Drug therapies for HIV-related metabolic disorders.

INTRODUCTION: Human immunodeficiency virus (HIV) has become a chronic disease often associated with dyslipidaemia and insulin resistance. Combination antiretroviral therapy (cART) may contribute to metabolic disturbances, eventually leading to increased cardiovascular disease (CVR) in this population. Escalating interventions to decrease CVR include promoting a healthy lifestyle, such as quitting smoking, diet and regular exercise. If they do not achieve the goals, a change of cART should be considered, followed by or used concomitantly with the use of chemical therapies. AREAS COVERED: The aim of this article is to review the available drug therapies for the treatment of metabolic disorders in HIV-infected patients and to examine their safety and effectiveness in this population. A review of the literature was conducted, highlighting the most relevant articles. EXPERT OPINION: Switching strategies can be useful but its expected benefit is not high. Therefore, chemical intervention is often needed. Statins have been proven to reduce CVR in the general population and in HIV-infected patients. Simvastatin is contraindicated in patients treated with boosted PI due to interactions; atorvastatin is safe at submaximal dose and needs close monitoring, while pravastatin lacks lipid-lowering potency, and rosuvastatin and pitavastatin are safe. Ezetimibe and fibrates are also safe and effective in HIV-infected patients and can be used in combination with statins. The management of glucose homeostatic disorders in HIV-infected patients follows the same guidelines as in the general population. However, there are specific considerations with respect to the interactions of particular medications with cART. When drug therapy is needed, metformin is the first-line drug. Decisions regarding second- and third-line drugs should be carefully individualized.

A 48-week study of fat molecular alterations in HIV naive patients starting tenofovir/emtricitabine with lopinavir/ritonavir or efavirenz.

BACKGROUND: Conflicting reports on the effects of efavirenz (EFV) and lopinavir/ritonavir (LPV/r) on subcutaneous adipose tissue (SAT) have been described. OBJECTIVE: The aim was to assess the 48-week molecular and clinical effects of LPV/r and EFV, combined with tenofovir/emtricitabine (TDF/FTC), on SAT of HIV-infected, antiretroviral-naive patients. METHODS: Forty-four adults were started on LPV/r or EFV combined with TDF/FTC. Fasting metabolic tests, HIV RNA, CD4 cell count, and fat measured by dual x-ray absorptiometry scans were obtained at study entry and week 48. Mitochondrial DNA (mtDNA) and transcripts for mtDNA-encoded proteins and genes involved in inflammation, adipocyte differentiation, and metabolism were assessed in paired SAT biopsies. RESULTS: Whole-body fat and limb fat mass increased in the LPV/r and EFV groups. MtDNA and cytochrome oxidase subunit II did not change, and cytochrome b increased significantly in EFV-treated patients. Tumor necrosis factor alpha and monocyte chemotactic protein-1 gene expression did not change in the LPV/r group, but these significantly increased in the EFV group. Interleukin 18 decreased in the LPV/r group, whereas it increased in the EFV group. CONCLUSIONS: Starting TDF/FTC plus EFV was associated with an increased expression of genes encoding for inflammatory cytokines in SAT in naive patients. Therapy with TDF/FTC plus LPV/r or EFV was associated with an increase in subcutaneous fat mass.