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The Journal of Clinical Endocrinology and Metabolism logoLink to The Journal of Clinical Endocrinology and Metabolism
. 2008 Aug;93(8):2937–2945. doi: 10.1210/jc.2008-1019

Approach to the Human Immunodeficiency Virus-Infected Patient with Lipodystrophy

Todd T Brown 1
PMCID: PMC2515075  PMID: 18685115

Abstract

Subcutaneous atrophy and central fat accumulation are common among HIV-infected patients receiving highly active antiretroviral therapy, and may be accompanied by dyslipidemia and insulin resistance. These fat changes, although commonly referred to together as lipodystrophy, are best considered as separate disorders, with distinct pathogeneses and treatment approaches. These morphological and metabolic abnormalities first appeared after introduction of protease inhibitors more than 10 yr ago, but research has demonstrated that their pathogenesis is multifactorial, with contributions from other antiretroviral medications, patient-related factors, and HIV itself. Switching to a less toxic highly active antiretroviral therapy regimen has shown partial effectiveness for the management of fat atrophy and lipid abnormalities. Lifestyle modification or surgical approaches are the treatment of choice for lipohypertrophy, although novel therapies targeting the GH axis show promise. HIV-related dyslipidemia may be difficult to treat, and can be complicated by drug-drug interactions between some lipid-lowering medications and antiretroviral medications. Treatment of diabetes in HIV-infected patients should generally follow established guidelines, but thiazolidinediones, rather than metformin, may be considered first-line treatment in a patient with lipoatrophy, given their potential to increase sc fat. The contribution of body fat changes and metabolic abnormalities to cardiovascular risk and the changing risk profiles of newer antiretroviral regimens are under intense investigation.

Subcutaneous fat atrophy and central fat accumulation are common among HIV-infected patients receiving highly active antiretroviral therapy (HAART) and may be accompanied by dyslipidemia and insulin resistance. This article suggests guidelines for treating HIV-infected patients with lipodystrophy.

A 59-yr-old white male is referred by his HIV provider for body composition changes, diabetes, and dyslipidemia in the setting of antiretroviral therapy. He was diagnosed with HIV 10 yr earlier with a nadir CD4 cell count of 166 cells per mm3. He was immediately started on highly active antiretroviral therapy (HAART), including stavudine, didanosine, and indinavir, with an excellent immunological and virological response. Within 12 months of HAART initiation, he began to notice reduced fat in his buttocks and thighs, with a prominence of the veins in his legs, and changes to his facial appearance. He also noticed increased fat in his abdomen. Triglycerides (TGs) increased to more than 2000 mg/dl, and a random glucose was found to be more than 600 mg/dl. Gemfibrozil and insulin were started, and he stopped HAART. His diabetes and hyperlipidemia did not resolve after HAART discontinuation. One year later, his CD4 cell count decreased less than 200 cells per mm3, and antiretroviral therapy was restarted.

Currently, his HIV disease is well controlled on tenofovir/emtricitabine/efavirenz. He reports a 20-lb weight gain in the past 3 yr. He admits that his diet is poor, and his physical activity level is low. In addition to his antiretroviral medications, he is receiving glyburide 20 mg daily, pioglitazone 45 mg daily, and pravastatin 80 mg daily. He has hypertension, and is on a regimen of diltiazem 360 mg daily and olmesartan 40 mg daily. He quit smoking in 2005. He has no family history of coronary artery disease.

On physical examination, blood pressure is 126/74, weight 184 lb, and body mass index (BMI) 28 kg/m2. Waist circumference (at the level of the iliac crest) is 107 cm, and hip circumference (at the level of the greater trochanter) is 87 cm. He has marked facial wasting in the malar region with prominence of the nasolabial folds and moderate lipoatrophy of the buttocks and thighs. A small dorsocervical fat pad is noted. Glycosylated hemoglobin is 6.6%, total cholesterol 182 mg/dl, TGs 254 mg/dl, high-density lipoprotein (HDL) 37 mg/dl, and low-density lipoprotein (LDL) 95 mg/dl. Serum creatinine is 1.7 mg/dl.

