Which once daily HIV regimen, such as Atripla (efavirenz), Stribild (elvitegravir), Odefsey (rilpivirine), or Biktarvy (bictegravir), has the greatest risk of weight gain?

Weight Gain Risk Among Once-Daily HIV Regimens

Biktarvy (bictegravir/TAF/FTC) has the greatest risk of weight gain among the regimens listed, followed closely by Odefsey (rilpivirine/TAF/FTC), while Atripla (efavirenz/TDF/FTC) has the lowest risk and may actually prevent weight gain. 1, 2, 3

Ranking by Weight Gain Risk (Highest to Lowest)

Highest Risk: Biktarvy

• Biktarvy causes approximately 3.9 kg greater weight gain in the first 6 months compared to Atripla 3
• The combination of bictegravir (an INSTI) with TAF creates a "double hit" for weight gain, as both INSTIs and TAF independently promote weight gain 1, 4
• Among INSTIs, bictegravir shows one of the highest weight gain profiles alongside dolutegravir 1

High Risk: Odefsey

• Odefsey (rilpivirine/TAF/FTC) carries substantial weight gain risk primarily due to the TAF component 1, 5
• Rilpivirine is associated with more weight gain than efavirenz among NNRTIs 4
• The TAF formulation causes greater weight gain than TDF formulations, with most gain occurring within the first year 5
• Women and Black individuals face particularly elevated risk with TAF-containing regimens 5

Moderate Risk: Stribild

• Stribild (elvitegravir/cobicistat/TDF/FTC) has moderate weight gain risk - lower than Biktarvy or Odefsey but higher than Atripla 3, 4
• The TDF component partially mitigates weight gain compared to TAF formulations 1, 4
• Elvitegravir/cobicistat is associated with less weight gain than dolutegravir or bictegravir among INSTIs 4

Lowest Risk: Atripla

• Atripla (efavirenz/TDF/FTC) has the lowest weight gain risk and may actually inhibit weight gain 1, 2, 4
• Mean weight gain on Atripla is only 2.3 kg over 96 weeks compared to 7.1 kg with dolutegravir/TAF regimens 2
• Both efavirenz and TDF are associated with weight loss when switching to these agents, making comparisons complex 6
• TDF may actively inhibit weight gain through mechanisms demonstrated in placebo-controlled PrEP studies 6

Clinical Implications

Monitoring Recommendations

• Document weight and BMI every 6 months for patients on INSTI- or TAF-based regimens (Biktarvy, Odefsey, Stribild) 6
• Most weight gain occurs within the first year, particularly with TAF-containing regimens 5

Management Considerations

• Switching regimens solely because of weight gain is not currently recommended due to known toxicities of alternatives like TDF (renal and bone effects) 6, 5
• Counsel all patients about potential weight gain and emphasize lifestyle modifications including diet and exercise 6
• If weight gain is a primary concern before starting therapy, avoid INSTI + TAF combinations and consider NNRTI-based regimens with TDF 1

Reversibility

• Switching from TAF back to TDF can result in weight loss, demonstrating the medication-related nature of this effect 5, 7
• One case report documented return to baseline weight after switching from Stribild back to Atripla 7
• However, this must be balanced against TDF's known renal and bone toxicities 5

Important Caveats

• The majority of patients experience weight changes <5% of body weight; only a minority gain >10% 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 6
• Risk factors for excessive weight gain include low baseline CD4 count, high viral load, female sex, and Black race 6, 4