Retreatment with injectable poly-l-lactic acid for HIV-associated facial lipoatrophy: 24-month extension of the Blue Pacific study.

BACKGROUND: Facial lipoatrophy occurs in HIV-positive patients taking highly active antiretroviral therapy and during natural aging. Injectable poly-l-lactic acid (PLLA) is a device approved internationally for restoration and correction of the signs of HIV-associated facial lipoatrophy. OBJECTIVE: To evaluate the long-term safety, duration of effect, and satisfaction with serial injections of PLLA for HIV-associated facial lipoatrophy. METHODS AND MATERIALS: In this single-site, open-label, retreatment study, 65 HIV-positive patients were treated with injectable PLLA every 5 weeks (until optimal recorrection). Presenting degree of lipoatrophy based on the James scale (1=mild, 4=severe) was reviewed. Skin thickness was measured at fixed points with calipers. Patients completed a post-retreatment satisfaction questionnaire. RESULTS: Nearly 10% of patients had persistent correction >36 months, based on patient report. Approximately 50% required three or fewer retreatments to maintain satisfactory correction (determined by patient and physician). Milder lipoatrophy on initial presentation required fewer retreatments and had more sustained correction. Time to first retreatment varied according to James scale score: 1 (21.4 months) and 4 (13.0 months). The mean patient satisfaction score was 4.9 (1=dissatisfied, 5=very satisfied) at study end. No serious adverse events were reported. CONCLUSION: Injectable PLLA is a safe and effective long-term treatment option for HIV-associated lipoatrophy.

Association between physical and echographic fat thickness assessments and a lipodystrophy grading scale in lipodystrophic HIV patients: practical implications.

A simple diagnostic method for detecting in clinical routine HAART-associated lipodystrophy in HIV-infected patients is lacking. We studied the relationships between the scores obtained with a subjective lipodystrophy severity grading scale (LSGS) and standard anthropometric and echographic measurements of the subcutaneous and visceral fat thickness of 74 HIV-infected patients. Patients were divided into four groups according to their LSGS score (0, 1-7, 8-14, 15-21). Significant correlations between the LSGS and the anthropometric and echographic measurements of fat thickness, mainly the limb circumferences (brachial: r= -0.43, p < 0.001; thigh: r= -0.41, p < 0.001), and, especially, the echographically assessed perirenal fat diameters either adjusted (r= 0.46, p < 0.001) or nonadjusted to the body mass index (r= 0.35, p < 0.001) were observed. Significant differences in most of these anthropometric parameters between either the lowest (score 0) and the highest (score 15-21) score groups and the remaining groups were found, but not between the two intermediate groups (scores 1-7 vs. 8-14). This suggests that lipodystrophy should be clinically categorized as absent, mild, or marked, and that even minor changes in physical aspect should be considered as indicative of this disorder. The combination of these subjective and objective parameters could be helpful in the early detection of lipodystrophy in clinical practice.

Reconstructive treatment for antiretroviral-associated facial lipoatrophy: a prospective study comparing autologous fat and synthetic substances.

Lipodystrophy is one of the foremost concerns among the HIV-positive population, and is often associated with psychosocial disorders. We evaluated the clinical efficacy of facial infiltrations with autologous fat, polylactic acid, and polyacrylamide gel using clinical inspection and facial photographs (ordinal scale). Additionally, we assessed the safety of the infiltration techniques and determined changes in patient satisfaction, emotional status, and quality of life. Evaluations were made at 48- and 96-week follow-up visits. This paper presents the 48- week follow-up results. The current analysis includes 138 patients: 8, 25, and 105 in the fat, polylactic acid, and polyacrylamide gel groups, respectively. At baseline, almost 50% of the patients (67/138) presented grades 3 and 4 lipoatrophy, but at week 48 only 7.5% (7/93) remained in these advanced grades (no patients from the polyacrylamide group). A new round of infiltrations at week 48 was necessary in 35% (33/93) of patients (88%, 84%, and 8% in the fat, polylactic, and polyacrylamide groups, respectively). No serious adverse events were detected with any of the substances. Patient satisfaction and quality of life improved significantly in all three groups. Infiltrations with autologous fat, polylactic acid, or polyacrylamide gel appear to be an effective and safe alternative to repair facial lipoatrophy, at least up to 48 weeks, significantly improving patient quality of life. Similar results were observed for all degrees of severity and between genders. Polyacrylamide gel provided the longest lasting benefits.

Psychometric properties of a lipodystrophy scale.