Background

With the introduction of HAART in the mid-1990s, HIV-related morbidity and mortality have been dramatically reduced (1,2). Coinciding with the clinical success of HAART, changes in body composition, including sc fat wasting and central fat accumulation, have been observed among HIV-infected patients, often in conjunction with dyslipidemia and insulin resistance, commonly called the HIV lipodystrophy syndrome or the fat redistribution syndrome (3). Because the HIV protease inhibitors (PIs) were important components of many early HAART regimens, this class of medications was implicated in playing the primary causative role in the pathogenesis of these disorders. However, over the past decade, intensive basic and clinical investigation has demonstrated that, whereas some PIs contribute to the development of adipose tissue alterations in HIV-infected patients (4), the pathogenesis of these problems is multifactorial, with contributions from other HIV medications, patient-related factors, and HIV infection itself. In addition, most current evidence suggests that sc lipoatrophy and central lipohypertrophy are distinct processes (5,6), and should be considered separately rather than collectively as a single syndrome of lipodystrophy or fat redistribution.

Clinical Features of Lipoatrophy

The generalized depletion of sc fat, which is commonly observed in the face, buttocks, legs, and arms, is the most frequent morphological change among HIV-infected patients receiving HAART, with prevalence estimates ranging from 13–34% (7,8,9,10), depending on the population studied and the measurement technique used. The proportion of patients with subclinical lipoatrophy is even larger (11) because at least 30% limb fat loss is necessary for lipoatrophy to be noticed by either the clinician or patient (12). This process is distinct from HIV-related wasting that is associated with advanced AIDS and loss of muscle mass.

Facial lipoatrophy generally begins as a symmetrical loss of fat in the malar regions, giving prominence to the nasolabial folds. In more severe cases, there is extension to the cheeks, with prominence of the bony landmarks and visibility of the underlying musculature (13) (Fig. 1). These changes may be particularly stigmatizing for patients and may affect antiretroviral adherence (14).

Figure 1.

Figure 1

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A 45-yr-old HIV-infected woman with moderate/severe facial lipoatrophy with marked fat wasting in the malar areas giving prominence to the nasolabial folds, appearance of the facial musculature (zygomaticus major) and bony landmarks through the skin, and extension of fat wasting to buccal and temporal areas.

There are multiple risk factors for the development of lipoatrophy. Fat wasting is more common in males, older patients, and those who started HAART with advanced HIV (7,8,10). Although lipoatrophy was initially recognized after the introduction of PIs (3), most evidence suggests that the medications most closely tied to its development are the nucleoside reverse transcriptase inhibitors (NRTIs), stavudine (Zerit, d4T; Bristol-Myers Squibb Co., Princeton, NJ) and, to a lesser extent, zidovudine (Retrovir, AZT; GlaxoSmithKline, Research Triangle Park, NC) (15). These medications inhibit the synthesis of mitochondrial DNA preferentially in adipocytes, leading to mitochondrial dysfunction and adipocyte apoptosis (16). Some members of the PI class, such as nelfinavir, can act synergistically with stavudine to worsen lipoatrophy (4). A recent large clinical trial showed unexpected worsening of lipoatrophy in HIV-infected patients randomized to the non-NRTI, efavirenz, but the mechanism underlying this observation is not clear (17).

This patient developed fat wasting in the first 12–24 months after initiation of the stavudine-containing HAART regimen. Although he has since changed to other antiretroviral medications, he has not experienced significant recovery of his sc fat. In the assessment of HIV-infected patients with body composition changes, it is useful to have objective measures of body composition to be able to gauge longitudinal changes. I typically measure the waist at the iliac crest, the hip around the greater trochanter, and thigh at a fixed distance from the top of the patella. In select patients who continue to receive stavudine or zidovudine and who have minimal or no lipoatrophy on physical examination, whole body dual x-ray absorptiometry can be a useful tool to document subclinical worsening of lipoatrophy, which may be an important factor in the consideration of modifying the antiretroviral regimen. Previous photographs can be useful for the assessment of facial lipoatrophy, and grading scales have been developed based on abnormalities in facial contour, prominence of bony structures, and visibility of the underlying musculature (13,18,19).

Clinical Features of Lipohypertrophy

In addition to lipoatrophy, this patient also presented with abdominal and dorsocervical fat accumulation. In other patients, circumscribed lipoma in other areas of the body (e.g. suprapubic) and lipomastia in both men and women can also be observed. Unlike lipoatrophy, the pathogenesis of lipohypertrophy among HIV-infected patients has been elusive and cannot be linked to a specific antiretroviral medication or class of medications. With the initiation of antiretroviral therapy, most studies have shown an increase in central fat over the first 6 months, which then levels off (4,20). Some of this increase may be due to a return to premorbid body composition with effective control of the HIV virus and “catch-up” to HIV-negative peers. However, visceral fat in HIV-infected patients with lipodystrophy exceeds that observed in HIV-negative controls when matched on BMI (21).

