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Treatment of HIV-associated lipodystrophy

Treatment of HIV-associated lipodystrophy
Literature review current through: May 2024.
This topic last updated: Mar 11, 2024.

INTRODUCTION — The term human immunodeficiency virus (HIV)-associated lipodystrophy typically refers to changes in fat distribution that are often associated with metabolic abnormalities, including dyslipidemia and insulin resistance [1]. Specifically, patients with lipoatrophy have loss of subcutaneous fat, most noticeably in the limbs, face, and/or buttocks areas. Patients with fat accumulation have gain of visceral fat in the abdomen and may have dorsocervical fat pad enlargement (buffalo hump) and breast enlargement.

Patients may present with lipoatrophy, fat accumulation, or a combination of the two [2]. Since potential management differs depending on the nature of the change in fat, lipoatrophy and fat accumulation will be discussed separately after a general consideration of the rationale for treating these disorders.

The treatment of HIV-associated lipodystrophy will be reviewed here. The epidemiology, clinical manifestations, and diagnosis of lipodystrophy are discussed separately. (See "Epidemiology, clinical manifestations, and diagnosis of HIV-associated lipodystrophy".)

RATIONALE FOR TREATMENT — There are multiple reasons to consider treating HIV-associated lipodystrophy, as there are several potential benefits beyond pure cosmesis.

Metabolic derangements associated with lipodystrophy (dyslipidemia and abnormal glucose metabolism) may predispose patients to cardiovascular disease. Behavioral and medical interventions to address HIV-associated lipodystrophy have the potential to favorably affect these metabolic parameters and ultimately reduce the risk of atherosclerosis and diabetes mellitus. (See "Epidemiology, clinical manifestations, and diagnosis of HIV-associated lipodystrophy", section on 'Metabolic abnormalities'.)

Patients are often distressed by the physical changes in their appearance, especially if they develop facial lipoatrophy. These morphologic abnormalities can have a significant impact on self-esteem [3].

The presence of lipodystrophy raises concern, for some patients, that their HIV status will be obvious to others [4].

Lipodystrophy, or fear of developing it, may impact adherence to antiretroviral therapy (ART) or the willingness to initiate such therapy [5].

Some patients with increased neck fat report restricted neck movement and women with breast enlargement may have chronic back pain. Amelioration of lipodystrophy may improve quality of life.

LIPOATROPHY

General approach — Potential interventions for lipoatrophy include modification of the antiretroviral regimen, surgical correction, and pioglitazone (table 1).

For patients with lipoatrophy who are taking a regimen that contains a thymidine analogue (ie, stavudine or zidovudine), we recommend switching the nucleoside reverse transcriptase inhibitor (NRTI) backbone to one containing other nucleoside analogues, such as tenofovir or abacavir. Neither stavudine nor zidovudine is a first-line NRTI for treatment-naïve patients with HIV initiating ART. However, some patients who initiated treatment years ago may still be on regimens that contain these agents. Although replacing an older-generation protease inhibitor (eg, lopinavir-ritonavir) with a different third agent (eg, non-nucleoside reverse transcriptase inhibitor [NNRTI], integrase inhibitor, or later-generation protease inhibitor) does not clearly improve lipoatrophy or limb fat loss, it may have other metabolic benefits. (See 'Switching antiretrovirals' below and "Management of cardiovascular risk (including dyslipidemia) in patients with HIV", section on 'Treatment-experienced patients'.)

For patients with severe facial atrophy who are willing to undergo a surgical approach to reverse the appearance, we suggest injectable temporary fillers. This intervention is generally effective but may not be accessible for financial reasons. (See 'Surgical approaches' below.)

For patients with lipoatrophy who also have impaired glucose tolerance, a trial of pioglitazone can increase limb fat. However, its efficacy has not been clearly established and a number of safety concerns have been raised with the use of thiazolidinediones. (See 'Thiazolidinediones' below.)

