Table 17b. Antiretroviral Therapy–Associated Adverse Effects and Management Recommendations—Dyslipidemia

PIs

• All PIs, especially RTV-boosted PIs; lower incidence reported with DRV/r and ATV, with or without RTV

NRTIs

• Lower incidence reported with TDF than with TAF

NNRTIs

• Lower incidence reported with NVP, RPV, and ETR than with EFV

INSTIs

• EVG/c

Onset

• As early as 2 weeks to months after beginning therapy

Presentation

PIs

• ↑ LDL-C, TC, and TG

NRTIs

• ↑ LDL-C, TC, and TG. Significant increase in plasma lipid values was observed in adults switching from TDF to TAF, regardless of third agent or presence of a boosting agent.

NNRTIs

• ↑ LDL-C, TC, and HDL-C

Reported frequency varies with specific ARV regimen, duration of ART, and the specific laboratory parameters used to diagnose lipid abnormalities.

10% to 20% of young children receiving LPV/r will have lipid abnormalities.

40% to 75% of older children and adolescents with prolonged ART history will have lipid abnormalities.

Pooled dyslipidemia prevalence of 39.5% and an incidence of 32% (191 per 1,000 person-years) reported in a recent meta-analysis and a recent review of a large consortium of prospective observational cohorts, respectively.

Advanced-stage HIV disease

High-fat, high‑cholesterol diet

Sedentary lifestyle

Obesity

Hypertension

Smoking

Family history of dyslipidemia or premature ASCVD

Metabolic syndrome

Fat maldistribution

Prevention

• Low-fat diet
• Exercise
• Smoking-prevention counseling
• Use of ARVs is associated with a lower prevalence of dyslipidemia, such as INSTIs, and to a lesser extent, newer PIs (e.g., ATV, DRV).
• When considering a TDF-based or TAF-based regimen, the lipid-lowering beneficial effect of TDF should be weighed against its potential for increased renal and bone toxicities.

Monitoring^a

• Obtain fasting (or non‑fasting) lipid profile (TC, HDL-C, non-HDL-C, LDL-C, and TG) twice (>2 weeks but ≤3 months apart) and average these results. Monitor every 6 months (for abnormal results) or every 12 months (for normal results).
• If TG or LDL-C is elevated or if a patient has additional risk factors, obtain FLP.

Children With Lipid Abnormalities and/or Additional Risk Factors

• Obtain 12-hour fasting lipid profile (FLP) before initiating or changing therapy and every 6 months thereafter (more often if indicated).

Children Receiving Lipid-Lowering Therapy With Statins or Fibrates

• Obtain 12-hour FLP, LFT, and CK at 4 weeks, 8 weeks, and 3 months after starting lipid therapy.
• If minimal alterations in AST, ALT, and CK are indicated, monitor every 3–4 months during the first year and every 6 months thereafter (or as clinically indicated).
• Repeat FLP 4 weeks after increasing doses of antihyperlipidemic agents.

Assess all patients for additional ASCVD risk factors. Patients with HIV are considered to be at moderate risk for ASCVD.^b

ARV regimen changes should be considered, especially when the patient is receiving older PIs (e.g., LPV/r) and/or RTV boosting. Switching to a PI-sparing regimen, a PI-based regimen with a more favorable lipid profile, or COBI boosting causes a decline in LDL‑C or TG values. The lipid-lowering effect of an ARV regimen switch on LDL-C is less pronounced than with statin therapy but may be enough to re-establish a healthy lipid profile.

Refer patients to a lipid specialist early if LDL-C is ≥250 mg/dL or TG is ≥500 mg/dL.

If LDL-C is ≥130 mg/dL but <250 mg or TG is ≥150 mg/dL but <500 mg/dL, the following staged treatment approach is recommended by the NHLBI guidelines^b:

• Implement diet, nutrition, and lifestyle management for 6‍–‍9 months. Consult with a dietician if one is available.
• If a 6- to 9-month trial of lifestyle modification fails and the patient is aged ≥10 years, consider implementing lipid-lowering therapy after consulting a lipid specialist.
• Statin therapy should be considered for patients with elevated LDL-C levels. NHLBI guidelines provide recommendations for statin therapy in patients with specific LDL-C levels and risk factors.^b Concurrent substitution—preferably to ARVs with no inhibitory or inducing effect on CYP3A4 or OATP1B1 (e.g., INSTI)—also should be considered as appropriate to limit drug–drug interaction potential.
• Drug therapy can be considered in cases of severe hypertriglyceridemia (TG ≥500 mg/dL). Fibrates (gemfibrozil and fenofibrate) may be used.

The long-term risks of lipid abnormalities in children who are receiving ART are unclear. However, persistent dyslipidemia in children may lead to premature ASCVD.