The assessment of HIV-lipohypertrophy can be difficult in practice, and there is no commonly accepted definition. Because central fat accumulation is common in the general population, it can be challenging to ascertain the contribution of the fat gain that is specific to HIV infection or its therapy. In addition, because some patients have a combination of sc lipoatrophy in the abdominal region and visceral lipohypertrophy, clinical measurements of central adiposity that do not distinguish between sc and visceral fat, such as waist circumference, may be misleading. For example, a waist circumference that is considered normal in the general population may indicate a significant amount of visceral fat in a HIV-infected patient with concomitant sc lipoatrophy.

Previously, it was believed that lipoatrophy and lipohypertrophy were reciprocal processes, whereby the loss of sc fat was associated with gains in the visceral compartment. This notion was challenged when it was found that those HIV-infected patients with clinical lipoatrophy were found to have either equal or less visceral fat compared with those HIV-infected patients without lipoatrophy, arguing against a strict “fat redistribution syndrome” (5,6).

Associated Metabolic Abnormalities: Dyslipidemia

Dyslipidemia, characterized by increased LDL cholesterol and TGs, and decreased HDL cholesterol, is common among HIV-infected patients receiving HAART (22). Before the HAART era, decreased HDL, LDL, and total cholesterol, accompanied by decrease TG clearance were recognized among HIV-infected patients (23). As was seen in this patient, initiation of antiretroviral therapy can be associated with dramatic changes in lipid concentrations, particularly TGs, although HDL and LDL also increase but to a lesser extent (24). In vitro studies have shown that certain PIs increase TG synthesis (25), and there is variability among the clinical effect of individual agents within the PI class (24). However, it should be noted that individual PIs are often given in combination low doses of ritonavir, a PI that inhibits cytochrome P450 3A4, which is the primary metabolic pathway of PIs. Coadministration with ritonavir increases PI serum concentrations and improves the pharmacokinetic profile. Although not active against HIV at these “boosting” doses, ritonavir may also worsen dyslipidemia (26). Other antiretroviral medications may contribute to dyslipidemia, including efavirenz, stavudine, and zidovudine (27,28,29). In addition, recent evidence suggests that both increases in visceral fat and reductions in lower body sc fat are independently associated with dyslipidemia in both HIV-infected men and women (30,31).

Associated Metabolic Abnormalities: Insulin Resistance/Diabetes Mellitus

The risk of diabetes mellitus and insulin resistance is higher among HAART-treated HIV-infected patients, compared with HIV-uninfected controls (32,33). Similar to the pathogenesis of dyslipidemia in this population, the etiology is multifactorial with contributions from the effects of HIV itself, patient-related characteristics, and antiretroviral therapy. Although some PIs may directly induce peripheral and hepatic insulin resistance (34,35,36,37,38), other medications such as stavudine and zidovudine also have a direct effect on glucose metabolism (39,40), and also may induce insulin resistance indirectly, through effects on body composition. Visceral fat accumulation and sc lipoatrophy have both been associated with insulin resistance (41,42).

Treatment Considerations

Stopping or switching HAART

After this patient developed severe hypertriglyceridemia and hyperglycemia in the setting of antiretroviral therapy, his HIV medications were discontinued. This type of structured treatment interruption showed initial promise as a strategy to minimize antiretroviral toxicity (43). However, a recent large randomized, controlled trial comparing structured treatment interruption with continued therapy not only showed a 2-fold increase in death and opportunistic disease in the structured treatment interruption arm but also, unexpectedly, showed an increase in non-AIDS-related complications, including myocardial infarction (44). These results, along with those of a similar trial (45), provide compelling evidence against structured treatment interruption as a safe and effective strategy for managing the metabolic toxicities of antiretroviral therapy.