Switching antiretrovirals

Switching the NRTI backbone — Exposure to thymidine analogues (in particular stavudine, but also zidovudine) is a major factor associated with lipoatrophy (see "Epidemiology, clinical manifestations, and diagnosis of HIV-associated lipodystrophy", section on 'Exposure to NRTIs'). Thus, modifying the antiretroviral regimen so that stavudine or zidovudine is replaced with a different NRTI, namely tenofovir or abacavir, is the main medical approach to lipoatrophy. This can result in modest gains in limb fat. In fact, tenofovir and abacavir are first-line NRTIs because of their efficacy, safety, and convenience, whereas stavudine and zidovudine are associated with an excess of other side effects and inferior virologic potency. Thus, such a switch would have additional potential benefits. Nevertheless, an individual's prior antiretroviral treatment history and resistance profile must be taken into account prior to changing antiretrovirals to ensure that the new regimen would have expected efficacy [6]. Considerations on choosing between tenofovir and abacavir in the absence of resistance concerns are discussed elsewhere. (See "Switching antiretroviral therapy for adults with HIV-1 and a suppressed viral load".)

Several trials have demonstrated improvement in lipoatrophy with this switch strategy [7-10]. However, gains in fat have been modest over the short term, and patients should be advised not to expect dramatic changes in appearance [11,12].

In a trial of 111 patients with moderate to severe lipoatrophy (85 on stavudine and 26 on zidovudine), patients were randomly assigned to either switch their thymidine analogue therapy to abacavir or to continue treatment without change [7]. At 24 weeks, patients who switched to abacavir had modest increases in limb fat compared with those who continued thymidine analogue therapy. In long-term follow-up of this trial, those switching to abacavir had a 36 percent increase in limb fat at two years [8].

In a trial of 105 patients with moderate to severe lipoatrophy (71 on stavudine and 34 on zidovudine), patients were randomly assigned to switch their thymidine analogue therapy to either abacavir or tenofovir [10]. At 48 weeks, patients in both groups had similar, modest increases in limb fat compared with baseline.

Another strategy involves switching to a protease inhibitor-containing, nucleoside-sparing regimen, although this has other drawbacks and is not generally done to address only lipoatrophy without other reasons for switching. This approach was evaluated in 62 patients with advanced HIV, but not necessarily lipoatrophy, who were switched from their initial successful antiretroviral regimen to one including lopinavir/ritonavir and efavirenz versus two nucleoside analogues and efavirenz (ACTG 5125) [13]. Although limb fat significantly increased in the nucleoside analog-sparing arm at 48 weeks, this was accompanied by a significant increase in triglycerides and total cholesterol as well. Additionally, some nucleoside-sparing regimens have inferior virologic potency compared with NRTI-based regimens. (See "Switching antiretroviral therapy for adults with HIV-1 and a suppressed viral load".)

Switching the third drug — Although some studies have suggested that protease inhibitors used with thymidine analogues synergistically increases the risk of lipoatrophy, there does not appear to be substantial benefit to lipoatrophy by switching a protease inhibitor to a different third drug. (See "Epidemiology, clinical manifestations, and diagnosis of HIV-associated lipodystrophy", section on 'Exposure to other ART classes'.)

Switching from a protease inhibitor to an NNRTI or abacavir has not resulted in improvement in lipoatrophy [14-17]. Moreover, switching from an older-generation protease inhibitor to atazanavir does not clearly improve lipoatrophy. In a trial of 201 patients with abdominal fat accumulation and viral suppression on a regimen containing a twice-daily ritonavir-boosted protease inhibitor, half of whom were taking thymidine analogues, there was a trend towards less limb fat loss at 48 weeks among those who were randomly assigned to switch to a regimen containing ritonavir-boosted atazanavir (0.9 versus -3.6 percent change in patients remaining on their original regimen) [18]. This difference, however, was not statistically significant. There was no difference in abdominal adiposity between the two groups, either. However, switching to atazanavir favorably affected lipid profiles, as seen in other studies, and thus may be warranted for reasons other than effects on lipoatrophy. (See "Management of cardiovascular risk (including dyslipidemia) in patients with HIV", section on 'Treatment-experienced patients'.)

