Lipid profile, cardiovascular risk factors and metabolic syndrome in a group of AIDS patients

Silva, Érika Ferrari Rafael da; Bassichetto, Katia Cristina; Lewi, David Salomão

doi:10.1590/S0066-782X2009000800008

Abstracts

BACKGROUND: Since the advent of AIDS, the anti-HIV therapy has developed significantly, including the highly active antiretroviral therapy (HAART) and the disease acquired a chronic characteristic. However, after the introduction of HAART, several metabolic alterations were observed, mainly related to the lipid profile. OBJECTIVES: to evaluate and compare lipid profiles, analyze cardiovascular risk, describe the prevalence of metabolic syndrome in AIDS patients with or without HAART. METHODS: Over an 18-month period, 319 patients treated at outpatient clinics in the city of São Paulo, Brazil were selected. RESULTS: The final sample included 215 patients receiving HAART and 69 HAART-naive patients. The mean age was 39.5 years, and 60.9% were males. The main cardiovascular risk factors were smoking (27%), hypertension (18%) and family history of atherosclerosis (40%). Mean total cholesterol, HDL-cholesterol, triglycerides and glucose were higher in the HAART group than in the non-HAART group (205 vs 180 mg/dl, 51 vs 43 mg/dl, 219 vs 164 mg/dl and 101 vs 93 mg/dl respectively; p < 0.001 for all). According to the Framingham risk score, the cardiovascular risk was moderate to high in 11% of the patients receiving HAART and 4% of the HAART-naïve patients. According to the Adult Treatment Panel III definition, the metabolic syndrome was observed in 13% and 12% of the patients with or without HAART, respectively. CONCLUSIONS: Although the mean values for total cholesterol, HDL-c and triglycerides were higher in the HAART group, a higher cardiovascular risk was not identified in the former. The prevalence of metabolic syndrome was comparable in both groups.

metabolic syndrome X; lipid metabolism disorders; cardiovascular disease; highly active antiretroviral therapy

FUNDAMENTO: Desde o advento da AIDS, a terapia antiretroviral desenvolveu-se significantemente, incluindo a terapia antiretroviral altamente ativa (HAART) e a doença adquiriu uma característica crônica. Entretanto, após a introdução da HAART, várias alterações metabólicas foram observadas, principalmente relacionadas ao perfil lipídico. OBJETIVO: Avaliar e comparar os perfis lipídicos, analisar o risco cardiovascular, e descrever a prevalência da síndrome metabólica em pacientes com AIDS tratados ou não com HAART. MÉTODOS: Durante um período de 18 meses, 319 pacientes tratados em ambulatórios na cidade de São Paulo, Brasil, foram selecionados. RESULTADOS: A amostra final incluiu 215 pacientes tratados com HAART e 69 pacientes virgens de tratamento com HAART. A idade média era 39,5 anos, e 60,9% eram do sexo masculino. Os principais fatores de risco cardiovascular eram o fumo (27%), hipertensão (18%) e histórico familiar de aterosclerose (40%). Os valores médios de colesterol total, HDL-colesterol, triglicérides e glicose foram mais altos no grupo HAART do que no grupo não-HAART (205 vs 180 mg/dl, 51 vs 43 mg/dl, 219 vs 164 mg/dl e 101 vs 93 mg/dl respectivamente; p < 0,001 para todos). De acordo com o escore de risco de Framingham, o risco cardiovascular era moderado a alto em 11% dos pacientes tratados com HAART e 4% dos pacientes não-HAART. De acordo com a definição do Adult Treatment Panel III, a síndrome metabólica foi observada em 13% e 12% dos pacientes, respectivamente, com e sem HAART. CONCLUSÃO: Embora os valores médios do colesterol total, HDL-c e triglicérides tenham sido mais altos no grupo HAART, um maior risco cardiovascular não foi identificado no primeiro grupo. A prevalência de síndrome metabólica foi comparável em ambos os grupos.

