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.

Impacto na qualidade de vida em pacientes usuários de medicação retroviral e submetidos à gluteoplastia: estudo de coorte histórica / Gluteal contour restoration in antiretroviral users and its quality-of-life related impacts: a historical cohort study

INTRODUÇÃO: Desde a introdução do tratamento do HIV com uso da terapia antirretroviral altamente ativa, a mortalidade por essa doença foi reduzida drasticamente em todo o mundo. Um dos parefeitos relacionados à utilização desses fármacos é a lipodistrofia glútea. O objetivo deste trabalho é verificar o impacto da correção dessa deformidade na qualidade de vida de pacientes com HIV. MÉTODOS: Foi conduzido um estudo de coorte histórica com 23 pacientes submetidos à gluteoplastia com implante intramuscular, entre janeiro de 2010 e dezembro de 2014, avaliando a qualidade de vida por meio do em Nottingham Health Profile em. As informações foram coletadas de julho a agosto de 2015. A análise estatística foi feita utilizando-se o em Related-Samples McNemar Test em. RESULTADOS: strong Houve diferença significativa entre o pré-operatório e pós-operatório em 19 das 38 perguntas. CONCLUSÃO: É possível afirmar que a reconstrução glútea melhora a qualidade de vida de pacientes HIV positivos acometidos por lipodistrofia glútea relacionada a antirretrovirais.

INTRODUCTION: Since the introduction of highly active antiretroviral therapy for the treatment of human immunodeficiency virus (HIV), disease mortality has been dramatically reduced worldwide. One related side effect from the use of these drugs is gluteal lipodystrophy. The aim of this study is to assess the quality-of-life impact of correcting this deformity in HIV patients. METHODS: A historical cohort study was conducted between January 2010 and December 2014 with 23 patients, assessing the quality of their lives using the Nottingham Health Profile. A statistical analysis was performed using the McNemar test for related samples. RESULTS: There was a significant difference between preoperative and postoperative response in 19 of the 38 questions. CONCLUSION: We may say that gluteal reconstruction plays a role in improving quality of life for HIV patients who have been affected by antiretroviral related gluteal lipodystrophy.

HIV-1/HAART-Related Lipodystrophy Syndrome (HALS) Is Associated with Decreased Circulating sTWEAK Levels.

BACKGROUND AND OBJECTIVES: Obesity and HIV-1/HAART-associated lipodystrophy syndrome (HALS) share clinical, pathological and mechanistic features. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a multifunctional cytokine that plays an important role in obesity and related diseases. We sought to explore the relationship between HALS and circulating levels of soluble (s) TWEAK and its scavenger receptor sCD163. METHODS: This was a cross-sectional multicenter study of 120 HIV-1-infected patients treated with a stable HAART regimen; 56 with overt HALS and 64 without HALS. Epidemiological and clinical variables were determined. Serum levels of sTWEAK and sCD163 levels were measured by ELISA. Results were analyzed with Student's t-test, Mann-Whitney U and χ2 test. Pearson and Spearman correlation were used to estimate the strength of association between variables. RESULTS: Circulating sTWEAK was significantly decreased in HALS patients compared with non-HALS patients (2.81±0.2 vs. 2.94±0.28 pg/mL, p = 0.018). No changes were observed in sCD163 levels in the studied cohorts. On multivariate analysis, a lower log sTWEAK concentration was independently associated with the presence of HALS (OR 0.027, 95% CI 0.001-0.521, p = 0.027). CONCLUSIONS: HALS is associated with decreased sTWEAK levels.

IL-4 and IL-6 levels and adipose tissue distribution in HIV-1 patients under antiretroviral therapy.