Surgical approaches — Plastic surgery is the main therapy for severe facial lipoatrophy; autologous fat transplantation or, more commonly, injections of biodegradable or nonbiodegradable gel fillers can be performed.

Fillers — Plastic surgeons, dermatologists, and others with specific training have treated facial lipoatrophy with various injectable fillers [19,20]. Fillers can be temporary or permanent. Overall, temporary fillers are preferred.

Temporary fillers are reinjected at regular intervals [21]. In the United States, two fillers are approved by the US Food and Drug Administration (FDA) specifically for HIV-associated lipoatrophy.

Poly-L-lactic acid (PLLA) is a biodegradable, biocompatible, immunologically inert substance that has been used in dissolvable sutures and dental implants. This product consists of microspheres of PLLA that are 40 to 60 microns in diameter that initially expand tissue after injection by purely mechanical means but gradually biodegrade and stimulate collagen formation as a foreign body [22,23].

A typical treatment course of PLLA is three to six injections separated by two or more weeks. Local adverse effects lasting several days, including bruising and edema, are common. Up to half of patients develop subcutaneous papules at the injection site a median of seven months after the initial injection, and one-quarter to one-half of these papules resolve spontaneously [23,24]. Although there are some encouraging reports regarding this technique, reimbursement issues preclude their use for some patients. (See "Injectable soft tissue fillers: Temporary agents", section on 'Poly-L-lactic acid (Sculptra)'.)

The use of PLLA for HIV-associated facial lipoatrophy has been supported by several trials and observational studies that have demonstrated improvement in patient appearance and cutaneous thickness as well as overall safety [22,25-37]. As an example, in an open-label study in 50 patients with severe facial lipoatrophy, the mean increase in dermal thickness assessed by ultrasound was approximately 7 mm at 96 weeks [25]. In another study of 101 patients with facial lipoatrophy randomly assigned to either immediate or deferred therapy with PLLA, subjective measures of lipoatrophy severity were better in the immediate therapy group even though there were no significant differences between the two groups in facial tissue volume as measured by computed tomography (CT) [32].

Calcium hydroxylapatite consists of hydroxylapatite microspheres that serve as scaffolding for collagen growth, and several observational studies have supported its use for HIV-associated lipoatrophy [38-43]. In an open-label study in 100 patients with facial lipoatrophy, 100 percent met the primary efficacy endpoint of improvement on the Global Aesthetic Improvement Scale at three months [42]. The subjective improvement was sustained through 12 months of follow-up, and skin thickness increased significantly by a mean of 2.3 mm at 12 months. Local adverse effects were generally mild and short-lived and included ecchymosis, edema, erythema, pain, and pruritus. Concerns about cost and reimbursement are similar to PLLA, as noted above. (See "Injectable soft tissue fillers: Temporary agents", section on 'Calcium hydroxylapatite (Radiesse)'.)

Experiences with other temporary fillers, none of which are FDA-approved for the indication of facial lipoatrophy, include bovine or human collagen and hyaluronic acid [21,44].

Permanent fillers are synthetic materials that are designed to permanently fill in the space vacated by loss of facial fat. These include purified silicone oil, polymethylmethacrylate, polyalkylimide, and polytetrafluoroethylene, none of which are approved by the FDA for dermal augmentation [21]. In general, use of permanent fillers is less desirable than temporary fillers due to potential worsening or improvement in facial lipoatrophy as a result of continuing or changing ART, which may result in undesirable cosmetic effects such as sagging of skin [45]. Furthermore, infectious complications have been reported with some permanent fillers. In a review of 267 patients who received a polyalkylimide filler for HIV-associated facial lipoatrophy, 56 patients (19 percent) developed an implant-associated infection at a median of 32 months following implantation [46]. (See "Injectable soft tissue fillers: Permanent agents".)