síndrome metabólica; desordens do metabolismo lipídico; doença cardiovascular; terapia antiretroviral de alta potência

FUNDAMENTO: Desde el surgimiento del SIDA, la terapia antiretroviral se desarrolló significantemente. Al incluir la terapia antiretroviral altamente activa (HAART), la enfermedad adquirió una característica crónica. Sin embargo, tras la introducción de HAART, diversas alteraciones metabólicas se observaron, principalmente relacionadas al perfil lipídico. OBJETIVO: Evaluar y comparar los perfiles lipídicos, analizar el riesgo cardiovascular, y describir la prevalencia del síndrome metabólico en pacientes con SIDA tratados o no con HAART. MÉTODOS: Durante un período de 18 meses, se seleccionaron a 319 pacientes tratados en ambulatorios en la ciudad de São Paulo, Brasil. RESULTADOS: La muestra final incluyó a 215 pacientes tratados con HAART y a 69 pacientes vírgenes de tratamiento con HAART. La edad promedio era de 39,5 años, y el 60,9% eran del sexo masculino. Los principales factores de riesgo cardiovascular eran el fumo (27%), hipertensión (18%) e histórico familiar de aterosclerosis (40%). Los valores promedios de colesterol total, HDL-colesterol, triglicéridos y glucosa fueron más altos en el Grupo HAART que en el Grupo no-HAART (205 vs. 180 mg/dL, 51 vs. 43 mg/dL, 219 vs. 164 mg/dL, 101 vs. 93 mg/dL respectivamente; p < 0,001 para todos). De conformidad con el score de riesgo de Framingham, el riesgo cardiovascular era moderado y alto en el 11% de los pacientes tratados con HAART y el 4% de los pacientes no-HAART. Según la definición del Adult Treatment Panel III, el síndrome metabólico se observó en el 13% y el 12% de los pacientes, respectivamente, con y sin HAART. CONCLUSIÓN: Aunque los valores promedios del colesterol total, HDL-c y triglicéridos fueron más altos en el Grupo HAART, un mayor riesgo cardiovascular no se identificó en el primer grupo. La prevalencia de síndrome metabólico fue comparable en ambos grupos.

Síndrome metabólico; desórdenes del metabolismo lipídico; enfermedad cardiovascular; terapia antiretroviral de alta potencia

ORIGINAL ARTICLE

Lipid profile, cardiovascular risk factors and metabolic syndrome in a group of AIDS patients

Érika Ferrari Rafael da Silva^I; Katia Cristina Bassichetto^II; David Salomão Lewi^I

^IUniversidade Federal de São Paulo, São Paulo, SP - Brasil

^IISecretaria Municipal de Saúde de São Paulo, São Paulo, SP - Brasil

Mailing address

SUMMARY

BACKGROUND: Since the advent of AIDS, the anti-HIV therapy has developed significantly, including the highly active antiretroviral therapy (HAART) and the disease acquired a chronic characteristic. However, after the introduction of HAART, several metabolic alterations were observed, mainly related to the lipid profile.

OBJECTIVES: to evaluate and compare lipid profiles, analyze cardiovascular risk, describe the prevalence of metabolic syndrome in AIDS patients with or without HAART.

METHODS: Over an 18-month period, 319 patients treated at outpatient clinics in the city of São Paulo, Brazil were selected.

RESULTS: The final sample included 215 patients receiving HAART and 69 HAART-naive patients. The mean age was 39.5 years, and 60.9% were males. The main cardiovascular risk factors were smoking (27%), hypertension (18%) and family history of atherosclerosis (40%). Mean total cholesterol, HDL-cholesterol, triglycerides and glucose were higher in the HAART group than in the non-HAART group (205 vs. 180 mg/dL, 51 vs. 43 mg/dL, 219 vs. 164 mg/dL and 101 vs. 93 mg/dL respectively; p < 0.001 for all). According to the Framingham risk score, the cardiovascular risk was moderate to high in 11% of the patients receiving HAART and 4% of the HAART-naïve patients. According to the Adult Treatment Panel III definition, the metabolic syndrome was observed in 13% and 12% of the patients with or without HAART, respectively.

