Ten-Year and Beyond Follow-up After Treatment With Highly Purified Liquid-Injectable Silicone for HIV-Associated Facial Lipoatrophy: A Report of 164 Patients.

BACKGROUND: Highly purified liquid-injectable silicone (LIS) has been established as a permanent agent for off-label correction of HIV-associated facial lipoatrophy (HIV-FLA). However, controversy exists about long-term safety. OBJECTIVE: To establish the safety and efficacy at 10 years or greater of LIS for HIV-FLA. METHODS: Patients from 3 practices with 10-year or greater in-person office follow-up were analyzed to determine the number of LIS treatments and total volume required to achieve optimal correction. The nature of any treated adverse events was noted. RESULTS: One hundred sixty-four patients had 10-year or greater in-office follow-up. All subjects maintained long-term correction with an average of 9 treatments, average of 1.56 mL per treatment, and an average total of 14.1 mL. Two patients had severe adverse events manifesting as temporary facial edema. Four patients experienced mild-to-moderate excess fibroplasia presenting as perceived overcorrection, and 6 patients had nondisfiguring subcutaneous firmness. All adverse events were successfully treatable, mostly with intralesional 5-fluorouracil and triamcinolone. CONCLUSION: Liquid-injectable silicone is an effective long-term treatment option for HIV-FLA. When injected in small quantities with the microdroplet serial puncture technique at monthly or greater intervals, optimal correction appears durable for more than 10 years. Adverse events consisted mostly of excess fibroplasia and were treatable.

Comparing Efficacy and Costs of Four Facial Fillers in Human Immunodeficiency Virus-Associated Lipodystrophy: A Clinical Trial.

BACKGROUND: The objective of this study was to evaluate and compare the safety and effectiveness of four different dermal fillers in the treatment of facial lipoatrophy secondary to human immunodeficiency virus. METHODS: The authors conducted a clinical trial including 147 patients suffering from human immunodeficiency virus-induced lipoatrophy treated with Sculptra (poly-L-lactic acid), Radiesse (calcium hydroxylapatite), Aquamid (polyacrylamide), or autologous fat. Objective and subjective changes were evaluated during a 24-month follow-up. Number of sessions, total volume injected, and overall costs of treatment were also analyzed. A comparative cost-effectiveness analysis of the treatment options was performed. RESULTS: Objective improvement in facial lipoatrophy, assessed by the surgeon in terms of changes from baseline using the published classification of Fontdevila, was reported in 53 percent of the cases. Patient self-evaluation showed a general improvement after the use of facial fillers. Patients reported being satisfied with the treatment and with the reduced impact of lipodystrophy on their quality of life. Despite the nonsignificant differences observed in the number of sessions and volume, autologous fat showed significantly lower costs than all synthetic fillers (p < 0.05). CONCLUSIONS: Surgical treatment of human immunodeficiency virus-associated facial lipoatrophy using dermal fillers is a safe and effective procedure that improves the aesthetic appearance and the quality of life of patients. Permanent fillers and autologous fat achieve the most consistent results over time, with lipofilling being the most cost-effective procedure.

Practical Review of Recognition and Management of Obesity and Lipohypertrophy in Human Immunodeficiency Virus Infection.

BACKGROUND: Obesity and lipohypertrophy are common in treated human immunodeficiency virus (HIV) infection and contribute to morbidity and mortality among HIV-infected adults on antiretroviral therapy (ART). METHODS: We present a consensus opinion on the diagnosis, clinical consequences, and treatment of excess adiposity in adults with treated HIV infection. RESULTS: Obesity and lipohypertrophy commonly occur among HIV-infected adults on ART and may have overlapping pathophysiologies and/or synergistic metabolic consequences. Traditional, HIV-specific, and ART-specific risk factors all contribute. The metabolic and inflammatory consequences of excess adiposity are critical drivers of non-AIDS events in this population. Although promising treatment strategies exist, further research is needed to better understand the pathophysiology and optimal treatment of obesity and lipohypertrophy in the modern ART era. CONCLUSIONS: Both generalized obesity and lipohypertrophy are prevalent among HIV-infected persons on ART. Aggressive diagnosis and management are key to the prevention and treatment of end-organ disease in this population and critical to the present and future health of HIV-infected persons.

A pilot study of brisk walking in sedentary combination antiretroviral treatement (cART)- treated patients: benefit on soluble and cell inflammatory markers.