PURPOSE: Combined antiretroviral therapy (cART) for the treatment of HIV-1 infection has been associated with complications, including lipodystrophy. Several interleukins have been implicated in the pathology and physiology of lipodystrophy. The present study aimed to compare the levels of IL-4 and IL-6 in HIV-1 patients under cART with and without, clinically and fat mass ratio defined, lipodystrophy and in four different groups of fat distribution: (1) no lipodystrophy; (2) isolated central fat accumulation; (3) isolated lipoatrophy and (4) mixed forms of lipodystrophy. METHODS: In the present cross-sectional study we evaluated IL-4 and IL-6 levels, insulin resistance and insulin sensitivity indexes in 86 HIV-infected adults under cART. RESULTS: No significant differences in IL-4 and IL-6 levels between the four groups of body composition were observed. Patients with HOMA-IR >4 presented higher levels of IL-6 and lower levels of IL-4, although without statistical significance. No correlation between IL-6, or IL-4, HOMA-IR and quantitative body fat mass distribution was found. CONCLUSION: Although there was a tendency for patients with isolated lipoatrophy and isolated fat accumulation to present higher IL-6 levels, these differences were not statistically significant. No differences were found relating IL-4 levels.

Correção cirúrgica da lipodistrofia relacionada ao uso da terapia antirretroviral: uma análise sobre os procedimentos realizados e o impacto sobre os pacientes / Surgical lipodystrophy correction associated with the use of antiretroviral therapy: an analysis of procedures performed and impact on the patients

Introdução: O tratamento de pacientes portadores da síndrome da imunodeficiência adquirida deve ser integral e se basear no controle da doença e das complicações relacionadas ao uso de medicações antirretrovirais, como a lipodistrofia. Esse estudo tem como objetivo avaliar as principais queixas, os aspectos epidemiológicos e os procedimentos cirúrgicos realizados para corrigir a lipodistrofia em pacientes em uso crônico de antirretrovirais. Método: Estudo retrospectivo, no qual foram coletados dados dos prontuários de 27 pacientes submetidos a 36 procedimentos cirúrgicos relacionados à correção de lipodistrofia no período de março de 2010 a junho de 2014 no serviço de Cirurgia Plástica do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto. Resultados: A idade média dos pacientes foi 47,2 anos, 22,2% homens e 77,8% mulheres. O tempo médio de uso da terapia antirretroviral (TARV) foi de 12,1 anos. As queixas mais encontradas foram: giba dorsal (44,4%), lipodistrofia abdominal (44,4%) e lipoatrofia glútea (37,04%). Na maioria dos pacientes (70,4%), foi realizada uma cirurgia. Quanto às cirurgias, a lipoaspiração de giba foi realizada em 48,1% dos pacientes, seguida da lipoaspiração de abdome, dorso ou flancos (44,4%) e gluteoplastia (22,2%). Entre todos os 36 procedimentos realizados, apenas dois apresentaram complicações. O tempo médio de seguimento pós-operatório foi de 11,2 meses. Do total, 70,4% dos pacientes mostraram-se satisfeitos após os procedimentos. Conclusões: O sucesso do tratamento cirúrgico da lipodistrofia causada pelo uso da TARV baseia-se na seleção pré-operatória adequada e em seguimento constante e prolongado. A melhoria da autoestima facilita a adesão ao tratamento com antirretrovirais.

Introduction: Treatment of patients with acquired immunodeficiency syndrome should be complete and based on controlling the disease and the complications related to the use of antiretroviral medications, such as lipodystrophy. This study aimed to evaluate the main complaints, epidemiological aspects, and surgical procedures performed for lipodystrophy correction among patients receiving long-term antiretroviral therapy. Method: In this retrospective study, data were collected from the medical records of 27 patients who underwent 36 surgical procedures associated with lipodystrophy correction, from March 2010 to June 2014, at the Plastic Surgery Service of the Hospital das Clínicas, Faculty of Medicine of Ribeirão Preto. Results: The average age of the patients was 47.2 years; 22.2% were men and 77.8% were women. The average duration of antiretroviral therapy (HAAR ) was 12.1 years. The most frequent complaints were dorsal hump (44.4%), abdominal lipodystrophy (44.4%), and gluteal lipoatrophy (37.04%). The majority of patients (70.4%) had undergone surgery . The most common type of surgery performed was hump liposuction (carried out in 48.1% of the patients), followed by abdominal, back, or flank liposuction (44.4%) and gluteoplasty (22.2%). Among all 36 procedures performed, only 2 resulted in complications. The average postoperative follow-up period was 11.2 months. In total, 70.4% of patients were satisfied with the results of their procedure. Conclusions: The success of surgical treatment of HAARinduced lipodystrophy is based on proper preoperative selection as well as constant and prolonged follow-up. Improved selfesteem facilitates the adherence to antiretroviral drug treatment.