CONCLUSIONS: Although the mean values for total cholesterol, HDL-c and triglycerides were higher in the HAART group, a higher cardiovascular risk was not identified in the former. The prevalence of metabolic syndrome was comparable in both groups.

Key words: metabolic syndrome X, lipid metabolism disorders, cardiovascular disease, highly active antiretroviral therapy.

Introduction

The introduction of the highly active antiretroviral therapy (HAART) has changed the course of HIV infection, increasing survival and improving quality of life in HIV-infected individuals¹. However, it has been shown that a high proportion of patients treated with HAART regimens, especially those including protease inhibitors (PIs), present metabolic disorders (dyslipidemia, insulin resistance) and physiological alterations (lipodystrophy and lipoatrophy), as well as being at greater risk for cardiovascular disease (coronary artery disease and stroke)^2-10. These findings have changed the scenario of HIV infection and treatment.

In 1998, Carr et al. described HIV-associated lipodystrophy¹¹, characterized by a dorsocervical fat pad (also known as a "buffalo hump"), larger abdominal girth, increased breast size, as well as by lipoatrophy of the face, buttocks and limbs, together with prominence of the superficial veins in the extremities. In AIDS patients receiving HAART, the overall prevalence of at least one physical abnormality is thought to be approximately 50%, although reported rates range from 18 to 83%¹⁰. Differences in prevalence rates might be attributable to age, gender or the type/duration of antiretroviral therapy, as well as to the lack of an objective and validated case definition¹⁰.

Data in the literature show that the prevalence of hyperlipidemia ranges from 28% to 80% in patients receiving HAART, including hypertriglyceridemia (40-80%) and high total cholesterol (10-50%)^4-7,12-14. These lipidic alterations are mainly related to the use of PIs^2,4-9.

There are conflicting data regarding the association between HAART and the incidence of coronary disease (angina or myocardial infarction) in AIDS patients^12-17. Although differences in study design, sample selection and statistical analyses might explain this disparity, longer exposure to HAART, mainly to PIs, appears to increase the risk of myocardial infarction. The Data Collection on Adverse Events of Anti-HIV Drugs study showed that the relative risk increase of myocardial infarction increases by 26% per year of HAART exposure¹⁴.

Several studies have demonstrated that the prevalence of metabolic syndrome is higher in AIDS patients receiving HAART than in HIV-negative individuals^18-20.

To date, there have been no studies evaluating metabolic alterations in AIDS patients receiving HAART in Brazil, which has an estimated 600,000 HIV-infected population, of whom 180,000 receive HAART, mostly in public outpatient health care facilities.

The aim of this study was to evaluate and compare lipid profiles, analyze cardiovascular risk, describe the prevalence of metabolic syndrome in AIDS patients receiving and not receiving HAART.

Methods

This was a descriptive, transversal study conducted at seven outpatient facilities in the city of São Paulo, Brazil: the Federal University of São Paulo and six outpatient clinics operated by the São Paulo Municipal Department of Health.

Consecutive patients were recruited during regularly-scheduled outpatient visits between December 2004 and May 2006. Patients were considered eligible for inclusion in the study if, at the time of data collection, they were undergoing active follow-up treatment, had been receiving HAART for at least two months, were not taking any medications that might affect the lipid profile (diuretics, statins, fibrats, hormones, etc.) or were not receiving antiretroviral therapy. A total of 319 patients met the inclusion criteria and were enrolled in the study.

