Highly active antiretroviral therapy
http://www.100md.com
《英国医生杂志》
Cardiovascular risk needs to be assessed before starting treatment
In the industrialised world the availability of highly active antiretroviral treatment (HAART) for advanced HIV-1 disease has dramatically improved patients' life expectancy.1 However, an unfailing lifelong commitment to antiviral drugs is expected. Furthermore, recent evidence is mounting that cardiovascular and cerebrovascular accidents might seriously impair the health of infected individuals,2 and the resulting morbidity and mortality have put an end to the unlimited optimism that was associated with the beginning of the HAART era. Here we look at the importance of assessing and targeting the risk of cardiovascular disease before starting HAART and consider what effect this risk has on determining the best time to start treatment.
For people infected with HIV-1, HAART may substantially increase the risk of cardiovascular mortality compared with non-infected individuals or with people infected with HIV who are not yet taking HAART.3 HAART is associated with known cardiovascular risk factors such as increased plasma concentrations of triglycerides, total cholesterol, possibly hypertension,4 and increased insulin resistance. In addition, HAART induces endothelial dysfunction, which is known to increase the risk of coronary heart disease.5
The medical management of cardiovascular risk factors in patients on HAART gives rise to other problems related to HIV and HAART, such as an additional pill burden, which may impair adherence and lead to increased resistance.6 This highlights the importance for such patients of reducing risk through changes in lifestyle, such as smoking cessation, salt restriction, and physical activity.
A proper assessment of current cardiovascular risk factors in HIV-1 infected individuals is of critical importance in order to implement strategies to reduce risk. Someone with HIV-1 infection should receive a cardiovascular risk profile as soon as possible and certainly before treatment is started, to inform timing and choice of regimen for HAART. The score most applicable for this purpose is the Framingham risk score corresponding to known cardiovascular risk factors.7 HAART may increase this score8 through alterations in triglycerides, total cholesterol, high density lipoprotein, and possibly through the emergence of hypertension.4 Currently the decision to start HAART is based on CD4T lymphocyte cell counts. Antiretroviral treatment will be started if the cell count drops below 350 x 106l cells (Yeni P, keynote lecture, 7th International Congress on Drug Therapy and HIV Infection, Glasgow, 14-18 November 2004).
A concentration of 200 x 106l cells is considered as the lower limit for starting HAART, since below this threshold the chances of developing an AIDS defining illness increase dramatically.9 Potentially, however, a considerable time span exists between 350 x 106l cells and 200 x 106l cells—given an average viral load, this could easily be two to five years.10
Strong efforts need to be made during the individual's pre-HAART period to reduce cardiovascular risk factors, whereby selecting the patients most likely to benefit from risk reduction strategies is essential. When the Framingham risk scale is used, a score of 23 for women and 15 for men corresponds with a 20% risk over 10 years of developing coronary heart disease.7 11 In this particular population, lifestyle changes (and eventually lipid lowering drugs) could substantially reduce the risk of coronary heart disease,11 12 but it has to be borne in mind that the cumulative risk of acquiring an AIDS defining event does not increase if HAART is postponed until a CD4T lymphocyte cell count of 200 x 106l is reached.13 Furthermore, during the years of delay, new treatment options might come into life that carry less risk for cardiovascular disease.
The start of a HAART regimen remains a decision that implies an individual and a holistic approach. A high cardiovascular risk score warrants that treatment is delayed if needed until the lower threshold of 200 x 106l CD4T lymphocyte cells is reached. Implementing cardiovascular risk reduction before the start of HAART, as well as for patients already taking HAART, deserves our attention in an era when we become more and more concerned with the long term side effects of HAART.10
Filip Moerman, head of HIV/STI outpatient department
Institute of Tropical Medicine, Unit of HIV/AIDS and STIs, Nationalestraat 155, 2000 Antwerp, Belgium(fmoerman@itg.be)
Alfons Van Gompel, associate professor
Institute of Tropical Medicine, Unit of HIV/AIDS and STIs, Nationalestraat 155, 2000 Antwerp, Belgium
Jan Nimmegeers, consultant cardiologist
Academic Hospital Saint-Lucas, 9000 Ghent, Belgium
Johan Moerman, general medical officer
Bromeliastreet 91, 9040 Ghent, Belgium
Competing interests: None declared.
References
Wood E, Hogg RS, Yip B, Harrigan PR, O'Shaughnessy MV, Montaner JS. Effect of medication adherence on survival of HIV-infected adults who start highly active antiretroviral therapy when the CD4+ cell count is 0.200 to 0.350 x 109 cells/L. Ann Intern Med 2003;139: 810-6.
The writing committee of the D:A:D Study Group. Cardio- and cerebrovascular events in HIV-infected persons. AIDS 2004;18: 1811-7.