Safety of poly-L-lactic acid (New-Fill®) in the treatment of facial lipoatrophy: a large observational study among HIV-positive patients.

BACKGROUND: Facial lipoatrophy is a frequently reported condition associated with use of antiretroviral (ARV) drugs. Poly-L-lactic acid (PLLA) acid has been used to correct facial lipoatrophy in people with HIV since 2004 both in Europe and the United States. The objective of this study was to establish, in real life conditions and in a large sample, the safety of PLLA (New Fill®, Valeant US, Sinclair Pharma Paris, France) to correct facial lipoatrophy among HIV-positive patients. METHODS: A longitudinal study was conducted between 2005 and 2008 in France. Data from 4,112 treatment courses (n = 4,112 patients) and 15,665 injections sessions (1 to 5 injection sessions per treatment course) were gathered by 200 physicians trained in the use of PLLA. RESULTS: The average age of patients (88.3% males) treated for lipoatrophy was 47.1 ± 8.1 years (Mean ± SD); 91.2% of patients had been receiving ARV treatment for 10.9 (±4.2) years; CD4 T-cell count was 535 ± 266 cells/mm3. The duration of facial lipoatrophy was 5 ± 2.8 years and the severity was such that 47.3% of patients required five injection sessions of PLLA and 81.9% of the sessions required two vials of the preparation. The final visit, scheduled two months after the last injection session, was attended by 66.0% of patients (n = 2,713). 48 treatment courses (2.8%) were discontinued due to adverse events (AEs). The overall incidence of AEs per course was 18.8%. Immediate AEs, bleeding (3.4%), bruising (2.3%), pain (2.0%), redness at injection site (1.6%), and swelling of the face (0.7%), occurred in 15.4% of courses and 7.0% of sessions (usually during the first session). Non-immediate AEs, mainly nodules (5.7%), inflammation (0.7%), granuloma (0.3%), discolouration (0.2%), and skin hypertrophy (0.1%), occurred in 6.7% of courses. Non-immediate AEs occurred within a time ranging from 21 days (inflammation) to 101 days (granuloma) and all but three of the 13 cases of granuloma resolved. Product efficacy was rated satisfactory by 95% of the patients and physicians. CONCLUSIONS: This study demonstrated, in real-life conditions and on a large sample, that PLLA injections were feasible, efficient, and safe when performed by trained physicians.

An update on the pharmacological strategies in the treatment of HIV-1-associated adipose redistribution syndromes.

INTRODUCTION: With the introduction of combination antiretroviral therapy (ART) for HIV infection in the mid-1990s, descriptions of morphological changes and metabolic disturbances in treated patients began to emerge. HIV-1/highly active ART-associated lipodystrophy syndrome (HALS) involves metabolic abnormalities and diverse forms of anomalous fat distribution. The current review focuses on the pathophysiological basis and the clinical evidence for the use of several medical strategies in the management of HALS. AREAS COVERED: We have covered the most relevant studies related to the pharmacological strategies in the treatment of HALS, with attention to the current and novel antiretroviral agents. EXPERT OPINION: The most commonly used strategies for HALS reversion have included modification of host-dependent factors, including those related to HIV-1 infection and those associated with ART. Preventive and medical strategies have been associated with moderate success. The only intervention that offers an immediate aesthetical improvement for patients with HALS so far has been plastic surgery.