Upon enrollment, a questionnaire was applied. The questionnaire consisted of questions concerning the use of HAART, family history of coronary heart disease, diabetes mellitus, cigarette smoking, blood pressure and the use of medications that might affect the lipid profile. Total cholesterol, low-density lipoprotein-cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c) and triglycerides, as well as CD4+ cell counts and HIV viral load, were also determined. When the levels of the triglycerides were above 400 mg/dL the Friedewald equation was used to determine the levels of the LDL-c. Cardiovascular risk was calculated using the Framingham risk score²¹ and the metabolic syndrome was evaluated based on the Adult Treatment Panel III (APT III) criteria²². These rules are: triglycerides > 150 mg /dL, abdominal waist for man > 102 cm and woman > 88 cm, blood glucose > 110 mg/dL, HDL-c < 40 mg/dL for man and < 50 mg/dL for woman and blood pressure > 130 x 85 mmHg²².

The sample size was calculated base on a initial analysis of the variables of interest. Mean values and standard deviations were considered. All data were transformed into a standardized format and merged into a central data set. The level of statistical significance was set at 0.05 (α = 5%), and the Statistical Package for the Social Sciences program, version 12.0 for Windows, was used in all analyses. All participating patients gave the written informed consent using a form that had been previously approved by the Federal University of São Paulo Ethics Committee and the São Paulo Municipal Department of Health.

Results

Of the 319 evaluated AIDS patients, 243 were receiving HAART (group 1), and 76 were HAART-naïve (group 2). The mean age was 39.5 years and 60.9% of the patients were male. The main cardiovascular risk factors observed in the sample were smoking (27%), hypertension (18%), family history of atherosclerosis (40%) and diabetes mellitus (4%). Baseline characteristics of the individuals are described in Table 1. In comparison with group 2, group 1 presented higher mean values of total cholesterol (205 vs. 180 mg/dL [p < 0.001], HDL-c (51 vs. 43 mg/dL [p < 0.001]), triglycerides (219 vs. 164 mg/dL [p = 0.004]) and glucose (101 vs. 93 mg/dL [p < 0.001) respectively. No significant difference was found between the two groups regarding LDL-c (p = 0.073).

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Some patients were excluded from the estimation through the Framingham risk score of the risk of coronary artery disease: 41 for being younger than 30 years; 31 because the lipid profile was incomplete; and 5 because blood pressure data were unavailable. Therefore, 242 patients were evaluated (193 patients in group 1 and 49 patients in group 2). According to the Framingham risk score, the cardiovascular risk was moderate to high in 11% (22) of the patients receiving HAART and in 4% (2) of the HAART-naïve patients. As shown in Table 2, no statistically significant differences were found between the two groups. Metabolic syndrome, according to the ATP III criteria²², was identified in 13% (27) of the patients in group 1 and 12% (8) of the patients in group 2 (p=0.832). The characteristics of the metabolic syndrome are described in Table 3.

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As shown in Table 4, the patients in group 1 were clustered into five groups according to the HAART regimen used, in order to evaluate the best regimen in terms of its effect on the metabolic profile: group A, receiving zidovudine (AZT)+lamivudine (3TC)+efavirenz; group B, receiving AZT+3TC+lopinavir/ritonavir and AZT+3TC+nelfinavir; group C, receiving AZT+3TC+atazanavir; group D, receiving stavudine (d4T)+3TC+efavirenz; group E, receiving d4T+3TC+lopinavir/ritonavir and d4T+3TC+nelfinavir and d4T+didanosine+lopinavir/ritonavir. Sixty-one patients were excluded because it was not possible to cluster them into one of the 5 more prevalent regimens used; therefore, 154 patients were evaluated. Average HDL-c was lower in group E (p = 0.049) than in group A (p = 0.011), group B (p = 0.026) or group D (p = 0.026). The lowest LDL-c and total cholesterol values were observed in group C. Although the highest triglycerides levels were observed in group E, there were no significant differences among the five groups (p = 0.495).