BACKGROUND: Chronic HIV infection is associated with low-level inflammation and increased risk of chronic diseases and mortality. The objective was to assess the effects of moderate intensity exercise on metabolic and inflammatory markers in HIV-infected treated persons. METHODS: This was a pilot study enrolling cART-treated, sedentary persons with metabolic complications in a 12-week protocol, consisting of three sessions per week of 60 min brisk walking with (strength-walk group) or without (walk group) 30 min circuit-training. Assessments at baseline and week 12 (W12) included body morphometrics and total body dual-energy X-ray absorptiometry; lipid and glucose blood profile; plasma level of high sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), D-dimer, interleukin-18 (IL-18), soluble CD14, and CD38 and HLA-DR expression on CD4+ and CD8+ T-cells. RESULTS: Forty-nine patients were included and 35 (71%) completed the program: 21 in the walk and 14 in the strength-walk group. At W12, significant improvements were observed of body mass index, waist and hip circumference, and total cholesterol both overall and in the walk group, and of LDL cholesterol in both training groups. In the whole group, significant reductions were observed in hsCRP, IL-6, D-dimer, IL-18, and of CD8+/CD38+/HLA-DR+ cell frequencies. HsCRP and CD8+/CD38+/HLA-DR+ frequency decreased significantly in both training groups when examined separately whereas IL-6 and D-dimer in the walk group only. CONCLUSIONS: Brisk walking, with or without strength exercise, could improve lipid profile and inflammatory markers in chronic HIV infection. TRIAL REGISTRATION: ACTRN12615001258549, registered 17 November 2015, "retrospectively registered" Web address of trial: http://www.ANZCTR.org.au/ACTRN12615001258549.aspx.

Clinical and color Doppler ultrasound evaluation of polyacrylamide injection in HIV patients with severe facial lipoatrophy secondary to antiretroviral therapy.

BACKGROUND/PURPOSE: Facial lipoatrophy in HIV patients, secondary to antiretroviral therapy (ART) with thymidine analogs, has been related to important psychosocial alterations and poor adherence to treatment. Polyacrylamide gel (PAAG) is a filler that has been used for treating facial lipoatrophy in HIV patients. The aim was to assess the clinical and sonographic anatomical changes after injection of PAAG in HIV patients with facial lipoatrophy secondary to ART. METHODS: HIV patients receiving ART and suffering from severe facial lipoatrophy were recruited and underwent clinical and color Doppler ultrasound evaluation prior to PAAG application (AQUAMID® ) and sonographically monitored at 18 months and clinically followed up for 36 months after the procedure. Adverse effects were recorded based on occurrence and complexity. RESULTS: A total of 33 patients were evaluated, 30 men (91%) and 3 women (9%) with an average age of 49.6 years (±8.4). Clinical improvement assessed by a dermatologist had an average score of 5.9 (±0.7) on a scale of 1-7. On color Doppler ultrasound there was a significant increase of the thickness of the subcutaneous tissue (SCT) in both nasofold lines when comparing before and after PAAG injection (P < 0.01) and no signs of inflammation (hypervascularity). User satisfaction was qualified as excellent or good in all cases. Only two patients experienced adverse effects (hematoma and puncture site infection), which was successfully managed without consequences. CONCLUSION: Treatment of facial lipoatrophy with PAAG seems to be effective in HIV patients and no signs of complications were observed in the monitoring at 36 months after injection. Color Doppler ultrasound can identify the filler deposits and the anatomical changes of the SCT non-invasively.

Quality of life outcomes associated with treatment of human immunodeficiency virus (HIV) facial lipoatrophy.

Facial lipoatrophy (FLA), characterized by a decrease in facial volume, has a high prevalence in patients with human immunodeficiency virus (HIV) infection treated with long-term highly active antiretroviral therapy (HAART). The social stigmatization that results from such changes in facial appearance has led some HIV patients to discontinue HAART. The use of fillers is one method of restoring facial volume. A critical outcome of treatment concerns the patient's quality of life (QoL). Although many studies have assessed patient satisfaction, as well as the social and psychological outcomes associated with the correction of HIV FLA, fewer studies have assessed QoL. We reviewed treatment options for HIV FLA with a specific focus on QoL outcomes. Our analysis revealed that the following treatments were associated with improvements in QoL: poly-l-lactic acid; calcium hydroxylapatite; hyaluronic acid; polyacrylamide gel; polyalkylamide gel; polymethylmethacrylate; silicone oil; and autologous fat transfer. The treatment of HIV FLA with these agents appears to improve QoL as assessed by various QoL instruments. Additional studies are required to identify a unifying QoL instrument to effectively assess longitudinal QoL outcomes and to compare treatment modalities.

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.

Soft tissue augmentation with PMMA-microspheres for the treatment of HIV-associated buttock lipodystrophy.

