Lipoatrophy In HIV-infected Patients Research Articles

Reversibility of Lipoatrophy in HIV-Infected Patients Taking Antiretroviral Therapy: a Cohort Study with Ultrasound Assessment

The aim of this study was to characterize and compare changes in subcutaneous fat in the malar, brachial and crural region in a cohort of HIV-infected patients taking antiretroviral therapy. This prospective longitudinal study included 77 patients who were selected from the initial cohort evaluated in 2007 and 2008. We examined reversibility of lipoatrophy measured by ultrasound over at least five-year period and factors related to its reversibility. All 46 patients who used stavudine switched from stavudine to another combination. Of 58 patients on zidovudine, 16 (28%) were on a zidovudine based regimen at the second follow up. There was evidence for subcutaneous fat increase in the malar area (p<0.001) and no increase in the brachial and crural areas. Patients who were smokers and had poor adherence to the Mediterranean diet had a thinner malar area at the follow up measurement (p=0.030) and smaller increase in subcutaneous malar fat compared to others (p=0.040). Our study suggested that modest increase of subcutaneous fat in malar area coincided with stopping stavudine and fewer usage of zidovudine. Lifestyle with non-adherence to the Mediterranean diet and smoking were associated with a smaller increase in subcutaneous malar fat.

Traitement de la lipoatrophie faciale par lipofilling chez les patients infectés par le VIH : étude rétrospective de 317 patients sur neuf ans

HIV infection and antiretroviral therapy are responsible in 20 to 40% of cases of facial lipoatrophy. This one has an impact in an important way on the quality of life with a major social impact. Several treatments are available to correct facial lipoatrophy. We evaluate the efficiency of autologous fat transfer described by Coleman (Lipostructure®). We recorded HIV-infected patients who had facial lipofilling between May 1999 and April 2008.Then, we estimated the severity of their lipoatrophy and the result of lipofilling after 1 month to 4 years follow-up. We have treated 317 patients by lipofilling. We have injected a mean of 8mL of fat on each side. There were no adverse events. Sixty-three percent had a good result on 1-year evaluation. Lipofilling is a safe and stable surgical procedure that makes the reference technique to correct facial lipoatrophy in HIV-infected patients. The use of facial fillers must be limited in case of impossibility to take fat tissue, which was exceptional in our study.

Fat Tissue Distribution Changes in HIV-Infected Patients Treated with Lopinavir/Ritonavir. Results of the MONARK Trial

Given the decline in mortality among HIV-infected patients, it has become increasingly important to consider delayed disease-related and/or anti-HIV therapy-related adverse effects, such as lipodystrophy, when choosing initial therapy. Data from the MONARK trial allowed for comparison of the potential lipodystrophic effects of lopinavir/ritonavir (LPV/r) monotherapy with those of triple therapy with LPV/r plus zidovudine (ZDV) and lamivudine (3TC). This was a randomized, open-label, multinational study that included 136 antiretroviral-naive HIV-infected patients. A portion of study patients underwent evaluations of limb and trunk fat tissue by dual-energy x-ray absorptiometry at baseline and after 48 weeks of treatment (and 96 weeks in some patients). Sixty-three patients had paired absorptiometry data at baseline and week 48 (13 patients at week 96). At week 48, median change in limb fat was -63 g on LPV/r monotherapy versus -703 g on LPV/r + ZDV/3TC triple therapy (p=0.014). The proportion of patients with fat loss (>20% loss in limb fat) was significantly lower with LPV/r monotherapy (4.9% versus 27.3%; p=0.018). Changes in trunk fat did not differ significantly between treatments. Nonetheless, limb fat and trunk fat varied in the same direction with both treatments. The decrease in arm lean mass was also significantly less in patients receiving LPV/r monotherapy. Only treatment type emerged as a significant predictor of fat loss (odds ratio, 7.06; 95% CI, 1.11-78.69). These results suggest that LPV/r, and possibly other protease inhibitors, may not be the main contributor to lipoatrophy in HIV-infected patients receiving triple therapy.

