indinavir-sulfate and Lipodystrophy

Fat redistribution (FR) occurring alone or in association with hyperlipidemia has been associated with protease inhibitors (PI) and nucleoside reverse transcriptase inhibitors (NRTIs); however, the relationship between FR features, relationship of FR to hyperlipidemia, and pathogenesis of FR is unknown.. To characterize the spectrum of FR, assess relationships among FR features, determine trends in occurrence of FR, and determine relationship of FR to hyperlipidemia.. Review of postmarketing indinavir reports of FR in Merck & Co. Inc.'s database.. 282 reports of FR among HIV-positive patients taking indinavir submitted through the passive postmarketing system to Merck through February 23, 1998.. 282 FR reports were compared across 3 groups: fat accumulation (FA) only, FA with peripheral wasting (FA with PW), and peripheral wasting only (PWO). Of 282 reports, 56% (159 of 282) had FA only, 22% (63 of 282) had FA with PW, and 21% (60 of 282) had PWO. The proportions of reports of PWO was higher in men, whereas the proportion of reports of FA was higher in women. Blood lipids were provided in 93 of 282 reports; were elevated in 69 of 93, and were normal in 24 of 93 reports. Proportions of hyperlipidemia and hypertriglyceridemia reports were significantly higher in the PWO group versus FA only group (p =.024 and.003, respectively) and versus FA with/without PW groups (p =.038 and.005, respectively). Weight gain was more frequently reported in those with FA (100%) or FA with PW (68%), whereas weight loss was usually reported in those with PWO (83%). In all, 98% of patients reporting FR on indinavir for whom a concomitant drug history was available were also taking lamivudine, stavudine, or both. A higher proportion of patients reporting PWO (34 of 60; 56.7%) versus FA (42 of 159; 26.4%) only took both lamivudine and stavudine.. Differences observed from analysis of cases in clinical features, gender, weight change, concomitant medications, and presence of hyperlipidemia among the three groups of FR cases reported to Merck suggests that PWO may be a distinct entity from other features of FR. The data suggest that certain antiretroviral combinations predispose HIV persons to development of FR.

Topics: Adipose Tissue; Adult; Aged; Body Composition; Databases, Factual; Drug Industry; Drug Monitoring; Female; HIV Infections; HIV Protease Inhibitors; Humans; Indinavir; Lipodystrophy; Male; Middle Aged

Protease inhibitors (PIs) effectively inhibit replication of the human immunodeficiency virus (HIV), and reduce mortality and prolong survival in patients with HIV infection. Newer PIs saquinavir (soft gelatin capsule) and amprenavir, as well as other PIs, may be effective when administered twice/day. Adverse reactions may occur, as well as metabolic complications and interactions between PIs and other drugs, including other PIs. The strategy of combining PIs is based on specific pharmacologic interactions among the agents.

Topics: Drug Interactions; HIV Infections; HIV Protease Inhibitors; Humans; Hyperlipidemias; Indinavir; Lipodystrophy; Nelfinavir; Ritonavir; Saquinavir

To compare information on body fat changes from questionnaire and clinical examination and to study lipoatrophy in HIV-1 patients on highly active antiretroviral therapy (HAART).. The study was cross-sectional within a randomized trial. One hundred and sixty-eight male HIV-1 patients were examined by questionnaire and clinical examination. Clinical lipoatrophy was studied and defined as fat wasting in the face, legs and/or arms. Fasting blood samples reflecting lipid and glucose metabolism were taken and the role of indinavir, ritonavir (RTV) and RTV/saquinavir (SQV) on lipoatrophy was investigated.. After a median of 17 months on HAART, concordance rates between information on changes in body fat from questionnaire and clinical examination were significant and varied from 70 to 96%. With a positive criteria of lipoatrophy in both assessments, 14% of patients had lipoatrophy. These patients had lower weight (P = 0.0007), weight loss from baseline (P = 0.003), lower circumferences at all measurements (P < 0.01), lower plasma triglycerides and low-density lipoprotein (LDL) (P < 0.05) and longer treatment with stavudine (P = 0.0009). Homeostasis model assessment (HOMA) estimates for insulin resistance and beta-cell function were comparable. Plasma cholesterol, triglycerides and very low-density lipoprotein (VLDL) were higher in patients receiving RTV or RTV/SQV (P < 0.03).. Questionnaire and clinical assessment provide concordant information on changes in body fat. Lipoatrophic patients on HAART with neither increase in abdominal circumference, nor hyperlipidaemia nor glucose intolerance may have side-effects to protease inhibitor treatment, to nucleoside reverse transcriptase inhibitor treatment (stavudine) or suffer from a drug-independent condition.

