Metabolic Syndrome in HIV/HCV Co-infected Patients

Purpose of reviewWe review the scope and burden of metabolic syndrome in HIV/HCV co-infected patients, risk factors, and potential mechanisms driving the increased cardio-metabolic risk in this population, and discuss relevant clinical considerations for management in the era of highly effective antiretroviral therapy (ART) and curative anti-HCV direct-acting antivirals.Recent findingsHIV/HCV co-infected patients are at elevated risk of metabolic syndrome, attributed to (1) patient-specific factors, (2) viral-mediated effects, and (3) ART exposure. Risk factors for cardio-metabolic disorders are common in this population and include poor socioeconomic conditions, substance use, cardiovascular comorbidities, and liver/kidney disease. Chronic HIV/HCV infection induces an inflammatory and immune-activated state in the host leading to alterations in glucose and lipid metabolism. Selection of life-saving ART must carefully consider the differential metabolic risk associated with each drug class and agent, such as dyslipidemia, hyperglycemia and insulin resistance, weight gain, and hypertension. Emerging evidence supports metabolic derangements in chronic HCV may be improved by viral eradication with direct-acting antivirals; however, additional study in HIV/HCV co-infected patients is needed.SummaryFuture research programs should aim to better characterize metabolic syndrome in HIV/HCV co-infected patients with the goal of improved screening, treatment, and prevention. Opinion statementPersons with HIV are living longer due to highly effective antiretroviral therapy (ART). Age-related non-AIDS comorbidities (e.g., cardiovascular and metabolic disorders) increasingly account for morbidity and mortality in this population. Chronic HCV is independently associated with dyslipidemia, hepatic steatosis, and insulin resistance. The role of curative anti-HCV direct-acting antiviral (DAA) therapy in reversing metabolic derangements is being actively investigated. Less is known regarding how HIV co-infection may influence HCV-induced metabolic sequelae and potential recovery with DAAs after viral cure. However, evidence consistently supports that compared with mono-infected counterparts, patients with HIV/HCV co-infection are at increased risk of metabolic syndrome, which predisposes to the development of type 2 diabetes and cardiovascular disease. This is likely multifactorial due to patient-specific factors, direct effects of chronic HIV/HCV infection on glucose and lipid metabolism, and cardio-metabolic toxicities associated with long-term ART use. Newer antiretrovirals, particularly integrase strand transfer inhibitors and tenofovir alafenamide, have been associated with weight gain and dyslipidemia, respectively. Additional investigation of the mechanisms-both viral- and ART-mediated-driving metabolic syndrome in HIV/HCV co-infection is needed; in addition to the potential for metabolic reversal following DAA therapy. Finally, further studies evaluating appropriate screening modalities and intervals, prevention tools, and therapeutics are needed to inform the clinical management of metabolic syndrome in patients with HIV/HCV co-infection.