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Discussion

Average values for total cholesterol, HDL-c, triglycerides and glucose were statistically higher in the patients receiving HAART than in the HAART-naïve patients with the exception of LDL-c (p = 0.073). These data are in agreement with those in the literature showing that AIDS patients receiving HAART present more metabolic alterations, mainly high triglycerides and cholesterol, than do those not receiving HAART². Of the patients receiving HAART in the present study, 41.4% (89) and 20.5% (44) presented high levels of triglycerides and total cholesterol, respectively. Data in the literature show that the prevalence of hyperlipidemia ranges from 28% to 80%, including hypertriglyceridemia (40-80%) and high total cholesterol (10-50%)^4-7,13,14. In the Brazilian study by Caramelli et al²³, the hypercholesterolemia was present in 43% and hypertriglyceridemia in 53% of the patients using PIs²³.

In our study sample as a whole, the main cardiovascular risk factors observed were smoking (27%), hypertension (18%) and a family history of atherosclerosis (40%). However, 88% of the patients had at least one cardiovascular risk factor. In the Swiss HIV Cohort Study, 57% of the patients were smokers, 35.7% had high triglyceride levels and 26.1% had high blood pressure²⁴. Our study sample was young for the development of cardiovascular disease (CVD). Nevertheless, our findings related to other cardiovascular risk factors (current smoking, high blood pressure and hypertriglyceridemia) are in agreement with those in the literature. Currier et al⁶ and Carr et al²⁵ showed that 60% of AIDS patients have hyperglycemia, dyslipidemia and central obesity, a combination seen in 88.3% of the subjects evaluated in the present study.

According to the Framingham risk score, the cardiovascular risk was moderate to high in 11% of the patients receiving HAART and in 4% of the HAART-naïve patients. The averages of total cholesterol (199 mg/dL) and HDL-c (49 mg/dL), the low frequency of diabetes (4%) and the younger age of the patients (39 years) in the sample as a whole could explain the slightly higher Framingham risk score in the HAART group. These characteristics are similar to those reported in a study conducted in Norway, in which patients receiving HAART were found to have an almost two-fold higher risk for CVD than those in the control group (11.9% vs. 6.3%)²⁶. The Framingham risk score has been broadly used for this purpose, as it has been validated in the literature.

According to the APT III criteria²², metabolic syndrome was present in 13% of patients in group 1 and 12% of patients in group 2. These findings differ from those by Estrada et al²⁰, who found that 15.8% of patients receiving HAART presented metabolic syndrome, compared with only 3.2% of the control patients.

All the HAART regimens caused alterations in the lipid profile when compared to the patients without HAART. The differences observed among the groups evaluated in terms of the lipid profile were not statistically significant. Consequently, it was not possible to determine the best regimen regarding the metabolic profile. Group C, treated with atazanavir, presented the lowest levels of total cholesterol and LDL-c, although no benefit was observed in terms of triglyceride levels. Unexpectedly, higher HDL-c levels were observed in the HAART group. There is no reasonable explanation for this fact, although it could be speculated that it was due to the fact that the HIV was controlled (85% of the patients in this group achieved an undetectable viral load), which decrease the inflammatory response.

Conclusions

Although it was observed that the mean values of total cholesterol, HDL-c and triglycerides were higher in the HAART group than in the non-HAART group, a higher cardiovascular risk was not identified in the former. The prevalence of metabolic syndrome was comparable in the two groups, despite the metabolic alterations induced by HAART.

Acknowledgements

We would like to thank the Ministry of Health of Brazil, UNESCO, the City Hall of the City of São Paulo and the Institute of Infectious and Parasitic Diseases for their support in this research. We would also like to thank the PGS Medical Statistics and all the people that helped us in this research: Denise S.M.Oskata, Edina Aparecida T. Trovões, Elenice M Morales Campos, Gabriela M. Vedovato, Helga Fuchs Piloto, Janice Chencinski, Iara Lobo Macedo, Marisia Nagamini, Marta C. Pereira, Nivania F. Zauith, Vânia Regina S. Garcia and Simone Tenore.

Potential Conflict of Interest

No potential conflict of interest relevant to this article was reported.