Switching strategies have been extensively evaluated in their effect on reversing body composition and metabolic abnormalities (46). Substituting less toxic NRTIs, such as abacavir or tenofovir, for stavudine or zidovudine, has clearly shown benefit in reversing lipoatrophy, although the extent of fat recovery after switching has not yet been determined (47,48,49). Switching off of these medications has also been associated with improvements in lipid profiles and insulin resistance markers (50,51,52). Substitutions for certain PIs have also been an important strategy to improve lipid concentrations (53). Of the most frequently used PIs, atazanavir, darunavir, and saquinavir are associated with the most favorable lipid profiles (24). However, because PIs generally require low-dose ritonavir for its boosting effect, the impact from switching from one ritonavir-boosted PI to another may be modest (54). Antiretroviral switch studies examining the changes in central fat have generally shown no benefit (55,56,57). Because alterations in the antiretroviral regimen may be an important strategy to improve the metabolic abnormalities in HIV-infected patients, close collaboration between endocrine and HIV specialists is essential.

Lipoatrophy

Pharmacological approaches aimed at increasing sc fat have shown only limited success. Thiazolidinediones have shown efficacy in in vitro models of antiretroviral-associated adipocyte loss (58), and have been effective in increasing sc fat and improving metabolic abnormalities among HIV-uninfected persons with lipodystrophy (59). However, results from clinical trials of rosiglitazone in HIV-infected patients with lipoatrophy have been mixed (60,61,62,63). A recent randomized 48-wk trial of pioglitazone in 131 HIV-infected patients with lipoatrophy showed significant improvements in limb fat (0.38 kg pioglitazone group vs. 0.05 kg placebo group; P = 0.05), thigh circumference, and skin-fold thickness, most pronounced in patients not taking d4T (64). Although statistically significant using these objective measures, the change in fat was not perceptible to the patient. It is unclear if continued improvement would be seen with longer exposure, and further studies are needed before thiazolidinediones can be routinely recommended for the treatment of lipoatrophy.

Statin therapy may also improve lipoatrophy. In one, small, randomized controlled trial designed to assess the effect of pravastatin (40 mg at bedtime) on lipid parameters over 16 wk, limb fat measured by dual x-ray absorptiometry was shown unexpectedly to increase in those receiving pravastatin compared with placebo (0.72 vs. 0.19 kg increase with placebo) (65). Further research is needed to confirm these findings, elucidate the underlying mechanism, and determine whether other statins have similar effects.

Another potential approach is supplementation with uridine. In in vitro models, uridine has prevented and reversed mitochondrial toxicity induced by stavudine (66). Clinical trial data are limited. One randomized trial of 20 HIV-infected patients with lipoatrophy showed that limb fat increased to a greater extent over 3 months in those receiving uridine compared with placebo (0.88 ± 0.14 vs. 0.23 ± 0.27 kg; P < 0.05) (67). A uridine-rich dietary supplement is currently available (www.nucleomaxx.com) and is being evaluated in a multicenter, randomized trial in the United States. The efficacy, safety, and optimal dosing are not known, and it is unclear if this approach will be successful in those who have already discontinued stavudine or zidovudine.

Given the negative psychological effects and stigmatization of facial lipoatrophy, facial fillers, generally administered by a plastic surgeon or dermatologist, have gained popularity. Both permanent and absorbable compounds have been successful in improving lipoatrophy grading, improving quality of life, and decreasing anxiety and depression symptoms (68,69,70).

Lipohypertrophy

Central fat accumulation is difficult to treat in HIV-infected patients. Lifestyle modification is an important treatment approach and should be recommended. However, although lipohypertrophy has been associated with lower activity levels (71), studies evaluating the effect of exercise regimens involving resistance training, aerobic exercise, or stretching and relaxation techniques have all showed only modest benefit in improving body composition and metabolic abnormalities in HIV-infected patients (72,73,74,75). Metformin decreases visceral fat in HIV-infected patients in some studies, as well as blood pressure and markers of impaired fibrinolysis (76,77,78,79), and its potential benefits are enhanced with concomitant aerobic and resistance training (80). However, some studies have not shown a similar benefit (81,82), and metformin may worsen lipoatrophy in HIV-infected patients with mixed lipodystrophy (83). Nevertheless, metformin, particularly in combination with exercise training, may be useful in HIV-infected patients with significant lipohypertrophy with minimal lipoatrophy.

