Sex-specific fat mass ratio cutoff value identifies a high prevalence of cardio-metabolic disorders in people living with HIV.

BACKGROUND AND AIMS: HIV-associated lipodystrophy syndrome (HALS) contributes to the increased cardiovascular risk connoting people living with HIV (PLHIV). HALS recognition, based on clinical ground, may be inaccurate urging an objective instrumental diagnosis. The aim of this study is to search for the DXA-derived fat mass ratio (FMR) threshold, among those suggested for the diagnosis of HALS, able to identify PLHIV at high cardiovascular risk. METHODS AND RESULTS: In a cross-sectional analysis of 101 PLHIV (age 53 ± 11 years, men 55%) and 101 age- and sex-matched uninfected controls, DXA-derived FMR and anthropometric as well as cardio-metabolic parameters were assessed. PLHIV showed a higher FMR (1.15 ± 0.42 vs 0.95 ± 0.18, p < 0.01) together with a greater cardio-metabolic derangement than controls, in spite of lower BMI (24.3 ± 4.3 vs 26.9 ± 4.0 kg/m2, p < 0.01) and fat mass index (FMI, 6.6 ± 3.0 vs 9.2 ± 3.1 kg/m2, p < 0.01). Particularly, PLHIV with HALS (n = 28), defined as those with a FMR above 1.260 and 1.329 for men and women, respectively, had a greater prevalence of type 2 diabetes mellitus (18% vs 1%), insulin resistance (68% vs 27%), hypertriglyceridemia (50% vs 29%), hypertension (61% vs 30%) and metabolic syndrome (32% vs 10%) than those without HALS (p < 0.05 for all comparisons) and controls. At multivariate analyses, FMR in PLHIV was significantly associated (p < 0.05) with fasting glucose (ß [95%CI] = 0.5, [0.1-0.9]), insulin (44.6, [14.9-74.2]), HOMA-IR (1.6, [0.5-2.7]), triglycerides (1.0, [ 0.2-1.8]) and HDL-cholesterol (-2.1, [-3.9/-0.4]) levels. CONCLUSION: Sex-specific FMR thresholds, proposed for diagnosis of HALS, could represent new indices of cardio-metabolic derangement in PLHIV.

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.

Association between lipodystrophy and length of exposure to ARTs in adult HIV-1 infected patients in Montreal.

BACKGROUND: The aim of this study was to establish the prevalence of lipodystrophy and its association to cumulative exposure to antiretroviral drugs. METHOD: We conducted a cross sectional study in all HIV- infected patients attending the HIV clinic in the Centre hospitalier universitaire de Montréal (CHUM) with DEXA scan. Lipodystrophy was defined as a trunk/limb fat ratio ≥ 1.5. Association between cumulative exposure to antiretroviral (measured in years of use) with trunk/limb fat ratio (coded as a continuous variable) was assessed using univariate and multivariate linear regression for each antiretroviral drug with at least 40 exposed patients. RESULTS: One hundred sixty-six patients were included. Seventy-five percent were male, median age was 56 years, 67% were Caucasian. Overall, prevalence of lipodystrophy was 47%, with a mean trunk/limb fat ratio of 1.87, SD = 1.03, min = 0.6 and max = 5.87. Each 10-year increase in age and HIV infection duration was associated with an average increase of 0.24 and 0.34 for the trunk/limb fat ratio respectively. (p = 0.003, p = 0.002, respectively) Patients classified as lipodystrophic were more likely to be diabetic (50 vs. 28%, p = 0.07) and to have dyslipidemia (47 vs. 19%, p = 0.01). According to viral load at DEXA test, each one log increase was associated with less probability (0.7) of lipodystrophy. (p = 0.01) Among ARV drugs tested, there was an association between years of use of d4T, ritonavir and raltegravir and higher trunk/limb fat ratio (indicating more lipodystrophy) (p < 0.05). CONCLUSION: Lipodystrophy is very common in HIV infected patients and is correlated with duration of some new antiretroviral drugs.

Patient Reported Outcomes from HIV Facial Lipoatrophy Treatment With a Volumizing Hyaluronic Acid Filler: A Prospective, Open-Label, Phase I and II Study.

