What is the timeline for weight gain associated with antiretroviral therapies (ART) like Biktarvy (bictegravir, emtricitabine, and tenofovir alafenamide), Juluca (dolutegravir and rilpivirine), Dovato (dolutegravir and lamivudine), and Cabenuva (cabotegravir and rilpivirine)?

Timeline for Weight Gain with Antiretroviral Therapy

Weight gain with modern antiretroviral regimens occurs primarily within the first year of treatment, with most changes happening in the first 24 weeks, after which weight typically plateaus by 48 weeks. 1, 2, 3, 4

Early Phase Weight Gain (0-24 Weeks)

• The majority of weight gain occurs during the first 24 weeks (approximately 6 months) after ART initiation or switch, representing the most rapid phase of weight change 4
• Weight gain is most pronounced in the first year following initiation or switch to TAF-containing regimens 2
• Differences in weight trajectories between different ART regimens are driven mainly by changes during the first year of treatment 3

Intermediate Phase (24-48 Weeks)

• Weight gain typically plateaus by 48 weeks (approximately 1 year) after ART switch or initiation 4
• By week 48,6.4% of patients who switched regimens gained ≥10% of their body weight, compared to only 2.2% who remained on stable baseline regimens 4
• The median weight gain at 48 weeks for those switching regimens was 1.6 kg (IQR: -0.05 to 4.0 kg) versus 0.4 kg (IQR: -1.8 to 2.4 kg) for those remaining on stable regimens 4

Long-Term Weight Changes (Beyond 48 Weeks)

• Weight gain continues but at a slower rate beyond the first year, with ongoing monitoring recommended every 6 months for patients on INSTI- or TAF-based regimens 1, 2
• At 96 weeks, DTG-based regimens showed a mean difference of 1.99 kg higher weight gain compared to efavirenz-based regimens (95% CI: 0.85-3.09) 5
• Weight gain was observed across all treatment groups through 144 weeks in clinical trials, though the rate of gain decreased substantially after the first year 6

Regimen-Specific Timeline Considerations

INSTI-Based Regimens (Biktarvy, Dovato, Cabenuva)

• Bictegravir and dolutegravir show higher weight gain profiles among INSTIs, with most gain occurring in the first 24-48 weeks 1
• INSTI-based regimens are associated with greater weight gain than NNRTI- or PI-based regimens, primarily observed with longer therapy duration 1

TAF-Containing Regimens (Biktarvy)

• Weight gain with TAF typically occurs within the first year following initiation or switch 2
• Switching from TDF to TAF results in greater weight gain than switching from abacavir to TAF 4
• The effect is reversible: switching from TAF back to TDF results in weight loss, demonstrating the medication-related nature 1, 2

Cabenuva (Long-Acting Injectable)

• While specific timeline data for cabotegravir/rilpivirine is limited in the provided evidence, the INSTI component (cabotegravir) would be expected to follow similar patterns to other INSTIs, with most weight gain in the first 24-48 weeks 1

Clinical Monitoring Algorithm

For patients initiating or switching to high-risk regimens (INSTI + TAF combinations):

• Baseline: Document weight and BMI before starting therapy 1, 2
• Weeks 12-24: Monitor closely as this is the period of most rapid weight gain 4
• Week 48: Assess total weight change; most patients will have plateaued by this point 4
• Every 6 months thereafter: Continue monitoring weight and BMI for all patients on INSTI- or TAF-based regimens 1, 2

Risk Factors Affecting Timeline

• Women and Black individuals experience greater and more rapid weight gain with TAF-containing regimens 2
• Younger age and lower baseline BMI are associated with greater weight gain regardless of regimen 4
• Low baseline CD4 count and high viral load are consistently associated with higher weight gain, as these patients may experience "return to health" weight restoration 7, 5

Management Implications

• Emphasize lifestyle changes including diet and exercise from the start of therapy, particularly for patients on INSTI + TAF combinations 1, 2
• Switching regimens solely because of weight gain is not currently recommended due to known toxicities of alternatives like TDF, though this must be balanced against individual patient concerns 1
• Consider NNRTI-based regimens with TDF if weight gain is a primary concern before starting therapy, as these have the lowest weight gain profile 1
• The reversibility of TAF-associated weight gain is limited, with return to pre-therapy weight rarely observed, making prevention more important than reversal 2