Autologous fat transplantation — Autologous fat transplantation involves harvesting of a small intact lump of fatty tissue from the abdomen, cervicodorsal area, or elsewhere that can be processed into small fat "parcels" that are injected by a syringe with local anesthesia [47]. Use of autologous fat implantation may be less costly than gel fillers but is often limited by the lack of suitable donor sites in patients with extensive lipoatrophy [48]. (See "Injectable soft tissue fillers: Permanent agents", section on 'Autologous fat'.)

Thiazolidinediones — Thiazolidinedione drugs are of possible benefit in the treatment of lipoatrophy, but their use remains investigational and a number of safety concerns have been raised. We suggest a therapeutic trial of pioglitazone in patients who desire medical treatment for lipoatrophy and who also have evidence of insulin resistance (eg, elevated fasting glucose or impaired glucose tolerance on a standard oral glucose tolerance test) [49].

The available thiazolidinediones are related structurally to troglitazone, which was removed from the market due to idiosyncratic hepatotoxicity, including liver failure. Consequently, clinicians should monitor liver enzymes closely in patients receiving pioglitazone (eg, at one month after initiation, then every two months for the first year and periodically thereafter). Additionally, patients should be advised to report immediately any potential signs of bladder cancer, such as hematuria, because of the association between pioglitazone and bladder cancer risk in patients with diabetes [50]. Additional risks with thiazolidinediones, including fluid retention, congestive heart failure, decreased bone mineral density, and increased fracture risk, are discussed elsewhere. (See "Thiazolidinediones in the treatment of type 2 diabetes mellitus", section on 'Safety'.)

Most of the evidence on thiazolidinedione use for HIV-associated lipoatrophy is with rosiglitazone, for which there have been concerns about increased risk of myocardial infarction and cardiovascular death in diabetics [51]. Although a large, randomized clinical trial designed to evaluate the cardiovascular safety of this drug was inconclusive [52], and the relevance of this controversy to nondiabetic patients is uncertain, pioglitazone is generally preferred over rosiglitazone when thiazolidinedione use is warranted. (See "Thiazolidinediones in the treatment of type 2 diabetes mellitus".)

Randomized trials of rosiglitazone for HIV-associated lipoatrophy have yielded conflicting efficacy results [53-58]; the discrepancies may be related to varied use of thymidine NRTIs (eg, stavudine) in these studies. In one randomized trial of 108 patients with lipoatrophy, there were no differences in the change in limb fat between the rosiglitazone and placebo arms after 48 weeks of follow-up [53]. However, a substudy noted that exposure to rosiglitazone, a peroxisome proliferator-activated receptor gamma (PPARG) agonist, did not affect PPARG expression at week 2 or 48 in those patients who were taking a thymidine NRTIs, whereas increased PPARG was noted in all patients not taking a thymidine NRTI, regardless of rosiglitazone receipt, and was associated with increases in limb fat [59]. These data suggested a link between mitochondrial toxicity associated with thymidine NRTI use and PPARG expression and thus may explain the limited therapeutic benefit of thiazolidinediones in the face of ongoing thymidine analogue use [60]. A subsequent randomized trial in 71 patients with lipoatrophy who were taking thymidine-sparing regimens a minimum of 24 weeks prior to enrollment demonstrated significant improvements in limb fat with rosiglitazone compared with placebo [57]. Lower insulin levels were also seen in the subset of patients who had evidence of insulin resistance at baseline.

Although less data exist on pioglitazone for lipoatrophy in patients with HIV, one placebo-controlled trial of 130 such patients demonstrated superior increase in limb fat at 48 weeks with pioglitazone compared with placebo [61]. The difference between the groups was greater and statistically significant in a pre-planned subgroup analysis of patients who were not taking stavudine, whereas those on stavudine had no benefit. Increases in both leg and trunk fat have also been demonstrated in an observational study of pioglitazone [62].