Worsening hypertriglyceridemia with oral contraceptive pills in an adolescent with HIV-associated lipodystrophy: a case report and review of the literature.

Abstract We report a case of a 17-year-old girl with a history of congenital human immunodeficiency virus (HIV) infection and lipodystrophy secondary to highly active antiretroviral therapy (HAART). She developed severe worsening of preexisting hypertriglyceridemia after treatment with oral contraceptive pills (OCP) for polycystic ovary syndrome. Her hypertriglyceridemia improved upon OCP discontinuation. Although it is known that estrogen combined with progestins have a negative effect on triglycerides and high-density lipoprotein (HDL) cholesterol levels, to our knowledge the association of HAART-related lipodystrophy and severe hypertriglyceridemia after OCP use has not been reported in the literature. We recommend avoiding the use of OCPs in patients with lipodystrophy due to the increased risk of worsening hypertriglyceridemia.

Safety and efficacy of one-step rehabilitation of human immunodeficiency virus-related facial lipoatrophy using an injectable calcium hydroxylapatite dermal filler.

BACKGROUND: Human immunodeficiency virus (HIV)-related facial lipoatrophy seems to be the most distressing manifestation for individuals with HIV. It can be stigmatizing, severely affecting quality of life and self-esteem. Ever-increasing numbers of individuals with HIV receiving medication for HIV infection are presenting to plastic surgeons and requesting reconstructive surgery to counteract the unwanted side effects of their treatment protocols, for example facial lipoatrophy. The authors show their results with a one-step rehabilitation in cases of facial lipoatrophy using an injectable calcium hydroxylapatite dermal filler mixed with local anesthetic and adrenaline. MATERIALS AND METHODS: This study was conducted as a clinical prospective study; 26 individuals with HIV receiving antiretroviral therapy and with facial lipoatrophy received injections of an injectable calcium hydroxylapatite dermal filler mixed with local anesthetic and adrenaline. RESULTS: No major complications were registered. A stable result was observed in all the cases at the end of follow-up (3 months). High patient satisfaction was achieved in all cases. CONCLUSION: The outcomes of this study confirm that calcium hydroxylapatite dermal filler safely and effectively ameliorates the appearance of patients with HIV-related facial lipoatrophy, and mixing it with local anaesthetic and adrenaline can reduce pain during injection and ecchymosis.

Psychopathology and psychosocial adjustment in patients with HIV-associated lipodystrophy

OBJECTIVE: To study whether patients with HIV-1 associated lipodystrophy (LD) on highly active antiretroviral treatment (HAART) have more psychopathology and worse psychosocial adjustment than a similar group without this syndrome. METHODS: In a cross-sectional, observational study we compared 47 HIV-1 infected patients with LD (LD group) with 39 HIV-1 infected patients without LD (non-LD group). All participants were on HAART. The Beck Depression Inventory (BDI), the State and Trait Anxiety Inventory (STAI) and the Goldberg Health Questionnaire (GHQ-60) were administered. Levels of familial, work and social adjustment and adjustment to stressful events were evaluated in a semi-structured interview. Clinical information was extracted from the clinical records. RESULTS: In the univariate analysis patients with LD showed higher state anxiety scores (p = 0.009) and worse work adjustment (p = 0.019) than those without LD. A total of 45.3% of LD patients scored above the cut-off point on the trait anxiety scale, and over 33.3% scored above the cut-off point on the BDI, GHQ and state anxiety scales. However, in multivariate analyses LD was not independently associated with psychopathology or with worse adjustment in the studied areas. CONCLUSIONS: The finding that LD was not a predictor of greater psychopathology or worse psychosocial adjustment in HIV-1 infected patients, despite the high scores found, suggests that factors not taken into account in this study, such as LD severity and self-perception should have been included in the analysis. Further studies including a greater number of variables and a larger sample size will advance our understanding of this complex condition.