Leptin replacement improves postprandial glycemia and insulin sensitivity in human immunodeficiency virus–infected lipoatrophic men treated with pioglitazone: a pilot study

Highly active antiretroviral therapy (HAART)–induced lipoatrophy is characterized by hypoleptinemia and insulin resistance. Evidence suggests that pioglitazone and recombinant methionyl human leptin (metreleptin) administration has beneficial effects in human immunodeficiency virus (HIV)–infected lipoatrophic patients. This proof-of-concept study aimed at evaluating whether the combination of metreleptin and pioglitazone has favorable effects, above and beyond pioglitazone alone, on both metabolic outcomes and peripheral lipoatrophy in HIV-infected patients on HAART. Nine HIV-positive men with at least 6 months of HAART exposure, clinical evidence of lipoatrophy, and low leptin concentrations (≤4 ng/mL) were placed on pioglitazone treatment (30 mg/d per os) and were randomized to receive either metreleptin (0.04 mg/kg subcutaneously once daily; n = 5) or placebo (n = 4) for 3 months in a double-blinded fashion. Compared with placebo, metreleptin reduced fasting serum insulin concentration, increased adiponectin concentration, reduced the homeostasis model assessment index of insulin resistance, and attenuated postprandial glycemia in response to a mixed meal (all P ≤ .02), but did not affect trunk and peripheral fat mass. HIV control was not affected, and no major adverse effects were observed. Metreleptin administration in HIV-positive, leptin-deficient patients with lipoatrophy treated with pioglitazone improves postprandial glycemia and insulin sensitivity. Results from this pilot study should be confirmed in larger clinical trials.

Reduced dose of stavudine and lipoatrophy in HIV-infected patients in Cameroon

This study assessed the effect of stavudine (d4T) 30 mg dosage on lipoatrophy in HIV-infected patients on antiretroviral treatment. A total of 243 patients from Cameroon receiving d4T or zidovudine (AZT) in combination with lamivudine and efavirenz or nevirapine for >6 months were clinically assessed for moderate to severe ('strict' definition) and mild to severe ('large' definition) lipoatrophy. Prevalence of lipoatrophy was compared between 69 patients who had received exclusively d4T 30 mg (d4T(30)), 64 patients who had received both d4T 30 and 40 mg dosages since treatment initiation (d4T(30/40)) and 110 patients on AZT-related therapy. Prevalence of lipoatrophy varied from 7% to 24%, according to the definition. After adjustment for gender, age, treatment duration and CD4(+) T-cell count, the risk of lipoatrophy in the d4T(30) group was lower than in the d4T(30/40) group (odds ratio [OR] 0.3, 95% confidence interval [CI] 0.1-0.8 with the large definition and OR 0.2, 95% CI 0.0-0.8 with the strict definition) and was comparable to that of the AZT group (OR 1.0, 95% CI 0.2-4.6 and OR 1.0, 95% CI 0.4-2.2 with the large and strict definitions, respectively). The risk was significantly higher in the d4T(30/40) group compared with the AZT group (OR 2.9, 95% CI 1.3-6.4 with the large definition and OR 5.5, 95% CI 1.3-23.5 with the strict definition). The use of d4T at a lower dosage might increase safety with regard to its effect on lipoatrophy.

Mitochondrial DNA Depletion and Respiratory Chain Activity in Primary Human Subcutaneous Adipocytes Treated with Nucleoside Analogue Reverse Transcriptase Inhibitors