BACKGROUND: Human immunodeficiency virus (HIV) facial lipoatrophy (FLA) is associated with the use of highly active antiretroviral therapy (HAART) and HIV disease. HIV FLA is primarily characterized by midface (cheeks and temples) volume loss, resulting in a "sunken" and aged appearance. Filler agents for treatment of HIV FLA can provide midface volumization and improve quality-of-life (QOL). A 20 mg/ml hyaluronic acid (HA) filler (Juvéderm Voluma® XC, Allergan plc, Irvine, CA) may provide an immediate, natural appearing facial enhancement outcome in one treatment. We hypothesized that this HA filler for treatment of HIV FLA is safe and efficacious and may help improve patients' QOL.
OBJECTIVE: To provide patient reported outcomes from HA filler for treatment of HIV FLA and suggest recommendations on use of validated QOL outcome measures to assess patient concerns specific to HIV FLA.
METHODS: This was a prospective, open-label, phase I and II study to evaluate patient reported outcomes, in addition to safety and efficacy, of this HA filler for treatment of HIV FLA in 20 subjects at the Sacramento Veterans Affairs Medical Center, Mather, CA (ClinicalTrials.gov NCT02342223). Outcome measures include the Dermatology Life Quality Index (DLQI) and a subject satisfaction questionnaire (SSQ).
RESULTS: Nineteen subjects completed the 12-month follow-up. There was no significant improvement of DLQI score. Subject comments revealed high degree of satisfaction and there were no negative comments on the SSQ.
CONCLUSIONS: In this study, we report that all subjects that completed this study were satisfied and had subjective improvement of their QOL post-treatment. We recommend against use of DLQI in the future as it may not fully encompass the emotional and mental health aspects that may be affected from HIV FLA. We recommend use of the Facial Appearance Inventory (FAI) and FACE-Q in future studies for HA filler treatment of HIV FLA.

J Drugs Dermatol. 2016;15(9):1064-1069.

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.

Involvement of the LPS-LPB-CD14-MD2-TLR4 inflammation pathway in HIV-1/HAART-associated lipodystrophy syndrome (HALS).

OBJECTIVES: A relationship between obesity and intestinal bacterial translocation has been reported. Very little information is available with respect to the involvement of the bacterial translocation mechanistic pathway in HIV-1/highly active antiretroviral therapy (HAART)-associated lipodystrophy syndrome (HALS). We determined whether lipopolysaccharide (LPS)-binding protein (LBP), cluster of differentiation 14 (CD14), myeloid differentiation protein 2 (MD2) and toll-like receptor 4 (TLR4) single-nucleotide polymorphisms and LPS, LBP and soluble CD14 (sCD14) plasma levels are involved in HALS. PATIENTS AND METHODS: This cross-sectional multicentre study involved 558 treated HIV-1-infected patients, 240 with overt HALS and 318 without HALS. Anthropometric, clinical, immunovirological and metabolic variables were determined. Polymorphisms were assessed by genotyping. Plasma levels were determined by ELISA in 163 patients (81 with HALS and 82 without HALS) whose stored plasma samples were available. Student's t-test, one-way ANOVA, two-way repeated measures ANOVA, the χ(2) test and Pearson and Spearman correlation analyses were carried out for statistical analysis. RESULTS: LBP rs2232582 T→C polymorphism was significantly associated with HALS (P = 0.01 and P = 0.048 for genotype and allele analyses, respectively). Plasma levels of LPS (P = 0.009) and LBP (P < 0.001) were significantly higher and sCD14 significantly lower (P < 0.001) in patients with HALS compared with subjects without HALS. LPS levels were independently predicted by triglycerides (P < 0.001) and hepatitis C virus (P = 0.038), LBP levels by HALS (P < 0.001) and sCD14 levels by age (P = 0.008), current HIV-1 viral load (P = 0.001) and protease inhibitor use (P = 0.018). CONCLUSIONS: HALS is associated with LBP polymorphism and with higher bacterial translocation.

Semipermanent filler treatment of HIV-positive patients with facial lipoatrophy: long-term follow-up evaluating MR imaging and quality of life.