Adipokines in the HIV/HAART-associated lipodystrophy syndrome.

The use of highly active antiretroviral therapy (HAART) in the treatment of human immunodeficiency virus has dramatically altered both the landscape of this disease and the prognosis for those affected. With more patients now receiving HAART, adverse effects such as lipodystrophy and metabolic syndrome have emerged. In HIV/HAART-associated lipodystrophy syndrome (HALS), patients demonstrate fat maldistribution with dyslipidemia, insulin resistance, and other metabolic complications. Recent studies have contributed to the elucidation of the pathophysiological abnormalities seen in this syndrome and have provided guidance for the study and use of potential treatments for these patients, but widely accepted guidelines have not yet been established. Two adipokines, leptin and adiponectin, are decreased in patients with HALS and lipoatrophy or lipodystrophy. Further, recent proof-of-concept clinical trials have proven the efficacy of leptin replacement and medications that increase circulating adiponectin levels in improving the metabolic profile of HALS patients. This review article highlights recent evidence on leptin replacement and compares leptin's efficacy to that of other treatments, including metformin and thiazolidinediones, on metabolic abnormalities such as impaired insulin-glucose homeostasis associated with lipodystrophy in patients receiving HAART. It is hoped that forthcoming large phase III clinical trials will allow the addition of leptin to our therapeutic armamentarium for use in patients suffering from this disease state.

Leptin's role in lipodystrophic and nonlipodystrophic insulin-resistant and diabetic individuals.

Leptin is an adipocyte-secreted hormone that has been proposed to regulate energy homeostasis as well as metabolic, reproductive, neuroendocrine, and immune functions. In the context of open-label uncontrolled studies, leptin administration has demonstrated insulin-sensitizing effects in patients with congenital lipodystrophy associated with relative leptin deficiency. Leptin administration has also been shown to decrease central fat mass and improve insulin sensitivity and fasting insulin and glucose levels in HIV-infected patients with highly active antiretroviral therapy (HAART)-induced lipodystrophy, insulin resistance, and leptin deficiency. On the contrary, the effects of leptin treatment in leptin-replete or hyperleptinemic obese individuals with glucose intolerance and diabetes mellitus have been minimal or null, presumably due to leptin tolerance or resistance that impairs leptin action. Similarly, experimental evidence suggests a null or a possibly adverse role of leptin treatment in nonlipodystrophic patients with nonalcoholic fatty liver disease. In this review, we present a description of leptin biology and signaling; we summarize leptin's contribution to glucose metabolism in animals and humans in vitro, ex vivo, and in vivo; and we provide insights into the emerging clinical applications and therapeutic uses of leptin in humans with lipodystrophy and/or diabetes.

Infectious complications of Bio-Alcamid filler used for HIV-related facial lipoatrophy.

BACKGROUND: Human immunodeficiency virus (HIV)-related facial lipoatrophy is a devastating adverse effect of antiretroviral therapy. At this time, the most viable treatment option is cosmetic surgery with synthetic fillers. Bio-Alcamid has many advantages over other fillers, and has become widely used. The objective of this study was to determine the incidence rate of infectious complications associated with Bio-Alcamid facial filler in patients with HIV-related facial lipoatrophy (FLA). METHODS: This retrospective study identified patients who had received treatment with Bio-Alcamid, and reviewed their long-term outcomes. RESULTS: Two hundred sixty-seven patients with Bio-Alcamid were reviewed. Infectious complications were documented in 56 (19%) patients. The incidence rate of infection was 0.07 per patient-year of follow-up. Among patients with infections, the median time from first Bio-Alcamid treatment to infection was 32 months (interquartile range, 21-42). We did not find an association between the development of infection and the level of immune suppression by HIV. Surgical drainage in addition to antibiotics was required for the majority of patients. Potential risk factors for infection include severity of FLA and a preceding history of facial manipulation, including Bio-Alcamid touch-up treatments, cosmetic surgery, facial trauma, and dental work. CONCLUSIONS: Bio-Alcamid treatment of HIV-related FLA was associated with a high rate of infectious complications, often presenting years after treatment. Antibiotic prophylaxis should be considered in patients with Bio-Alcamid prior to dental work or facial manipulation.