Mitochondrial dysfunction as a consequence of mitochondrial DNA (mtDNA) depletion due to therapy with nucleoside analogue reverse transcriptase inhibitors (NRTI) has been proposed as a pathogenic mechanism leading to lipoatrophy in HIV-infected patients. The aim of our study was to investigate the impact of NRTI treatment on mtDNA abundance and the activities of respiratory chain complexes in primary human subcutaneous preadipocytes (phsPA). We studied adipocyte phenotypes, viability, and differentiation (CCAAT/enhancer-binding protein alpha [C/EBPalpha] and peroxisome proliferator-activated receptor gamma [PPARgamma] expression) and adiponectin production, mtDNA content, mitochondrial membrane potential, mitochondrial mass, and respiratory chain enzyme and citrate synthase activities in both proliferating and differentiating phsPA. Cells were exposed to zidovudine (6 microM), stavudine (d4T; 3 microM), and zalcitabine (ddC; 0.1 microM) for 8 weeks. NRTI-induced mtDNA depletion occurred in proliferating and differentiating phsPA after exposure to therapeutic drug concentrations of d4T and ddC. At these concentrations, ddC and d4T led to an almost 50% decrease in the number of mtDNA copies per cell without major impact on adipocyte differentiation. Despite mtDNA depletion by NRTI, the activities of the respiratory chain complexes, the mitochondrial membrane potential, and the mitochondrial mass were found to be unaffected. Severe NRTI-mediated mtDNA depletion in phsPA is not inevitably associated with impaired respiratory chain activity or altered mitochondrial membrane potential.

Assessment of Ultrasound for Use in Detecting Lipoatrophy in HIV-Infected Patients Taking Combination Antiretroviral Therapy

The aim of this study was evaluation of ultrasound (US) as a tool for the assessment of lipoatrophy in a population of HIV-infected patients. We enrolled a convenience sample of 151 HIV-infected Caucasian participants (males, 79%) who were treated for at least 1 year with combination antiretroviral therapy (CART) in Zagreb, Croatia. US measurements of subcutaneous fat thickness were done over the malar, brachial, and crural region. We determined sensitivity and specificity of US as a diagnostic tool for lipoatrophy using receiver-operating curves and concordant patient and clinician assessment as our reference for the presence of lipoatrophy. HIV was acquired through heterosexual contact in 50% of participants and by sex between men in 42%. The mean current CD4 cell count was 503.1 cells=mm3 (standard deviation [SD] = 250.8). Seventy-seven (51%) participants were treated with stavudine and 91 (64%) with a protease inhibitor for at least 6 months. Nineteen (13%)participants had lipoatrophy in at least one anatomic site. Sensitivity of US ranged from 67%-71%, specificity from 65%-71%, positive and negative predictive values ranged from 11%-20% and 96-97%, respectively. US diagnosed lipoatrophy was more frequently found in patients with a history of stavudine treatment and in females. Patients with lipoatrophy had a longer duration of CART than those without lipoatrophy. US is a useful tool in ruling out the presence of clinical lipoatrophy in patients on CART. Using this objective measure of subcutaneous fat may be useful in helping clinicians make decisions about changing therapy.

Contribution of metabolic and anthropometric abnormalities to cardiovascular disease risk factors.

Patients with human immunodeficiency virus (HIV) infection have sustained alterations in metabolism (lipids and insulin/glucose homeostasis) and body composition (fat distribution) that are proatherogenic (the Figure). HIV infection itself and/or its therapies may contribute to these alterations (the Table); although most effects are reversible, there are some possibly irreversible consequences of treatment. With the relative restoration to health seen in the era of highly active antiretroviral therapy (HAART), many traditional risk factors and promoters of dyslipidemia and diabetes also are present; they interact with HIV-specific inducers to worsen dyslipidemia and to increase the prevalence of insulin resistance and diabetes. Figure. Overview of the effects of HIV and its therapies on CVD risk. The contribution of traditional risk factors must be kept in mind, and they may occur with increased prevalence in people with HIV infection (eg, smoking). HIV, likely through the inflammatory response, and antiretroviral therapies independently affect many of the mediators of CVD risk. The effects on lipids are a prominent but complex example; HIV infection lowers LDL levels, but antiretroviral therapy raises LDL back up to normal levels. The bidirectional arrows indicate associations, but there is not yet adequate proof of causality. The dotted arrow between body composition and CVD indicates that body fat is known to affect the mediators such as dyslipidemia and insulin resistance but may also have a direct effect. FFA indicates free fatty acids; ARV, antiretroviral. View this table: Table. Effects of HIV Treatment These disturbances in lipid and glucose metabolism and renal disease may contribute, at least in part, to the excess cardiovascular disease (CVD) morbidity and mortality observed in HIV-infected individuals (the Figure). However, the relative contribution to excess CVD risk of traditional CVD risk factors, especially smoking, compared with these infection- and treatment-specific complications requires clarification. More prospective data with multivariable modeling are needed. …

