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Published on 1 November 2006

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Metabolic syndrome and antiretroviral therapy

teaser

José Manuel Martínez Sesmero
PhD
Clinical Pharmacist
Department of Pharmacy
Hospital Virgen
de la Salud
Toledo
Spain
E:mano24@ono.com

Studies have shown that up to 40% of patients with HIV infection on different highly active antiretroviral therapy (HAART) regimens may experience metabolic abnormalities. The rates and types of these abnormalities vary by stage of HIV disease and by specific antiretrovirals.(2)

Protease inhibitors (PIs) are the most often implicated drug group,(3) but nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) have more recently been shown to play a role. These drugs, which have a variety of effects (Table 1), may be related to the pathogenesis of body fat changes. However, at present it is not known whether lipodystrophy is a unique syndrome or several different overlapping syndromes. Several metabolic features (such as dyslipidaemia and insulin resistance, as well as body fat abnormalities consisting of a generalised decrease in subcutaneous fat with or without intra-abdominal, breast or dorsocervical accumulation) have been commonly reported, although the intensity and associations of those changes have been highly variable.

[[HPE29_table1_61]]

Even in treatment-naive patients with HIV, abnormalities in lipid levels appear to be more common than in the general population. The aetiology of lipodystrophy is not known, but these changes may occur as a result of an inflammatory response to the virus or as a direct effect of the virus itself.(4) In addition, recent data also suggest that endothelial dysfunction and impaired fibrinolysis may also contribute to increased cardiovascular risk in this patient population.

HIV-associated lipodystrophy may affect up to half or even more of HIV-infected patients receiving HAART,(5) but metabolic syndrome prevalence is still not well known.

The major characteristics of metabolic syndrome include insulin resistance, abdominal obesity, elevated blood pressure and lipid abnormalities (ie, elevated levels of triglycerides and low levels of HDL-cholesterol). The combination of cardiovascular risk factors in the metabolic syndrome raises the question of its impact on future cardiovascular disease, thereby the identification of patients with metabolic syndrome might provide opportunities for initiation of coronary heart disease prevention strategies.

The objective of this study is to determine metabolic syndrome prevalence in our HIV-patients receiving HAART and the risk factors associated.

Methods
Data for 119 consecutive adult patients ­undergoing HAART dispensing were collected between 01/09/2005 and 30/0920/05. Data collected included sex, age, waist circumference, blood pressure, HAART regimens (3 NRTIs, 2 NRTIs + NNRTI, 2 NRTIs + PI, and others), duration of therapy (<12 months; ≥12 months and <60 months; ≥60 months), viral load, CD(4) cell count, fasting glucose, LDL-cholesterol, HDL-cholesterol and triglycerides. Metabolic syndrome was initially defined by an expert panel of the World Health Organization (WHO) in 1998, but NCEP ATP (Adult treatment panel)-III(6) has created an operational definition (see Table 2) taking into account abdominal obesity (defined as waist circumference >102cm in men and 88cm in women), atherogenic dyslipidaemia (triglycerides >150mg/dl, HDL-cholesterol <40mg/dl in men and <50mg/dl in women), blood pressure (130/85mmHg), insulin resistance indirectly measured by fasting plasma glucose of 100–125mg/dl,and prothrombotic and proinflammatory states. The presence of at least three of these components is needed to make a diagnosis of metabolic syndrome.

[[HPE29_table2_62]]

The statistical analysis was performed using descriptive statistics and binomial logistic regression (SPSS 10.0®). The dependent variable was metabolic syndrome (yes [1] or no [0]), and the independent variables were sex (male or female), age (years), HAART regimen (3 NRTIs [0], 2 NRTIs + NNRTI [1], 2 NRTIs + PI [2] and others [3]), duration of therapy (months), viral load (number of copies per ml), CD(4) cell count (number per μl).

Results
Of the 119 patients (82.4% male, 17.6% female; median age 41 years [minimum 24 years, maximum 75 years]; 8.9% 3 NRTIs, 50.4% 2 NRTIs + NNRTI, 38.7% 2 NRTIs + PI, 2% other combinations; duration of therapy 1.6% [< 12 months], 38.7% [≥12 months and <60 months], 59.7% [≥60 months]). Metabolic syndrome occurred in 16% (94.8% male, 5.2% female) of patients. Age was the only statistically significant variable in the logistic regression model (p=0.08, odds ratio=1.057).

Conclusions
The metabolic syndrome prevalence in this sample of patients seems to be similar to that of non-HIV patients in Spain (15.5%–19.3%),(7) but the comparison is difficult because of different definitions of the metabolic syndrome and the small number of HIV female patients in our setting. In this study, the relationship between metabolic syndrome and pharmacological risk factors is inconclusive, despite several studies suggesting that the effects on the lipid profile are specific to different antiretroviral drug classes.(2)

Available antiretroviral therapies may contribute to an increased future risk of coronary heart disease. This elevated risk may be explained at least in part by the development of metabolic syndrome in HIV patients on therapy. HIV patients receiving HAART present with a number of metabolic changes that need to be treated or modified. As is the case for non-HIV patients, strategies include lifestyle modifications and lipid-lowering drugs, and also the use of newer antiretroviral drugs with a better lipid profile.

References

  1. Obiamiwe C, Umeh MD, Judiht S.Curr HIV/AIDS Rep 2005;2:132-9.
  2. Calza L, Manfredi R, Farneti B,et al. Int J Antimicrob Agents 2003;22:54-9.
  3. Steven K, Grinspoon MD.Am J Med 2005;118:23S-28S.
  4. Hadigan C, Meigs JC, Corcoran C,et al. Clin Infect Dis 2001;32:130-9.
  5. Milinkovic A, Martínez E. J Antimicrob Chemother 2005;56:6-9.
  6. National Institutes of Health: Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Executive Summary. Bethesda, MD: National Institutes of Health, National Heart Lung and Blood Institute, 2001 (NIH publication no. 01-3670). Available from: http://www.nhlbi.nih.gov/guidelines/cholesterol/index.htm
  7. Banegas JR, Ruilope LM. Med Clin (Barc) 2003;120:99-100.

Resources
Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III)
W:www.nhlbi.nih.gov/guidelines/cholesterol/index.htm
A Guide to Primary Care for People with HIV/AIDS, 2004 ed.
W:hab.hrsa.gov/tools/primarycareguide/PCGchap6.htm



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