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Andrew Carr - One of the best experts on this subject based on the ideXlab platform.

  • proinflammatory markers insulin sensitivity and cardiometabolic risk factors in treated hiv infection
    Obesity, 2009
    Co-Authors: Andrew Carr, Katherine Samaras, Seng Khee Gan, Phillip W Peake, Lesley V Campbell
    Abstract:

    Treated HIV infection and HIV-Lipoatrophy increases risk of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). Circulating inflammatory molecules may, in part, explain this increased risk. This study examined circulating inflammatory molecules in treated HIV infection in relation to insulin sensitivity, lipids total body, and intramyocellular fat, compared to insulin-resistant obesity (an index group at high risk of diabetes). Detailed metabolic phenotypes were measured in 20 treated HIV-infected men (with and without subcutaneous Lipoatrophy) vs. 26 insulin-resistant obese men (IR-O, n = 26), including inflammatory molecules, insulin sensitivity, total body fat (TBF), visceral fat (visceral adipose tissue (VAT)), and intramyocellular lipid (IMCL). C-reactive protein (CRP) levels in treated HIV were similar to those in IR-O, despite lower TBF and greater insulin sensitivity in treated HIV. In HIV-Lipoatrophy, CRP was higher than that found in IR-O. Adiponectin was similar between treated HIV and IR-O, but significantly lower in those with HIV-Lipoatrophy. In treated HIV, subjects with higher CRP had significantly higher total cholesterol, VAT, and IMCL. In treated HIV, subjects with lower adiponectin had significantly lower HDL and higher triglycerides, glucose, VAT, and IMCL. In conclusion, a proinflammatory milieu equivalent to that of insulin-resistant obesity characterizes lean men with treated HIV infection, worse in those with subcutaneous Lipoatrophy. These factors may contribute to the accelerated diabetogenesis and cardiac risk observed in treated HIV infection.

  • a randomized multicenter open label study of poly l lactic acid for hiv 1 facial Lipoatrophy
    Journal of Acquired Immune Deficiency Syndromes, 2007
    Co-Authors: Dianne Carey, Sean Emery, David A Cooper, David Baker, Gary David Rogers, Kathy Petoumenos, John Chuah, Nicole Easey, Kirsty Machon, Andrew Carr
    Abstract:

    BACKGROUND: Facial Lipoatrophy can stigmatize and can reduce quality of life, self esteem, and antiretroviral adherence. Poly-L-lactic acid (PLA) injections seem safe and effective, but no randomized study has included objective endpoints. METHODS: HIV-positive adults with moderate/severe facial Lipoatrophy were randomized to 4 open-label PLA treatments administered every 2 weeks from week 0 (immediate group, n = 51) or after week 24 (deferred group, n = 50). The primary endpoint was mean change in facial soft tissue volume (FSTV), as assessed by spiral computed tomography. Analyses were by intention to treat. RESULTS: At week 24, mean changes in FSTV were 0 cm in the intermediate group and -10 cm in the deferred group (between-group difference of 10 [95% confidence interval (CI): -7 to 28] cm; P = 0.24). The immediate group had a greater mean change in soft tissue depth at the maxilla (2.2 mm [95% CI: 1.6 to 2.9]; P < 0.0001) and base of the nasal septum (1.0 mm [95% CI: 0.3 to 1.6]; P = 0.003) levels. PLA did not have an impact on peripheral fat mass, viral load, or antiretroviral adherence. Patient and physician subjectively assessed facial Lipoatrophy severity (P < 0.0001), 2 of 8 Short Form-36 Health Survey and 2 of 5 Multidimensional Body-Self Relations Questionnaire-Appearance Scales, scores improved significantly. The median duration of treatment-related adverse events was 2 (interquartile range: 1 to 3) days. CONCLUSIONS: PLA did not increase FSTV, although tissue thickness in injection planes increased modestly, an improvement observed by patients. PLA was safe and well tolerated. Facial Lipoatrophy severity and some quality-of-life domains improved.