Progression of lipodystrophy syndrome is a big challenge in HIV treatment. Nowadays, fat loss at the lower part of buttocks has become another problem as patients have started to complain that it is painful to be seated for a long time and/or on hard surfaces. We developed a method for buttock lipoatrophy treatment with PMMA-microspheres, as silicone prostheses and autologous fat transplant were not completely efficient. The treatment consisted of net-crossed injections, in the subcutaneous layer, of a 30% PMMA-microspheres solution on the atrophic areas of the buttock. One hundred and fifty-four patients were included. The amount of PMMA-microspheres used to treat buttock lipoatrophy depended on the degree of atrophy and size of the area to be treated. Patients were satisfied with this treatment and reported to be more comfortable to be seated for longer period of time. We demonstrated that soft tissue augmentation with PMMA-microspheres is safe and efficient for the treatment of buttock lipoatrophy associated with HIV lipodystrophy.

Adolescents with HIV and facial lipoatrophy: response to facial stimulation.

OBJECTIVES: This study evaluated the effects of facial stimulation over the superficial muscles of the face in individuals with facial lipoatrophy associated with human immunodeficiency virus (HIV) and with no indication for treatment with polymethyl methacrylate. METHOD: The study sample comprised four adolescents of both genders ranging from 13 to 17 years in age. To participate in the study, the participants had to score six or less points on the Facial Lipoatrophy Index. The facial stimulation program used in our study consisted of 12 weekly 30-minute sessions during which individuals received therapy. The therapy consisted of intra- and extra-oral muscle contraction and stretching maneuvers of the zygomaticus major and minor and the masseter muscles. Pre- and post-treatment results were obtained using anthropometric static measurements of the face and the Facial Lipoatrophy Index. RESULTS: The results suggest that the therapeutic program effectively improved the volume of the buccinators. No significant differences were observed for the measurements of the medial portion of the face, the lateral portion of the face, the volume of the masseter muscle, or Facial Lipoatrophy Index scores. CONCLUSION: The results of our study suggest that facial maneuvers applied to the superficial muscles of the face of adolescents with facial lipoatrophy associated with HIV improved the facial area volume related to the buccinators muscles. We believe that our results will encourage future research with HIV patients, especially for patients who do not have the possibility of receiving an alternative aesthetic treatment.

HIV and metabolic, body, and bone disorders: what we know from low- and middle-income countries.

Globally, the HIV epidemic is evolving. Life expectancy for HIV-infected individuals has been extended because of more effective and more widely available antiretroviral therapy. As a result, chronic noncommunicable diseases (NCDs) have become important comorbid conditions. In particular, HIV-infected persons are increasingly at risk of developing metabolic (diabetes, dyslipidemias), body composition (lipodystrophy, overweight/obesity) and bone mineral density abnormalities. We have summarized the published epidemiological and clinical literature regarding these HIV-NCD comorbidities in low- and middle-income countries (LMICs). We found important gaps in knowledge. Specifically, there are few studies that use standardized methods and metrics; consequently, prevalence or incidence data are not comparable. There are very little or no data regarding the effectiveness or cost-effectiveness of clinical monitoring or therapeutic interventions for metabolic disorders in HIV-infected individuals. Also, although NCDs continue to grow in the HIV-negative population of most LMICs, there are few data comparing the incidence of NCD comorbidities between HIV-infected and HIV-negative populations. To address these gaps, we describe potential research and capacity development priorities for the future.

From wasting to obesity, changes in nutritional concerns in HIV/AIDS.

Optimal nutrition is an important part of human immunodeficiency virus (HIV) care; to support the immune system, limit HIV-associated complications as well as maintain better quality of life and survival. The presentation and nature of malnutrition in patients with HIV has changed dramatically over the past 30 years from predominantly a wasting syndrome to lipodystrophy and, now, frailty. Nevertheless, we continue to see all 3 presentations in patient care today. The pathogenesis of poor nutrition in HIV-infected patients depends on caloric intake, intestinal nutrient absorption/translocation, and resting energy expenditure, which are features seen in all chronic diseases.

Treatment of facial lipoatrophy with polymethylmethacrylate among patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS): impact on the quality of life.

BACKGROUND: The lipodystrophy syndrome is characterized by selective loss of subcutaneous fat on the face and extremities (lipoatrophy) and/or accumulation of fat around the neck, abdomen, and thorax (lipohypertrophy). The aim of this study has been to assess the impact of polymethylmethacrylate facial treatment on quality of life, self-perceived facial image, and the severity of depressive symptoms in patients living with HIV/AIDS. METHODS: A non-randomized before and after interventional study was developed. Fifty-one patients underwent facial filling. The self-perceived quality of life, facial image, and degree of depressive symptoms were measured by the Short-Form 36 and HIV/AIDS--Targeted quality of life questionnaires, by a visual analogue scale and by the Beck depression inventory, respectively, before and three months after treatment. RESULTS: Six of the eight domains of Short-Form 36 and eight of the nine dimensions of the HIV/AIDS--Targeted quality of life questionnaires, together with the visual analogue scale and by the Beck depression inventory scores, revealed a statistically significant improvement. The only adverse effects registered were edema and ecchymosis. CONCLUSION: The treatment of facial lipoatrophy improved the self-perceived quality of life and facial image as well as any depressive symptoms among patients with HIV/AIDS.