The GH axis has also been the target of pharmacological strategies to improve visceral fat accumulation. HIV-infected patients with body composition changes have demonstrated reduced GH mean pulse amplitude on overnight testing, which has been correlated with central fat accumulation (84) and failure rates of 18–38% on standard GHRH-arginine stimulation testing depending on the cutpoint used (3.3 vs. 7.5 ng/ml peak GH response) (85), providing a rationale for this approach. GHRH (86), a GHRH analog (tesamorelin) (87), and human GH (hGH) at both physiological and supraphysiological doses (88,89,90,91,92) have been evaluated in clinical trials. Although Phase III trials are ongoing, none of these therapies are currently approved for use in HIV-infected patients with central fat accumulation. However, the studies to date are promising. For example, tesamorelin decreases visceral adipose tissue by 15% at 6 months, and is associated with improved lipid parameters and body image compared with placebo in a recent large, randomized trial (87).

Supraphysiological hGH may be associated with worsening of lipoatrophy and impaired glucose tolerance (90,91,93,94), which is dose dependent. These adverse effects were not observed with GHRH or tesamorelin (86,87). Similar to other interventions, such as lifestyle modifications or metformin, the treatment effect of hGH, GHRH, or tesamorelin reverses upon discontinuation. Although visceral fat accumulation has a strong association with metabolic abnormalities and cardiovascular disease in the general population, it is unclear whether visceral fat reduction with GH axis-targeted therapies is associated with reduction in clinical endpoints.

Surgical approaches, including liposuction, have been used with success in patients with dorsocervical fat pad accumulation or sc fat accumulation in other sites (95), but recurrence is a potential problem.

Dyslipidemia

The treatment of dyslipidemia should follow the same guidelines as in the general population (96), although guidelines specific to HIV-infected patients are available (97,98), and the risk of myocardial infarction may be underestimated using risk equations derived from the general population (99). LDL cholesterol should be the first target of therapy for those with fasting TGs less than 500 mg/dl. 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors are the preferred therapy, but simvastatin and lovastatin should be avoided in HIV-infected patients receiving ritonavir to avoid potential drug-drug interactions (100). Atorvastatin also interacts with ritonavir, but to a lesser extent, such that lower doses are safe in a patient receiving ritonavir (101). Although a drug-drug interaction with ritonavir was not predicted based on in vitro models, rosuvastatin concentrations increased by more than 2-fold in a recent pharmacokinetic study, whereas its LDL-lowering efficacy was attenuated (102) (Table 1). Conversely, coadministration of statins with efavirenz reduces atorvastatin, simvastatin, and pravastatin serum concentrations, through induction of statin metabolism, thereby diminishing the effect (103). Modest LDL lowering with ezetimibe has also been observed in HIV-infected patients, although its effect on clinical endpoints is unclear (104,105).

Table 1.

The Risk of Pharmacologic Interactions between HMG coA-reductase inhibitors and ritonavir (Norvir), a common component of protease inhibitor containing HAART regimens

Safe to coadminister Use with caution Contraindicated
Pravastatin Atorvastatin Simvastatin
Fluvastatin Rosuvastatin Lovastatin
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For patients whose LDL goal has been reached or who have TG levels more than 500 mg/dl, fibric acid derivatives (106,107), omega-3 fatty acids (108,109), and niacin (110) have each shown efficacy in the reduction of TGs and non-HDL cholesterol. HIV-associated dyslipidemia can be difficult to treat, and often multiple agents are necessary to reach target lipid concentrations, in addition to dietary modifications (111).

Diabetes mellitus/insulin resistance

In general, treatment guidelines outlined by the American Diabetes Association and European Association for the Study of Diabetes should be followed in HIV-infected patients with diabetes mellitus (112). However, in patients with lipoatrophy, metformin should be used with caution because further reductions in sc fat may be seen (82). Thiazolidinediones can be considered the preferred approach in those with lipoatrophy, given the possibility of increasing sc fat, albeit modest. Among the members of this class, pioglitazone is associated with a more favorable cardiovascular risk profile in the general population (113,114,115). Because of the severity of insulin resistance in many HIV-infected patients with diabetes, it is reasonable to favor insulin sensitizers over insulin secretagogues. Incretin mimetics have not been systematically evaluated in HIV-infected patients, but similar effects to the general population would be expected. There are no known pharmacological interactions between any hypoglycemic agents and antiretroviral agents.

