Antiretroviral medications associated with elevated blood pressure among patients receiving highly active antiretroviral therapy
ABSTRACT To examine the effect of antiretroviral agents and clinical factors on the development of elevated blood pressure (BP).
Observational cohort study of patients initiating their first HAART regimen. We evaluated mean BP prior to HAART and while receiving HAART in relation to antiretroviral classes and individual agents, and demographic and clinical characteristics including change in body mass index (BMI) while on HAART. We used logistic regression analysis to examine factors associated with elevated BP [> or = 10 mmHg increase in systolic BP (SBP), diastolic BP (DBP) or new diagnosis of hypertension].
Among 444 patients who had 4592 BP readings, 95 patients developed elevated SBP (n = 83), elevated DBP (n = 33), or a new diagnosis of hypertension (n = 11) after initiating HAART. In multivariate analysis, patients on lopinavir/ritonavir had the highest risk of developing elevated BP [odds ratio (OR), 2.5; P = 0.03] compared with efavirenz-based regimens. When change in BMI was added to the model, increased BMI was significantly associated with elevated BP (OR, 1.3; P = 0.02), and the association between lopinavir/ritonavir and elevated BP was no longer present. Compared with lopinavir/ritonavir-based regimens, patients receiving atazanavir (OR, 0.2; P = 0.03), efavirenz (OR, 0.4; P = 0.02), nelfinavir (OR, 0.3; P = 0.02), or indinavir (OR, 0.3; P = 0.01) had significantly lower odds of developing elevated BP.
Treatment with lopinavir/ritonavir is significantly associated with elevated BP, an effect that appears to be mediated through an increase in BMI. Patients receiving atazanavir were least likely to develop elevated BP. The impact of antiretroviral medications on cardiovascular disease risk factors will increasingly influence treatment decisions.
- SourceAvailable from: Linda R Peterson
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- "HIV infection and combination anti-retroviral therapy (cART) directly impair peripheral nutrient metabolism [7,8] however their effects on myocardial metabolism and their relationship to left ventricular dysfunction are unknown. Approximately 50% of HIV-infected people treated with cART develop a cluster of peripheral metabolic complications (MC)  that include traditional cardiovascular disease risk factors such as dyslipidemia [10-12], peripheral insulin resistance [13-15], elevated blood pressure  and abdominal adiposity : all components of "the metabolic syndrome" . HIV infection/cART  and metabolic syndrome  also are associated with a pro-inflammatory state which further increases cardiovascular disease risk. "
ABSTRACT: In the general population, peripheral metabolic complications (MC) increase the risk for left ventricular dysfunction. Human immunodeficiency virus infection (HIV) and combination anti-retroviral therapy (cART) are associated with MC, left ventricular dysfunction, and a higher incidence of cardiovascular events than the general population. We examined whether myocardial nutrient metabolism and left ventricular dysfunction are related to one another and worse in HIV infected men treated with cART vs. HIV-negative men with or without MC. Prospective, cross-sectional study of myocardial glucose and fatty acid metabolism and left ventricular function in HIV+ and HIV-negative men with and without MC. Myocardial glucose utilization (GLUT), and fatty acid oxidation and utilization rates were quantified using 11C-glucose and 11C-palmitate and myocardial positron emission tomography (PET) imaging in four groups of men: 23 HIV+ men with MC+ (HIV+/MC+, 42 ± 6 yrs), 15 HIV+ men without MC (HIV+/MC-, 41 ± 6 yrs), 9 HIV-negative men with MC (HIV-/MC+, 33 ± 5 yrs), and 22 HIV-negative men without MC (HIV-/MC-, 25 ± 6 yrs). Left ventricular function parameters were quantified using echocardiography. Myocardial glucose utilization was similar among groups, however when normalized to fasting plasma insulin concentration (GLUT/INS) was lower (p < 0.01) in men with metabolic complications (HIV+: 9.2 ± 6.2 vs. HIV-: 10.4 ± 8.1 nmol/g/min/μU/mL) than men without metabolic complications (HIV+: 45.0 ± 33.3 vs. HIV-: 60.3 ± 53.0 nmol/g/min/μU/mL). Lower GLUT/INS was associated with lower myocardial relaxation velocity during early diastole (r = 0.39, p < 0.001). Men with metabolic complications, irrespective of HIV infection, had lower basal myocardial glucose utilization rates per unit insulin that were related to left ventricular diastolic impairments, indicating that well-controlled HIV infection is not an independent risk factor for blunted myocardial glucose utilization per unit of insulin. NIH Clinical Trials NCT00656851.Cardiovascular Diabetology 12/2011; 10(1):111. DOI:10.1186/1475-2840-10-111 · 4.02 Impact Factor
