Weight Gain and Antiretroviral Therapy

Abstract

Antiretroviral therapy (ART) agents as a determinant of body weight in ART-naïve and ART-experienced persons with human immunodeficiency virus (HIV) (PWH) has become a major focus area in research and clinical settings. Recent studies demonstrating weight-suppressing properties of efavirenz and tenofovir disoproxil fumarate led to re-evaluation of weight gain studies, and a reassessment of whether other agents are weight promoting versus weight neutral. In this review, the authors synthesize recent literature on factors related to obesity, clinical measurements of adiposity, weight gain in ART-naïve and ART-experienced PWH, metabolic consequences of ART and weight gain, and the clinical management of weight gain in PWH.

Keywords: Antiretroviral therapy; HIV; Metabolism; Obesity; Weight gain.

Figure 1.

Untreated HIV is characterized by anorexia, decreased nutrient absorption, increased inflammatory cytokines, increased basal metabolic requirements in the setting of opportunistic infections, and an overall catabolic state that results in a negative energy balance and weight loss as HIV progresses. After antiretroviral therapy (ART) initiation, basal metabolic rate decreases, inflammatory cytokines decrease, and metabolism is shifted towards an overall anabolic state. Complex contributions of genetic, psychological stressors, socioeconomic status, neurohormonal regulation of energy intake and usage, physical inactivity, and access to food contribute to net positive energy balance and overall maintenance of weight.

Figure 2.

Example of the limitations of body mass index (BMI) in predicting metabolic disease. Despite the same BMI, the person on the left has a smaller waist circumference, smaller visceral adipose tissue (VAT) volume, and no evidence of insulin resistance whereas the person on the right has a larger waist circumference, larger VAT volume, and significant evidence of insulin resistance.

Figure 3.

Potential models of antiretroviral therapy (ART) agents and relationship with weight gain. In model 1, all excess weight gain is due to their weight promoting effects. Model 1 is not compatible with the most recent data. In model 2, ART agents are only weight suppressing or weight neutral. In model 3, ART agents can be weight suppressing, neutral, or promoting. It is not clear whether model 2 or model 3 is correct. Abbreviation: EFV, efavirenz; INSTIs, integrase strand transfer inhibitors; PIs, protease inhibitors; TAF, tenofovir alafenamide; TDF, tenofovir disoproxil fumarate