Less useful interventions — Several other interventions have been evaluated for lipoatrophy, but these either remain investigational or did not appear effective in trials.

Uridine – In vitro data suggest that uridine, a pyrimidine nucleoside, can protect adipocytes from the adverse effects of thymidine analogues [63]. A small, randomized trial of a uridine supplement in patients receiving thymidine analogues suggested a favorable effect on limb fat [64]. However, a subsequent multicenter clinical trial of 165 participants found that uridine supplementation did not improve limb fat after 48 weeks of treatment compared with placebo [65].

Leptin – A pilot crossover study evaluated the efficacy of recombinant methionyl leptin supplementation in seven men with HIV with leptin deficiency and lipoatrophy [66]. Compared with placebo, two months of leptin therapy improved fasting insulin levels, insulin resistance, and high-density lipoprotein levels. Another study in eight hypoleptinemic patients demonstrated similar findings in addition to decrease in visceral fat [67]. In the United States, the leptin analog metreleptin is FDA-approved for the treatment of leptin deficiency in patients with congenital generalized or acquired generalized lipodystrophy but not HIV-associated lipodystrophy. (See "Lipodystrophic syndromes".)

FAT ACCUMULATION

General approach — Potential interventions for fat accumulation (lipodeposition) include diet and exercise, metformin, tesamorelin, and surgical interventions (table 1) [68].

For all patients with HIV with fat accumulation, we start with standard methods of weight reduction such as aerobic exercise training and dietary modification. Although the data on the efficacy of exercise for HIV-associated fat accumulation, specifically, are limited, the general beneficial effects of physical activity are well established, and the intervention is generally safe. (See 'Diet and exercise' below.)

In addition to exercise, for individuals with HIV with fat accumulation and diabetes mellitus who have indications for glucose-lowering therapy, we suggest metformin for glycemic control. Metformin is the preferred initial therapy for patients with type 2 diabetes mellitus in general, and it is associated with reductions in visceral and subcutaneous abdominal fat. However, because of limited supporting data, metformin cannot yet be recommended to reduce abdominal fat in patients with HIV without diabetes. (See 'Metformin' below.)

For those patients who have not responded to other interventions, have distressing severe abdominal fat accumulation, and do not have active underlying malignancy, we suggest tesamorelin to treat excess abdominal fat. Of note, tesamorelin is administered subcutaneously daily, its effect wanes after treatment discontinuation, and long term safety data are limited. We regularly monitor insulin-like growth factor 1 (IGF-1) and hemoglobin A1c during tesamorelin treatment. (See 'Tesamorelin' below.)

For patients with fat accumulation in delimited areas, certain surgical interventions, such as dorsocervical fat pad liposuction or reduction mammoplasty, may be effective, although recurrent fat accumulation in these sites can occur. (See 'Surgical approaches' below.)

Diet and exercise — Dietary modifications and exercise are safe and potentially useful interventions for patients with abdominal fat accumulation, though efficacy data are quite limited [69]. In a study of 17 patients with HIV, 15 of whom had fat accumulation and/or lipoatrophy, an individualized, supervised aerobic training program led to preferential loss of visceral fat and improvements in total cholesterol, triglycerides, and high-density lipoprotein (HDL) cholesterol at four months [70].

Approaches to diet and exercise counselling for reduction of abdominal obesity in the population with HIV are the same as for the general population and are discussed in detail elsewhere. (See "Obesity in adults: Overview of management".)

Metformin — Metformin is a preferred initial therapy for patients with type 2 diabetes mellitus. For patients with HIV who have diabetes mellitus, it has the added benefit of reducing truncal fat. However, metformin should be avoided in patients who also have lipoatrophy of moderate to severe severity since it may further reduce subcutaneous fat [71]. Additionally, metformin cannot be recommended to reduce truncal fat in nondiabetic patients, as the risk/benefit ratio is not well defined. (See "Initial management of hyperglycemia in adults with type 2 diabetes mellitus", section on 'Initial pharmacologic therapy'.)