Correction Options for Lipoatrophy in HIV-Infected Patients

Lipoatrophy (LA) is a form of lipodystrophy, characterized by volume depletion caused by fat loss in the limbs, buttocks, and face. Facial volume loss is the most obvious outward sign of LA because it alters the facial contours in the cheeks, temples, and orbits. Lipodystrophy and LA are most commonly seen in patients with HIV on highly active antiretroviral therapy (HAART), which was introduced in the mid-1990s for the management of HIV, and is currently considered the mainstay therapy for HIV-infected patients. However, the etiology of LA is likely multifactorial as underlying patient conditions, including duration and severity of HIV and increasing age, have also been found to contribute to its occurrence. The volume loss of LA can be very dramatic with some patients exhibiting no signs of facial fat. As a result, many HIV-infected patients with associated LA suffer from psychological and lifestyle effects, which can lead to noncompliance with HAART. Thus, increases in facial volume and improvement in morphology is anticipated to reduce anxiety caused by LA in HIV-infected patients, and improve quality of life. This review discusses the benefits and limitations of several treatment options available to correct the volume depletion associated with LA, including antiretroviral switching, permanent surgical implants and injectables, poly-L-lactic acid, collagen, and hyaluronic acid derivatives.

Deep Subcutaneous Application of Poly-L-Lactic Acid as a Filler for Facial Lipoatrophy in HIV-Infected Patients

Introduction: Facial lipoatrophy is a crucial problem of HIV-infected patients undergoing highly active antiretroviral therapy (HAART). Poly-L-lactic acid (PLA), provided as New-Fill^®/Sculptra™, is known as one possible treatment option. In 2004 PLA was approved by the FDA as Sculptra™ for the treatment of lipoatrophy of the face in HIV-infected patients. While the first trials demonstrated relevant efficacy, this was to some extent linked to unwanted effects. As the depth of injection was considered relevant in this context, the application modalities of the preparation were changed. The preparation was to be injected more deeply into subcutaneous tissue, after increased dilution. Material and Methods: To test this approach we performed a pilot study following the new recommendations in 14 patients. Results: While the efficacy turned out to be about the same, tolerability was markedly improved. The increase in facial dermal thickness was particularly obvious in those patients who had suffered from lipoatrophy for a comparatively small period of time. Conclusion: With the new recommendations to dilute PLA powder and to inject it into the deeper subcutaneous tissue nodule formation is a minor problem. However, good treatment results can only be achieved if lipoatrophy is not too intense; treatment intervals should be about 2–3 weeks.

Evaluation of Coleman Lipostructure for Treatment of Facial Lipoatrophy in Patients With Human Immunodeficiency Virus and Parameters Associated With the Efficiency of This Technique

To evaluate the efficiency of Coleman lipostructure in patients infected with human immunodeficiency virus (HIV). Open-label study and survey. Ambulatory dermatosurgery department of a university hospital. Thirty-three consecutive HIV-infected patients undergoing Coleman lipostructure between 2000 and 2001. Clinical examination, blood tests, and standardized photographs at baseline and 1 year after the lipostructure. Efficiency was assessed by the agreement of 3 independent medical specialists on facial lipodystrophy improvement after surgery and by patient satisfaction. Facial lipoatrophy was improved in 12 patients (36%; 95% confidence interval, 20%-52%) as judged by all 3 evaluators. Quantity of fat injected (P = .01) and a low serum triglyceride level before surgery (P = .03) were significantly associated with improvement of facial lipoatrophy. Of the 33 patients, 14 (43%) were very satisfied, 17 (50%) were partly satisfied, and 27 (81%) had a better quality of life. The most common comment was that the patient looked better and appeared less ill. Our 1-year evaluation of Coleman lipostructure for correction of facial lipoatrophy in HIV-infected patients proved the efficiency of this treatment when measured conservatively by agreement on improvement by 3 independent specialists and demonstrated a patient satisfaction rate of 93%.

