We searched PubMed and ClinicalTrials.gov for articles relevant to the pathogenesis and treatment of adipose tissue dysfunction, disorder of glucose insulin homoeostasis, dyslipidaemia, and cardiovascular disease in patients with HIV. Articles published in English between Jan 1, 2011, and Aug 1, 2013, that provided insight into the pathogenesis of these disorders or advanced patient care were reviewed. ClinicalTrials.gov also provided citations for ongoing trials relevant to the treatment of
ReviewMetabolic disease in HIV infection
Introduction
Comorbid disease management is becoming increasingly important in the long-term management of patients with well controlled HIV on antiretroviral therapy (ART). Metabolic disease in HIV probably develops in the setting of traditional risk factors (such as obesity, tobacco use, and genetic predisposition) and HIV-specific and ART-specific contributors (including chronic inflammation and immune activation). In this Review, we discuss present data on the pathophysiology of and treatment options for the management of adipose tissue dysfunction, disorders of insulin–glucose homoeostasis, dyslipidaemia, and cardiovascular disease in patients with HIV, with a focus on the contributions of ART to these comorbid states.
Section snippets
Pathogenesis of adipose tissue dysfunction
Lipoatrophy and lipohypertrophy are clinically significant problems in patients with long-term HIV treated with ART, especially in people given older antiretroviral drugs; however, our knowledge of how lipodystrophic and non-lipodystrophic adipose tissue function differently remains incomplete, with few available treatments options for patients with lipodystrophy. Additionally, whether adipose tissue dysfunction in the absence of clinically apparent fat changes contributes to the development of
Epidemiology and pathogenesis of glucose disorders
Disorders of insulin–glucose homoeostasis are common in people with HIV, with estimates of prevalence of diabetes mellitus in ART-naive people at 3%,54, 55 of diabetes mellitus in patients on highly active ART up to 10%, and up to 25% for any disorder of insulin–glucose homoeostasis.56 Glucose disorders have been associated with traditional risk factors in addition to HIV-associated factors such as lipodystrophy and ART.56, 57, 58, 59 Although obesity plays a part in development of diabetes
Effects of ART on lipids in adults
Lipid changes after ART initiation partly reflect a return to health after treatment of HIV infection.88 However, increased lipid concentrations might require intervention (especially in patients with other cardiovascular risk factors), and expected lipid disturbances could be an important consideration when selecting ART. Fortunately, measurement of fasting lipid concentrations has become a standard component of clinical trials assessing new antiretroviral drugs, and new drugs show minimum
Effects of ART of cardiovascular risk
Whether specific lipid changes associated with individual antiretroviral drugs affect cardiovascular risk remains uncertain. Several studies show that total and LDL cholesterol concentrations might increase slightly more in patients given efavirenz compared with those given integrase inhibitors; however, HDL cholesterol also rises to a greater extent with efavirenz and the total:HDL cholesterol ratio remains unchanged. Investigators of a pilot study suggested that patients given efavirenz-based
Conclusions
Metabolic perturbations in patients with HIV on ART have a substantial role in morbidity and mortality, but our understanding of how (and whether) these disease states develop differentially in the setting of HIV infection is incomplete. Similarly, optimum interventions to prevent and treat comorbid, metabolic disease in patients with HIV are yet to be defined. Further research is needed to fully elucidate the pathophysiology of metabolic disease in this patient population, with particular
Search strategy and selection criteria
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