  • evaluation of ultrasound for assessing facial Lipoatrophy in a randomized placebo controlled trial
    AIDS, 2005
    Co-Authors: Dianne Carey, Sean Emery, Allison Martin, Handan Wand, Sharyn Rothwell, David A Cooper, Andrew Carr
    Abstract:

    We investigated the utility of ultrasonography for assessing facial Lipoatrophy changes in HIV-infected adults receiving antiretroviral therapy who participated in a 48-week, randomized, placebo-controlled trial of rosiglitazone. Ultrasound was performed at weeks 0, 24 and 48 to determine the subcutaneous fat thickness over the malar bone. Changes in facial fat assessed by ultrasonography did not correlate significantly with more established objective measures of Lipoatrophy severity. The measurement of malar fat using ultrasonography is not recommended.

  • no effect of rosiglitazone for treatment of hiv 1 Lipoatrophy randomised double blind placebo controlled trial
    The Lancet, 2004
    Co-Authors: Andrew Carr, Matthew Law, Katherine Samaras, Cassy Workman, Allison Martin, Dianne Carey, Handan Wand, David Baker, Gary David Rogers, Sean Emery
    Abstract:

    Summary Background Lipodystrophy commonly complicates antiretroviral therapy of HIV-1 infection. Thiazolidinediones such as rosiglitazone promote subcutaneous fat growth in type 2 diabetics and adults with congenital lipodystrophy, and can prevent HIV-1 protease inhibitor toxicity to adipocytes in vitro. We postulated that rosiglitazone would improve HIV Lipoatrophy. Methods 108 HIV-1-infected lipoatrophic adults on antiretroviral therapy were randomised to rosiglitazone 4 mg twice daily (n=53) or matching placebo (n=55) for 48 weeks. The study had 80% power to detect a 0·5 kg difference in changes in limb fat (using dual-energy X-ray absorptiometry) between groups at week 48 by intention-to-treat analysis, and a 0·7 kg difference within each protease inhibitor stratum. Findings Limb fat increased by 0·14 kg in the rosiglitazone group and 0·18 kg in the placebo group (mean difference –0·04 kg [95%CI –0·29 to 0·21]; p=0·74 by t test), with three participants (one on rosiglitazone and two controls), lost to follow-up. Rosiglitazone had no significant benefit on any other measure of lipodystrophy, despite large relative increases in plasma adiponectin (4·2 mmol/L [102%]; p Interpretation Rosiglitazone for 48 weeks did not improve Lipoatrophy in HIV-1-infected adults receiving antiretroviral therapy. Use of less toxic antiretroviral treatment is necessary to prevent Lipoatrophy.

  • hiv lipodystrophy prevalence severity and correlates of risk in australia
    Hiv Medicine, 2003
    Co-Authors: John Miller, Andrew Carr, Sean Emery, Matthew Law, S Mallal, Dewleen G Baker, Don Smith, John M Kaldor
    Abstract:

    Objective To establish the prevalence, severity and factors associated with the HIV lipodystrophy syndrome. Methods Cross-sectional study of lipodystrophy conducted in high HIV caseload primary care sites and HIV outpatient clinics. A subset of patients was examined using dual energy X-ray absorptiometry (DEXA) and single cut abdominal computerized tomography (CT) at the L4 vertebral level to quantify regional and total body fat. Factors associated with lipodystrophy, Lipoatrophy and lipohypertrophy were assessed using multiple logistic regression based on assignment of cases and non-cases. Results One thousand, three hundred and forty-eight patients (95% male) were surveyed, 20% had AIDS, the mean CD4 lymphocyte count was 486 cells/μL, and 55% had <500 HIV-1 RNA copies/mL. Most participants (87%) had previously received or were currently receiving combination antiretroviral therapy, 73% with at least one protease inhibitor (PI) and 14% a non-PI-containing regimen. Lipodystrophy prevalence was 53% and of these, 55% reported both peripheral Lipoatrophy and central lipohypertrophy, 31% experienced peripheral Lipoatrophy only and 14% had central lipohypertrophy only. The prevalence of any body habitus change was 62% in PI-experienced patients, 33% in PI-naive patients and 21% in antiretroviral-naive patients. Lipodystrophy severity was less in antiretroviral-naive patients and most severe in PI-experienced patients. Increasing severity of lipodystrophy was both positively and significantly correlated with elevated liver enzymes, decreased testosterone levels, decreased skin-fold thickness, lower levels of total and peripheral fat (DEXA) and higher levels of visceral fat (CT). Lipodystrophy was also significantly associated with increasing age, symptomatic HIV disease, effective viral suppression, and increasing duration of therapy with both nucleoside reverse transcriptase inhibitors and PIs. Conclusions The prevalence and severity of lipodystrophy reflects both length and type of treatment with antiretroviral therapy and is associated with decreased testosterone, increases in liver enzymes and greater suppression of HIV RNA. The reports of lipodystrophy in a small percentage of antiretroviral-naive patients suggests that factors other than antiretroviral therapy may be involved in the aetiology of this syndrome or that some conditions, such as wasting or age-associated obesity, may mimic Lipoatrophy and lipohypertrophy, respectively.

Christos S Mantzoros - One of the best experts on this subject based on the ideXlab platform.

  • narrative review the role of leptin in human physiology emerging clinical applications
    Annals of Internal Medicine, 2010
    Co-Authors: Theodore Kelesidis, Iosif Kelesidis, Sharon H Chou, Christos S Mantzoros
    Abstract:

    Leptin is a hormone secreted by adipose tissue in direct proportion to amount of body fat. The circulating leptin levels serve as a gauge of energy stores, thereby directing the regulation of energy homeostasis, neuroendocrine function, and metabolism. Persons with congenital deficiency are obese, and treatment with leptin results in dramatic weight loss through decreased food intake and possible increased energy expenditure. However, most obese persons are resistant to the weight-reducing effects of leptin. Recent studies suggest that leptin is physiologically more important as an indicator of energy deficiency, rather than energy excess, and may mediate adaptation by driving increased food intake and directing neuroendocrine function to converse energy, such as inducing hypothalamic hypogonadism to prevent fertilization. Current studies investigate the role of leptin in weight-loss management because persons who have recently lost weight have relative leptin deficiency that may drive them to regain weight. Leptin deficiency is also evident in patients with diet- or exercise-induced hypothalamic amenorrhea and Lipoatrophy. Replacement of leptin in physiologic doses restores ovulatory menstruation in women with hypothalamic amenorrhea and improves metabolic dysfunction in patients with Lipoatrophy, including Lipoatrophy associated with HIV or highly active antiretroviral therapy. The applications of leptin continue to grow and will hopefully soon be used therapeutically.

  • recombinant methionyl human leptin therapy in replacement doses improves insulin resistance and metabolic profile in patients with Lipoatrophy and metabolic syndrome induced by the highly active antiretroviral therapy
    The Journal of Clinical Endocrinology and Metabolism, 2006
    Co-Authors: Jennifer Lee, Jean L Chan, Epaminondas Sourlas, Vassilios Raptopoulos, Christos S Mantzoros
    Abstract:

    Context: Highly active antiretroviral therapy (HAART) for HIV-1 infection has been associated with a metabolic syndrome characterized by insulin resistance, hyperlipidemia, and redistribution of body fat (lipodystrophy). A subset of patients with predominant Lipoatrophy has low levels of the adipocyte-secreted hormone leptin. Objective: The objective of the study was to assess whether administration of recombinant methionyl human leptin (r-metHuLeptin) improves insulin resistance and other metabolic abnormalities in HIV+ leptin-deficient subjects with HAART-induced Lipoatrophy. Design, Setting, Patients, and Intervention: We conducted a randomized, placebo-controlled, double-blinded, crossover study from 2002 to 2004 in seven HIV+ men with HAART-induced Lipoatrophy, serum leptin level less than 3 ng/ml, and fasting triglyceride level greater than 300 mg/dl, who were administered placebo for 2 months before or after administration of r-metHuLeptin at physiological doses for an additional 2 months. Main Out...