Correction par produit biodégradable des lipoatrophies faciales des malades infectés par le VIH

Facial lipoatrophy in HIV-infected patients under tri-therapy occurs frequently and alters their quality of life. No systemic treatment is capable of curing this problem.Eighty-one patients were included in an open, prospective, compassionate study. A strict intradermal injection of a biodegradable, polyacrylamide cationic copolymer was administered in several sessions.In all the patients, the correction of the facial lipoatrophy was considered satisfactory and stable over a period of 6 months using comparative photographic clichés. The thickness of the dermal skin, assessed by sonography, was doubled. No local or systemic side effect was reported.Our study shows that is it possible to durably correct the facial lipoatrophy of HIV-infected patients under tri-therapy by using a biodegradable implant.

Single-Slice Computed Tomography and Anthropometric Skinfold Analysis for Evaluation of Facial Lipoatrophy in HIV-Infected Patients

We assessed the value of computed tomography (CT) and anthropometric skinfold analysis for evaluating subcutaneous facial fat in human immunodeficiency virus-infected patients. Patients with facial lipoatrophy had smaller areas of facial adipose tissue, lower ratios of adipose tissue area to total tissue area of the face, and lower malar skinfold values, compared with patients without facial wasting. CT may be a useful technique to diagnose and monitor facial lipoatrophy.

Bilateral enophthalmos as a manifestation of HIV infection‐related lipoatrophy

Infectious Diseases Unit, University Hospital de Valme,Carretera de Ca´diz, s/n 41014, Seville, SpainReceived: 6 February 2004, accepted 26 May 2004Lipodystrophy in HIV-infected patients can present in threedifferent forms: the pure atrophic form, the fat accumulationform and the mixed type [1]. The atrophic form ischaracterizedbyalossofsubcutaneousfatintheextremities,the buttocks and the face, mainly at the temporal areas andat the cheeks. We present herein a case of lipoatrophy whichled rapidly to an enophthalmos as a consequence of a loss oforbitary fat. To our knowledge, this is the first reported caseof enophthalmos as a manifestation of lipoatrophy in HIV-infected patients (on the basis of a MEDLINE search, 1985–2003, with keywords HIV, antiretroviral therapy, lipodystro-phy, lipoatrophy and enophthalmos).A 42-year-old man infected with HIV and hepatitis Cvirus (HCV), who had previously been an injecting druguser, started highly active antiretroviral therapy (HAART)in June 1998. Initially, he was given zidovudine (ZDV),lamivudine (3TC) and indinavir (IDV). In December 1998,IDV was replaced with nelfinavir (NFV) because ofrecurrent renal colics. In order to simplify the therapy,the regimen was switched to ZDV, 3TC and efavirenz (EFV)in November 2000. In October 2001, ZDVwas replaced withstavudine (d4T) because of persistent neutropenia. Thepatient had remained asymptomatic from the start oftherapy and reported taking more than 98% of theprescribed doses during the follow-up period. The plasmaHIV RNA load dropped below the detection level at 6months of follow up and in all determinations thereafter.The initial CD4 cell count was 50 cells/mL. Two years afterstarting HAART, the CD4 cell count had increased to 4350cells/mL and remained at this level during the remainder ofthe follow-up period. Treatment for chronic HCV infectionwith interferon (IFN) plus ribavirin (RBV) was givenbetween January and December 2002, with only a partialresponse. The patient’s weight at the beginning and end ofthe anti-HCV therapy was 72 and 70.9 kg, respectively.In January 2002, the patient showed painful unilateralgynecomastia. Plasma triglyceride levels, which werenormal at all previous visits, became elevated at this time.While the gynaecomastia decreased subsequently, until itdisappeared 1 year later, triglyceride levels remainedelevated. Until that moment of the follow up there wereno (even minor) signs of enophthalmos.In September 2002, modest facial lipoatrophy, with lossof Bichat’s fat, was present. There were no other signs oflipodystrophy. In March 2003, the patient complained ofmild ocular discomfort and recession of both eyes withinthe orbits. Physical examination revealed bilateral en-ophthalmos. The patient’s weight at that time was 74.7 kg.He did not report traumatisms. d4T was then replaced withtenofovir (TDF). An orbital computed tomography scanshowed bilateral orbital fatty tissue atrophy (Fig. 1).Neither facial lipoatrophy nor enophthalmos was objec-tively found to progress in the next 6 months. The patientdid not feel further ocular discomfort.Enophthalmos is a process in which the ocular globesinks into the orbit. It can have a variety of causes:structural bone alterations (orbital floor fractures), meta-static carcinoma, cicatricial orbitary lesions, chronicinflammatory orbital disease or orbital tissue atrophy.Bilateral enophthalmos in the absence of previous traumais rare. Experimental observations suggest that the loss ofintraconal fat generates enophthalmos [2]. The role oforbital fat changes in post-traumatic enophthalmos hasbeen extensively discussed [3], and orbital fat changes arealso assumed to play a role in nontraumatic enophthalmos.At least three cases have been reported in association withhydrocephalus and ventriculo-peritoneal shunting, withatrophy of the orbital fatty tissue as a related phenomenon[4]. In the patient reported here, enophtalmos was probablyalso a result of orbital fat atrophy. Thus, the emergence oforbital fat atrophy as a cardinal sign of lipoatrophy shouldbe taken into account in the diagnosis of enophthalmos inHIV-infected patients.The atrophic form of lipodystrophy has been reported tobe associated with exposure to d4T more frequently than

