TC.

A longitudinal evaluation of the impact of a polylactic acid injection therapy on health related quality of life amongst HIV patients treated with anti-retroviral agents under real conditions of use.

BACKGROUND: Many HIV patients receiving antiretroviral treatment develop lipodystrophy. NEW-FILL® is a polylactic acid injected to treat facial lipoatrophy. The objectives of this study were to describe (1) change in quality of life (QoL) of HIV patients treated with NEW-FILL® in the management of facial lipoatrophy; (2) efficacy of NEW-FILL® using facial photographs and (3) a patient-reported "Overall Treatment Effect" (OTE) scale; and (4) safety of NEW-FILL®. METHODS: Doctors from 13 treatment centres recruited 230 HIV patients to receive up to 5 sessions of NEW-FILL® injections. Patients self-reported QoL with the ABCD questionnaire before the first set of injections, at 2 months and at 12 to 18 months after the last session of injections. Efficacy was evaluated at each interval through photographs and OTE scale. Safety was evaluated via Case Report Form (CRF) data. RESULTS: 64.4% of patients reported QoL improvements of >10% at 2 months, and 58.8% at 12-18 months. Lipoatrophy grades improved at each visit ("no lipoatrophy" or "limited lipoatrophy": 20.3% at inclusion, 77.4% at 2 months, 58.4% at 12-18 months). Average OTE scores of 5.3 and 5.0 at 2 and 12-18 months indicated "moderate improvement". Minimum Important Difference (MID) in QoL score was 7.1 points at 2 months; 7.4 points at 12-18 months. For 911 injection sessions performed, 3.4% resulted in "immediate" adverse events, 7% in "non-immediate" events, and 1.7% in "other" events. CONCLUSIONS: Improvements to quality of life and diminished lipoatrophy visibility were observed in the months immediately following NEW-FILL® treatment and were maintained 12-18 months post-treatment. Most adverse events were mild and transient. ABCD MID thresholds provide clinicians with means to assess the impact of lipoatrophy therapies on QoL.

Regional fat deposition and cardiovascular risk in HIV infection: the FRAM study.

HIV-infected individuals are at increased risk for cardiovascular disease (CVD) and lipodystrophy, but the relationship between regional adipose tissue (AT) depots and CVD risk is not well described. We determined regional AT volumes and CVD risk in an analysis of 586 HIV-infected and 280 control FRAM study subjects using whole-body magnetic resonance imaging (MRI) and the Framingham Risk Score (FRS). Median FRS and FRS >10% were higher in HIV than control men (4.7% vs. 3.7%, p=0.0002; 16% vs. 4%, p<0.0001). HIV and control women had similarly low FRS (1.1% vs. 1.2%, p=0.91). In controls, total AT and all regional AT depots showed strong positive correlations with FRS (p<0.001) in men and weaker positive correlations in women. Greater visceral AT (VAT) and lower leg subcutaneous AT (SAT) volumes were associated with elevated FRS in HIV subjects with a trend for upper trunk SAT. Controls in the lowest quartile of leg SAT had the lowest FRS (1.5%), whereas HIV with similarly low leg SAT had the highest FRS (4.0%, p<0.001 vs. controls). Increased VAT is associated with CVD risk, but the risk is higher in HIV-infected individuals relative to controls at every level of VAT. Peripheral lipoatrophy (as measured by leg SAT) is associated with striking increased CVD risk in HIV-infected patients even after controlling for VAT, whereas low leg SAT is associated with low CVD risk in controls.

Assessment of body fat composition disturbances by bioimpedance analysis in HIV-infected adults.