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.

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.

[Polyalkylimide filler in human immunodeficiency virus-associated facial lipodystrophy: ophthalmic complications]. / Rellenos de polialquilamida en lipodistrofia facial asociada al virus de la inmunodeficiencia humana: complicaciones oftalmológicas.

CASE REPORT: A 54 year old male, who consulted for acute inflammatory palpebral edema. The patient has HIV infection (on antiretroviral treatment) and an associated facial lipodystrophy that was filled with polyalkylimide in both frontotemporal regions one year before. MRI revealed subcutaneous abscesses in the filled areas, which led to preseptal cellulitis. Complete remission was achieved with antibiotic therapy and monitoring. DISCUSSION: Polyalkylimide is a hydrogel that is recently used as facial filler without FDA approval. Although it was believed to be safe and useful for treating HIV lipodystrophy, it is not exempt from adverse effects (infection, abscesses, granulomas) that can compromise the eye area.

HIV-associated lipodystrophy: impact of antiretroviral therapy.

In the late 1990s, reports of unusual changes in body fat distribution named 'lipodystrophy' (LD) began to appear in HIV patients mitigating the enormous enthusiasm about improvement of survival and quality of life provided by the combinations of antiretroviral (ARV) drug classes, the so-called highly active antiretroviral therapy (HAART), which had just become available at that time. The objective of this paper is to critically review the literature on LD and to discuss the impact of newer ARV agents, namely atazanavir, darunavir and raltegravir, as well as strategies of the late HAART era, including single-tablet regimens and nucleoside-sparing regimens. Studies in which LD was measured by dual-energy x-ray absorptiometry or by abdominal computed tomography or magnetic resonance imaging scan only, were included. We were unable to identify studies depicting a negative impact of drugs or ARV regimens on limb fat loss. On the contrary, a few studies identified a negative impact of atazanavir/ritonavir or darunavir/ritonavir on trunk fat increase. It should be noted that this anthropometric measure is a poor instrument since it cannot distinguish between subcutaneous and visceral fat. We conclude that presumably the body fat changes currently observed in HIV-infected patients is the net result of competing phenomena: on one side the natural history of lipohypertrophy as a result of HIV and HAART impact, and on the other side the physiological body fat changes observed in the aging population.

Treatment of HIV-associated facial lipoatrophy: impact on infection progression assessed by viral load and CD4 count.

BACKGROUND: HIV/AIDS-Associated Lipodystrophy Syndrome includes changes in body fat distribution, with or without metabolic changes. The loss of fat from the face, called facial lipoatrophy, is one of the most stigmatizing signs of the syndrome. OBJECTIVES: To evaluate the effect of FL treatment using polymethylmethacrylate (PMMA) implants on disease progression, assessed by viral load and CD4 cell count. METHODS: This was a prospective study of 44 patients treated from July 2009 to December 2010. Male and female patients, aged over 18 years, with clinically detectable FL and who had never been treated were included in the study. PMMA implantation was done to fill atrophic areas. Laboratory tests were conducted to measure viral load and CD4 count before and after treatment. RESULTS: Of the 44 patients, 72.72% were male and 27.27% female, mean age of 44.38 years. Before treatment, 82% of patients had undetectable viral load, which increased to 88.6% after treatment, but without statistical significance (p = 0.67). CD4 count before treatment ranged from 209 to 1293, averaging 493.97. After treatment, the average increased to 548.61. The increase in CD4 count after treatment was statistically significant with p = 0.02. CONCLUSION: The treatment of FL with PMMA implants showed a statistically significant increase in CD4 count after treatment, revealing the impact of FL treatment on disease progression. Viral load before and after treatment did not vary significantly.

Current treatment methods for combination antiretroviral therapy-induced lipoatrophy of the face.

Combination antiretroviral therapy (CART) reduces the mortality and morbidity in HIV-infected patients. However, facial lipoatrophy (FLA) is one of the well-known side-effects of this treatment and subsequently imposes major problems for HIV-infected patients. In the last decade, ample experience has been obtained with both local therapeutic options as well as possible systemic treatment options. Soft tissue fillers are a relatively simple and efficient treatment option for FLA. Especially, the biodegradable semi-permanent fillers combine a good effect with durability and an acceptable safety profile. The best way to prevent or restrict the development of FLA remains the exclusion of thymidine analogue nucleoside reverse-transcriptase inhibitors from the CART schedule.