Several studies have demonstrated a reduction in abdominal fat with metformin in patients with HIV. In a small, randomized, placebo-controlled trial of patients with HIV with central obesity and hyperinsulinemia, metformin 500 mg twice daily for three months improved insulin sensitivity, tended to reduce both visceral and subcutaneous abdominal fat, and improved markers of impaired fibrinolysis [72,73]. In another randomized trial comparing metformin alone with metformin with a supervised aerobic and resistance training exercise program, patients in the exercise plus metformin arm had statistically significant reductions in both visceral and subcutaneous abdominal fat and greater improvements in specific cardiovascular risk markers [74]. In this small study (n = 37), two patients were withdrawn due to asymptomatic elevations in lactate and two due to liver enzyme elevations.

Tesamorelin — The growth hormone-releasing hormone (GHRH) analogue tesamorelin is a reasonable treatment option for patients with HIV without active malignancy who are distressed by moderate to severe abdominal fat accumulation. However, therapy should not be continued beyond six months if there is no treatment response, assessed by a decrease in waist circumference. Moreover, the rapid reaccumulation of fat after treatment discontinuation and the lack of long-term safety data present challenges for defining the optimal use of tesamorelin. Although safety data do not exist for long term treatment, patients can use this agent for periods of time longer than one year. In accordance with the prescribing information, treatment can be continued if the patient continues to show clinical benefit and has no significant adverse events. Tesamorelin is given as a subcutaneous injection daily.

Efficacy — The efficacy of tesamorelin has been demonstrated in several clinical trials [75-78]. As examples, two large randomized trials reported significant reductions in visceral fat during treatment with tesamorelin, although the effect waned after treatment discontinuation.

These two trials included a total of 806 patients who were on antiretroviral therapy (ART) and had excessive abdominal fat accumulation, as measured by sex-specific waist circumference and waist-to-hip ratios [76,78]. In a pooled analysis of the trials, visceral adipose tissue (VAT) decreased by 15.4 percent at 26 weeks among those randomly assigned to daily tesamorelin compared with a 0.6 percent decrease with placebo [79]. In both trials, patients who had originally taken tesamorelin were re-randomized to tesamorelin or placebo for another 26 weeks. The decrease in VAT was sustained over 52 weeks of treatment with tesamorelin. However, VAT reaccumulated to baseline levels in those who switched to placebo.

Modest improvements in body satisfaction in both trials were only slightly greater with tesamorelin than placebo. Other favorable effects of tesamorelin have been observed in these and other trials. In one of the large trials described above, lipid profiles also improved in the tesamorelin arm; triglyceride levels decreased by 50 mg/dL (0.57 mmol/L), and the ratio of total cholesterol to HDL cholesterol decreased by approximately one-third [76]. Tesamorelin use also has been associated with reductions in hepatic fat, as measured by magnetic resonance spectroscopy [80,81].

The effects of tesamorelin are mediated by its stimulation of growth hormone secretion by the pituitary gland. Growth hormone induces hepatic synthesis of insulin-like growth factor 1 (IGF-1), which, in turn, mediates most of the peripheral actions of growth hormone. (See "Physiology of insulin-like growth factor 1".)

Safety and monitoring — The main concerns of tesamorelin use include potential exacerbation of glucose intolerance and increased IGF-1 levels. Additionally, long-term safety data on the use of tesamorelin are not yet available.

A pooled analysis of two large trials of tesamorelin noted a small but statistically significant increase in hemoglobin A1C (2.9 percent relative increase) at week 26 in individuals receiving tesamorelin [79]. Due to the potential for tesamorelin to adversely affect glucose tolerance, we recommend obtaining a hemoglobin A1c at baseline and every three to four months during therapy to screen for new-onset diabetes and to monitor glycemic control in patients with preexisting diabetes.

