Cardiovascular and Cerebrovascular Events in Patients Treated for Human Immunodeficiency Virus Infection

Bozzette, Samuel A.; Ake, Christopher F.; Tam, Henry K.; Chang, Sophia W.; Louis, Thomas A.

doi:10.1056/nejmoa022048

Cited by 553 publications

(369 citation statements)

References 21 publications

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“…Some of this risk was associated with dyslipidemia [83]. Other cohorts have not shown an increased risk for cardiovascular disease for patients on any type of ARV [84]. The reason for this discrepancy is not clear but will hopefully be clarified as more data are available.…”

Section: Protease Inhibitorsmentioning

confidence: 99%

A Review of the Toxicity of HIV Medications

et al. 2013

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Antiretroviral therapy has changed human immunodeficiency virus (HIV) infection from a near-certainly fatal illness to one that can be managed chronically. More patients are taking antiretroviral drugs (ARVs) for longer periods of time, which naturally results in more observed toxicity. Overdose with ARVs is not commonly reported. The most serious overdose outcomes have been reported in neonates who were inadvertently administered supratherapeutic doses of HIV prophylaxis medications. Typical ARV regimens include a "backbone" of two nucleoside reverse transcriptase inhibitors (NRTI) and a "base" of either a protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor. New classes of drugs called entry inhibitors and integrase inhibitors have also emerged. Older NRTIs were associated with mitochondrial toxicity, but this is less common in the newer drugs, emtricitabine, lamivudine, and tenofovir. Mitochondrial toxicity results from NRTI inhibition of a mitochondrial DNA polymerase. Mitochondrial toxicity manifests as myopathy, neuropathy, hepatic failure, and lactic acidosis. Routine lactate assessment in asymptomatic patients is not indicated. Lactate concentration should be obtained in patients taking NRTIs who have fatigue, nausea, vomiting, or vague abdominal pain. Mitochondrial toxicity can be fatal and is treated by supportive care and discontinuing NRTIs. Metabolic cofactors like thiamine, carnitine, and riboflavin may be helpful in managing mitochondrial toxicity. Lipodystrophy describes changes in fat distribution and lipid metabolism that have been attributed to both PIs and NRTIs. Lipodystrophy consists of loss of fat around the face (lipoatrophy), increase in truncal fat, and hypertriglyceridemia. There is no specific treatment of lipodystrophy. Clinicians should be able to recognize effects of chronic toxicity of ARVs, especially mitochondrial toxicity.

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Section: Protease Inhibitorsmentioning

confidence: 99%

A Review of the Toxicity of HIV Medications

et al. 2013

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“…Several other studies have also reported an association between PI and CVD, 24,51,74,75 although others have not. 76 Data on the association between NRTI and NNRTI use and CVD are more limited. In the D:A:D study, NNRTI was not associated with increased MI risk, 16 and data from the Veterans Affair also were unable to demonstrate an association.…”

Section: Antiretroviral Treatment and Cvdmentioning

confidence: 99%

HIV infection, aging and cardiovascular disease: epidemiology and prevention

Petoumenos

Worm

2011

Sex. Health

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Abstract. In the developed world, HIV infection is now well managed with very effective and less toxic antiretroviral treatment. HIV-positive patients therefore are living longer, but are now faced by challenges associated with aging. Several non-AIDS associated morbidities are increased in this population, including cardiovascular disease (CVD). It is suggested that CVD occurs earlier among HIV-positive patients compared with HIV-negative patients, and at a higher rate. Several factors have been proposed to contribute to this. First, the traditional CVD risk factors are highly prevalent in this population. High rates of smoking, dyslipidaemia and a family history of CVD have been reported. This population is also aging, with estimates of more than 25% of HIV-positive patients in the developed world being over the age of 50. Antiretroviral treatment, both through its effect on lipids and through other, sometimes less well understood, mechanisms, has been linked to increased CVD risk. HIV infection, especially untreated, is a further contributing factor to increased CVD risk in HIV-positive patients. As the HIV-positive population continues to age, the risk of CVD will continue to increase. Guidelines for the management and prevention of CVD risk have been developed, and are largely modelled on those used in the general population. However, the data currently suggest that these interventions, such as the use of lipid-lowering medications and smoking cessation programs, remain quite low. A better understanding the mechanisms of CVD risk in this aging population and further efforts in improving uptake of prevention strategies will remain an important research area.

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“…hypertension, diabetes or increased plasma homocysteine levels) might be at raised risk of developing coronary artery disease because of accelerated atherosclerosis. Conflicting data exist, however, on the relationship between HAART and incidence of acute coronary syndromes, such as unstable angina or myocardial infarction, among HIV-infected patients receiving PI-containing HAART [85][86][87][88][89] . Differences in the study design, selection of patients and statistical analyses might explain this disparity.…”

Section: Haart-associated Coronary Artery Diseasementioning

confidence: 99%