Clinical Context

There has been a shift in the general management of people living with HIV (PLWH) to recognize higher rates of chronic illness as patients grow older. One of the most significant of these disease states is type 2 diabetes (T2D). Even though highly active antiretroviral therapy (HAART) has had significant impact on morbidity and mortality in PLWH, it has not been without adverse effects. There has been a shift in the general management of PLWH to recognize higher rates of chronic illness as patients grow older. One of the most significant of these disease states is T2D. Others include dyslipidemia and insulin resistance. A review by Monroe and colleagues, published in the February 1, 2015 issue of Clinical Infectious Diseases,^[1] summarizes the interaction between HIV infection and diabetes.

Up to 14% of PLWH have diabetes, although the role of HIV infection as an independent risk factor for diabetes is controversial. Less controversial is the role of antiretroviral (ARV) therapy in the development of diabetes complications. Patients with HIV tend to have increased incidence of hepatitis C infection, HIV-related inflammation, ART-associated lipoatrophy as well as low testosterone, which present as influential factors in the development of diabetes. Use of some medications in this population serves as a contributing factor as well (ie, corticosteroids, atypical antipsychotics, opiates, and some HIV medications). Protease inhibitors can both reduce insulin secretion and increase insulin resistance, and first-generation ARV agents such as stavudine and indinavir were associated with a higher risk for incident T2D; however, the phasing out of these drugs during the decade of the 2000s resulted in a lower incidence rate of T2D.

The current study by Duncan and colleagues evaluates what has happened to the epidemiology of T2D and dysglycemia between 2005 and 2015 among PLWH.

Study Synopsis and Perspective

Modern treatment offers highly effective and well-tolerated means to treat HIV infection, and thus PLWH infection are living longer. This is something to be celebrated as we mark the 40th anniversary of the discovery of HIV infection in the United States; however, increased longevity as well as some adverse effects of treatment for HIV infection have resulted in higher rates of detection of chronic illness among PLWH.

A new study investigates how the prevalence of T2D has progressed among PLWH over the decade between 2005 and 2015. Researchers purposefully sampled a diverse group of PLWH who were receiving care in clinics around London, England that were not specifically focused on the care of HIV. They compared 337 patients during the 2005 period with 338 from the 2014-2015 period. 

The 2014-2015 cohort was significantly older (median age, 49 [interquartile range (IQR), 42-57] years vs 41 (IQR, 35-47) years; P < .001), had higher body mass index (BMI) values (27.4 [IQR, 23.3-29.9] vs 24.9 [IQR, 22.4-28] kg/m² respectively; P = .019), and higher rates of hypertension (37.9% vs 19.6%, respectively, P < .001) compared with the 2005 cohort. The prevalence rates of T2D in 2014-2015 and 2005 were 15.1% and 6.8%, respectively (P = .003). The relative risk for T2D in the 2015 cohort was estimated at 2.4; however, the prevalence of impaired fasting glucose was similar in the 2 cohorts (2005: 18.1% vs 2015: 17.2%; P = .763). The 2015 cohort showed strong predictors of dysglycemia to be hepatic steatosis and hypertension (odds ratio [OR] = 6.74 [95% CI: 3.48, 13.03] and 2.92 [95% CI: 1.66, 5.16], respectively), and HIV-related factors of weight gain after initiation of ARV and longer duration of infection (OR = 1.07 [95% CI: 1.04, 1.11] and 1.06 [95% CI: 1.02, 1.1] respectively).

One interesting finding from the study was that common risk factors for T2D such as sedentary behavior were more impactful than HIV-related variables, such as the type of ARV therapy employed.

“The alarmingly high prevalence of [T2D] in HIV requires improved screening, targeted to older patients and those with a longer duration of exposure to [ARVs],” the authors of the study wrote.

The authors concluded that “effective diabetes prevention and management strategies are needed urgently to reduce this risk; such interventions should target both conventional risk factors, such as abdominal obesity, and HIV-specific risk factors such as weight gain following initiation of [ARVs].”

Since the study was published in Plos One,^[2] concerns with weight gain in the HIV population have continued to increase, noted first author Alastair Duncan, PhD, principal dietician at Guy’s & St. Thomas’ Hospital and lecturer, King’s College London.

“As in the general population, [PLWH] experienced significant weight gain during COVID-related lockdowns. Added to the higher number of [PLWH] being treated with integrase inhibitors, weight gain remains a challenge,” Duncan told Medscape Medical News.

In addition, “there are not enough studies comparing [PLWH] with the general population,” Duncan added. “We need to conduct studies where participants are matched.”

Overall, the study results suggest that healthcare providers should be screening PLWH for diabetes risk factors, promoting improvement of modifiable risk factors, and routinely testing these patients for T2D.

Clinical Implications

• Older ARVs such as stavudine and indinavir are associated with higher risks for T2D among PLWH.
• In the current study of PLWH by Duncan and colleagues, the prevalence of T2D more than doubled between 2005 and 2015. Hepatic steatosis and hypertension stood out as the most significant risk factors for dysglycemia.
• Implications for the healthcare team: The healthcare team should encourage PLWH to improve modifiable risk factors for T2D and test for diabetes routinely.

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