In addition, approximately half of the individuals on tesamorelin in these trials developed IGF-1 elevations [76-78]. Given epidemiological associations between IGF-1 levels and malignancy risk in the general population [82,83] and the increased risk of specific malignancies in patients with HIV [84], there are theoretical long-term safety concerns about prolonged elevations of IGF-1 levels induced by tesamorelin. In the absence of data or guidelines to support drug management in the setting of IGF-1 elevations, we suggest that clinicians monitor IGF-1 at least every six months in patients on tesamorelin and aim to keep IGF-1 within the normal range of the assay used. We stop tesamorelin if IGF-1 elevations persist, though some experts suggest dose reduction [85].

Other adverse events include urticaria, which developed in 2.2 percent of individuals on tesamorelin in one trial; one of them had transient systemic symptoms [76].

Glucagon-like peptide 1 (glp-1) receptor agonists — Data are limited on GLP-1 receptor agonists in people with HIV and lipohypertrophy. Preliminary results from a randomized, double-blinded, placebo-controlled trial of semaglutide 1.0 mg weekly by subcutaneous injection in 108 non-diabetic people with HIV and increased waist circumferences and waist-to-hip ratios demonstrated safety and reductions in visceral more than subcutaneous adipose tissue area over 32 weeks [86]. Body weight declined and there was a trend for decreased lean body mass. High-sensitivity C-reactive protein (hsCRP), interleukin-6, and sCD163 levels declined significantly in the semaglutide arm; changes in hsCRP did not correlate with changes in weight or VAT area [87].

Surgical approaches — Suction-assisted lipectomy (liposuction) has been used successfully to manage dorsocervical fat accumulation, though some patients have recurrent fat accumulation [88,89]. Anecdotally, reduction mammoplasty has been successful for women with breast enlargement [90]. The visceral nature of abdominal fat accumulation precludes surgical management.

Less useful interventions — Other interventions have not had clear beneficial effect on HIV-associated fat accumulation or have other drawbacks that limit their use.

Thiazolidinediones – Although thiazolidinediones reduce visceral adipose tissue volume in diabetics without known HIV infection, controlled studies have generally not demonstrated such favorable effects in patients with HIV, including those with insulin resistance.

Recombinant human growth hormone – Although recombinant human growth hormone (rhGH) is known to be lipolytic and patients with acquired immunodeficiency syndrome (AIDS)-related wasting treated with supraphysiologic doses of rhGH lose body fat while gaining lean body mass [91], the role of rhGH for HIV-associated fat accumulation has not been clearly defined. In clinical trials, therapy with rhGH did decrease visceral fat compared with placebo, although there was rapid rebound of visceral fat to levels above baseline after treatment discontinuation and impaired glucose intolerance was greater with rhGH [92-94]. The optimal strategy for maintaining visceral fat reduction that may be achieved from rhGH induction is uncertain, and its clinical development for this indication was terminated.

PREVENTION — Prevention of HIV-associated lipoatrophy consists mainly of avoidance of antiretroviral agents (mainly thymidine analogues, and in particular, stavudine) that have been associated with its development. Neither stavudine nor zidovudine is a first-line nucleoside reverse transcriptase inhibitor (NRTI) for treatment-naïve patients with HIV initiating antiretroviral therapy (ART), and stavudine is very rarely used. However, some patients who initiated treatment years ago may still be on regimens that contain these agents. (See "Epidemiology, clinical manifestations, and diagnosis of HIV-associated lipodystrophy", section on 'Exposure to NRTIs'.)

By contrast, associations between fat accumulation and specific antiretroviral agents are less apparent. Thus, other than encouraging exercise and monitoring weight, no specific prevention measures can be recommended to avoid HIV-associated fat accumulation. (See "Epidemiology, clinical manifestations, and diagnosis of HIV-associated lipodystrophy", section on 'Risk factors'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Primary care of adults with HIV".)

SUMMARY AND RECOMMENDATIONS

Definitions − Lipoatrophy (fat atrophy) and fat accumulation (lipodeposition) appear to be separate processes that should be addressed independently in a given patient if they coexist. (See 'Introduction' above.)