Prior HIV lipodystrophy (LD) scales have been unidimensional, often combining changes of fat loss with fat accumulation with retinoid changes. Our objective was to determine the psychometric properties of a LD scale used in an outpatient LD subspecialty clinic at a university hospital HIV clinic. A patient and clinician self-administered LD scale was used to evaluate 107 patients referred to the Owen LD Clinic from March of 1999 to August of 2002. Sixteen measures of the LD syndrome were assessed on a severity scale ranging from 0 (none) to 3 (severe). SPSS was used to perform a reliability and factor analysis. A total of 150 paired patient and clinician assessments were performed. Thirty-one patients had repeat assessments. Reliability analysis of the patient and clinician self-administered LD scale revealed an alpha of 0.76 and 0.73, respectively. Factor analysis of patient self-assessment of LD identified 3 factors, which clustered in the following order: fat loss, fat accumulation, and retinoid changes. Factor analysis of clinician self-assessment of LD identified 4 factors. The first factor clustered around items of fat loss. A second cluster consisted of retinoid changes. The final 2 factors clustered around items consistent with fat accumulation. The patient and clinician self-administered Owen Clinic LD scale was found to be highly reliable and useful in the assessment of LD. Our analysis confirms clinical intuition that the evaluation of LD is a multidimensional construct and that 3 subscales may be used to evaluate dimensions of fat loss, fat accumulation, and retinoid changes.

HIV lipodystrophy case definition using artificial neural network modelling.

OBJECTIVE: A case definition of HIV lipodystrophy has recently been developed from a combination of clinical, metabolic and imaging/body composition variables using logistic regression methods. We aimed to evaluate whether artificial neural networks could improve the diagnostic accuracy. METHODS: The database of the case-control Lipodystrophy Case Definition Study was split into 504 subjects (265 with and 239 without lipodystrophy) used for training and 284 independent subjects (152 with and 132 without lipodystrophy) used for validation. Back-propagation neural networks with one or two middle layers were trained and validated. Results were compared against logistic regression models using the same information. RESULTS: Neural networks using clinical variables only (41 items) achieved consistently superior performance than logistic regression in terms of specificity, overall accuracy and area under the ROC curve. Their average sensitivity and specificity were 72.4 and 71.2%, as compared with 73.0 and 62.9% for logistic regression, respectively (area under the ROC curve, 0.784 vs 0.748). The discriminating performance of the neural networks was largely unaffected when built excluding 13 parameters that patients may not have readily available. The average sensitivity and specificity of the neural networks remained the same when metabolic variables were also considered (total 60 items) without a clear advantage against logistic regression (overall accuracy 71.8%). The performance of networks considering also body composition variables was similar to that of logistic regression (overall accuracy 78.5% for both). CONCLUSIONS: Neural networks may offer a means to improve the discriminating performance for HIV lipodystrophy, when only clinical data are available and a rapid approximate diagnostic decision is needed. In this context, information on metabolic parameters is apparently not helpful in improving the diagnosis of HIV lipodystrophy, unless imaging and body composition studies are also obtained.

Practical applications of the HIV lipodystrophy case definition.

Diagnosis of HIV-associated lipodystrophy (LD) has been limited by the absence of a validated case definition and the frequent lack of objective body composition measures. An international, objective, case-control study recruited HIV-infected, adult outpatients free of active AIDS, and a case definition model for LD was developed. The relative merits and limitations of this definition as a practical tool for the long-term monitoring of a patient's LD status over the duration of clinical treatment are discussed.

[Polylactic acid injections: usefullness for the treatment of facial lipoatrophy in HIV+ patients under tritherapy]. / Injections d'acide polylactique: intérêt dans la correction des lipoatrophies faciales chez les patients VIH+ sous trithérapie.

BACKGROUND: The aim of the study was to evaluate the mean-term efficacy and tolerance of the polylactic acid injections (New-Fill) for the correction of facial lipoatrophy occurring in HIV-positive patients under tri-therapy. MATERIAL AND METHOD: The patients were managed at the University Hospitals of Besançon and Strasbourg (France) from January 2002 to December 2005 for a prospective study. The patients were consecutively included in this study once their consent was obtained. Patients not stabilized by their antiretroviral treatment were excluded. Facial lipoatrophy was classified in four clinical stages (stage I: mild, stage II: moderate, stage III: important, stage IV: severe) after a clinical examination. The polylactic acid solution was prepared according to the manufacturer's recommendations, and injected in a retrotracing manner in the hypoderm at the rate of one 5 ml flask per side, with an interval of one month. The number of sessions varied according to the severity of the stage. Treatment efficacy, assessed after a minimal follow-up of one year, was established clinically by comparing the initial and final photographs (changes in the clinical stage) and by the patient's and surgeon's satisfaction rate (from zero to ten). Treatment tolerance was established on the painfulness of injections and on socioprofessional constraints reported by the patients and made on a visual analogical scale. The occurrence of adverse-effects was checked. Finally, we compared the cost of the treatment with that of lipostructure. RESULTS: Twenty-five patients were included (mean age: 44, sex-ratio: 23 male/2 female patients). The mean body mass index was 21. The mean CD4 cell count was 600/mm(3). The mean HIV-1 RNA was 276 copies/ml. The severity of the lipoatrophy was stage one in two patients (8%), stage two in 12 patients (48%), stage three in nine patients (36%), and stage four in two patients (8%). The mean number of sessions was 5.2. The mean follow-up time was 26 months. In 76% of the cases we observed a complete correction of lipoatrophy (100% of stages I, 92% of stages II, 66% of stages III, 0% of stages IV). However, among stages II, III, and IV that were incompletely corrected, an improvement was noticed in all patients (grading to an inferior stage, at least). The mean satisfaction rate was 8/10 by patients and 7.2/10 by surgeons. In six patients (24%) a renewal of the treatment was proposed because of inadequate results. The painfulness of injections was rated at 3.3/10 and constraints at 3/10 by patients. One single case of visible and palpable sub-cutaneous granuloma was noticed in a patient at the end of the follow-up period (18 months). DISCUSSION: The use of polylactic acid is a safe and efficient procedure for the treatment of facial lipo-atrophy in HIV-infected patients, however severe the clinical stage may be, after a two-year follow-up period. We recommend hypodermic (and not dermic) injections to prevent adverse effects. This treatment is not more expensive then lipo-structure and the progressive correction is considered as an important advantage by patients. Considering our results, the simplicity of the procedure, and the low rate of complications observed, the injection of poly-lactic acid has become our first intention treatment for this condition.