Topics: Adult; Aged; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Body Composition; Cross-Sectional Studies; Drug Therapy, Combination; Glucose Intolerance; HIV Infections; HIV Protease Inhibitors; HIV Wasting Syndrome; Humans; Hyperlipidemias; Indinavir; Lipodystrophy; Male; Middle Aged; Ritonavir; Saquinavir; Stavudine; Surveys and Questionnaires

Subcutaneous adipocyte apoptosis occurs in lipotrophic areas of patients with highly active antiretroviral therapy (HAART)-associated lipodystrophy. Fourteen patients with HAART-associated lipodystrophy had 2 subcutaneous biopsies for evidence of adipocyte apoptosis, the second after a randomized change to nevirapine (n=8) or after remaining on a regimen of indinavir-based HAART (n=6). Apoptosis was assessed by the terminal deoxynucleotidyl transferase dUTP-digoxigenin nick end-labeling method. Patients who were switched to nevirapine had a significant decrease in insulinemia and a significant increase in the glucose:insulin ratio. Overall, subcutaneous adipocyte apoptosis increased in 3 patients who were switched to nevirapine and in 3 who continued to receive indinavir but decreased in 2 patients switched to nevirapine and another 2 who continued to receive indinavir. Subcutaneous adipocyte apoptosis continues to occur in lipotrophic areas of patients with HAART-associated lipodystrophy despite switching from indinavir to nevirapine, suggesting that such a strategy will be useless for reversal of lipoatrophy.

Topics: Adipocytes; Adult; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Apoptosis; Blood Glucose; Female; HIV Infections; Humans; In Situ Nick-End Labeling; Indinavir; Insulin; Lipodystrophy; Male; Middle Aged; Nevirapine; Reverse Transcriptase Inhibitors

Topics: Adult; Drug Therapy, Combination; HIV Infections; HIV Protease Inhibitors; Humans; Indinavir; Lamivudine; Lipodystrophy; Male; Reverse Transcriptase Inhibitors; Zidovudine

HIV protease inhibitor-related lipodystrophy is characterized by peripheral fat loss, hyperlipidemia, and insulin resistance. Increased availability of lipid to muscle may be one of the mechanisms that induce insulin resistance. Regional fat, intramyocellular lipid (by (1)H-magnetic resonance spectroscopy), serum lipids, and insulin-stimulated glucose disposal (by hyperinsulinemic-euglycemic clamp) were quantified in 10 men who had HIV-1 infection with moderate to severe lipodystrophy and a control group of 10 nonlipodystrophic men who had HIV-1 infection and were naïve to protease inhibitors to examine the effects of lipodystrophy on glucose and lipid metabolism. Lipodystrophic subjects showed lower insulin-stimulated glucose disposal than control subjects (P = 0.001) and had increased serum triglycerides (P = 0.03), less limb fat (P = 0.02), increased visceral fat as a proportion of total abdominal fat (P = 0.003), and increased intramyocellular lipid (1.90 +/- 0.15 vs. 1.23 +/- 0.16% of water resonance peak area; P = 0.007). In both groups combined, visceral fat related strongly to intramyocellular lipid (r = 0.83, P < 0.0001) and intramyocellular lipid related negatively to insulin-stimulated glucose disposal (r = -0.71, P = 0.0005). Fasting serum cholesterol and triglycerides related positively to intramyocellular lipid and visceral fat in lipodystrophic subjects only. The data indicate that lipodystrophy is associated with increased lipid content in muscle accompanying impaired insulin action. The results do not establish causation but emphasize the interrelationships among visceral fat, myocyte lipid, and insulin action.

Topics: Absorptiometry, Photon; Acquired Immunodeficiency Syndrome; Adipose Tissue; Adult; Anti-HIV Agents; Blood Glucose; Body Composition; HIV Protease Inhibitors; Homeostasis; Humans; Indinavir; Insulin; Leptin; Lipids; Lipodystrophy; Magnetic Resonance Imaging; Male; Middle Aged; Nelfinavir; Ritonavir; Saquinavir

Highly active antiretroviral therapy in HIV-1 infected patients is associated with a lipodystrophy syndrome, characterized by wasting of peripheral fat, central adiposity, hyperlipidaemia and insulin resistance. The CT findings are presented and the differential diagnosis is discussed.