Phase I study of nelfinavir in liposarcoma.

PURPOSE: HIV protease inhibitors are associated with HIV protease inhibitor-related lipodystrophy syndrome. We hypothesized that liposarcomas would be similarly susceptible to the apoptotic effects of an HIV protease inhibitor, nelfinavir. METHODS: We conducted a phase I trial of nelfinavir for liposarcomas. There was no limit to prior chemotherapy. The starting dose was 1,250 mg twice daily (Level 1). Doses were escalated in cohorts of three to a maximally evaluated dose of 4,250 mg (Level 5). One cycle was 28 days. Steady-state pharmacokinetics (PKs) for nelfinavir and its primary active metabolite, M8, were determined at Levels 4 (3,000 mg) and 5. RESULTS: Twenty subjects (13 males) were enrolled. Median (range) age was 64 years (37-81). One subject at Level 1 experienced reversible, grade 3 pancreatitis after 1 week and was replaced. No other dose-limiting toxicities were observed. Median (range) number of cycles was 3 (0.6-13.5). Overall best responses observed were 1 partial response, 1 minor response, 4 stable disease, and 13 progressive disease. Mean peak plasma levels and AUCs for nelfinavir were higher at Level 4 (7.3 mg/L; 60.9 mg/L × h) than 5 (6.3 mg/L; 37.7 mg/L × h). The mean ratio of M8:nelfinavir AUCs for both levels was ~1:3. CONCLUSIONS: PKs demonstrate auto-induction of nelfinavir clearance at the doses studied, although the mechanism remains unclear. Peak plasma concentrations were within range where anticancer activity was demonstrated in vitro. M8 metabolite is present at ~1/3 the level of nelfinavir and may also contribute to the anticancer activity observed.

Diferenças ultrassonográficas da quantidade de gordura corporal e os antirretrovirais / Differences in body fat distribution assessed by ultrasonography in patients receiving antiretroviral drugs

OBJETIVO: Este estudo procurou avaliar o conteúdo de gordura dos portadores do HIV segundo o tempo de uso da terapia antirretroviral (TEMPARV), < 1 ano e > 1 ano. MÉTODOS: A regressão linear múltipla foi utilizada para investigar a associação entre as variáveis ultrassonográficas dos compartimentos corporais de gordura (CCG) da face, braço, abdômen subcutâneo e visceral e as seguintes variáveis explanatórias: sexo, idade, IMC e TEMPARV. RESULTADOS: Do total de pacientes (187), 102 com TEMPARV > 1ano eram portadores de lipodistrofia relacionada ao HIV (LD-HIV), diagnosticados de acordo com os questionários clínicos. Já aqueles com TEMPARV < 1 ano (n= 85, ≈46%) não apresentavam LD-HIV. Com relação ao compartimento visceral, a diferença entre os pacientes com TEMPARV > 1 ano e < 1 ano foi de 11 mm de gordura adicionais naqueles em TEMPARV > 1 ano. As mulheres tinham mais gordura que os homens em todos os CCG periféricos, enquanto eles tinham 7,2 mm a mais de gordura visceral que elas, em média. CONCLUSÃO: A ultrassonografia é um método capaz de medir a espessura de gordura dos CGC aplicável à prática clínica para diagnosticar a LD-HIV.