Polylactic acid implants (New-Fill) to correct facial lipoatrophy in HIV-infected patients: results of the open-label study VEGA.

In the absence of currently available therapy to manage facial lipoatrophy, strategies used to compensate for facial fat loss warrant clinical evaluation. The goal of this open-label, single-arm, pilot study was to evaluate the efficacy and safety of facial injections of poly-L-lactic acid (PLA) (New-Fill) in HIV-infected patients with severe facial lipoatrophy. Patients received four sets of injection at day 0 and then every 2 weeks for 6 weeks. Patients were evaluated by clinical examination, facial ultrasonography, and photography at screening and at weeks 6, 24, 48, 72, and 96. Fifty patients were enrolled. At entry, the median facial fat thickness was equal to zero (range, 0.0-2.1 mm). The median total cutaneous thickness (TCT) increased significantly from baseline : +5.1 mm (range, 2.2-8.6 mm) at week 6, +6.4 mm (range, 3.1-9.1 mm) at week 24, +7.2 mm (range, 4.2-9.6 mm) at week 48, +7.2 mm (range, 3.5-9.6 mm) at week 72 and +6.8 mm (range, 3.9-10.1 mm) at week 96 (P < 0.001). The proportion of patients with TCT > 10 mm was observed in 19% at week 6, 41% at week 24, 61% at week 48, 52% at week 72 and 43% at week 96. In 22 (44%) patients, palpable but non-visible subcutaneous micronodules were observed with a spontaneous resolution in six patients at week 96. The benefit of PLA for the correction of the facial lipoatrophy in HIV-infected patients was clearly demonstrated, with an evident aesthetic and quality of life improvement. The efficacy, safety profile, and the simplicity of the injection schedule of PLA make this filling material a potentially attractive treatment.

