Drugs and Cardiotoxicity in HIV and AIDS

Abstract

A BSTRACT : The advent of potent antiretroviral drugs in recent years has had an impressive impact on mortality and disease progression in HIV-infected patients, so that issues related to long-term effects of drugs are of growing importance. Hyperlipidemia, hyperglycemia, and lipodystrophy are increasingly described adverse effects of highly active antiretroviral therapy (HAART), in particular when protease inhibitors are used. Hyperlipidemia is strikingly associated with the use of most available protease inhibitors, with an estimated prevalence of up to 50%. Because of the short observation period and the small number of cardiovascular events, epidemiological evidence for an increased risk of coronary heart disease in HIV-infected patients treated with HAART is not adequate at present; however, it is likely that shortly more data will accumulate to quantify this risk. Before starting HAART and during treatment it is reasonable to evaluate all patients for traditional coronary risk factors, including lipid profile. Among the drugs that are currently used in HIV + patients, antibacterials, antifungals, psychotropic drugs and anti-histamines have been associated with QT prolongation or torsade de pointe, a lifethreatening ventricular arrhythmia. Among the risk factors that may precipitate an asymptomatic electrocardiographic abnormality into a dangerous arrhythmia is the concomitant use of drugs that share the CYP3A metabolic pathway. Since most protease inhibitors are potent inhibitors of CYP3A, clinicians should be aware of this potentially dangerous effect of HAART. Anthracyclines are potent cytotoxic antibiotics that have been widely used for the treatment of HIV-related neoplasms. Their cardiotoxicity is well known, ranging from benign and reversible arrhythmias to progressive severe cardiomyopathy. The increased survival and quality of life of HIV + patients emphasize the importance of a high awareness of adverse drug-related cardiac effects. K EYWORDS : cardiotoxicity; antiretrovirals; HAART; dyslipidemia; cardiomyopathy Cardiac involvement in HIV disease is estimated to be approximately 6-7 %. 1 A proportion of cardiac morbidity may be ascribed to the toxic effect of drugs used for the treatment of HIV + patients. The pharmacological treatment of AIDS and HIV-related diseases includes the use of antiretroviral and other anti-infective or anti-neoplastic drugs. Moreover, patients with HIV infection are at higher risk for conditions such as psychiatric diseases or allergic diseases that require additional drug treatments. Until recently the prognosis for people with the acquired immunodeficiency

A review of cardiovascular complications accompanying AIDS

“…31 Also, certain drugs, particularly the antiblastic variety, employed for concomitant AIDScorrelated neoplasms, have cardiotoxic effects which range from benign arrhythmias to progressive severe cardiomyopathy. 32 Finally, HIV-correlated cardiomyopathy may depend not only on the action of HIV, but also of other cardiotropic viruses. This seems to occur particularly in consequence of the autoimmune processes induced by HIV only or in association with other viruses.…”

Neglected cardiomyopathies in Africa

“…Similarly to other parts of the globe, some antiretroviral drugs have several side effects that can lead to cardiac dysfunction. (32) Although important due to the high number of people at risk in Africa, we will not discuss HIV-related cardiomyopathy in detail.…”

HIV-Tat induces a decrease in I Kr and I Ks via reduction in phosphatidylinositol-(4,5)-bisphosphate availability

“…Among them, numerous drugs currently prescribed to HIV-positive individuals have been associated with a QT prolongation, such as macrolides, pentamidine, azole antifungals, fluoroquinolones [10] and methadone [11]. On the other hand, QT prolongation on ECGs of HIV-positive individuals is correlated to the duration of HIV infection rather than the anti-HIV treatment [12].…”