Recommended First-Line Antiretroviral Therapy Regimens and Risk of Diabetes Mellitus in HIV-Infected Adults in Resource-Limited Settings

Abstract

Objective The use of some antiretroviral drugs has been associated with a higher risk of diabetes mellitus (DM) in HIV-infected patients, but the risk associated with antiretroviral drug combinations remains unclear. We investigated the association between first-line antiretroviral therapy (ART) regimens, recommended by the World Health Organization (WHO) in 2016, and the risk of DM in adults. Method We selected all HIV-infected adults within the Thai National AIDS Program who started a first-line ART regimen consisting the following between October 2006 and September 2013: zidovudine+lamivudine+nevirapine; tenofovir disoproxil fumarate (TDF)+lamivudine+nevirapine; zidovudine+lamivudine+efavirenz; TDF+lamivudine/emtricitabine+efavirenz; zidovudine+lamivudine+ritonavir-boosted lopinavir (LPV/r); or TDF+lamivudine+LPV/r. Diagnosis of DM was defined as having at least 2 of the following characteristics: fasting plasma glucose ≥126 mg/dl, 2010 WHO ICD-10 codes E11-E14, or prescription of antidiabetic drugs. To identify ART regimens associated with DM, we used competing risks regression models that considered mortality without DM as a competing event and adjusted for sex, age, pancreas disease, and stratified by groups defined by a score summarizing the propensity to receive a specific first-line ART regimen. Results Data from 35 710 adults (49.1% male; median age, 35.0 years; median follow-up, 2.0 years) were included. In the multivariable analysis with zidovudine+lamivudine+nevirapine as the reference group, a higher risk of DM was observed with TDF+lamivudine/emtricitabine+efavirenz (adjusted sub-distribution hazard ratio [aSHR], 1.6; 95% confidence interval [CI], 1.3–1.9), zidovudine+lamivudine+efavirenz (aSHR, 2.0; 95% CI, 1.7–2.3), and TDF+lamivudine+LPV/r (aSHR, 2.7; 95% CI, 1.9–3.9). Conclusions Several of the WHO recommended ART regimens, particularly tenofovir + lamivudine +LPV/r and regimens containing efavirenz, may be associated with an increased risk of DM.

COVID-19 in people with diabetes: understanding the reasons for worse outcomes

“… 99 Conversely, antiviral drugs such as lopinavir and ritonavir could lead to hyperglycaemia and worsen glycaemic control. 102 These agents can cause hepatic and muscle toxicity so caution is recommended when they are used in combination with statins and in patients with fatty liver disease. 103 Pharmacokinetic interactions with antidiabetic drugs are also common, causing over-exposure or under-exposure to either antivirals or anti-diabetic drugs.…”

New onset diabetes, type 1 diabetes and COVID-19

“…Hydroxychloroquine, an immunomodulatory that was extensively used during the initial phases of the pandemic, can decrease insulin degradation at the cellular level and stimulate insulin-mediated glucose transport, resulting in potential hypoglycemia [ 54 , 55 ]. On the other hand, antiviral drugs such as lopinavir and ritonavir could lead to hyperglycemia and worsen glycemic control [ 56 ]. Glucocorticoids, which were seen to improve outcomes in COVID-19 related severe acute respiratory distress syndrome and hence became an integral part of treatment regime for hospitalized patients, can lead to marked hyperglycemia by reducing insulin sensitivity as well as by interfering with the actions of glucagon like peptide-1 and stimulating production of glucagon [ 57 ].…”

Review: Roles of human serum albumin in prediction, diagnoses and treatment of COVID-19

“…Treatment with chloroquine or hydroxychloroquine can cause hypoglycaemia, especially in patients on insulin or sulfonylureas, in light of their consequences for insulin discharge, debasement, and activity [122] . Then again, antiviral medications, for example, lopinavir and ritonavir could prompt hyperglycaemia and intensify glycaemic control [123] . These agents can cause hepatic and muscle poisonousness so an alert is suggested when they are utilized in mix with statins and patients with greasy liver sickness [124] .…”