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      Drugs & Diseases > Dermatology

      Lipodystrophy in HIV Treatment & Management

      Updated: Aug 13, 2021
      • Author: David T Robles, MD, PhD, FAAD; Chief Editor: Dirk M Elston, MD  more...
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      Treatment

      Medical Care

      Lipodystrophy is often progressive and, in limited cases, may regress after the withdrawal of protease inhibitor (PI) therapy. Withdrawal of thymidine analogues (eg, switching from PIs to efavirenz) has shown to be effective for reversing lipoatrophy. [44, 65]

      Treatment of the underlying metabolic derangements of glucose and lipid metabolism is necessary. The evaluation and management of glucose intolerance, diabetes, and hyperlipidemia are discussed elsewhere (see Type 1 Diabetes Mellitus, Type 2 Diabetes Mellitus, Polygenic Hypercholesterolemia, and Hypertriglyceridemia).

      Tesamorelin, a growth hormone–releasing factor analog, was approved by the US Food and Drug Administration (FDA) for treatment of Human immunodeficiency virus (HIV)–associated lipodystrophy in November 2010. Approval was based on two studies that showed visceral adipose tissue was significantly decreased from baseline at 26 weeks and sustained at 52 weeks. [66, 67, 68] These were multicenter, randomized, double-blind, placebo-controlled, phase 3 studies in 816 HIV-infected patients with excess abdominal fat associated with lipodystrophy.

      In 2015, the FDA approved metreleptin, a synthetic leptin analog, for the treatment of non–HIV lipodystrophy. [69] In a 2020 study, metreleptin mitigated elevated lipoprotein lipase inhibitors, mediating a reduction in circulating as well as hepatic triglycerides, but this has not proven worthy to reverse acquired lipodystrophy in patients already on antiretroviral therapy (ART). [70, 71]

      For the treatment of hyperlipidemia, fibrates and/or statins, as well as dehydroepiandrosterone (DHEA) alone, improve the lipid profile. [72]

      For treatment of hyperglycemia, metformin, [73] insulinlike growth factor–1, [74, 75] and DHEA improve glycemic control.

      Studies of thiazolidinedione treatment for HIV lipodystrophy have yielded conflicting results. One randomized controlled trial demonstrated positive effects of rosiglitazone on lipoatrophy, insulin sensitivity, and metabolic indices [76] ; another randomized controlled trial of rosiglitazone did not show a benefit for lipoatrophy or metabolic parameters. [77]

      A meta-analysis of six placebo-controlled trials found that pioglitazone therapy was more effective than placebo for increasing limb fat mass in HIV lipoatrophy, but rosiglitazone was not significantly more effective. [78] A meta-analysis of 16 trials concluded that rosiglitazone should not be used in HIV-associated lipodystrophy; that pioglitazone may be safer, but any benefits appear small; and that metformin was the only insulin-sensitizer to demonstrate beneficial effects on insulin resistance, lipids, and body fat redistribution. [79]

      An improvement in lipohypertrophy and/or lipoatrophy in individuals treated with human growth hormone, [80, 81] anabolic steroids, naltrexone, and a combination of DHEA and a cyclooxygenase inhibitor (eg, indomethacin 100 mg/day, naproxen 1000 mg/day) has been reported in some cases.

      A case report has shown that the use of oral contraceptive pills worsens hypertriglyceridemia; therefore, this is not the recommended method of birth control while dealing with lipodystrophy. [82]

      In a study comparing efficacy and cost of treatment, both surgeons and patients assessed the results of Sculptra, Radiesse, Aquamid, or autologous fat. Dermal fillers were shown to be both safe and effective. Permanent filler and autologous fat showed the most consistent results over time. Ultimately, the autologous fat filling was noted to be the most cost effective for patients. All options show improvement of aesthetic outcome and quality of life. [83]

      New treatment methods for HIV are also optimistic in addressing complications of HIV viral latency and acquired lipodystrophy. While the HIV-1 virus remains dormant in CD4+ cells and recurs approximately 2 weeks after ART interruption, a new treatment regimen consisting of latency-promoting agents (LPAs) is promising in that selective inhibition of viral transcription is made possible. LPAs have been proven to prevent viral rebound for up to 6 weeks following HIV treatment interruption in studies from 2019-2021. [84]