Rationale for treatment − There are several potential benefits to treating HIV-associated lipodystrophy beyond pure cosmesis. Changes in body morphology can be associated with psychologic distress that affects self-esteem and/or adherence to antiretroviral therapy (ART). Additionally, certain therapeutic interventions for HIV-associated lipodystrophy have the potential to favorably affect associated metabolic derangements, such as dyslipidemia and abnormal glucose metabolism. (See 'Rationale for treatment' above.)

Management of lipoatrophy − Potential therapeutic interventions for HIV-associated lipoatrophy include modification of the antiretroviral regimen, surgical correction, and pioglitazone (table 1):

Switching antiretrovirals − For patients with lipoatrophy who are taking a regimen that contains a thymidine analogue (ie, stavudine or zidovudine), we recommend switching the nucleoside reverse transcriptase inhibitor (NRTI) backbone to one containing other nucleoside analogues, such as tenofovir or abacavir (Grade 1B). The presence of pre-existing HIV drug resistance and the patient's treatment history must be considered prior to changing antiretrovirals to reduce the risk of virologic failure. (See 'Switching antiretrovirals' above.)

Surgical approaches − Injectable temporary fillers are a potential option for patients who desire cosmetic remodeling for severe facial lipoatrophy. Cost issues generally preclude their use for many patients. (See 'Surgical approaches' above.)

Thiazolidinediones − For patients who desire medical treatment for lipoatrophy and who have coexisting hyperinsulinemia or impaired glucose tolerance, we suggest a therapeutic trial of pioglitazone in order to increase limb fat (Grade 2C). Pioglitazone should be avoided in patients with histories of congestive heart failure or osteoporosis. Clinicians should monitor liver enzymes closely in patients receiving pioglitazone (eg, at one month after initiation), then every two months for the first year and periodically thereafter. (See 'Thiazolidinediones' above.)

Management of fat accumulation − Potential interventions for HIV-associated fat accumulation (lipodeposition) include diet and exercise, metformin, the growth hormone-releasing factor analogue tesamorelin, and surgical interventions (table 1):

Diet and exercise − The management of patients with HIV with fat accumulation begins with a combination of diet and exercise. Although the data on the efficacy of diet and exercise for HIV-associated fat accumulation, specifically, are limited, their general beneficial effects are well established, and the interventions are overall safe. (See 'Diet and exercise' above and "Obesity in adults: Overview of management".)

Metformin − Metformin is the preferred initial therapy for patients with type 2 diabetes mellitus. For patients with HIV who have diabetes mellitus, it has the added benefit of reducing visceral and abdominal fat. However, further reductions in subcutaneous fat may be undesirable in patients who also have moderate to severe lipoatrophy. (See 'Metformin' above.)

Tesamorelin − For those patients who have not responded to other interventions, are distressed by severe abdominal fat accumulation, and do not have active underlying malignancy, we suggest tesamorelin to treat excess abdominal fat (Grade 2C). Several trials have demonstrated reduction in visceral adipose tissue with tesamorelin and modest improvements in body image, but the effect wanes after treatment discontinuation and long-term safety data are limited. We regularly monitor insulin-like growth factor 1 (IGF-1) levels and hemoglobin A1c during tesamorelin treatment. (See 'Tesamorelin' above.)

Semaglutide — Data are insufficient to recommend semaglutide or related drugs for the management of fat accumulation.

Surgical approaches − For patients with fat accumulation in delimited areas, certain surgical interventions, such as dorsocervical fat pad liposuction or reduction mammoplasty, may be effective, although recurrent fat accumulation in these sites can occur. (See 'Surgical approaches' above.)

ACKNOWLEDGMENT — UpToDate gratefully acknowledges John G Bartlett, MD (deceased), who contributed as Section Editor on earlier versions of this topic and was a founding Editor-in-Chief for UpToDate in Infectious Diseases.

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Topic 3700 Version 41.0

References

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