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HIV & Aging Clinical Recommendations
The incidence of type 2 diabetes mellitus is reported to be as much as four times higher in patients living with HIV compared to uninfected patients and increases with increasing age. The incidence of the metabolic syndrome is also higher. The increase in risk in ART-treated patients may be related to the use of certain antiretroviral drugs, such as thymidine analogues and protease inhibitors (Llibre 2009; De Wit 2008), obesity, hepatitis C coinfection. It appears that newer protease inhibitors and integrase strand transfer inhibitors do not promote glucose intolerance (Rasmussen 2012). Prevention of diabetes is similar to the approach in uninfected older patients, focusing on lifestyle changes such as weight loss, aerobic exercise and proper diet. Screening for glucose intolerance should be performed regularly, before and after initiation of ART (Simone 2008). There is some debate on whether screening should be done with fasting blood glucose levels (FBG) or using glycated hemoglobin. The American Diabetes Association has recommended that glycated hemoglobin is an acceptable screening tool, with a diagnosis of diabetes when the glycated hemoglobin is equal to or greater than 6.5% (Chamberlain 2016). However, studies have shown that while this test is highly specific, it is insensitive and should be combined with FBG (≥126) for screening (Eckhardt 2012; Sangarlangkarn 2016a). Management of patients may include switching to less glucose intolerant antiretroviral drugs and following the American Diabetes Association guidelines (Chamberlain 2016). For younger patients and healthy older patients, the target glycated hemoglobin should less than 7% (Chamberlain 2016) but should be increased to 8% for frail patients, especially if their life expectancy is less than 5 years, are at high risk for hypoglycemia, polypharmacy or drug interactions (Reuben 2015). Recent studies have shown no benefit and possible harm from tight glucose control in type 2 diabetes mellitus (Wilson 2011). The glycated hemoglobin should be checked at least twice yearly. Care of patients living with both HIV and diabetes should focus on prevention of complications (such as foot ulcers, retinopathy, hypertension and vascular disease) as much as with HIV-uninfected patients. Renal function and presence of proteinuria should also be carefully monitored as both diabetes and HIV increase the risk of renal disease. Luckily the incidence of end stage renal disease due to diabetes in patients living with HIV has declined (Abraham 2015). There is increasing prevalence of obesity in the older population and since obesity is a risk factor for development of the metabolic syndrome and hyperglycemia, clinicians should counsel their older patients living with HIV to maintain proper BMI. In one cohort study, the increase in body mass following the initiation of ART was associated with an increased risk of diabetes (Achhra 2016).
Morphologic changes are common in older patients living with HIV/AIDS. Increasing age is risk factor for loss of subcutaneous fat (lipoatrophy) and/or increase in central fat deposition (lipohypertrophy) but newer ART regimens are less likely to promote these changes. Older patients should be switched from thymidine analogues to INSTI’s which are less likely to cause morphologic changes. Treatment options for patients with lipohypertrophy can include surgical removal of fat or use of growth hormone or analogues.
Lifestyle modification (diet and exercise) should be the first step in managing patients with diabetes. Pharmacologic treatment of diabetes for patients living with HIV follows the same guidelines as for those patients without HIV. Metformin, which will result in a 1% decline in glycosylated hemoglobin, should be the first-line medication, unless there is a contraindication such as significant renal insufficiency (eGFR <30 ml/min). Sulfonylureas, incretins or insulin can be used as second agents if necessary. Saxagliptin, a DPP-4 inhibitor, should be used with caution with CYP3A inhibitors (Monroe 2015).
The approach to screening for and managing the complications of diabetes in patients living with HIV are similar to those in uninfected patients. Screening for hypertension, renal disease, hyperlipidemia, microvascular complications (retinopathy, neuropathy and nephropathy) need to be done on a regular basis. The JNC 8 guidelines recommend treating systolic pressures above 140 and diastolic pressures above 90 (Sangarlangkarn 2016a). BP targets for frail elderly can be higher due to the increased risk of orthostatic hypotension. Unless contraindicated, aspirin therapy should be initiated. For the treatment of hyperlipidemia, pitavastatin is the only oral lipid lowering agent that does not interact with ART (Monroe 2015). Lower dose atorvastatin may also be used. Pregabalin and duloxetine are recommended as initial treatment for painful peripheral neuropathy. Gabapentin may be considered but it does have an approved indication for this (Pop-Busui 2017).
Reuben DB, Herr KA, Pacala JT, Potter JF, American Geriatrics S. Geriatrics at your fingertips. New York. eBook: American Geriatrics Society; 2016.