      In monotherapy trials for ABX464, the most tested LPA, lipodystrophy has not been reported as a adverse effect. [13, 85] When administered in conjunction with ART, a remarkable reduction of proinflammatory cytokine levels was also noted, reducing cytokine-mediated lipodystrophy for those who still rely on ART for HIV treatment. [86] Phase 2a of an ABX464 trial proved the LPA to be tolerated well and substantially metabolized. [12, 84, 87, 88] Conclusively, LPAs like ABX464 are an optimistic alternative for ART; thus, they have the potential to diminish the frequency of HIV-associated lipodystrophy in HIV-positive patients. [12, 89, 90]

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      Surgical Care

      A variety of plastic surgery procedures have been studied for the treatment of HIV-associated lipodystrophy. [91] For lipohypertrophy, the effects of treatment with liposuction or lipectomy are variable, and recurrence is common. Fat harvested during liposuction of the dorsocervical fat pad can be used for autologous fat transfer to facial areas exhibiting lipoatrophy. [92] Facial fat grafting is further addressed in Facial Fat Grafting. Additional treatment for lipohypertrophy, classically the buffalo hump, can be accomplished with adipocitolitic aqueous microgelatinous solution. [93]

      For lipoatrophy, free flaps, lipotransfer, or commercial fillers or implants can be used to replace adipose tissue. Poly-L-lactic acid (Sculptra) has been used as a semipermanent injectable filler in these patients. [94] Sculptra is approved by the FDA for the treatment of facial lipoatrophy in HIV-positive patients. In addition, the use of polymethylmethacrylate (PMMA) has been proven to benefit those patients experiencing lipoatrophy. Individuals who experience the benefits of PMMA have improved quality of life and body image, which has been shown to aid in reducing depression and increasing the compliance of antiretroviral therapy. [95, 96]

      Calcium hydroxylapatite (Radiesse) is a soft-tissue filler consisting of 30% calcium hydroxylapatite microspheres and 30% carboxylmethylcellulose. It is also FDA-approved for the treatment of facial lipoatrophy in HIV-positive patients.

      A 5-year study has also shown that a polyacrylamide hydrogel‒based filler is a safe and effective treatment for facial wasting. [97]

      Other filler options include injectable bovine and human collagens, hyaluronic acid, [98, 99] and autologous free fat transfer. See Soft Tissue Implants for more information.

      Rare cases of persistent granulomatous inflammatory reactions to some fillers have been reported [100] ; thus, patients undergoing such treatment should understand possible risks.

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      Complications

      Alternative treatment with LPAs may produce adverse effects of nausea, vomiting, and headache. [13, 85, 90]

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      Consultations

      Dermatologist consultation can be useful for an evaluation of the underlying causes of lipodystrophy and for consideration of surgical options. Plastic surgeons also may be considered for fillers, fat transfers, and liposuction.

      Internal medicine or endocrinology specialist consultations help for an evaluation of the underlying causes of lipodystrophy and for the management of hyperlipidemia and hyperglycemia.

      Infectious diseases specialist consultation is useful for the management of HIV infection.

      Psychiatrist or psychologist consultation may be necessary because of the psychological impact of body shape changes.

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      Diet

      No specific dietary regimen is used in the management of HIV-associated lipodystrophy. Adequate nutrition and exercise may result in modest improvement in lipodystrophy and improve central obesity. A balanced low-fat, low-carbohydrate diet is preferable when hypertriglyceridemia is present. [101]

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      Activity

      Exercise has been proven to improve insulin sensitivity. One study showed that progressive resistance training with an aerobic component may reduce trunk fat mass. [102] Physical activity has also been shown to yield metabolic improvements and a decreased risk of cardiovascular disease and mortality. [103]

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      Long-Term Monitoring

      Follow-up laboratory testing should include assessments of the following:

      • Viral load and/or CD4+ T-cell counts to evaluate HIV disease progression

      • Fasting lipid profile to evaluate hyperlipidemia

      • Fasting blood glucose and/or glucose tolerance test to evaluate hyperglycemia and insulin resistance

      Patients should receive follow-up care every 3-6 months, and the aforementioned laboratory examinations should be performed as necessary.

      Patients with HIV lipodystrophy may report feelings of anxiety, depression, loss of self-esteem, poor body image, and social and sexual dysfunction. It is important to ask about these issues and consider referral to a psychiatrist when appropriate.

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