  • human immunodeficiency virus type 1 related Lipoatrophy and lipohypertrophy are associated with serum concentrations of leptin
    Clinical Infectious Diseases, 2003
    Co-Authors: Sonia G Nagy, Sotirios Tsiodras, Lizabeth Martin, Anchalee Avihingsanon, Alina Gavrila, William C Hsu, Adolf W Karchmer, Christos S Mantzoros
    Abstract:

    The relationship between the adipocyte-derived hormone leptin, insulin resistance, and fat redistribution in patients with human immunodeficiency virus (HIV) infection has not been established. We classified a cohort of HIV type 1 (HIV-1)-infected patients with >or=6 months of antiretroviral exposure as having no lipodystrophy (51 patients [43% of the cohort]), Lipoatrophy (23 patients [19% of the cohort]), mixed lipodystrophy (29 patients [24% of the cohort]), or lipohypertrophy (17 patients [14% of the cohort]), on the basis of physical examination, anthropometric measurements, and the findings of dual-emission x-ray absorptiometry and computed tomography. Measurements of insulin resistance were higher for patients with each category of lipodystrophy, compared with those observed for patients with no lipodystrophy (P<.001). Mean leptin levels (+/- standard deviation) were lowest in patients with Lipoatrophy (1.76+/-1.20 ng/mL), highest in patients with lipohypertrophy (9.10+/-6.86 ng/mL), and significantly different from those in patients without lipodystrophy (3.14+/-2.30 ng/mL; both P<.01). In this cohort of antiretroviral-experienced HIV-infected patients, a low serum level of leptin was independently associated with insulin resistance in patients with Lipoatrophy, after controlling for total and regional body fat.

Grace A Mccomsey - One of the best experts on this subject based on the ideXlab platform.

  • changes in fat mitochondrial dna and function in subjects randomized to abacavir lamivudine or tenofovir df emtricitabine with atazanavir ritonavir or efavirenz aids clinical trials group study a5224s substudy of a5202
    The Journal of Infectious Diseases, 2013
    Co-Authors: Grace A Mccomsey, Eric S Daar, Maryann Oriordan, Ann C Collier, Lisa A Kosmiski, Jorge Santana, Carl J Fichtenbaum, Heidi Fink, Daniel E Libutti, Mariana Gerschenson
    Abstract:

    Patients with human immunodeficiency virus type 1 (HIV-1) infection receiving thymidine nucleoside reverse-transcriptase inhibitors (NRTIs) experience a high rate of metabolic abnormalities, including Lipoatrophy. Depletion of adipose tissue mitochondrial DNA (mtDNA) and impairment of the oxidative phosphorylation system are associated with Lipoatrophy induced by thymidine NRTI–containing regimens [1]. Mitochondrial oxidative phosphorylation enzymes nicotinamide adenine dinucleotide (reduced; NADH) dehydrogenase (complex I) and cytochrome c oxidase (complex IV) contain polypeptides of mtDNA-encoded subunits and so are affected by mtDNA depletion. In the current era of nonthymidine NRTI–containing regimens, Lipoatrophy incidence has significantly decreased but has not been completely prevented [2]. In addition, subjects who have established Lipoatrophy while taking thymidine NRTI–containing regimens experience only a slow and incomplete resolution of Lipoatrophy after switching to nonthymidine NRTI–based therapy [3–5], putting into question the mitochondrial toxicity–free characteristics of nonthymidine NRTIs. Prospective randomized studies have also yielded conflicting findings about the independent effects on mitochondria of other antiretroviral therapy (ART) classes, such as nonnucleoside analogue reverse-transcriptase inhibitor (NNRTI) or protease inhibitor (PI) therapy. Because of the remaining uncertainty about the effect of nonthymidine NRTI–containing regimens on mitochondrial toxicity and the potential effect of the concomitant PI or NNRTI therapy, we sought to compare changes in mitochondrial indices in the context of a randomized trial.