Sources of Funding

This study was funded by Ministério da Saúde e UNESCO processo CSV 067/06 contrato número: SA - 2223/2006 e controle UNESCO: 16270..

Study Association

This article is part of the thesis of Master submitted by Érika Ferrari Rafael da Silva, from Universidade Federal de São Paulo.

Referências

1. Palella FJ, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. N Engl J Med. 1998; 338: 853-60.
2. Mulligan K, Grunfeld C, Tai VW, Algren H, Pang M, Chernoff DN, et al. Hyperlipidemia and insulin resistance are induced by protease inhibitors independent of changes in body composition in patients with HIV infection. J Acquir Immune Defic Syndr. 2000; 23: 35-43.
3. Carr A. HIV protease inhibitor-related lipodystrophy syndrome. Clin Infect Dis. 2000; 30 (Suppl 2): 135-42.
4. Dube M, Sattler F. Metabolic complications of antiretroviral therapies. AIDS Clin Care. 1998; 10: 41-4.
5. Sweet DE. Metabolic complications of antiretroviral therapy. Top HIV Med. 2005; 13 (2): 70-74.
6. Currier JS, Havlir DV. Complications of HIV disease and antiretroviral therapy. Top HIV Med. 2005; 13 (1): 16-23.
7. Stein J. Dyslipidemia in the era of HIV protease inhibitors. Prog Cardiovasc Dis. 2003; 45: 293-304.
8. Barbaro G. Metabolic and cardiovascular complications of highly active antiretroviral therapy for HIV infection. Curr HIV Res. 2006, 4: 79-85.
9. Barbaro G. Highly active antiretroviral therapy-associated metabolic syndrome: pathogenesis and cardiovascular risk. Am J Therapeutics. 2006; 13: 248-60.
10. Grinspoon S, Carr A. Cardiovascular risk and body fat abnormalities in HIV-infected adults. N Engl J Med. 2005; 352: 48-62.
11. Carr A, Samaras K, Burton S, Law M, Freund J, Chisholm DJ, et al. A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance in patients receiving HIV protease inhibitors. AIDS. 1998; 12, F51-F58.
12. Hajjar LA, Calderaro D, Yu PC, Giuliano I, Lima EMO, Barbaro G, et al. Cardiovascular manifestations in patients with the human immunodeficiency virus. Arq Bras Cardiol. 2005; 85 (5): 365-77.
13. Bozzette SA, Ake CF, Tam HK, Chang SW, Louis TA. Cardiovascular and cerebrovascular events in patients treated for human immunodeficiency virus infection. N Engl J Med. 2003; 348: 702-10.
14. Friis-Moller N, Weber R, Reiss P, Thiebaut R, Kirk O, D'Arminio Monforte A, et al. For the D.A.D Study Group. Cardiovascular disease risk factors in HIV patients - associations with antiretroviral therapy: results from the DAD Study. AIDS. 2003; 17: 1179-93.
15. Holmberg SD, Moorman AC, Willianson JM, Tong TC, Ward DJ, Wood KC, et al and the HIV Outpatient Study (HOPS) Investigators. Protease inhibitors and cardiovascular outcomes in patients with HIV-1. Lancet. 2002; 360: 1747-8.
16. Mary-Krause M, Cotte L, Simon A, Partisani M, Costagliola D and the Clinical Epidemiology Group from the French Hospital Database. Increased risk for myocardial infarction with duration of protease inhibitor therapy in HIV-infected men. AIDS. 2003; 17: 2479-86.
17. Currier J, Taylor A, Boyd F, Dezii CM, Kawabata H, Burtcel B, et al. Coronary heart disease in HIV-infected individuals. J Acquir Immune Defic Syndr. 2003; 33: 506-12.
18. Gazzaruso C, Bruno C, Garzaniti A, Giordanetti S, Fratino P, Sacchi P, et al. Hypertension among HIV patients: prevalence and relationships to insulin resistance and metabolic syndrome. J Hypertens. 2003; 21: 1377-82.
19. Bruno R, Gazzaruso C, Sacchi P, Zocchetti C, Giordanetti C, Garzaniti A, et al. High prevalence of metabolic syndrome among HIV-infected patients: link with the cardiovascular risk. J Acquir Immune Defic Syndr. 2002; 31: 363-5.
20. Estrada V, Martinez-Larrad T, Gonzalez-Sanchez JL, de Villar NGP, Zabena C, Fernandez C, et al. Lipodystrophy and metabolic syndrome in HIV-infected patients treated with antiretroviral therapy. Metabolism. 2006; 55 (7): 940-5.
21. Dawber TR, Meadors GF, Moore FE Jr. Epidemiolofical approaches to heart disease: the Framingham Study. Am J Public Health. 1951; 41 (3): 279-81.
22. Third Report of the National Cholesterol Education Program (NCEP). Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Circulation. 2002; 106: 3143-421.
23. Caramelli B, de Bernoche CYSM, Sartori AMC, Sposito AC, Santos RD, Monachini TS, et al. Hyperlipidaemia related to the use of HIV protease inhibitors: natural history and results of treatment with Fenofibrate. Braz J Infect Dis. 2001; 5 (6): 332-8.
24. Glass TR, Ungsedhapand C, Wolbers M, Weber R, Vernazza PL. Bucher HC, et al. Prevalence of risk factors for cardiovascular disease in HIV-infected patients over time: the Swiss HIV Cohort Study. HIV Med. 2006; 7 (6): 404-10.
25. Carr A, Samaras K, Chisholm DJ, Cooper DA. Pathogenesis of HIV-1 protease inhibitor-associated peripheral lipodystrophy, hyperlipidaemia and insulin resistance. Lancet. 1998; 351: 1881-3.
26. Bergensen BM, Sandvik L, Brunn JN, Tonstad S. Elevated Framingham risk score in HIV-positive patients on highly active antiretroviral therapy: results from a Norwegian study of 721 subjects. Eur J Clin Microbiol Infect Dis. 2004; 23: 625-30.

