An Interview With Todd T. Brown, M.D., Ph.D.
Referral and Antiretroviral Interactions
Mascolini: Are there glucose-related clinical developments in HIV patients that should prompt HIV clinicians to refer those patients to an endocrinologist?
Brown: Referral really depends on how comfortable the provider is in dealing with diabetes. As an endocrinologist, I see patients with the full gamut of severity of diabetes. Some physicians get me involved after a patient has tried one drug, for example, metformin, and they clearly need additional drugs. Other providers will get me involved when two drugs have failed. Others will call me in when a patient has diabetes complications that make overall care complicated. Others will get me involved when the consideration of insulin is on the table.
So it depends on the provider's comfort level and infrastructure in dealing with diabetes. It is a resource-intensive disease, and oftentimes endocrinologists might be better equipped in terms of having certified diabetes educators and nutritionists available to help care for these patients.
Mascolini: Are there any other clinical issues related to HIV and diabetes that you'd like to bring to the attention of HIV clinicians?
Brown: One important issue with all comorbidities is the potential interaction between antiretrovirals and drugs used to treat the comorbidities. In the diabetes world we've been fortunate in that many of the drugs used to treat diabetes can be used without a problem in HIV-infected patients regardless of what antiretrovirals they're taking.
There are a few notable exceptions. Some of the new DPP-4 inhibitors -- the gliptin class of hypoglycemics -- can interact with antiretrovirals. Saxagliptin, for example, is a substrate for CYP3A4, so it should probably be avoided in HIV-infected patients taking a CYP3A4 inhibitor like ritonavir or cobicistat.5
The other interaction that can affect many HIV patients with diabetes is the interaction between metformin and the integrase inhibitor dolutegravir.6 Depending on the dose of dolutegravir, metformin concentrations can increase by 50% to 100%. So I generally go with metformin dose reductions in those patients. That's an important interaction that clinicians should know as more and more patients start integrase inhibitor-based regimens.
|Making Diet and Exercise Part of the Glucose-Control Plan|
A recently published review by Todd Brown and colleagues offers guidance on integrating diet and exercise into a glucose-control plan for people with HIV:
- "Referral to a registered dietician for medical nutrition therapy is recommended for all patients with diabetes mellitus, as even modest weight loss (as little as 2 kg) can have an impact on glycemic control."
- "Calorie guidelines for weight loss are (1) 1200-1500 calories/day for women or 1500-1800 calories/day for men; (2) an energy deficit of 500 or 750 calories per day, based on the individual; or (3) an evidence-based diet that restricts a certain food type (eg, high-carbohydrate foods) to create an energy deficit."
- "Dietary recommendations for patients with DM include monitoring carbohydrate intake, limiting consumption of sugar-sweetened beverages, and following a Mediterranean-style diet."
- "A patient-friendly diet guide."
- "Aerobic exercise is recommended for at least 150 minutes a week, spread out over at least 3 days per week, along with strength training twice a week."
- "An exercise partner, use of a pedometer with a target (eg, 10 000 steps/day), or individualized counseling with exercise prescription" may encourage people to exercise."
- "Linking patients with community- or workplace-based programs may increase exercise uptake."
The article also analyzes the impact of antiretrovirals and statins on diabetes risk, individualized management of diabetes, drug therapy for diabetes, comprehensive cardiovascular risk reduction, and other issues.
Monroe AK, Glesby MJ, Brown TT. Diagnosing and managing diabetes in HIV-infected patients: current concepts. Clin Infect Dis. 2015;60:453-462.
- Brown TT, Cole SR, Li X, et al. Antiretroviral therapy and the prevalence and incidence of diabetes mellitus in the Multicenter AIDS Cohort Study. Arch Intern Med. 2005;165:1179-1184.
- Justman JE, Benning L, Danoff A, et al. Protease inhibitor use and the incidence of diabetes mellitus in a large cohort of HIV-infected women. J Acquir Immune Defic Syndr. 2003;32:298-302.
- Butt AA, McGinnis K, Rodriguez-Barradas MC, et al. HIV infection and the risk of diabetes mellitus. AIDS. 2009;23:1227-1234.
- Brown TT, Tassiopoulos K, Bosch RJ, Shikuma C, McComsey GA. Association between systemic inflammation and incident diabetes in HIV-infected patients after initiation of antiretroviral therapy. Diabetes Care. 2010;33:2244-2249.
- Patel CG, Li L, Girgis S, Kornhauser DM, Frevert EU, Boulton DW. Two-way pharmacokinetic interaction studies between saxagliptin and cytochrome P450 substrates or inhibitors: simvastatin, diltiazem extended-release, and ketoconazole. Clin Pharmacol. 2011;3:13-25.
- Zong J, Borland J, Jerva F, Wynne B, Choukour M, Song I. The effect of dolutegravir on the pharmacokinetics of metformin in healthy subjects. J Int AIDS Soc. 2014;17(4 Suppl 3):19584.
- Capeau J, Bouteloup V, Katlama C, et al. Ten-year diabetes incidence in 1046 HIV-infected patients started on a combination antiretroviral treatment. AIDS. 2012;26:303-314.
- Lennox JL, Landovitz RJ, Ribaudo HJ, et al. Efficacy and tolerability of 3 nonnucleoside reverse transcriptase inhibitor-sparing antiretroviral regimens for treatment-naive volunteers infected with HIV-1: a randomized, controlled equivalence trial. Ann Intern Med. 2014;161:461-471.
- Impact of antiretroviral therapy on metabolic, skeletal, and cardiovascular parameters. ClinicalTrials.gov NCT00851799.
- Slama L, Palella FJ Jr, Abraham AG, et al. Inaccuracy of haemoglobin A1c among HIV-infected men: effects of CD4 cell count, antiretroviral therapies and haematological parameters. J Antimicrob Chemother. 2014;69:3360-3367.