An objective case definition of lipodystrophy in HIV-infected adults: a case-control study.

BACKGROUND: Lipodystrophy (peripheral lipoatrophy, central fat accumulation, and lipomatosis) is a common and disfiguring problem in adult patients with HIV-1 infection on antiretrovirals. However, an objective, validated definition of the disorder does not exist. We aimed to develop an objective, sensitive, specific, and broadly applicable case definition of HIV lipodystrophy. METHODS: In a case-control study, 1081 consecutive, HIV-infected, adult outpatients (261 [15%] women) without active AIDS were recruited from 32 sites worldwide. We classed patients with at least one moderate or severe subjective lipodystrophic feature, identified by lipodystrophy-specific physical examination and patient questionnaire, and apparent to both doctor and patient as cases (n=417). We classed patients with no such feature as controls (n=371), and patients without a clear diagnosis as non-assigned. We used objective clinical, metabolic, and body composition measurements to construct a logistic regression model with a subset of randomly selected cases and controls. The model was validated in the remaining patients. FINDINGS: A model including age, sex, duration of HIV infection, HIV disease stage, waist to hip ratio, anion gap, serum HDL cholesterol concentration, trunk to peripheral fat ratio, percentage leg fat, and intra-abdominal to extra-abdominal fat ratio had 79% (95% CI 70-85) sensitivity and 80% (95% CI 71-87) specificity for diagnosis of lipodystrophy. Models that incorporated only clinical, or only clinical and metabolic variables had lower sensitivity and specificity than the inclusive model. Models for lipoatrophy, fat accumulation, and lipomatosis could not be developed since pure phenotypes occurred in fewer than 10% of patients with clinical diagnoses of these disorders. INTERPRETATION: Our objective case definition of HIV-associated lipodystrophy should improve assessment of lipodystrophy prevalence, risk factors, and pathogenesis; prevention and treatment approaches; and assist in diagnosis.

An objective lipodystrophy severity grading scale derived from the lipodystrophy case definition score.

HIV lipodystrophy can be objectively diagnosed using a score derived from the 10 parameters in the HIV lipodystrophy case definition (LDCD). Lipodystrophy severity remains subjectively determined by physical examination and patient assessment. Regional dual-energy x-ray absorptiometry (DEXA) and single-slice abdominal computed tomography (CT) scanning are objective but are gender-dependent body composition measures. The LDCD score may provide a means of generating an objective and lipodystrophy grading/severity scale applicable to both men and women. Total and regional clinical lipodystrophy severity scores (generated using the HIV Outpatient Study [HOPS] scale: nil (0), mild (1), moderate (2), and severe (3) lipoatrophy or fat accumulation in 8 body regions) were correlated with objective measures of LD (LDCD score, DEXA, abdominal CT) and metabolic (lipid, glycemic, acid-base) parameters known to correlate significantly with lipodystrophy severity. Analysis was based on 417 lipodystrophic adults and 371 controls recruited to the HIV LDCD study. Correlation coefficients were used to compare physician and patient assessments (rPhysician, rPatient) with objective LD measures and metabolic parameters. The strongest objective correlate of total clinical lipodystrophy severity was the LDCD score (rPhysician = 0.641 [95% CI, 0.584-0.698]; rPatient = 0.620 [95% CI, 0.561-0.678]), whereas the strongest imaging correlate (trunk:limb fat ratio on DEXA) was significantly lower (rPhysician = 0.483 [95% CI, 0.420-0.546]; rPatient = 0.475 [95% CI, 0.412-0.538]; P < 0.001). The LDCD score also yielded significantly greater correlations with 7 of the 8 metabolic parameters than did clinical lipodystrophy severity scores. Based on quartiles of physician-rated severity, the LDCD scores were categorized to allow for rating of lipodystrophy as absent (LDCD score < 0), grade 1 (0-9.9), grade 2 (10-14.9), grade 3 (15-22.9), and grade 4 (>or=23). In conclusion, the LDCD score is the best objective measure of lipodystrophy severity and, in contrast to DEXA and CT, it is also gender independent. Subjective assessment of lipodystrophy severity could possibly be abandoned in cross-sectional studies. The LDCD score and its derived lipodystrophy grading scale merit prospective evaluation.