Correspondência:

Érika Ferrari Rafael da Silva

Rua Loefgren, 1588, Vila Clementino

04040-002, São Paulo, SP - Brasil

E-mail:

erikaferrari@uol.com.br

Publication Dates

Publication in this collection
13 Oct 2009
Date of issue
Aug 2009

History

Received
03 Mar 2008
Reviewed
24 Apr 2008
Accepted
08 May 2008

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. Palella FJ, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. N Engl J Med. 1998; 338: 853-60.

[2] 2. Mulligan K, Grunfeld C, Tai VW, Algren H, Pang M, Chernoff DN, et al. Hyperlipidemia and insulin resistance are induced by protease inhibitors independent of changes in body composition in patients with HIV infection. J Acquir Immune Defic Syndr. 2000; 23: 35-43.

[3] 3. Carr A. HIV protease inhibitor-related lipodystrophy syndrome. Clin Infect Dis. 2000; 30 (Suppl 2): 135-42.

[4] 4. Dube M, Sattler F. Metabolic complications of antiretroviral therapies. AIDS Clin Care. 1998; 10: 41-4.

[5] 5. Sweet DE. Metabolic complications of antiretroviral therapy. Top HIV Med. 2005; 13 (2): 70-74.

[6] 6. Currier JS, Havlir DV. Complications of HIV disease and antiretroviral therapy. Top HIV Med. 2005; 13 (1): 16-23.

[7] 7. Stein J. Dyslipidemia in the era of HIV protease inhibitors. Prog Cardiovasc Dis. 2003; 45: 293-304.

[8] 8. Barbaro G. Metabolic and cardiovascular complications of highly active antiretroviral therapy for HIV infection. Curr HIV Res. 2006, 4: 79-85.

[9] 9. Barbaro G. Highly active antiretroviral therapy-associated metabolic syndrome: pathogenesis and cardiovascular risk. Am J Therapeutics. 2006; 13: 248-60.