Topics: Adult; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Body Mass Index; HIV Infections; Humans; Indinavir; Lamivudine; Lipodystrophy; Male; Tomography, X-Ray Computed; Treatment Outcome; Zidovudine

To identify clinical factors associated with prevalence of fat atrophy (lipoatrophy) and fat accumulation (lipoaccumulation) in HIV-1 infected patients.. Evaluation of HIV-1 infected patients seen for routine care between 1 October and 31 December 1998 in the eight HIV Outpatient Study (HOPS) clinics.. Eight clinics specializing in the care of HIV-1 infected patients.. A total of 1077 patients were evaluated for signs of fat maldistribution.. A standardized set of questions and specific clinical signs were assessed. Demographic, clinical and pharmacological data for each patient were also included in the analysis.. Demographic, immunologic, virologic, clinical, laboratory, and drug treatment factors were assessed in stratified and multivariate analyses for their relationship to the presence and severity of fat accumulation and atrophy.. Independent factors for moderate/severe lipoatrophy for 171 patients were increasing age, any use of stavudine, use of indinavir for longer than 2 years, body mass index (BMI) loss, and measures of duration and severity of HIV disease. Independent risk factors for moderate/severe fat accumulation for 104 patients were increasing age, BMI gain, measures of amount and duration of immune recovery, and duration of antiretroviral therapy (ART). The number of non-drug risk factors substantially increased the likelihood of lipoatrophy. If non-drug risk factors were absent, lipoatrophy was unusual regardless of the duration of drug use.. HIV-associated lipodystrophy is associated with several host, disease, and drug factors. While prevalence of lipoatrophy increased with the use of stavudine and indinavir, and lipoaccumulation was associated with duration of ART, other non-drug factors were strongly associated with both fat atrophy and accumulation.

Topics: Acquired Immunodeficiency Syndrome; Adult; Age Factors; Anti-HIV Agents; Body Mass Index; CD4 Lymphocyte Count; Cohort Studies; Data Interpretation, Statistical; Female; HIV Protease Inhibitors; Humans; Indinavir; Lipodystrophy; Male; Middle Aged; Prevalence; Reverse Transcriptase Inhibitors; Risk Factors; Stavudine; Viral Load

Topics: Adult; Blood Glucose; HIV Infections; HIV Protease Inhibitors; Humans; Indinavir; Insulin; Lipodystrophy; Male

Since the availability of protease inhibitors in 1997, there has been a great change in antiretroviral therapy but also new long term side effects have emerged, mainly metabolic changes such as hypertriglyceridemia, hypercholesteremia and hyperglycemia. Besides, fat redistribution has been observed. Fat wastes in the face and limbs but accumulates in the adipose tissue of the dorsocervical and abdominal region and the breasts. The mechanism of these changes remains unclear. For therapy a protease inhibitor free therapy or lipid lowering drugs may be tried. 29 of our 224 patients developed lipodystrophy. 27 of these patients had been treated with a protease inhibitor (17 patients with indinavir); 2 of the patients had never received protease inhibitors.

Topics: Female; HIV Infections; HIV Protease Inhibitors; Humans; Hypercholesterolemia; Hyperglycemia; Hypertriglyceridemia; Indinavir; Lipodystrophy; Male; Syndrome

HIV-protease inhibitors demonstrated such high efficacy in short-term studies that they have been approved by the FDA, even though possible toxicity still needs further investigation. In the period between January 1997 and August 1998, 101 patients, staying at San Patrignano Medical Centre (Italy), received an HIV protease inhibitor (indinavir) plus two nucleoside reverse transcriptase inhibitors (NRTI's) selected from the following: AZT, didanosine, zalcitabine, lamivudine or stavudine. Seventy-three patients were male, 28 female and their ages ranged from 25 to 60 years, with an average of 34. At the end of the study, 84 patients were suitable for evaluation, as the other 17 dropped out for various reasons. Forty-eight patients (57.1%) developed cheilitis, 34 (40.5%) experienced diffuse cutaneous dryness and pruritus, 10 (11.9%) developed asteatotic dermatitis on the trunk, arms and thighs and another 10 (11.9%) complained of scalp defluvium. A severe alopecia was observed in only 1 patient (1.2%), while 6 reported that their body hair had become fairer, thinner and shed considerably. Multiple pyogenic granulomas were observed in the toenails of 5 patients (5. 9%). Softening of the nail plate was noted in 5 subjects as well. A peripheral lipodystrophy syndrome was noted in 12 patients (14.3%). Among these, one patient only developed a "buffalo hump" and another had diffused lipomatosis. The temporal relationship between the taking of indinavir and the onset of such cutaneous effects was striking. This was confirmed by the regression of symptoms in those patients who later discontinued indinavir. The emerging side effects of protease inhibitors require a multidisciplinary team for adequate diagnosis and treatment. Cutaneous toxicity involving the patient's own body image has a peculiar influence on compliance to the treatment and the patient's quality of life.