Traitement chirurgical des lipoatrophies faciales

The lipodystrophy syndrome is one of the major event of potent antiretroviral therapy. This treatment results in lipoatrophy, lipohypertrophy or mixed syndrome. Lipoatrophy is characterized by a loss of subcutaneous fat. The psychological impact may be severe when it is localized at the face. The aim of this study was to show the possibilities of improve lipoatrophy by autologuous fatty tissue transplantation with the Coleman method. Since december 1999 we have a plastic surgery consultation for lipodystrophy. From December 1999 to march 2002 we have seen 87 patients in consultation and 29 patients have been treated for facial lipoatrophy with Coleman method. The patients were evaluated clinically and with serial photography at 1 and 6 months post operatively. Coleman method is the ideal treatment for facial lipoatrophy in HIV infected patients. This technique is reliable and preliminary results show durability of fat graft after 6 months. Nevertheless, Coleman method is restricted by fat availability and can not be used for all lipoatrophy.

Evidence of nucleoside analogue reverse transcriptase inhibitor--associated genetic and structural defects of mitochondria in adipose tissue of HIV-infected patients.

To investigate if possible mitochondrial injury can be found in adipose tissue of nucleoside analogue reverse transcriptase inhibitor (NRTI)-treated patients, subcutaneous fat was taken from the buttocks of 24 HIV-positive patients and 8 HIV-negative controls. The content of mitochondrial DNA (mtDNA) was quantified using a Southern blot technique. Fat biopsies were examined by electron microscopy and screened by restriction fragment length polymorphism analysis for the presence of the nt 8344 and 3243 mtDNA point mutations. Age, sex, and body mass index did not differ between the HIV-negative controls, the HIV-positive patients currently treated with NRTIs (NRTI group, n = 19), and the HIV-positive patients without NRTIs (no-NRTI group, n = 5). The mean mtDNA content was 44% lower in the NRTI group compared with the no-NRTI group ( p =.01) but did not differ between the control group and the no-NRTI group. When the HIV-infected patients were stratified to a group with clinical signs of lipoatrophy at the biopsy site (LA group, n = 11) and a group without lipoatrophy (no-LA group, n = 13), the mean mtDNA content in the LA group was 39% lower than that in the no-LA group ( p =.02). No point mutations or deletions were observed. The adipocytes of patients with lipoatrophy contained multiple small lipid vacuoles, and the mitochondria harbored inclusions reminiscent of mtDNA cytopathies. mtDNA depletion and ultrastructural abnormalities of adipocytes suggest a link between mitochondrial damage, the use of NRTIs, and lipoatrophy in HIV-infected patients.

Evidence of Nucleoside Analogue Reverse Transcriptase Inhibitor–Associated Genetic and Structural Defects of Mitochondria in Adipose Tissue of HIV-Infected Patients

To investigate if possible mitochondrial injury can be found in adipose tissue of nucleoside analogue reverse transcriptase inhibitor (NRTI)-treated patients, subcutaneous fat was taken from the buttocks of 24 HIV-positive patients and 8 HIV-negative controls. The content of mitochondrial DNA (mtDNA) was quantified using a Southern blot technique. Fat biopsies were examined by electron microscopy and screened by restriction fragment length polymorphism analysis for the presence of the nt 8344 and 3243 mtDNA point mutations. Age, sex, and body mass index did not differ between the HIV-negative controls, the HIV-positive patients currently treated with NRTIs (NRTI group, n = 19), and the HIV-positive patients without NRTIs (no-NRTI group, n = 5). The mean mtDNA content was 44% lower in the NRTI group compared with the no-NRTI group (p = .01) but did not differ between the control group and the no-NRTI group. When the HIV-infected patients were stratified to a group with clinical signs of lipoatrophy at the biopsy site (LA group, n = 11) and a group without lipoatrophy (no-LA group, n = 13), the mean mtDNA content in the LA group was 39% lower than that in the no-LA group (p = .02). No point mutations or deletions were observed. The adipocytes of patients with lipoatrophy contained multiple small lipid vacuoles, and the mitochondria harbored inclusions reminiscent of mtDNA cytopathies. mtDNA depletion and ultrastructural abnormalities of adipocytes suggest a link between mitochondrial damage, the use of NRTIs, and lipoatrophy in HIV-infected patients.