Risk of Myocardial Infarction in Patients with HIV Infection Exposed to Specific Individual Antiretroviral Drugs from the 3 Major Drug Classes: The Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) Study

Copenhagen HIV Programme, University of Copenhagen, Copenhagen, Denmark. <>
The Journal of Infectious Diseases (Impact Factor: 6). 02/2010; 201(3):318-30. DOI: 10.1086/649897
Source: PubMed


BACKGROUND. The risk of myocardial infarction (MI) in patients with human immunodeficiency virus (HIV) infection has been assessed in 13 anti-HIV drugs in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study. METHODS. Poisson regression models were adjusted for cardiovascular risk factors, cohort, calendar year, and use of other antiretroviral drugs and assessed the association between MI risk and cumulative (per year) or recent (current or in the past 6 months) use of antiretroviral drugs, with >30,000 person-years of exposure. RESULTS. Over 178,835 person-years, 580 patients developed MI. There were no associations between use of tenofovir, zalcitabine, zidovudine, stavudine, or lamivudine and MI risk. Recent exposure to abacavir or didanosine was associated with an increased risk of MI. No association was found between MI risk and cumulative exposure to nevirapine, efavirenz, nelfinavir, or saquinavir. Cumulative exposure to indinavir and lopinavir-ritonavir was associated with an increased risk of MI (relative rate [RR] per year, 1.12 and 1.13, respectively). These increased risks were attenuated slightly (RR per year, 1.08 [95% confidence interval {CI}, 1.02-1.14] and 1.09 [95% CI, 1.01-1.17], respectively) after adjustment for lipids but were not altered further after adjustment for other metabolic parameters. CONCLUSIONS. Of the drugs considered, only indinavir, lopinavir-ritonavir, didanosine, and abacavir were associated with a significantly increased risk of MI. As with any observational study, our findings must be interpreted with caution (given the potential for confounding) and in the context of the benefits that these drugs provide.

