Introduction

Diabetes mellitus (DM) is increasingly recognized among people living with HIV (PLHIV). The relationship is bidirectional:

• HIV infection causes chronic inflammation and immune activation, increasing insulin resistance.

• Antiretroviral therapy (ART), particularly protease inhibitors, contributes to metabolic complications.

• Diabetes worsens cardiovascular risk, renal disease, and infection outcomes in PLHIV.

Metabolic abnormalities associated with HIV include:

• Insulin resistance

• Impaired glucose tolerance

• Dyslipidemia

• Lipodystrophy

• Metabolic syndrome

As survival of PLHIV improves with ART, non-communicable diseases like diabetes are becoming major causes of morbidity and mortality.

Risk Factors

HIV-related

• Long duration of HIV infection

• Chronic immune activation

• High viral load

• Low CD4 count

• Use of Protease Inhibitors (PIs)

• Use of older ART regimens

Traditional diabetes risk factors

• Age > 40 years

• Obesity (especially central obesity)

• Family history of diabetes

• Sedentary lifestyle

• Hypertension

• Dyslipidemia

• Smoking

ART-related metabolic risks

• Lipodystrophy

• Weight gain after ART initiation

• Metabolic syndrome

Signs and Symptoms

Diabetes symptoms

• Polyuria

• Polydipsia

• Polyphagia

• Blurred vision

• Fatigue

• Recurrent infections

HIV-related metabolic complications

• Central fat accumulation

• Peripheral fat wasting

• Dyslipidemia

• Weight gain (especially with newer integrase inhibitors)

Advanced complications

• Diabetic ketoacidosis (rare but possible)

• Hyperosmolar hyperglycemic state

• Cardiovascular disease

Diagnostic Criteria

Diagnosis of diabetes in people with HIV follows standard criteria:

Any one of the following:

• Fasting plasma glucose ≥ 7.0 mmol/L

• Random plasma glucose ≥ 11.1 mmol/L with symptoms

• HbA1c ≥ 6.5%

• 2-hour OGTT ≥ 11.1 mmol/L

Screening Recommendations

• Screen all PLHIV at ART initiation

• Repeat screening annually

• Screen earlier if CVD risk factors present

Investigations

For Diabetes

• Fasting blood glucose

• Random blood glucose

• HbA1c

• Urinalysis

• Lipid profile

• Renal function tests

For HIV monitoring

• CD4 count

• Viral load

• Liver function tests

• ART drug review

Additional metabolic assessment

• BMI

• Waist circumference

• Blood pressure

Management

General Principles

• Standards of diabetes management in HIV are similar to those without HIV.

• Review ART regimen if severe metabolic complications occur.

• Lifestyle modification is essential.

• Insulin is preferred if severe insulin resistance is present.

ARVs and Metabolic Dysfunction

• Protease Inhibitors (PIs) increase insulin resistance.

• PIs interfere with GLUT-4 mediated glucose transport.

• Some ARVs contribute to dyslipidemia and lipodystrophy.

• Chronic inflammation worsens insulin resistance.

Non-Pharmacological Management

• Weight control

• Balanced diabetic diet

• Increased physical activity

• Smoking cessation

• Alcohol reduction

• Stress reduction

• Adequate sleep

Lifestyle modification significantly reduces cardiovascular risk in PLHIV.

Pharmacological Management

First-line (if no contraindications)

• Metformin (if no renal or hepatic impairment)

Caution:

• Avoid in advanced renal dysfunction.

• Monitor lactic acidosis risk (rare but possible).

Sulfonylureas

• May be less effective in severe insulin resistance.

• Avoid escalating dose excessively.

Insulin

Indications:

• Severe insulin resistance

• Poor glycemic control despite oral agents

• Advanced HIV disease

• Acute illness

• Hospitalized patients

Insulin should be initiated rather than increasing multiple oral medications if glycemic control deteriorates.

Drug Interaction Considerations

• Rifampicin (if TB co-infection) may reduce effectiveness of oral agents.

• Some ART drugs affect hepatic metabolism.

• Monitor for hypoglycemia if ART is modified.

Monitoring

• Fasting glucose every 3–6 months

• HbA1c every 6 months

• Annual lipid profile

• Annual renal function

• Monitor weight and waist circumference

Prevention

Prevent Diabetes in PLHIV

• Routine annual screening

• Early ART initiation

• Weight management

• Physical activity

• Dietary counseling

• Control of hypertension and dyslipidemia

Prevent Complications

• Strict glycemic control

• Cardiovascular risk reduction

• Smoking cessation

• Regular follow-up

Key Clinical Message