Bergerson BM, Sandvik L, Bruun 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.
Bergersen BM, Sandvik L, Dunlop O, Birkeland K, Bruun JN. Prevalence of hypertension in HIV-positive patients on highly active antiretroviral treatment (HAART) compared with HAART-na?ve and HIV-negative controls: results from a Norwegian study of 721 patients. Eur J Clin Microbiol Infect Dis 2003;22: 731-6.
Friis-Moller N, Sabin CA, Weber R, d'Arminio Monforte A, El-Sadr WM, Reiss P, et al. Combination antiretroviral therapy and the risk of myocardial infarction. Data collection on adverse events of Anti-HIV Drugs (DAD) Study Group. N Engl J Med 2003;349: 1993-2003.
Bangsberg DR, Moss AR, Deeks SG. Paradoxes of adherence and drug resistance to HIV antiretroviral therapy. J Antimicrob Chemother 2004;53: 696-9.
Special communication. Executive summary of the 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). JAMA 2001;285: 2486-97.
Calza L, Manfredi R, Chiodo F. Dislipidaemia associated with antiretroviral therapy in HIV-infected patients. J Antimicrob Chemother 2004;53: 10-4.
Egger M, May M, Chene G, Phillips AN, Lederberger B, Dabis F, et al. Prognosis of HIV-1 infected patients starting highly active antiretroviral therapy: a collaborative analysis of prospective studies. Lancet 2002;360: 119-29.
Concerted Action on Seroconversion to AIDS and Death in Europe (CASCADE Collaboration). Is the time from HIV seroconversion a determinant of the risk of AIDS after adjustment for updated CD4 cell counts? J Acquir Immun Defic Syndr 2001;28: 158-65.
Gluckman Ty J, Baranowski B, Ashen D, Henrikson C, McAllister M, Braunstein JB, et al. A practical and evidence-based approach to cardiovascular risk reduction. Arch Intern Med 2004;164: 1490-1500.
Adams MR. Prevention of myocardial infarction. Intern Med J 2002;32: 595-600.
Phillips A, Cozzi Lepri A, Lampe F, Johnson M, Sabin C. When should antiretroviral therapy be started for HIV infection? Interpreting the evidence from observational studies. AIDS 2003;17: 1863-9.
Bonnet F, Morlat P, Chene G, Mercie P, Neau D, Chossat I, et al. Causes of death among HIV-infected patients in the era of highly active antiretroviral therapy. HIV Med 2002;3: 195-9.
In the industrialised world the availability of highly active antiretroviral treatment (HAART) for advanced HIV-1 disease has dramatically improved patients' life expectancy.1 However, an unfailing lifelong commitment to antiviral drugs is expected. Furthermore, recent evidence is mounting that cardiovascular and cerebrovascular accidents might seriously impair the health of infected individuals,2 and the resulting morbidity and mortality have put an end to the unlimited optimism that was associated with the beginning of the HAART era. Here we look at the importance of assessing and targeting the risk of cardiovascular disease before starting HAART and consider what effect this risk has on determining the best time to start treatment.
For people infected with HIV-1, HAART may substantially increase the risk of cardiovascular mortality compared with non-infected individuals or with people infected with HIV who are not yet taking HAART.3 HAART is associated with known cardiovascular risk factors such as increased plasma concentrations of triglycerides, total cholesterol, possibly hypertension,4 and increased insulin resistance. In addition, HAART induces endothelial dysfunction, which is known to increase the risk of coronary heart disease.5
The medical management of cardiovascular risk factors in patients on HAART gives rise to other problems related to HIV and HAART, such as an additional pill burden, which may impair adherence and lead to increased resistance.6 This highlights the importance for such patients of reducing risk through changes in lifestyle, such as smoking cessation, salt restriction, and physical activity.
A proper assessment of current cardiovascular risk factors in HIV-1 infected individuals is of critical importance in order to implement strategies to reduce risk. Someone with HIV-1 infection should receive a cardiovascular risk profile as soon as possible and certainly before treatment is started, to inform timing and choice of regimen for HAART. The score most applicable for this purpose is the Framingham risk score corresponding to known cardiovascular risk factors.7 HAART may increase this score8 through alterations in triglycerides, total cholesterol, high density lipoprotein, and possibly through the emergence of hypertension.4 Currently the decision to start HAART is based on CD4T lymphocyte cell counts. Antiretroviral treatment will be started if the cell count drops below 350 x 106l cells (Yeni P, keynote lecture, 7th International Congress on Drug Therapy and HIV Infection, Glasgow, 14-18 November 2004).
