Weight Gain Risk in Antiretroviral Therapy

Comparison of Antiretroviral Drug Classes

Integrase strand transfer inhibitors (INSTIs) cause the most weight gain, followed by protease inhibitors, with NNRTIs causing the least weight gain among antiretroviral drug classes 1
INSTI-based regimens are associated with greater weight gain than either NNRTI- or PI-based regimens, though this is primarily observed with longer therapy duration 1
Among INSTIs, bictegravir and dolutegravir show higher weight gain profiles 1
PI class-specific metabolic complications include insulin resistance, diabetes, dyslipidemia, and lipodystrophy 1, 2
NNRTIs are not specifically associated with weight gain as a class effect 2, 3
The primary adverse effects of NNRTIs are CNS toxicity, rash, and hyperlipidemia—not weight gain 2, 3

Greater weight gain occurs with regimens containing tenofovir alafenamide (TAF) compared to tenofovir disoproxil fumarate (TDF), regardless of the third agent class 4
Weight gain with TAF typically occurs within the first year following initiation or switch 4
Women and Black individuals are at higher risk for weight gain with TAF-containing regimens 4
Switching from TAF back to TDF results in weight loss, demonstrating the medication-related nature of this effect 4

Avoid INSTI + TAF combinations if weight gain is a primary concern 1, 4
Consider NNRTI-based regimens (particularly efavirenz or doravirine) with TDF as they have the lowest weight gain profile 3, 4
Document weight and BMI every 6 months for patients on TAF-based regimens 4
Emphasize lifestyle changes including diet and exercise for managing established weight gain 4
Switching from TAF to TDF can reverse weight gain, though this must be balanced against TDF's known renal and bone toxicities 4

The American Medical Association recommends documenting weight and BMI every 6 months for all patients on INSTI- or TAF-based regimens to identify excessive weight gain 5
Emphasizing lifestyle changes including diet and exercise is recommended for all patients on these regimens 5
Switching regimens solely because of weight gain is not currently recommended due to known toxicities of alternatives like TDF, as stated by the Journal of the American Medical Association 5

The use of GLP-1 receptor agonists shows similar efficacy for weight loss in people with HIV as in the general population, though loss of muscle mass is a concern in older patients at risk for sarcopenia, according to the Journal of the American Medical Association 5

Both efavirenz and TDF are associated with weight loss when switching to these agents, making comparisons complex, as noted by the American Medical Association 6
TDF may actively inhibit weight gain through mechanisms demonstrated in placebo-controlled PrEP studies, according to the American Medical Association 7
The majority of patients experience weight changes <5% of body weight; only a minority gain >10%, as reported by the American Medical Association 6
Weight gain can represent appropriate "return to health" in patients with HIV-related weight loss, but can also lead to obesity in those starting with normal or elevated baseline weight, as noted by the American Medical Association 7
Risk factors for excessive weight gain include low baseline CD4 count, high viral load, female sex, and Black race, according to the American Medical Association 7

Document weight and BMI every 6 months for patients on INSTI- or TAF-based regimens (Biktarvy, Odefsey, Stribild), as recommended by the American Medical Association 6
Counsel all patients about potential weight gain and emphasize lifestyle modifications including diet and exercise, as advised by the American Medical Association 6, 7