HIV-lipodystrophy syndrome is characterized by different patterns of body fat distribution (BFD) which are identified by clinical and body composition (BC) assessment, including bioimpedance analysis (BIA). Our aim was to compare BC in HIV-infected patients on combination antiretroviral therapy (cART) according to 4 distinct phenotypes of BFD (G1-no lipodystrophy, G2-isolated central fat accumulation, G3-lipoatrophy, G4-mixed forms of lipodystrophy) and assessed factors associated with them. Anthropometry and BIA were performed in 344 HIV-1 patients. G2 and G4 phenotype patients had significantly higher fat mass (FM) but no differences were observed in fat-free mass (FFM) and total body water among the 4 phenotypes. Significant negative associations were found between the presence of lipoatrophy and female gender, body mass index (BMI), waist (WC), hip (HC) and thigh circumferences, and total body FM estimated by BIA. After adjustment for gender, cART duration and BMI, G3 had significant lower WC [odds ratio (OR)=0.84; 0.78- 0.90] and HC (OR=0.88; 0.81-0.96) mean. Independently of gender, cART duration and BMI, G2 remained significantly associated with higher WC (OR=1.11; 1.05-1.18) and HC (OR=1.15; 1.07-1.23) mean, and with FM estimated by BIA [FM as %, OR=1.17 (1.09-1.26); and FM as kg, OR=1.15 (1.06- 1.25)]. There was a significant positive association between G4 and female gender (OR=1.66; 1.01-2.75), BMI (OR=1.10; 1.04-1.17) and WC (OR=1.15; 1.09-1.21). The similar FFM along the BFD spectrum describes the actual BC of these patients without sarcopenia. In a clinical setting, BIA is an easy and useful tool to evaluate fat mass and FFM and gives us a picture of BC that was not possible with anthropometry.

MRI signal changes of the bone marrow in HIV-infected patients with lipodystrophy: correlation with clinical parameters.

OBJECTIVE: To assess the prevalence, imaging appearance, and clinical significance, of bone marrow MR signal changes in a group of human immunodeficiency virus (HIV)-infected patients with lipodystrophy syndrome. MATERIALS AND METHODS: Twenty-eight HIV-infected patients with lipodystrophy syndrome treated with highly active antiretroviral therapy, and 12 HIV-negative controls underwent MRI of the legs. Whole-body MRI, SPECT/CT, and a complete radiographic skeletal survey were obtained in subjects with signal changes in bone marrow. MRI and clinical evaluations were reviewed 6 months after baseline to determine changes after switching from thymidine analogs (TA) to tenofovir-DF (TDF). MRI results correlated with clinical parameters. RESULTS: We observed foci of a serous-like pattern (low signal and no enhancement on T1-weighted, high signal on T2-weighted images) in 4 out of 28 patients (14.3%) and an intermediate signal on T1-weighted images in 4 out of 28 patients (14.3%). Serous-like lesions were located in the lower limbs and scattered in the talus, calcaneus, femurs, and humeral bones; they showed slight uptake on SPECT bone scans and were normal on CT and radiographs. Patients with serous-like lesions had significantly lower peripheral and total fat at baseline than other groups (P < 0.05). No changes at 6 months were observed on MRI, and the serous-like lesion group showed good peripheral fat recovery after changing drug treatment. CONCLUSION: A serous-like MRI pattern is observed in the peripheral skeletons of HIV-infected patients with lipodystrophy, which correlates with peripheral lipoatrophy, and should not be misdiagnosed as malignant or infectious diseases. Although the MR lesions did not improve after switching the treatment, there was evidence of lipoatrophy recovery.

Skeletal muscle mitochondrial DNA content and aerobic metabolism in patients with antiretroviral therapy-associated lipoatrophy.

OBJECTIVES: To assess whether mitochondrial dysfunction in skeletal muscle characterizes antiretroviral therapy (ART)-associated lipoatrophy (LA). METHODS: A cross-sectional study comparing HIV-infected, antiretroviral-treated patients with LA (n = 5; LA+) and without LA (n = 5; non-LA) was conducted. Positron emission tomography was used to measure blood flow, oxygen extraction and oxygen consumption in quadriceps femoris muscle during rest and aerobic exercise. Mitochondrial DNA (mtDNA) was quantified by PCR. Body composition was measured by dual-energy X-ray absorptiometry and magnetic resonance imaging. All data are given as means +/- SEM. RESULTS: Compared with the non-LA group, the LA+ group had significantly less limb fat and more intra-abdominal fat, but similar leg muscle mass. The LA+ group versus the non-LA group had reduced mtDNA content per nucleus in adipose tissue (173 +/- 38 versus 328 +/- 62; P = 0.067), but not in skeletal muscle (2606 +/- 375 versus 2842 +/- 309; P = 0.64). Perfusion in resting muscle (34 +/- 7 versus 28 +/- 6 mL/kg/min in the LA+ group versus the non-LA group; P = 0.5), and the mean absolute (277 +/- 30 versus 274 +/- 43 mL/kg/min, respectively; P = 0.95) and relative (10.6 +/- 2.5- versus 11.9 +/- 1.5-fold change, respectively; P = 0.67) increases in perfusion during exercise were similar between the groups. Oxygen consumption at rest (2.2 +/- 0.7 versus 2.1 +/- 0.3 mL/kg/min in the LA+ group versus the non-LA group; P = 0.9), and the mean absolute (14.6 +/- 1.7 versus 24.3 +/- 8.8 mL/kg/min, respectively; P = 0.3) and relative (10.3 +/- 2.8- versus 11.7 +/- 2.4-fold change, respectively; P = 0.73) exercise-induced increases in oxygen consumption were similar between the groups. The oxygen extraction fraction was comparable between the groups, both at rest and during exercise. Plasma lactate concentrations remained unchanged in both groups during exercise. CONCLUSIONS: HIV-infected patients with ART-associated LA have similar mtDNA content in skeletal muscle and comparable skeletal muscle aerobic exercise metabolism to antiretroviral-treated non-lipoatrophic patients.