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    • "Several hypotheses have been formulated to explain a potential increase in the incidence of premature aging and coronary events in these patients [3, 4, 18–23]. Some mechanisms are related to antiretroviral therapy, such as the mitochondrial dysfunction and oxidative stress induced by thymidine analogues [10] [11] [12] or protease inhibitor-(PI-) related dyslipemia [8] [9] [13] [14], while the virus itself contributes to increased cardiovascular risk by a chronic inflammatory effect or a direct effect on endothelial and other cells [4] [20] [21]. These factors, together with the increased incidence of traditional CVRF in HIV-1-infected patients, could pave the way to the development of coronary events [4, 8–14, 16, 19–24]. "
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    ABSTRACT: Background: There are conflicting data on the prevalence of coronary events and the quality of the management of modifiable cardiovascular risk factors (CVRF) in HIV-infected patients. Methods: We performed a retrospective descriptive study to determine the prevalence of coronary events and to evaluate the management of CVRF in a Mediterranean cohort of 3760 HIV-1-infected patients from April 1983 through June 2011. Results: We identified 81 patients with a history of a coronary event (prevalence 2.15%); 83% of them suffered an acute myocardial infarction. At the time of the coronary event, CVRF were highly prevalent (60.5% hypertension, 48% dyslipidemia, and 16% diabetes mellitus). Other CVRF, such as smoking, hypertension, lack of exercise, and body mass index, were not routinely assessed. After the coronary event, a significant decrease in total cholesterol (P = 0.025) and LDL-cholesterol (P = 0.004) was observed. However, the percentage of patients who maintained LDL-cholesterol > 100 mg/dL remained stable (from 46% to 41%, P = 0.103). Patients using protease inhibitors associated with a favorable lipid profile increased over time (P = 0.028). Conclusions: The prevalence of coronary events in our cohort is low. CVRF prevalence is high and their management is far from optimal. More aggressive interventions should be implemented to diminish cardiovascular risk in HIV-infected patients.
    BioMed Research International 08/2014; 2014:823058. DOI:10.1155/2014/823058 · 3.17 Impact Factor
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    • "However, ART does not sufficiently remove the virus from the host and is accompanied by incomplete CD4+ T cell recovery. Clinical risk factors such as cardiovascular diseases [9] including myocardial infarction [10,11], have also been associated with ART. Most importantly, ART is too expensive for developing countries, where one-third of all AIDS-related human deaths have occurred. "
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    ABSTRACT: More than 60 million people in the world have been diagnosed with human immunodeficiency virus (HIV) infections since the virus was recognized as the causative agent of acquired immunodeficiency syndrome (AIDS) in the 1980s. Even though more than half of the infected patients have died, effective disease treatment and prevention measures have not been established. Antiretroviral therapy is the only proven HIV treatment which sustains suppression of patient viremia. Current routine approaches to treat HIV infections are targeted at developing vaccines that will induce humoral or cell memory immune responses. However, developing an effective vaccine has been challenging because the HIV mutates rapidly, which allows the virus to evade immune surveillances established against the previous strain. In addition, the virus is able to quickly establish a reservoir and treatment is difficult because of the general lack of knowledge about HIV immune response mechanisms. This review introduces common disease symptoms and the progression of HIV infection with a brief summary of the current treatment approaches. Different cellular immune responses against HIV are also discussed, with emphasis on a nanotechnology research that has focused on probing T cell response to HIV infection. Furthermore, we discuss recent noteworthy nanotechnology updates on T cell response screening that are focused on HIV infection. Finally, we review potential future treatment strategies based on the correlations between T cell response and HIV infection.
    Bioscience Reports 07/2014; 34(4). DOI:10.1042/BSR20140097 · 2.64 Impact Factor
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    • "This finding has not been reported previously and could suggest that PIs, despite their antiviral efficacy, may have less effect on controlling monocyte-macrophage activation. Consistent with this suggestion, the relationship between PIs and cardiovascular disease in HIV infected patients is well recognized [6], [56], [57]. "
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    ABSTRACT: Patients infected with the human immunodeficiency virus (HIV) have an increased risk of cardiovascular disease due to increased inflammation and persistent immune activation. CD163 is a macrophage scavenger receptor that is involved in monocyte-macrophage activation in HIV-infected patients. CD163 interacts with TWEAK, a member of the TNF superfamily. Circulating levels of sTWEAK and sCD163 have been previously associated with cardiovascular disease, but no previous studies have fully analyzed their association with HIV. The aim of this study was to analyze circulating levels of sTWEAK and sCD163 as well as other known markers of inflammation (hsCRP, IL-6 and sTNFRII) and endothelial dysfunction (sVCAM-1 and ADMA) in 26 patients with HIV before and after 48 weeks of antiretroviral treatment (ART) and 23 healthy subjects. Patients with HIV had reduced sTWEAK levels and increased sCD163, sVCAM-1, ADMA, hsCRP, IL-6 and sTNFRII plasma concentrations, as well as increased sCD163/sTWEAK ratio, compared with healthy subjects. Antiretroviral treatment significantly reduced the concentrations of sCD163, sVCAM-1, hsCRP and sTNFRII, although they remained elevated when compared with healthy subjects. Antiretroviral treatment had no effect on the concentrations of ADMA and sTWEAK, biomarkers associated with endothelial function. The use of protease inhibitors as part of antiretroviral therapy and the presence of HCV-HIV co-infection and/or active HIV replication attenuated the ART-mediated decrease in sCD163 plasma concentrations. HIV-infected patients showed a proatherogenic profile characterized by increased inflammatory, immune-activation and endothelial-dysfunction biomarkers that partially improved after ART. HCV-HIV co-infection and/or active HIV replication enhanced immune activation despite ART.
    PLoS ONE 03/2014; 9(3):e90541. DOI:10.1371/journal.pone.0090541 · 3.23 Impact Factor
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