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ABSTRACT: There is increasing evidence that metabolic adverse effects associated with antiretroviral therapy may translate into an increased cardiovascular risk in HIV-1-infected patients. To determine the prevalence of risk factors for cardiovascular disease (CVD) among HIV-1-infected persons, and to investigate any association between them, stage of HIV-1 disease, and use of antiretroviral therapies. Multicentric, cross-sectional analysis of CVD risk factors of treated patients in the VACH cohort. The data collected includes: demographic variables, cigarette smoking, diabetes mellitus, hypertension, dyslipidemia, body mass index, stage of HIV-1 infection, and antiretroviral therapy. The analysis included 2358 patients. More than 18% of the study population was at an age of appreciable risk of CVD. 1.7% had previous CVD and 59.2% were smokers. Increased prevalence of elevated total cholesterol was observed among subjects receiving an NNRTI but no PI [odds ratio (OR), 3.34; 95% confidence interval (CI), 1.77-6.31], PI but no NNRTI (OR, 4.04; 95% CI, 2.12-7.71), or NNRTI + PI (OR, 17.77; 95% CI, 7.24-43.59) compared to patients treated only with nucleoside reverse transcriptase inhibitors (NRTI). Higher CD4 cell count, lower plasma HIV-1 RNA levels, clinical signs of lipodystrophy, longer exposure times to NNRTI and PI, and older age were all also associated with elevated cholesterol levels. The use of lipid lowering agents was very low among our patients. Patients in the VACH cohort present multiple known risk factors for CVD, and a very low rate of lipid lowering therapy use. NNRTI and/or PI-based antiretroviral therapies are associated with the worst lipid profile. This is more frequent in older subjects with greater CD4 counts and controlled HIV-1 replication.The Open AIDS Journal 02/2008; 2(1):26-38. DOI:10.2174/1874613600802010026
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ABSTRACT: Human immunodeficiency virus (HIV) infection is a global pandemic, with cases reported virtually from every country. HIV/AIDS being one of the world's recent most devastating diseases, nearly 25 million people have died world over due to HIV infection since June 1981, when it was first diagnosed. According to the WHO, 33 million people worldwide are living with HIV. To provide access to highly active antiretroviral therapy (HAART), to the whole HIV suffering population remains a major goal to accomplish. Several studies have suggested that HAART improves renal function and prognosis for patients with HIV. Many individuals diagnosed are already with advanced renal disease and then due to lack of renal replacement therapies the mortality rate rises. HIV associated nephropathy (HIVAN) outcomes correlate with the clinical stage of the disease suggesting that early detection improves patient survival. On the other hand, with significant reductions in mortality and risk of progression to AIDS in the era of HAART, complications of long standing HIV infection and treatment should be dwelt with extreme importance. Most common nephrotoxic effects of antiretroviral include crystal-induced obstruction secondary to the use of protease inhibitors (indinavir and atanavir) and proximal tubule damage related to nucleoside reverse transcriptase inhibitors tenofovir. Acute kidney injury (AKI) can occur following tenofovir induced tubular dysfunction or because of mitochondrial dysfunction and lactic acidosis induced by nucleoside reverse transcriptase inhibitors. However looking to the benefits of HAART, fear of nephrotoxic effects can never be a valid reason for physicians to withhold antiretroviral therapy. Hence, identification of patients with pre-existing chronic kidney disease, who are at increased risk of renal damage, enables appropriate dose modifications, close monitoring and avoiding potential nephrotoxic drugs. Putting into practice some of the guidelines can further help save the renal complications. Introduction Kidney proves to be the major excretory pathway for many drugs and their metabolites. Proximal tubule plays an important role due to its high rate of blood flow and the high level of toxins it has to process and hence this part of the kidney is always vulnerable to develop drug related damage. With the introduction of HAART, which has led to a dramatic decline in the mortality and morbidity of HIV infection, varieties of adverse renal effects have come up. Furthermore, improved survival among patients with HIV is anticipated to result in an increase in the risk of chronic HAART-associated metabolic complications, such as diabetes and dyslipidemia, which in turn can contribute to vascular damage and decreased renal function. Understanding the pathogenesis of HIV/AIDS, the HIV replication cycle and the mechanisms of HAART-related kidney disease is essential to adapt to future preventive measures such as dose adjustments, avoiding nephrotoxic drugs in patients at risk of developing kidney disease or having underlying renal diseases. Anti-retroviral for the treatment of HIV/AIDS Anti-retroviral drugs acting against the HIV are divided into 4 classes, which have received FDA approval: protease inhibitors (PIs), fusion inhibitors, non-nucleoside analog reverse transcriptase inhibitors (NNRTIs) and nucleoside/nucleotide analog reverse transcriptase inhibitors (NRTIs) (Table I). Of the 25 ARVs that have been approved, 3 are no longer being manufactured, either because of the development of improved formulations (i.e., amprenavir* replaced by fosamprenavir*) or because of limited use (i.e., delavirdine and zalcitabine). Currently, there are 22 antiretroviral agents available for clinical use. Several others are in various stages of basic and clinical development. As of February 2009, 17 of these have an approved pediatric treatment indication (noted with * below), and 16 are available as a pediatric formulation or capsule size.