HIV infection and diabetes

HIV-infected individuals are at high risk for abnormal glucose metabolism, speculated to be multifactorial in etiology, including, but not limited to, the effects of HIV infection itself, common comorbidities, and the use of antiretroviral medications. Since the introduction of highly active HAART therapy, it has been well recognized that there is considerable variability among individual agents with newer medications generally being associated with a less severe metabolic profile. The postulated mechanisms by which antiretroviral causes dysglycemia include via direct effects on peripheral and hepatic insulin sensitivity, as well as pancreatic β-cell function, mitochondrial toxicity, and the development of peripheral lipoatrophy and/or visceral fat accumulation. Changes in body composition, including peripheral lipoatrophy (rarely seen in the setting of contemporary antiretroviral agents) and lipohypertrophy, are also seen. It is recommended that HIV-infected individuals be screened for the presence of glucose abnormalities with a fasting glucose prior to the initiation of ARV therapy, 1-3 months after starting treatment and then every 3-6 months. There are increasing data that the HbA1c may underestimate glucose derangements. Overall, avoidance of older ARV regimens associated with metabolic disease is recommended when possible. Oral diabetes medications and insulin can safely be used in individuals with HIV. First-line treatment is with metformin, though one must screen for risk factors associated with lactic acidosis. Use of PPARs has fallen out of favor in the setting of adverse cardiovascular effects reported with rosiglitazone use. Limited data exist on the use of other oral agents (sulfonylureas, SGLT2 inhibitors, DPP4 inhibitors) and injectables (GLP-1 agonists) in HIV-infected individuals. The current recommended strategy of peripheral lipoatrophy is to replace the older NRTIs most closely associated with lipoatrophy with more commonly used and newer NRTIs. Tesamorelin, a growth hormone releasing hormone analogue, may be useful in reduction of VAT in the setting of lipohypertrophy.