BACKGROUND: Injectable fillers such as poly-L-lactic acid (PLLA) and calcium hydroxylapatite (CaHA) have shown promising results in the treatment of combination antiretroviral therapy (cART)-induced facial lipoatrophy (FLA). However, the effects of these substances on magnetic resonance imaging (MRI) have not yet been described. OBJECTIVE: The authors analyze the association between the effects of treatment with semipermanent fillers on MRI and changes in quality of life (QOL). METHODS: Eighty-two human immunodeficiency virus (HIV)-positive patients with cART-induced FLA (grades 2-4) were enrolled in this prospective study. A mean volume of 58.2 mL (range, 12-105 mL) of PLLA (n = 41 patients) and 9.1 mL (range, 3-23 mL) of CaHA (n = 41) was injected in multiple sessions. The MRI examinations were performed prior to treatment and again 12 months after. The self-reported severity of FLA as well as QOL was measured using questionnaires based on Short Form 36, Medical Outcomes Study HIV Health Survey, and Center for Epidemiologic Studies Depression Scale formats. RESULTS: Significant increases in total subcutaneous thickness (TST) of the injected regions could be identified on MRI in nearly all patients 1 year posttreatment. Patients reported that mental health and social and role functioning improved; depressive symptoms decreased after treatment. In addition, the increase in TST was positively associated with improvement of QOL. CONCLUSIONS: This study confirms that treatment with both PLLA and CaHA not only increases TST but also is associated with improved QOL for HIV-infected patients. Furthermore, the study also demonstrates that MRI can show filler-induced neocollagenesis and quantify FLA treatment effects.

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.

Reduction in visceral adiposity is associated with an improved metabolic profile in HIV-infected patients receiving tesamorelin.

BACKGROUND: Tesamorelin, a growth hormone-releasing hormone analogue, decreases visceral adipose tissue (VAT) by 15%-20% over 6-12 months in individuals with human immunodeficiency virus (HIV)-associated abdominal adiposity, but it is unknown whether VAT reduction is directly associated with endocrine and metabolic changes. METHODS: In 2 phase III, randomized, double-blind studies, men and women with HIV-associated abdominal fat accumulation were randomly assigned (ratio, 2:1) to receive tesamorelin or placebo for 26 weeks. At week 26, patients initially receiving tesamorelin were randomly assigned to continue receiving tesamorelin or to receive placebo for an additional 26 weeks. In per-protocol analysis of 402 subjects initially randomly assigned to receive tesamorelin, those with ≥8% reduction in VAT were defined a priori as responders per the statistical analysis plan. Post hoc analyses were performed to assess differences between responders and nonresponders. RESULTS: Compared with tesamorelin nonresponders, responders experienced greater mean (±SD) reduction in triglyceride levels (26 weeks: -0.6 ± 1.7 mmol/L vs -0.1 ± 1.2 mmol/L [P = .005]; 52 weeks: -0.8 ± 1.8 mmol/L vs 0.0 ± 1.1 mmol/L [P = .003]) and attenuated changes in fasting glucose levels (26 weeks: 1 ± 16 mg/dL vs 5 ± 14 mg/dL [P = .01]; 52 weeks: -1 ± 14 mg/dL vs 8 ± 17 mg/dL [P < .001]), hemoglobin A1c levels (26 weeks: 0.1 ± 0.3% vs 0.3 ± 0.4% [P < .001]; 52 weeks: 0.0 ± 0.3% vs 0.2 ± 0.5% [P = .003]), and other parameters of glucose homeostasis. Similar patterns were seen for adiponectin levels, with significant improvement in responders vs nonresponders. Changes in lipid levels and glucose homeostasis were significantly associated with percentage change in VAT. CONCLUSIONS: In contrast to nonresponders, HIV-infected patients receiving tesamorelin with ≥8% reduction in VAT have significantly improved triglyceride levels, adiponectin levels, and preservation of glucose homeostasis over 52 weeks of treatment. CLINICALTRIALS.GOV REGISTRATION: NCT00123253, NCT00435136, NCT00608023.

Erectile dysfunction is not a mirror of endothelial dysfunction in HIV-infected patients.