[10] 10. Grinspoon S, Carr A. Cardiovascular risk and body fat abnormalities in HIV-infected adults. N Engl J Med. 2005; 352: 48-62.

[11] 11. Carr A, Samaras K, Burton S, Law M, Freund J, Chisholm DJ, et al. A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance in patients receiving HIV protease inhibitors. AIDS. 1998; 12, F51-F58.

[12] 12. Hajjar LA, Calderaro D, Yu PC, Giuliano I, Lima EMO, Barbaro G, et al. Cardiovascular manifestations in patients with the human immunodeficiency virus. Arq Bras Cardiol. 2005; 85 (5): 365-77.

[13] 13. Bozzette SA, Ake CF, Tam HK, Chang SW, Louis TA. Cardiovascular and cerebrovascular events in patients treated for human immunodeficiency virus infection. N Engl J Med. 2003; 348: 702-10.

[14] 14. Friis-Moller N, Weber R, Reiss P, Thiebaut R, Kirk O, D'Arminio Monforte A, et al. For the D.A.D Study Group. Cardiovascular disease risk factors in HIV patients - associations with antiretroviral therapy: results from the DAD Study. AIDS. 2003; 17: 1179-93.

[15] 15. Holmberg SD, Moorman AC, Willianson JM, Tong TC, Ward DJ, Wood KC, et al and the HIV Outpatient Study (HOPS) Investigators. Protease inhibitors and cardiovascular outcomes in patients with HIV-1. Lancet. 2002; 360: 1747-8.

[16] 16. Mary-Krause M, Cotte L, Simon A, Partisani M, Costagliola D and the Clinical Epidemiology Group from the French Hospital Database. Increased risk for myocardial infarction with duration of protease inhibitor therapy in HIV-infected men. AIDS. 2003; 17: 2479-86.

[17] 17. Currier J, Taylor A, Boyd F, Dezii CM, Kawabata H, Burtcel B, et al. Coronary heart disease in HIV-infected individuals. J Acquir Immune Defic Syndr. 2003; 33: 506-12.

[18] 18. Gazzaruso C, Bruno C, Garzaniti A, Giordanetti S, Fratino P, Sacchi P, et al. Hypertension among HIV patients: prevalence and relationships to insulin resistance and metabolic syndrome. J Hypertens. 2003; 21: 1377-82.

[19] 19. Bruno R, Gazzaruso C, Sacchi P, Zocchetti C, Giordanetti C, Garzaniti A, et al. High prevalence of metabolic syndrome among HIV-infected patients: link with the cardiovascular risk. J Acquir Immune Defic Syndr. 2002; 31: 363-5.

[20] 20. Estrada V, Martinez-Larrad T, Gonzalez-Sanchez JL, de Villar NGP, Zabena C, Fernandez C, et al. Lipodystrophy and metabolic syndrome in HIV-infected patients treated with antiretroviral therapy. Metabolism. 2006; 55 (7): 940-5.

[21] 21. Dawber TR, Meadors GF, Moore FE Jr. Epidemiolofical approaches to heart disease: the Framingham Study. Am J Public Health. 1951; 41 (3): 279-81.

[22] 22. Third Report of the National Cholesterol Education Program (NCEP). Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Circulation. 2002; 106: 3143-421.

[23] 23. Caramelli B, de Bernoche CYSM, Sartori AMC, Sposito AC, Santos RD, Monachini TS, et al. Hyperlipidaemia related to the use of HIV protease inhibitors: natural history and results of treatment with Fenofibrate. Braz J Infect Dis. 2001; 5 (6): 332-8.

[24] 24. Glass TR, Ungsedhapand C, Wolbers M, Weber R, Vernazza PL. Bucher HC, et al. Prevalence of risk factors for cardiovascular disease in HIV-infected patients over time: the Swiss HIV Cohort Study. HIV Med. 2006; 7 (6): 404-10.

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