  • uridine supplementation in the treatment of hiv Lipoatrophy results of actg 5229
    AIDS, 2010
    Co-Authors: Grace A Mccomsey, Ulrich A Walker, Lisa A Kosmiski, Chakra Budhathoki, Judith S Currier, Linda Naini, Stephannie Charles, Kathy Medvik, Judith A Aberg
    Abstract:

    Lipoatrophy is prevalent on thymidine nucleoside reverse transcriptase inhibitors (tNRTIs). A pilot trial showed that uridine (NucleomaxX) increased limb fat.

  • endothelial activation markers are linked to hiv status and are independent of antiretroviral therapy and Lipoatrophy
    Journal of Acquired Immune Deficiency Syndromes, 2008
    Co-Authors: Allison C Ross, Maryann Oriordan, Rachel Armentrout, Norma Storer, Nesrine Rizk, Danielle Harrill, Dalia El Bejjani, Grace A Mccomsey
    Abstract:

    Objectives: To assess the association of inflammatory and endothelial activation biomarkers with the presence of Lipoatrophy in HIV-infected subjects and to examine the role of HIV, antiretroviral therapy (ART), and metabolic parameters in endothelial activation and inflammation. Design: Prospective, cross-sectional study including 4 groups: HIV+ on ART with HIV-1 RNA <1000 copies/mL with and without clinical Lipoatrophy, HIV+ ART naive, and healthy controls. Methods: We measured plasma levels of inflammatory cytokines (tumor necrosis factor-a, soluble tumor necrosis factor receptors I and II, interleukin-6, C-reactive protein, and myeloperoxidase) and endothelial activation markers (soluble intercellular and vascular cell adhesion molecules and von Willebrand factor). Results: We enrolled 182 subjects. Limb fat and Lipoatrophy status were not correlated with endothelial markers. Endothelial markers were higher in HIV+ ART naive when compared with healthy controls and with HIV+ on ART but were similar between HIV+ on ART and healthy controls. Neither endothelial nor inflammatory markers were correlated with HIV duration, CD4 count, lipids, glucose, or specific ART. Strong correlations were found between some inflammatory cytokines and endothelial markers. Conclusions: There is enhanced endothelial activation in ART naive, whereas HIV+ on ART has similar values to healthy controls. Lipoatrophy did not seem to affect endothelial activation. Results highlight a potential association between heightened inflammation and endothelial activation.

  • improvement in Lipoatrophy associated with highly active antiretroviral therapy in human immunodeficiency virus infected patients switched from stavudine to abacavir or zidovudine the results of the tarheel study
    Clinical Infectious Diseases, 2004
    Co-Authors: Grace A Mccomsey, Douglas J. Ward, Siegrid M Hessenthaler, Michael Sension, Peter Shalit, Tyler J Lonergan, Robin L Fisher, Vanessa C Williams, Jaime E Hernandez
    Abstract:

    Stavudine use is a contributing factor for Lipoatrophy, whereas use of abacavir or zidovudine is less likely to cause this complication. The TARHEEL study was a 48-week, open-label study that assessed changes in Lipoatrophy after abacavir (86 patients [73%]) or zidovudine (32 patients [27%]), 300 mg twice daily, was substituted for stavudine for 118 human immunodeficiency virus (HIV)‐infected patients (HIV type 1 RNA level, !400 copies/mL) with virological suppression who had developed Lipoatrophy after 6 months of stavudine-based treatment. At week 48, full-body dual-energy x-ray absorptiometry demonstrated a median increase in arm fat of 35%, leg fat of 12%, and trunk fat of 18%, compared with the baseline level. These improvements coincided with fat gain in lipoatrophic areas that was documented by computerized tomography. Results of a “body image” questionnaire showed that a substantial percentage of patients reported some or a lot of fat gain in the arms (22%), legs (18%), buttocks (19%), and face (27%). HIV suppression was maintained over the study period. In conclusion, replacing stavudine with abacavir or zidovudine resulted in improvement in stavudine-induced Lipoatrophy.

  • lipid oxidative markers are significantly increased in Lipoatrophy but not in sustained asymptomatic hyperlactatemia
    Journal of Acquired Immune Deficiency Syndromes, 2003
    Co-Authors: Grace A Mccomsey, Jason D Morrow
    Abstract:

    The exact mechanism of Lipoatrophy remains unclear. One hypothesized mechanism is accumulation of reactive oxygen free radicals, which is possibly related to dysfunctional mitochondria. We evaluated plasma levels of F2-isoprostanes-the most accurate method to measure oxidant stress in vivo-in a group of 59 nucleoside reverse transcriptase inhibitor-treated HIV-1-infected subjects. All had serial measurements of venous lactate levels as well as clinical evaluations for assessment of Lipoatrophy and symptoms of mitochondrial toxicity. Overall, 16 subjects had sustained hyperlactatemia (4 of whom were symptomatic) and 43 had serial normal lactate levels. We found a significant increase in circulating products of lipid peroxidation, F2-isoprostanes (nanograms per milliliter), in subjects with Lipoatrophy when compared with subjects without Lipoatrophy (0.060 +/- 0.025 vs. 0.0420 +/- 0.02, respectively; P = 0.02). Interestingly, there was no significant difference in F2-isoprostane levels (nanograms per milliliter) between patients with persistently normal lactate and those who exhibited a sustained asymptomatic hyperlactatemia (0.053 +/- 0.027 vs. 0.053 +/- 0.021, respectively; P > 0.05). This could be explained by the yet unclear significance of asymptomatic hyperlactatemia, even in a setting like ours, where lactate levels were measured with close attention to the method of collection and processing. In contrast, the 4 subjects with symptomatic hyperlactatemia/lactic acidosis had a significant increase in their F2-isoprostanes compared with subjects with asymptomatic sustained hyperlactatemia (0.082 +/- 0.021 vs. 0.053 +/- 0.021, respectively; P < 0.05).

Ulrich A Walker - One of the best experts on this subject based on the ideXlab platform.

John Miller - One of the best experts on this subject based on the ideXlab platform.

  • hiv lipodystrophy prevalence severity and correlates of risk in australia
    Hiv Medicine, 2003
    Co-Authors: John Miller, Andrew Carr, Sean Emery, Matthew Law, S Mallal, Dewleen G Baker, Don Smith, John M Kaldor
    Abstract:

    Objective To establish the prevalence, severity and factors associated with the HIV lipodystrophy syndrome. Methods Cross-sectional study of lipodystrophy conducted in high HIV caseload primary care sites and HIV outpatient clinics. A subset of patients was examined using dual energy X-ray absorptiometry (DEXA) and single cut abdominal computerized tomography (CT) at the L4 vertebral level to quantify regional and total body fat. Factors associated with lipodystrophy, Lipoatrophy and lipohypertrophy were assessed using multiple logistic regression based on assignment of cases and non-cases. Results One thousand, three hundred and forty-eight patients (95% male) were surveyed, 20% had AIDS, the mean CD4 lymphocyte count was 486 cells/μL, and 55% had <500 HIV-1 RNA copies/mL. Most participants (87%) had previously received or were currently receiving combination antiretroviral therapy, 73% with at least one protease inhibitor (PI) and 14% a non-PI-containing regimen. Lipodystrophy prevalence was 53% and of these, 55% reported both peripheral Lipoatrophy and central lipohypertrophy, 31% experienced peripheral Lipoatrophy only and 14% had central lipohypertrophy only. The prevalence of any body habitus change was 62% in PI-experienced patients, 33% in PI-naive patients and 21% in antiretroviral-naive patients. Lipodystrophy severity was less in antiretroviral-naive patients and most severe in PI-experienced patients. Increasing severity of lipodystrophy was both positively and significantly correlated with elevated liver enzymes, decreased testosterone levels, decreased skin-fold thickness, lower levels of total and peripheral fat (DEXA) and higher levels of visceral fat (CT). Lipodystrophy was also significantly associated with increasing age, symptomatic HIV disease, effective viral suppression, and increasing duration of therapy with both nucleoside reverse transcriptase inhibitors and PIs. Conclusions The prevalence and severity of lipodystrophy reflects both length and type of treatment with antiretroviral therapy and is associated with decreased testosterone, increases in liver enzymes and greater suppression of HIV RNA. The reports of lipodystrophy in a small percentage of antiretroviral-naive patients suggests that factors other than antiretroviral therapy may be involved in the aetiology of this syndrome or that some conditions, such as wasting or age-associated obesity, may mimic Lipoatrophy and lipohypertrophy, respectively.

  • a syndrome of Lipoatrophy lactic acidaemia and liver dysfunction associated with hiv nucleoside analogue therapy contribution to protease inhibitor related lipodystrophy syndrome
    AIDS, 2000
    Co-Authors: John Miller
    Abstract:

    BACKGROUND: Lipodystrophy (LD; peripheral Lipoatrophy, central adiposity) hyperlipidaemia and insulin resistance often complicate protease inhibitor-containing antiretroviral therapy. Lipoatrophy and abdominal distension were observed in protease inhibitor-naive nucleoside analogue reverse transcriptase inhibitor (NRTI) recipients with lactic acidaemia and hepatic impairment, which are known NRTI-induced mitochondrial toxicities. DESIGN AND SETTING: Case-control study in a university-based outpatient clinic. PATIENTS AND METHODS: The patients studied included 14 NRTI recipients with Lipoatrophy, 32 antiretroviral-naive patients without LD, 28 NRTI recipients without LD, 44 combined NRTI-protease inhibitor recipients without LD, and 102 NRTI-protease inhibitor recipients with LD. Data was obtained on body composition (questionnaire, physical examination, dual-energy x-ray absorptiometry and abdominal computerized tomography), with biochemical, lipid and glycaemic parameters. RESULTS: The NRTI-LD syndrome was characterized by recent onset fatigue and nausea, peripheral Lipoatrophy (6 kg loss over 4 months), abdominal distension (ascites +/- hepatomegaly) and elevated lactate (4.6, 1.1, 1.2, 1.4 and 1.7 mmol/l, respectively; P< 0.0001) and liver enzymes. Cases without hepatic involvement also had lower body fat and greater lactate than unaffected controls. Metabolic disturbances and weight improved after cessation. The NRTI-LD syndrome differed from protease inhibitor-related LD syndrome by the presence of recent onset symptoms and weight loss, higher lactate and alanine aminotransferase, and lower albumin, cholesterol, triglycerides, glucose and insulin. In treated controls, current stavudine therapy, protease inhibitor duration, and lactic acidaemia were independently associated with both Lipoatrophy and abdominal obesity; total NRTI duration was also associated with Lipoatrophy, and lamivudine and protease inhibitor duration with buffalo hump. CONCLUSIONS: A syndrome of Lipoatrophy, constitutional illness, lactic acidaemia and hepatic dysfunction can complicate NRTI therapy. Both protease inhibitor and NRTI therapies, particularly if associated with lactic acidaemia, contribute to LD syndrome, but have some distinguishable clinical and metabolic effects.