Topics: Adult; Alopecia; Didanosine; Drug Eruptions; Drug Therapy, Combination; Female; HIV; HIV Infections; HIV Protease Inhibitors; Humans; Indinavir; Lamivudine; Lipodystrophy; Male; Middle Aged; Pruritus; Pyoderma Gangrenosum; Retrospective Studies; Reverse Transcriptase Inhibitors; RNA, Viral; Scalp Dermatoses; Skin; Stavudine; Zalcitabine; Zidovudine

Topics: Anti-HIV Agents; Drug Therapy, Combination; HIV Infections; Humans; Indinavir; Lipodystrophy; Male; Middle Aged

The development of lipodystrophy as evidenced by central obesity, "moon facies," and a "buffalo hump" is a classical feature of Cushing's disease. Recently an association of "lipodystrophy" with the use of protease inhibitors has been reported. We describe a patient with lipodystrophy secondary to protease inhibitor therapy for HIV infection.

Topics: Female; HIV Protease Inhibitors; HIV Seropositivity; Humans; Indinavir; Lipodystrophy; Middle Aged; Neck

Lipodystrophy and other fat distribution disorders have been reported in patients receiving protease inhibitor therapy for HIV infection.. A 50-year-old HIV-positive patient was given protease inhibitor therapy (indinavir) for 6 months when he developed a lipomatous formation in the retrocervical area. Abdominal fat also increased in volume and the subcutaneous fat on the lower limbs decreased.. We describe the main clinical features of these fat distribution disorders and discuss the pathogenic hypothesis of an interaction between antiprotease activity and hepatic lipoprotein receptor binding.

Topics: Abdomen; Adipose Tissue; Anti-HIV Agents; Connective Tissue Diseases; HIV Protease Inhibitors; HIV Seropositivity; Humans; Indinavir; Leg; Lipodystrophy; Male; Middle Aged; Neck

Topics: Abdomen; Adult; Female; HIV Infections; HIV Protease Inhibitors; Humans; Indinavir; Lipodystrophy; Magnetic Resonance Imaging; Syndrome; Time Factors

Since 1997, new side effects like lipodystrophia have been described in HIV-1-infected patients treated with protease inhibitors. The evolution is not specified in the most reported cases.. A 44-year-old man treated for HIV 1 infection developed a Buffalo hump 12 months after initiating a new treatment including indinavir-protease inhibitor (Crixivan). Ten months later, we observe neither other fat accumulation nor fat loss and significant metabolic disorders.. Many publications emphasized the relationship that would exist between protease inhibitors therapy and the occurrence of lipodystrophia. Clinical features of this syndrome appear like an accumulation of fatty tissue anywhere on the trunk, or a fat loss on the limbs, the buttocks and the face. It is sometimes associated with metabolic disorders. The pathogenesis of these lipodystrophia is unclear. Larger studies have to be led to highlight the incidence of these lipodystrophia and their subsequent effects on the HIV-1 infection.

Topics: Adipose Tissue; Adult; HIV Protease Inhibitors; Humans; Indinavir; Lipodystrophy; Lipomatosis; Male; Neck

The objectives of this study were to document the prevalence of facial lipodystrophy in patients with HIV infection receiving protease inhibitors and to identify associated factors. All patients with HIV infection receiving protease inhibitors seen at an HIV clinic in Hong Kong during a 2-month period, from August to October 1997, were assessed for facial lipodystrophy. Among 29 patients who had been receiving indinavir for 3 months or more, facial lipodystrophy was found in 7 (24%). Facial lipodystrophy in these patients was found to be an isolated event and was not associated with noticeable wasting elsewhere. The development of facial lipodystrophy was not found to be associated with age, sex, ethnicity, route of HIV transmission, CD4 cell count, history of AIDS-defining illness, or concurrent anti-retroviral treatment. Facial lipodystrophy was not observed in patients who had received indinavir for less than 3 months. The condition was also not found in patients taking other protease inhibitors, although this could be due to the small sample size. Prospective study of this condition with a larger sample and with objective anthropomorphic measurements would be desirable. In conclusion, facial lipodystrophy is a common occurrence among patients receiving indinavir, and physicians should be alerted to this condition.