INTRODUCTION: The penis has been compared to a barometer of endothelial health, erectile dysfunction (ED) being an early sign of endothelial dysfunction. AIM: The aim of the study was to investigate the extent of the association between ED and endothelial dysfunction in patients with human immunodeficiency virus (HIV) infection on antiretroviral therapy. METHODS: In this observational cross-sectional study, we evaluated the prevalence and factors associated with ED in a cohort of 133 HIV-infected men. MAIN OUTCOME MEASURES: The International Index of Erectile Function, ultrasound assessment of brachial artery flow mediated dilatation (FMD), and multi-slice computed tomography for coronary artery calcifications (CAC) as surrogates of endothelial dysfunction, the Adult Treatment Panel III criteria to diagnose metabolic syndrome (MS), plasma total testosterone (hypogonadism), and a visual analogue scale (VAS) of aesthetic satisfaction of the face and of the body (psychological distress associated with lipodystrophy). RESULTS: Thirty-nine (29.32%) patients had mild ED, 14 (10.52%) patients had moderate ED, and 26 (19.55%) patients had severe ED. Prevalence of ED ranged from 45% to 65%, respectively, in patients less than 40 and more than 60 years old. MS was present in 20 (25%) patients with ED and 13 (24%) patients without ED (P value = 0.87). Prevalence of ED neither appeared to be associated with MS as a single clinical pathological entity nor with the numbers of its diagnostic components. FMD < 7% was present in 25 (32%) patients with ED and 18 (33%) patients without ED (P value = 0.83), and CAC > 100 was present in 8 (10%) patients with ED and 5 (9%) patients without ED (P value = 0.87). A stepwise multivariable logistic regression analysis was used to find predictors of ED. Independent predictors were VAS face (odds ratio [OR] = 0.85, 95% confidence interval [CI] 0.73-0.99, P = 0.049) and age per 10 years of increase (OR = 1.73, 95% CI 1.02-2.94, P = 0.04). CONCLUSIONS: Age constituted the most important risk factor for ED, which was related to aesthetic dissatisfaction of the face leading to negative body image perception.

High prevalence of lipoatrophy in pre-pubertal South African children on antiretroviral therapy: a cross-sectional study.

BACKGROUND: Despite changes in WHO guidelines, stavudine is still used extensively for treatment of pediatric HIV in the developing world. Lipoatrophy in sub-Saharan African children can be stigmatizing and have far-reaching consequences. The severity and extent of lipoatrophy in pre-pubertal children living in sub-Saharan Africa is unknown. METHODS: In this cross-sectional study, children who were 3-12 years old, on antiretroviral therapy and pre-pubertal were recruited from a Family HIV Clinic in South Africa. Lipoatrophy was identified and graded by consensus between two HIV pediatricians using a standardized grading scale. A professional dietician performed formal dietary assessment and anthropometric measurements of trunk and limb fat. Previous antiretroviral exposures were recorded. In a Dual-Energy X-ray Absorbtiometry (DXA) substudy body composition was determined in 42 participants. RESULTS: Among 100 recruits, the prevalence of visually obvious lipoatrophy was 36% (95% CI: 27%-45%). Anthropometry and DXA measurements corroborated the clinical diagnosis of lipoatrophy: Both confirmed significant, substantial extremity fat loss in children with visually obvious lipoatrophy, when adjusted for age and sex. Adjusted odds ratio for developing lipoatrophy was 1.9 (95% CI: 1.3 - 2.9) for each additional year of accumulated exposure to standard dose stavudine. Cumulative time on standard dose stavudine was significantly associated with reductions in biceps and triceps skin-fold thickness (p=0.008). CONCLUSIONS: The prevalence of visually obvious lipoatrophy in pre-pubertal South African children on antiretroviral therapy is high. The amount of stavudine that children are exposed to needs review. Resources are needed to enable low-and-middle-income countries to provide suitable pediatric-formulated alternatives to stavudine-based pediatric regimens. The standard stavudine dose for children may need to be reduced. Diagnosis of lipoatrophy at an early stage is important to allow timeous antiretroviral switching to arrest progression and avoid stigmatization. Diagnosis using visual grading requires training and experience, and DXA and comprehensive anthropometry are not commonly available. A simple objective screening tool is needed to identify early lipoatrophy in resource-limited settings where specialized skills and equipment are not available.

A facial marker in facial wasting rehabilitation.