Improvement of mitochondrial toxicity in patients receiving a nucleoside reverse-transcriptase inhibitor-sparing strategy: results from the Multicenter Study with Nevirapine and Kaletra (MULTINEKA).

BACKGROUND: Nucleoside reverse-transcriptase inhibitor (NRTI)-related mitochondrial toxicity has been suggested as a key factor in the induction of antiretroviral-related lipoatrophy. This study aimed to evaluate in vivo the effects of NRTI withdrawal on mitochondrial parameters and body fat distribution. METHODS: A multicenter, prospective, randomized trial assessed the efficacy and tolerability of switching to lopinavir-ritonavir plus nevirapine (nevirapine group; n = 34), compared with lopinavir-ritonavir plus 2 NRTIs (control group; n = 33) in a group of human immunodeficiency virus-infected adults with virological suppression. A subset of 35 individuals (20 from the nevirapine group and 15 from the control group) were evaluated for changes in the mitochondrial DNA (mtDNA) to nuclear DNA ratio and cytochrome c oxidase (COX) activity after NRTI withdrawal. Dual-energy X-ray absorptiometry (DEXA) scans were used to objectively quantify fat redistribution over time. RESULTS: The nevirapine group experienced a progressive increase in mtDNA content (a 40% increase at week 48; P = .039 for comparison between groups) and in the COX activity (26% and 32% at weeks 24 and 48, respectively; P = .01 and P = .09 for comparison between groups, respectively). There were no statistically significant between-group differences in DEXA scans at week 48, although a higher fat increase in extremities was observed in the nevirapine group. No virologic failures occurred in either treatment arm. CONCLUSIONS: Switching to a nucleoside-sparing regimen of nevirapine and lopinavir-ritonavir maintained full antiviral efficacy and led to an improvement in mitochondrial parameters, which suggests a reversion of nucleoside-associated mitochondrial toxicity. Although DEXA scans performed during the study only revealed slight changes in fat redistribution, a longer follow-up period may show a positive correlation between reduced mitochondrial toxicity and a clinical improvement of lipodystrophy.

Evolving perspectives on HIV-associated lipodystrophy syndrome: moving from lipodystrophy to non-infectious HIV co-morbidities.

This article will provide insight into the evolving perspectives on HIV-related lipodystrophy syndrome: recent changes in epidemiology, a shifting focus from individual component assessment towards a more comprehensive risk evaluation for organ dysfunction and disease, the impact of patient-related outcomes in heath-related quality of life and the integration of this syndrome into a wider scenario of a premature ageing process in HIV-infected people will be discussed. The time has come to proceed beyond lipodystrophy studies based on blood concentrations of lipids and glucose and body fat evaluation. Surrogate markers of organ disease associated with lipodystrophy better identify patients vulnerable to non-infectious co-morbidities (NICMs) rather than statistical risk algorithms. In this evolving perspective NICMs take the place of lipodystrophy in the description of the clinical spectrum of HIV disease and allow integration of this syndrome into the wider scenario of a premature ageing process in HIV-infected people. Management of NICMs needs to be considered as part of a multi-disciplinary holistic approach that accommodates the increasing number of factors influencing non-infectious HIV-related outcomes.

Improvements in cheek volume in lipoatrophic individuals switching away from thymidine nucleoside reverse transcriptase inhibitors.