Similar to the general population, pharmacological treatment of insulin resistance, impaired fasting glucose, or impaired glucose tolerance is not currently indicated, except for perhaps younger patients with a BMI more than or equal to 35 kg/m2, with both impaired glucose tolerance and impaired fasting glucose, in whom the use of metformin may be considered along with lifestyle modifications to reduce the risk of progression to diabetes (116).

Controversial and Unanswered Questions

Risk of cardiovascular disease

There is widespread concern that the metabolic and morphological abnormalities in HIV-infected patients lead to an increased risk of cardiovascular disease. Some observational studies suggest an increased risk of cardiovascular disease among HIV-infected patients compared with the general population (117) and an increased risk of myocardial infarction in HIV-infected persons with each year of HAART exposure, particularly to the PI class (118). Other observational data sets have shown that the risk of cardiovascular mortality has not changed in the HAART era (119), and that cardiovascular events in HIV-infected patients are most closely associated with traditional cardiovascular risk factors (120), such as dyslipidemia and impaired glucose tolerance, which may be more common among HIV-infected patients. The extent of the increased risk of cardiovascular disease in this population and its association with factors related to HIV infection, antiretroviral therapy, and its metabolic consequences are topics of intense investigation.

Role of new antiretroviral agents

Antiretroviral therapy is rapidly evolving. In the last 2 yr, two new classes of antiretrovirals have been introduced, as well as several new additions to existing classes. In general, newer antiretroviral agents have been associated with fewer toxicities (121,122). However, the optimal combination of these medications has not yet been determined, and the recent finding of unexpected cardiovascular toxicity with short-term exposure to a preferred nucleoside analog reminds us that careful scrutiny of the metabolic and cardiovascular effects of antiretroviral medications is warranted (123).

Back to the Patient

Although the patient had significant lipoatrophy, his central fat accumulation had the largest negative impact on his quality of life. Strategies to increase his physical activity were discussed in detail with the patient, including 20–30 min walking during his weekday lunch break and adopting a regular walking regimen on the weekends. He was referred to a dietician for recommendations regarding medical nutrition therapy for diabetes mellitus and dyslipidemia, including mild caloric restriction with the goal of a 10% weight loss in the next 6 months.

With a glycosylated hemoglobin of 6.6%, no intensification of his diabetes regimen was recommended. However, it was discussed that, with adoption of lifestyle changes, discontinuation of his sulfonylurea may be possible and may enhance further weight loss. Metformin was not considered because of his elevated serum creatinine. His LDL cholesterol was at a goal with 80 mg pravastatin given his cardiovascular risk factors (<100 mg/dl). We discussed the fact that his non-HDL cholesterol (145 mg/dl) was above the goal (<130 mg/dl) but elected to evaluate the effects of weight loss before further pharmacological intervention was considered. Low-dose aspirin was recommended for primary prevention of cardiovascular disease.

Conclusions

Lipoatrophy, lipohypertrophy, dyslipidemia, and abnormalities in glucose metabolism are common among HIV-infected patients receiving HAART. Although these problems are interrelated, they can be seen independently, and their pathophysiologies are distinct. Switching to less-toxic antiretroviral regimens is an important treatment strategy for lipoatrophy and dyslipidemia, and close communication between endocrine and HIV-specialists is essential. Specific pharmacological therapies for fat changes are limited, but new agents are currently being evaluated. Dyslipidemia and diabetes mellitus should be treated using established guidelines in the general population. However, the choice of pharmacological agent may be complicated by pharmacokinetic interactions with certain antiretroviral medication and additional considerations regarding toxicity profiles of individual agents (e.g. metformin in a patient with lipoatrophy). Further research is underway to clarify the risk of cardiovascular disease in HIV-infected populations, evaluate newer antiretroviral agents for metabolic and cardiovascular toxicity, and identify other treatment strategies.

Footnotes

This work was supported by National Institutes of Health Grant K23 AT002862-01.

Disclosure Summary: T.T.B. has served as a consultant for EMD-Serono and Abbott Laboratories and has received research support from Reliant Pharmaceuticals, Theratechnologies, Abbott Laboratories, GlaxoSmithKline, and Merck.

Abbreviations: BMI, Body mass index; HAART, highly active antiretroviral therapy; HDL, high-density lipoprotein; LDL, low-density lipoprotein; NRTI, nucleoside reverse transcriptase inhibitor; PI, protease inhibitor; TG, triglyceride.

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