BACKGROUND: Facial lipoatrophy is one of the most distressing manifestation for HIV patients. It can be stigmatizing, severely affecting quality of life and self-esteem, and it may result in reduced antiretroviral adherence. Several filling techniques have been proposed in facial wasting restoration, with different outcomes. The aim of this study is to present a triangular area that is useful to fill in facial wasting rehabilitation. METHODS: Twenty-eight HIV patients rehabilitated for facial wasting were enrolled in this study. Sixteen were rehabilitated with a non-resorbable filler and twelve with structural fat graft harvested from lipohypertrophied areas. A photographic pre-operative and post-operative evaluation was performed by the patients and by two plastic surgeons who were "blinded." The filled area, in both patients rehabilitated with structural fat grafts or non-resorbable filler, was a triangular area of depression identified between the nasolabial fold, the malar arch, and the line that connects these two anatomical landmarks. RESULTS: The cosmetic result was evaluated after three months after the last filling procedure in the non-resorbable filler group and after three months post-surgery in the structural fat graft group. The mean patient satisfaction score was 8.7 as assessed with a visual analogue scale. The mean score for blinded evaluators was 7.6. CONCLUSION: In this study the authors describe a triangular area of the face, between the nasolabial fold, the malar arch, and the line that connects these two anatomical landmarks, where a good aesthetic facial restoration in HIV patients with facial wasting may be achieved regardless of which filling technique is used.

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.

Facial lipodystrophy in an HIV-positive patient using an orthodontic appliance.

The aim of this article was to relate the clinical case of an HIV-positive orthodontic patient who reported that her cheeks had been hurting since treatment began. We started with the data collected in anamnesis and by contact with the patient's physician, and a diagnosis of facial lipodystrophy as a result of the use of retroviral drugs was reached. The patient was referred to a dermatologist for treatment of the facial lipodystrophy.

Fat mass ratio: an objective tool to define lipodystrophy in hiv-infected patients under antiretroviral therapy.

Human immunodeficiency virus (HIV) infection and its treatment with antiretroviral therapy (ART) have been associated with lipodystrophy. Different clinical methodologies have been used to define the syndrome. The aim of this study was to propose gender-specific reference values using objective measurements for defining lipodystrophy in HIV-infected patients. Using dual-energy X-ray absorptiometry (DXA), total body composition was analyzed in 221 HIV-infected patients under ART (146 men). We used fat mass ratio (FMR) as the ratio between the percent of the trunk fat mass and the percent of the lower-limb fat mass. One hundred forty patients (63.6%) presented clinically defined lipodystrophy. In men, the optimal cutoff value for the FMR was 1.961 (area under the receiver operating characteristic curve [AUC]: 0.74 [95% confidence interval (CI): 0.66-0.82], p<0.001), with a sensitivity 58.3%, a specificity 83.7%, a positive predictive value (PPV) of 89.6% and a negative predictive value (NPV) of 45.5%. In women, the optimal cutoff value for the FMR was 1.329 (AUC: 0.74 [95% CI: 0.63-0.86], p<0.001), with a sensitivity 51.4%, a specificity 94.6%, a PPV of 90.5%, and an NPV of 66.0%. The FMR evaluated by DXA with the gender-specific cutoffs defined here is an objective way to define HIV-related lipodystrophy.

Longitudinal study of body composition of 101 HIV men with lipodystrophy: dual-energy X-ray criteria for lipodystrophy evolution.

The aim of this study was to define evolution profiles of body composition among human immunodeficiency virus (HIV)-infected men with lipodystrophy. The design is a retrospective analysis using observational data collected longitudinally. We included 101 HIV-infected men with lipodystrophy managed in routine practice and who had 2 dual energy X-ray absorptiometry scans within a minimum interval of 18 mo. Lipodystrophy was defined as a fat mass ratio (FMR, defined as the ratio of the percentage of the trunk fat mass over the percentage of the lower limbs fat mass) equal or superior to 1.5. Patients were classified in "improved" group (IG: increase of lower limbs fat mass >/= 10%) or "nonimproved" group (NIG). Body composition, immunovirological and epidemiological data were collected and compared between the 2 groups. In the whole population, over a 4-yr period, a significant increase was observed for total fat mass, trunk fat mass, and lower limbs fat mass, whereas total lean mass was stable. Total body mineral density decreased. Fifty-nine patients (IG), less exposed to zidovudine than the NIG, had an increase of lower limbs fat mass higher than 10%. But only 13 (22%) regained a normal distribution of fat mass (FMR < 1.5), showing that lipodystrophy was slowly reversible. Among the NIG, 5 patients (11.9%), less exposed to zidovudine and with a higher mean of viral load, reached an FMR below 1.5. It was mainly because of a loss of trunk fat mass, which could be the sign of a lipodystrophy worsening. Lipodystrophy improved for 58.4% of men. The improvement was very slow. Recovery was observed only in patients with an earlier intervention. No correlation was observed between lipodystrophy and total body bone mineral density. The loss of trunk fat mass without gain of lower limbs fat mass may indicate a worsening of HIV disease.