BACKGROUND: Thymidine nucleoside reverse transcriptase inhibitors (NRTIs) are associated with subcutaneous fat loss. Facial changes cannot be assessed by dual-energy X-ray absorptiometry (DEXA) scans. There are limited objective data on the reversibility of facial lipoatrophy. METHODS: We performed a facial volume substudy of a randomized thymidine NRTI replacement study carried out in HIV-infected subjects with moderate to severe lipoatrophy. Facial volume changes were assessed using validated 3D laser imaging. Changes in body composition were measured using DEXA scans. The association between changes in facial volume and body composition parameters at 48 weeks was measured using Spearman's rank correlation. RESULTS: Forty-seven individuals (46 male), 11 receiving zidovudine and 36 receiving stavudine, switched to either tenofovir disoproxil fumarate (DF) (n=23) or abacavir (ABC) (n=24). Thirty-nine of these 47 patients (84.8%) reported facial lipoatrophy at baseline. The median volume increase in both cheeks from baseline was 1857.3 mm(3). These volume changes and increases in limb fat at 48 weeks were similar in the two groups and correlated significantly (Spearman's r=0.41, P=0.004). CONCLUSIONS: Facial volume in lipoatrophic individuals was found to increase after thymidine NRTI replacement. We demonstrated a significant correlation between improvements in facial and limb fat parameters. Switching from thymidine NRTIs in patients with facial lipoatrophy could potentially reduce the need for cosmetic interventions.

Human immunodeficiency virus atropy induces modification of subcutaneous adipose tissue architecture: in vivo visualization by high-resolution magnetic resonance imaging.

BACKGROUND: Human immunodeficiency virus (HIV) infection generally induces lipodystrophy. For targeted treatment a better understanding of its development is necessary. The utility of high-resolution magnetic resonance imaging (MRI) is explored. OBJECTIVES: The present study presents a way to visualize the adipose tissue architecture in vivo and to inspect modifications associated with the atrophy. METHODS: High-resolution MRI scans with surface coils were performed on the calf and at the lumbar region of three groups of patients: HIV patients with lipoatrophy, HIV patients without lipoatrophy and healthy volunteers. All patients underwent a clinical examination. In addition, dual energy X-ray absorptiometry (DEXA) measurements were taken. On the MRI scans adipose tissue thickness and adipose nodule size were measured. Results High-resolution MRI enabled identification of a clear disorganization of adipose tissue in patients with lipoatrophy. In addition, these patients presented a very small adipose tissue thickness on the calf and a very small nodule size. RESULTS: led to the hypothesis that adipose tissue disorganization appears before changes in DEXA measurements or clinically visible modifications. CONCLUSIONS: High-resolution MRI enabled visualization in vivo of precise changes in tissue organization due to HIV lipoatrophy. This imaging technique should be very informative for better monitoring of the atrophy.

Patient satisfaction and duration of effect with PLLA: a review of the literature.

Poly-L-lactic acid (PLLA) has been available to the European medical community as a treatment for Human Immunodeficiency Virus (HIV)-associated facial lipoatrophy for nearly a decade, gaining U.S. Food and Drug Administration (FDA) approval for this indication in 2004. PLLA has been utilized in an off-label manner in the U.S. to treat lipoatrophy of aging in the non-HIV population. The literature regarding safety and efficacy of PLLA is well-documented, while studies regarding patient satisfaction and duration are more limited. The following review article discusses the currently available literature pertaining to the durability and patient satisfaction after PLLA treatment. Patients treated for HIV-related facial lipoatrophy and cosmetic use of PLLA for lipoatrophy of aging are discussed separately.

[Treatment of HIV facial lipoatrophy with a submalar porous polyethylene implant (Medpor)]. / Traitement des lipoatrophies faciales utilisant des implants de Medpor en polyéthylène poreux.

Human immunodeficiency virus associated facial lipoatrophy is becoming epidemic and is a distressing sign for patients. Non permanent fillers provide only temporary results and cannot be the solution for severe cases. Lipodystrophy makes the lipofilling difficult to perform with a fibrous low quality fat difficult to harvest. We propose another solution using porous polyethylene implants (Medpor). Eight patients underwent submalar augmentation through an upper gingivobuccal sulcus incision that allows a subperiosteal dissection. The implants are carved to provide the desired augmentation. Overall, eight patients had good or very good aesthetic postoperative outcomes as determined by the patient and the surgeon. No complications occurred and results remain natural. Porous polyethylene implant (Medpor) is our treatment of choice for mild to severe facial lipoatrophy. Besides these implants could be removed easily later if needed.