OBJECTIVE: This study aimed to evaluate the body fat content of HIV patients according to the duration of antiretroviral therapy use (DURARV), < 1 year and > 1 year. METHODS: Multiple linear regression was used to investigate the association between ultrasonographic variables of body fat compartments (BFCs) of the face, arm, subcutaneous and visceral abdomen, and the following explanatory variables: gender, age, BMI, and DURARV. RESULTS: Of all patients (187), 102 of them with DURARV > 1 year were suffering from HIV-related lipodystrophy (HIV-LD), diagnosed through clinical questionnaires. Those with DURARV < 1 year (n = 85, = 46%) did not have HIV-LD. Regarding the visceral compartment, the difference between those with DURARV > 1 year and < 1 year was 11 mm of additional fat content in those with DURARV > 1 year. Women had more fat than men in all peripheral BFCs, while men had 7.2 mm more visceral fat than women, on average. CONCLUSION: Ultrasonography is a method capable of measuring the thickness of BFCs and is applicable to clinical practice to diagnose HIV-LD.

Mitochondrial function, inflammation, fat and bone in HIV lipoatrophy: randomized study of uridine supplementation or switch to tenofovir.

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

High-density hyaluronic acid for the treatment of HIV-related facial lipoatrophy.

BACKGROUND: Facial lipoatrophy is a stigmatizing hallmark of HIV. The injection of facial fillers has an essential role in the treatment of this condition. The objective of our study was to verify the safety and efficacy of a new formulation of high-density hyaluronic acid for the injectable treatment of HIV-related facial lipoatrophy. METHODS: We treated with high-density hyaluronic acid injections HIV patients affected by moderate to severe facial lipoatrophy and evaluated them at last follow-up, at a minimum of 36 weeks. Physician-related outcomes included pre-and post-treatment ultrasound measurement of the soft-tissue thickness of the cheeks and qualitative assessment of aesthetic results by means of the Global Aesthetic Improvement Scale using pre- and post-treatment photos of the patients. Patient satisfaction outcomes were evaluated with the VAS-face scale and Freiburg test. RESULTS: Fifty-four patients were studied. The median number of treatment sessions was 3 and the median length of treatment was 5.5 months. The thickness of the soft tissues of the cheek increased significantly from 9.45 to 13.12 mm (p<0.0001). On the basis of the Global Aesthetic Improvement Scale, 87.5% of the patients were judged as "much improved" or "improved." Patient satisfaction at 1 year from the end of treatment was proven (VAS-face: 77.9; Freiburg questionnaire: 93.6% of patients were satisfied or very satisfied). Complications were limited to mild redness and swelling in the early postoperative period. CONCLUSION: Long-term improvement of facial contour and excellent patient satisfaction, in the absence of severe side effects, were obtained by the injection of high-density hyaluronic acid (STYLAGE® XL) in HIV patients with facial lipoatrophy.

Polyacrylamide gel for facial wasting rehabilitation: how many milliliters per session?

BACKGROUND: Facial lipoatrophy is most distressing for HIV patients in pharmacologic treatment. Nonabsorbable fillers are widely used to restore facial features in these patients. We evaluated the safety and aesthetic outcomes of two samples of HIV+ patients affected by facial wasting who received different filling protocols of the nonabsorbable filler Aquamid® to restore facial wasting. METHODS: Thirty-one HIV+ patients affected by facial wasting received injections of the nonabsorbable filler Aquamid for facial wasting rehabilitation. Patients were randomly divided into two groups: A and B. In group A, the facial defect was corrected by injecting up to 8 ml of product in the first session; patients were retreated after every 8th week with touch-up procedures until full correction was observed. In group B, facial defects were corrected by injecting 2 ml of product per session; patients were retreated after every 8th week until full correction was observed. RESULTS: Patients of group A noted a great improvement after the first filling procedure. Patients in group B noted improvement of their face after four filling procedures on average. Local infection, foreign-body reaction, and migration of the product were not observed in either group during follow-up. CONCLUSION: The rehabilitation obtained with a megafilling session and further touch-up procedures and that with a gradual build-up of the localized soft-tissue loss seem not to have differences in terms of safety for the patients. However, with a megafilling session satisfaction is achieved earlier and it is possible to reduce hospital costs in terms of gauze, gloves, and other items.