Dermatological aspects of medicine: highly active antiretroviral therapy and the treatment of human immunodeficiency virus.

This is the sixth in a series of CPD articles aimed at reviewing the recent general medical literature relating to topics that may be of interest to dermatologists. In this issue the new classes of anti-retroviral drugs will be described in the context of the replication cycle of human immunodeficiency virus (HIV). The regimens of drug treatments and the more common side-effects including HIV-lipodystrophy syndrome will be discussed along with the recommendations for testing of people for HIV from new guidelines.

Lipodystrophy - a sign for metabolic syndrome in patients of the HIV-HEART study.

BACKGROUND: After the introduction of antiretroviral therapy, the life expectancy of HIV patients has increased to more than 30 years after initial diagnosis. Cardiovascular disease now is an important cause of death in HIV-infected patients. PATIENTS AND METHODS: In the multicenter, prospective HIV-HEART study, 222 (38 %) patients suffered from lipodystrophy. Women were more often affected than men (41.5 % vs. 25.3 %). Patients with lipodystrophy were on average 5 years older and had been infected longer (10.4 vs. 6.6 years) then patients without lipodystrophy. RESULTS: Lipodystrophy in HIV patients was a clinical sign of cardiovascular risk factors like hyperlipidemia (total cholesterol 19 mg/dl higher, HDL 2.8 mg/dl lower, triglycerides 53 mg/dl higher) and type 2 diabetes (11.3 % vs. 2.8 %). Patients with lipodystrophy were more likely to be co-infected with hepatitis B (34.7 % vs. 28.8 %, p = 0.122) or C (13.1 % vs. 9.3 %, p = 0.16) than patients without lipodystrophy. The quality of life was reduced in patients with lipodystrophy. In 6 of 8 scales of the SF-36 questionnaire, patients with lipodystrophy had lower scores. CONCLUSIONS: Lipodystrophy syndrome is an early warning system for a number of illnesses which reduce life expectancy. Dermatologists must help insure that HIV-infected patients receive treatment for these disorders.

[HIV lipodystrophy]. / HIV lipodystrofie.

Combined antiretroviral therapy results in extraordinary decrease of morbidity and mortality of HIV-infected patients and in an essential change of the HIV/AIDS disease prognosis. However, long-term intake of antiretroviral medicaments is related to occurrence of metabolic and morphological abnormalities, of which some have been combined into a new syndrome--the so called HIV lipodystrophy. The HIV lipodystrophy syndrome covers metabolic and morphological changes. Metabolic changes include dyslipidaemia with hypercholesterolaemia and/or hypertriglyceridaemia, insulin resistance with hyperinsulinaemia and hyperlaktataemia. Morphological changes have the nature of lipoatrophia (loss of subcutaneous fat--on the cheeks, on extremities, on buttocks and marked prominence of surface veins) or lipohypertrophia (growth of fat tissue--on the chest, in the dorsocervical area, lipomatosis of visceral tissues and organs, fat accumulation in the abdominal area). Several HIV lipodystrophy features are very similar to the metabolic syndrome of the general population. That is why this new syndrome represents a prospective risk of premature atherosclerosis and increase of the cardiovascular risk in young HIV positive individuals. The article mentions major presented studies dealing with the relation of antiretroviral treatment and the cardiovascular risk. The conclusions of the studies are not unequivocal--this is, among others, given by the reason that their length is short from the viewpoint of atherogenesis. The major risk of subclinical atherosclerosis acceleration seems to be related to the deep immunodeficiency and low number of CD4+ lymphocytes and florid, uncontrolled HIV infection with a high number of HIV-1 RNA copies actually circulating in the plasma. The question, whether metabolic and morphological changes related to HIV and cART carry a similar atherogenic potential as in the general population, remains open for future.

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.