Topics: Adult; Face; Female; HIV Infections; HIV Protease Inhibitors; Hong Kong; Humans; Indinavir; Lipodystrophy; Male; Middle Aged; Prevalence; Retrospective Studies

Lipodystrophies are rare cutaneous disorders characterized by the symmetrical loss of subcutaneous fat from the body surface. The cause of lipodystrophy is not known, but a possible genetic predisposition is likely and either overt diabetes mellitus or insulin resistance are often associated.. Case study.. Eight patients who developed either partial or generalized lipodystrophy after protease inhibitor therapy.. In all eight patients lipodystrophy occurred after 2-12 months of starting indinavir and was not preceded by weight loss or inflammatory skin disease. Short-term follow-up after withdrawal of therapy showed no change in the patients' appearance. One patient developed glycosuria as lipodystrophy became manifest. In three cases glucose tolerance test was performed revealing a high level of insulin between the first and third hour of loading.. In our view, lipodystrophy is an unwanted side-effect of protease inhibitor therapy causing noticeable disfigurement.

Topics: Adult; Anti-HIV Agents; Female; HIV Infections; Humans; Indinavir; Lipodystrophy; Male; Middle Aged; Protease Inhibitors

To describe a syndrome of peripheral lipodystrophy (fat wasting of the face, limbs and upper trunk), hyperlipidaemia and insulin resistance in patients receiving potent HIV protease inhibitor therapy.. Cross-sectional study.. Outpatient clinic of a university teaching hospital.. HIV-infected patients either receiving at least one protease inhibitor (n=116) or protease inhibitor-naive (n=32), and healthy men (n=47).. Lipodystrophy was assessed by physical examination and questionnaire and body composition by dual-energy X-ray absorptiometry. Fasting triglyceride, cholesterol, free fatty acid, glucose, insulin, C-peptide and fructosamine levels, other metabolic parameters, CD4 lymphocyte counts, and HIV RNA load were also assessed.. HIV protease inhibitor-naive patients had similar body composition to healthy men. HIV protease inhibitor therapy was associated with substantially lower total body fat (13.2 versus 18.7 kg in protease inhibitor-naive patients; P=0.005), and significantly higher total cholesterol and triglyceride levels. Lipodystrophy was observed clinically in 74 (64%) protease inhibitor recipients after a mean 13.9 months and 1(3%) protease inhibitor-naive patient (P=0.0001). Fat loss occurred in all regions except the abdomen after a median 10 months. Patients with lipodystrophy experienced a relative weight loss of 0.5 kg per month and had significantly higher triglyceride, cholesterol, insulin and C-peptide levels and were more insulin-resistant than protease inhibitor recipients without lipodystrophy. Patients receiving ritonavir and saquinavir in combination had significantly lower body fat, higher lipids and shorter time to lipodystrophy than patients receiving indinavir. Three (2%) patients developed new or worsening diabetes mellitus.. A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance is a common complication of HIV protease inhibitors. Diabetes mellitus is relatively uncommon.

Topics: Adult; Anti-HIV Agents; Body Composition; Cross-Sectional Studies; Diabetes Mellitus; Female; HIV Infections; HIV Protease Inhibitors; Humans; Hyperlipidemias; Indinavir; Insulin Resistance; Lipodystrophy; Male; Nelfinavir; Risk Factors; Ritonavir; Saquinavir; Syndrome

Topics: Adipose Tissue; Anti-HIV Agents; Body Composition; Face; Female; Humans; Indinavir; Lipodystrophy; Male; Protease Inhibitors

Topics: Abdomen; Acquired Immunodeficiency Syndrome; Dilatation, Pathologic; Drug Therapy, Combination; HIV Protease Inhibitors; Humans; Indinavir; Lipodystrophy; Male; Middle Aged

Topics: HIV Infections; HIV Protease Inhibitors; Humans; Indinavir; Lipodystrophy; Male; Middle Aged

In three patients, a 36-year-old HIV seropositive homosexual man and two women aged 35 and 59 years who had acquired HIV infection through heterosexual contact, signs of lipodystrophy developed after prolonged anti-HIV triple therapy. The observed syndrome is seen after prolonged use of HIV protease inhibitors: it is characterized by peripheral fat wasting, central fat accumulation, hyperlipidaemia and insulin resistance. Typically the subcutaneous fatty tissue disappears resulting in prominent zygomata, veins and muscles and thinning of extremities and buttocks. In addition to abdominal fat accumulation, there have been reports on the occurrence of a dorsocervical fat pad, the so-called buffalo hump. Lipodystrophy caused by protease inhibitors is a risk factor for cardiovascular disease. Recognition of the syndrome is essential for adequate follow-up and possible treatment.

Topics: Adult; Cardiovascular Diseases; CD4 Lymphocyte Count; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; HIV Infections; HIV Protease Inhibitors; Humans; Hyperlipidemias; Indinavir; Insulin Resistance; Lipodystrophy; Male; Middle Aged; Nevirapine; Reverse Transcriptase Inhibitors; Treatment Outcome; Wasting Syndrome