Diabetes mellitus and human immunodeficiency virus (HIV) infection increasingly coexist because of improved survival among people living with HIV (PLHIV) receiving antiretroviral therapy (ART). HIV infection and certain antiretroviral medicines contribute to metabolic abnormalities that increase the risk of developing diabetes mellitus and other cardiovascular risk factors.

Chronic HIV infection is associated with persistent immune activation and inflammation, while some antiretroviral drugs, particularly protease inhibitors (PIs), promote insulin resistance, dyslipidaemia, lipodystrophy, and impaired insulin secretion. Consequently, PLHIV have an increased risk of type 2 diabetes mellitus and cardiovascular disease. Early screening, appropriate lifestyle modification, and timely treatment are essential to reduce morbidity and mortality.

Pathophysiology

The development of diabetes in people living with HIV is multifactorial. Chronic HIV infection causes persistent inflammation and immune activation, which impair insulin sensitivity and contribute to insulin resistance. Antiretroviral therapy further increases this risk through drug-induced metabolic disturbances. Protease inhibitors interfere with glucose transporter type 4 (GLUT-4)-mediated glucose transport, reducing glucose uptake by peripheral tissues and impairing pancreatic β-cell insulin secretion. These effects promote hyperglycaemia, dyslipidaemia, lipodystrophy, and metabolic syndrome. Progressive insulin resistance may eventually overwhelm pancreatic β-cell function, resulting in type 2 diabetes mellitus.

Risk factors

Risk factors for diabetes among people living with HIV include:

HIV-related factors

• Long duration of HIV infection

• Chronic immune activation

• High viral load

• Low CD4 cell count

• Use of protease inhibitor-based antiretroviral therapy

• Long-term antiretroviral therapy

Traditional diabetes risk factors

• Age 40 years or older

• Overweight or obesity

• Central obesity

• Family history of diabetes mellitus

• Physical inactivity

• Hypertension

• Dyslipidaemia

• Smoking

ART-related metabolic risk factors

• Lipodystrophy

• Weight gain following ART initiation

• Metabolic syndrome

• Protease inhibitor therapy

Clinical presentation

Patients may present with features of diabetes mellitus, HIV-related metabolic complications, or both.

Symptoms of diabetes

• Polyuria

• Polydipsia

• Polyphagia

• Fatigue

• Blurred vision

• Unexplained weight loss

• Recurrent infections

HIV-related metabolic manifestations

• Central fat accumulation

• Peripheral lipoatrophy

• Dyslipidaemia

• Weight gain following initiation of ART

• Features of metabolic syndrome

Diagnosis

The diagnosis of diabetes mellitus in people living with HIV follows the same criteria as in the general population.

Diabetes is diagnosed if any one of the following is present:

• Fasting plasma glucose ≥7.0 mmol/L

• Random plasma glucose ≥11.1 mmol/L with symptoms of hyperglycaemia

• Two-hour plasma glucose ≥11.1 mmol/L following a 75 g oral glucose tolerance test

• HbA1c ≥6.5%

Screening

People living with HIV should be screened for diabetes:

• Before or at initiation of antiretroviral therapy where feasible

• At least once every year while receiving antiretroviral therapy

• More frequently in individuals with cardiovascular disease risk factors or metabolic syndrome

• Whenever symptoms suggest hyperglycaemia

Investigations

Assessment of diabetes

• Fasting plasma glucose

• Random blood glucose

• HbA1c

• Oral glucose tolerance test when indicated

• Urinalysis

• Lipid profile

• Renal function tests

• Liver function tests

HIV assessment

• CD4 cell count

• HIV viral load

• Review of antiretroviral regimen

Cardiovascular risk assessment

• Blood pressure

• Body mass index

• Waist circumference

Management

General principles

The management of diabetes in people living with HIV is generally similar to that of patients without HIV. Treatment should aim to achieve good glycaemic control while minimizing cardiovascular risk and maintaining effective HIV control.

Patients should:

• Continue antiretroviral therapy unless modification is clinically indicated.

• Receive individualized diabetes treatment.

• Be assessed regularly for cardiovascular risk factors.

• Undergo routine monitoring for diabetes complications.

Non-pharmacological management

Lifestyle modification remains the foundation of treatment.

Patients should be advised to:

• Maintain a healthy body weight.

• Follow a balanced diabetic diet.

• Engage in regular physical activity.

• Stop smoking.

• Limit alcohol consumption.

• Manage hypertension and dyslipidaemia.

• Maintain adherence to antiretroviral therapy.

Pharmacological management

Management generally follows standard diabetes treatment recommendations.

Oral glucose-lowering medicines

Metformin remains an appropriate first-line medicine for most patients without contraindications.

Sulphonylureas may be used when indicated; however, they may be less effective in patients with severe insulin resistance associated with HIV infection or antiretroviral therapy.

If glycaemic control deteriorates despite appropriate oral therapy, insulin should be initiated rather than repeatedly increasing the dosage or adding multiple oral medicines.

Insulin therapy

Insulin should be considered in patients with:

• Severe insulin resistance

• Poor glycaemic control despite oral glucose-lowering medicines

• Acute illness

• Hospitalization

• Contraindications to oral medicines

Early initiation of insulin is preferred when progressive insulin resistance results in inadequate glycaemic control.

Antiretroviral therapy considerations

Certain antiretroviral medicines contribute to metabolic complications.

Important considerations include:

• Protease inhibitors increase insulin resistance.

• Protease inhibitors reduce insulin secretion by interfering with GLUT-4-mediated glucose transport.

• Some antiretroviral medicines contribute to dyslipidaemia.

• Lipodystrophy may develop during long-term ART.

• Changes to antiretroviral therapy should be considered only when clinically indicated and in consultation with HIV specialists.

Monitoring

Patients should undergo regular assessment of:

• Blood glucose

• HbA1c

• Blood pressure

• Body weight

• Waist circumference

• Lipid profile

• Renal function

• Liver function

• HIV viral load

• CD4 cell count

Patients receiving antiretroviral therapy should be screened for diabetes at least once yearly, particularly if other cardiovascular risk factors are present.

Prevention

Preventive strategies include:

• Annual diabetes screening for people receiving antiretroviral therapy

• Early identification of metabolic abnormalities

• Healthy diet

• Regular physical activity

• Weight management

• Smoking cessation

• Control of hypertension and dyslipidaemia

• Regular monitoring during antiretroviral therapy

• Early treatment of insulin resistance and hyperglycaemia

Outcome

Most people living with HIV achieve good glycaemic control when diabetes is diagnosed early and managed according to standard diabetes treatment principles while maintaining effective antiretroviral therapy. Regular screening, lifestyle modification, and appropriate pharmacological treatment reduce the risk of cardiovascular disease and other diabetes-related complications. Patients with severe insulin resistance may require early insulin therapy to achieve optimal glycaemic control, and continued multidisciplinary follow-up is essential to optimize both HIV and diabetes outcomes.