Antiretroviral Associated Adverse Effects and Management Recommendations for Lipodystrophies and Weight Gain

Adverse Effects	Associated ARVs	Onset/Clinical Manifestations	Estimated Frequency	Risk Factors	Prevention/Monitoring	Management
Lipodystrophy (Fat Maldistribution) General Information	See below for specific associations.	Onset Increase in trunk and limb fat is the first sign; peripheral fat wasting may not appear for 12–‍24 months after ART initiation.	Frequency is low (<5%) with current regimens.	Genetic predisposition Puberty HIV-associated inflammation Older age Longer duration of ART Body habitus	Prevention Initiate a calorically appropriate low-fat diet and an exercise regimen. Monitoring BMI measurement Waist circumference and waist-hip ratio	Physicians should perform a regimen review and consider changing the regimen when lipodystrophy occurs. Improvement in fat maldistribution can vary following a regimen change. Improvement may occur after several months or years, or it may not occur at all.
Central Lipohypertrophy or Lipo-accumulation	Can occur in the absence of ART, but these conditions most often are associated with the use of PIs and EFV.	Presentation Central fat accumulation with increased abdominal girth, which may include a dorsocervical fat pad (buffalo hump). Gynecomastia may occur in males, or breast hypertrophy may occur in females, particularly with the use of EFV.	Frequency is low (<5%) with current regimens.	Obesity before initiation of therapy Sedentary lifestyle	Prevention Initiate a calorically appropriate low-fat diet and an exercise regimen. Monitoring BMI measurement Waist circumference and waist-hip ratio measurements	Counsel patient on lifestyle modification and dietary interventions (e.g., maintaining a calorically appropriate diet that is low in saturated fats and simple carbohydrates and starting an exercise regimen, especially strength training). Recommend smoking cessation (if applicable) to decrease future CVD risk. Consider using an INSTI instead of a PI or EFV, although some INSTIs may be associated with generalized weight gain (see below). Data Are Insufficient to Allow the Panel to Safely Recommend Use of Any of the Following Modalities in Children: Recombinant human growth hormone Growth hormone–releasing hormone Metformin Thiazolidinediones Recombinant human leptin Anabolic steroids Liposuction
Facial/Peripheral Lipoatrophy	Most cases are associated with the use of ZDV, a thymidine analogue NRTI.	Presentation Thinning of subcutaneous fat in the face, buttocks, and extremities, measured as a decrease in trunk/limb fat by DXA or triceps skinfold thickness. Preservation of lean body mass distinguishes lipoatrophy from HIV-associated wasting.	Frequency is low (<5%) with current regimens.	Underweight before ART initiation	Prevention Limit the use of ZDV. Monitoring Patient self-report and physical examination are the most sensitive methods of monitoring lipoatrophy.	Replace ZDV with another NRTI when possible. Data Are Insufficient to Allow the Panel to Safely Recommend Use of Any of the Following Modalities in Children: Injections of poly-L-lactic acid Recombinant human leptin Autologous fat transplantation Thiazolidinediones
Weight Gain	Significant weight gain may occur with all ARV regimens, but it appears to be more pronounced with INSTIs (DTG, BIC, EVG, RAL) and TAF.	Onset Gradual weight gain after initiating ARV drugs is common with all currently used regimens. The mechanism for weight gain is unclear and under investigation.	Rate of development of obesity is unclear.	In Infants and Children Limited evaluation has demonstrated weight gain, but such observations have not been consistently attributable to specific ARVs In Adolescents Female sex Pre-treatment obesity In Adults Low pre-treatment BMI Older age Female sex Black race Possible genetic polymorphisms	Prevention Initiate a calorically appropriate low-fat diet and an exercise regimen. Monitoring BMI measurement Waist circumference and waist-hip ratio measurements	Counsel patient on lifestyle modifications and dietary interventions (e.g., maintaining a calorically appropriate healthy diet that is low in saturated fats and simple carbohydrates and starting an exercise regimen, especially strength training). Children with HIV and significant weight gain should be managed according to standard AAP recommendations for weight management.
Key: AAP = American Academy of Pediatrics; ART = antiretroviral therapy; ARV = antiretroviral; BIC = bictegravir; BMI = body mass index; CVD = cardiovascular disease; DTG = dolutegravir; DXA = dual energy X-ray absorptiometry; EFV = efavirenz; EVG = elvitegravir; INSTI = integrase strand transfer inhibitor; NRTI = nucleoside reverse transcriptase inhibitor; the Panel = the Panel on Antiretroviral Therapy and Medical Management of Children Living With HIV; PI = protease inhibitor; RAL = raltegravir; TAF = tenofovir alafenamide; ZDV = zidovudine

References

Table 17h. Antiretroviral Therapy-Associated Adverse Effects and Management Recommendations—Lipodystrophies and Weight Gain