A concentration of 200 x 106l cells is considered as the lower limit for starting HAART, since below this threshold the chances of developing an AIDS defining illness increase dramatically.9 Potentially, however, a considerable time span exists between 350 x 106l cells and 200 x 106l cells—given an average viral load, this could easily be two to five years.10
Strong efforts need to be made during the individual's pre-HAART period to reduce cardiovascular risk factors, whereby selecting the patients most likely to benefit from risk reduction strategies is essential. When the Framingham risk scale is used, a score of 23 for women and 15 for men corresponds with a 20% risk over 10 years of developing coronary heart disease.7 11 In this particular population, lifestyle changes (and eventually lipid lowering drugs) could substantially reduce the risk of coronary heart disease,11 12 but it has to be borne in mind that the cumulative risk of acquiring an AIDS defining event does not increase if HAART is postponed until a CD4T lymphocyte cell count of 200 x 106l is reached.13 Furthermore, during the years of delay, new treatment options might come into life that carry less risk for cardiovascular disease.
The start of a HAART regimen remains a decision that implies an individual and a holistic approach. A high cardiovascular risk score warrants that treatment is delayed if needed until the lower threshold of 200 x 106l CD4T lymphocyte cells is reached. Implementing cardiovascular risk reduction before the start of HAART, as well as for patients already taking HAART, deserves our attention in an era when we become more and more concerned with the long term side effects of HAART.10
Filip Moerman, head of HIV/STI outpatient department
Institute of Tropical Medicine, Unit of HIV/AIDS and STIs, Nationalestraat 155, 2000 Antwerp, Belgium(fmoerman@itg.be)
Alfons Van Gompel, associate professor
Institute of Tropical Medicine, Unit of HIV/AIDS and STIs, Nationalestraat 155, 2000 Antwerp, Belgium
Jan Nimmegeers, consultant cardiologist
Academic Hospital Saint-Lucas, 9000 Ghent, Belgium
Johan Moerman, general medical officer
Bromeliastreet 91, 9040 Ghent, Belgium
Competing interests: None declared.
References
Wood E, Hogg RS, Yip B, Harrigan PR, O'Shaughnessy MV, Montaner JS. Effect of medication adherence on survival of HIV-infected adults who start highly active antiretroviral therapy when the CD4+ cell count is 0.200 to 0.350 x 109 cells/L. Ann Intern Med 2003;139: 810-6.
The writing committee of the D:A:D Study Group. Cardio- and cerebrovascular events in HIV-infected persons. AIDS 2004;18: 1811-7.
Bergerson BM, Sandvik L, Bruun 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.
Bergersen BM, Sandvik L, Dunlop O, Birkeland K, Bruun JN. Prevalence of hypertension in HIV-positive patients on highly active antiretroviral treatment (HAART) compared with HAART-na?ve and HIV-negative controls: results from a Norwegian study of 721 patients. Eur J Clin Microbiol Infect Dis 2003;22: 731-6.
Friis-Moller N, Sabin CA, Weber R, d'Arminio Monforte A, El-Sadr WM, Reiss P, et al. Combination antiretroviral therapy and the risk of myocardial infarction. Data collection on adverse events of Anti-HIV Drugs (DAD) Study Group. N Engl J Med 2003;349: 1993-2003.
Bangsberg DR, Moss AR, Deeks SG. Paradoxes of adherence and drug resistance to HIV antiretroviral therapy. J Antimicrob Chemother 2004;53: 696-9.
Special communication. Executive summary of the 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). JAMA 2001;285: 2486-97.
Calza L, Manfredi R, Chiodo F. Dislipidaemia associated with antiretroviral therapy in HIV-infected patients. J Antimicrob Chemother 2004;53: 10-4.
Egger M, May M, Chene G, Phillips AN, Lederberger B, Dabis F, et al. Prognosis of HIV-1 infected patients starting highly active antiretroviral therapy: a collaborative analysis of prospective studies. Lancet 2002;360: 119-29.
Concerted Action on Seroconversion to AIDS and Death in Europe (CASCADE Collaboration). Is the time from HIV seroconversion a determinant of the risk of AIDS after adjustment for updated CD4 cell counts? J Acquir Immun Defic Syndr 2001;28: 158-65.
Gluckman Ty J, Baranowski B, Ashen D, Henrikson C, McAllister M, Braunstein JB, et al. A practical and evidence-based approach to cardiovascular risk reduction. Arch Intern Med 2004;164: 1490-1500.
Adams MR. Prevention of myocardial infarction. Intern Med J 2002;32: 595-600.
Phillips A, Cozzi Lepri A, Lampe F, Johnson M, Sabin C. When should antiretroviral therapy be started for HIV infection? Interpreting the evidence from observational studies. AIDS 2003;17: 1863-9.
Bonnet F, Morlat P, Chene G, Mercie P, Neau D, Chossat I, et al. Causes of death among HIV-infected patients in the era of highly active antiretroviral therapy. HIV Med 2002;3: 195-9.