Introduction

Weight gain and metabolic alterations are commonly observed in people living with HIV (PWH) who start antiretroviral therapy (ART). Recent analyses of randomized trials indicate that individuals initiating treatment with integrase strand transfer inhibitors (INSTIs), such as bictegravir (BIC) and dolutegravir (DTG), exhibit a higher risk of weight gain compared to those receiving protease inhibitors or non-nucleoside reverse transcriptase inhibitors.

Aim

The SOLAR study compared weight and metabolic changes in people living with HIV (PWH) switching to long-acting cabotegravir plus rilpivirine (CAB + RPV LA) dosed every 2 months (Q2M) versus continuing daily oral bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF).

Patient Profile

• PWH on BIC/FTC/TAF with undetectable HIV-1 RNA levels (<50 copies/mL) for at least 6 months
• Had a median prior ART duration of 2.5 years, with only prior INSTI exposure and at least 6 months of BIC/FTC/TAF as their first or second regimen.

Methods

• Phase 3b, randomized, open-label study conducted in 118 centers across 14 countries.

Study Outcomes

• At month 12 , changes in body weight, body mass index (BMI), waist circumference (WC), hip circumference (HC), waist-to-height ratio (WHtR), waist-to-hip ratio (WHR), muscle mass, body fat, and proportion with insulin resistance or metabolic syndrome were assessed.

Results

Changes in Weight

• Median weight change at Month 12:
  • CAB + RPV LA: -0.40 kg (IQR -2.95 to +2.10).
  • BIC/FTC/TAF: +0.05 kg (IQR -2.30 to +1.95).
• Weight increases ≥10% occurred in 3% of CAB + RPV LA participants and 4% of BIC/FTC/TAF participants.

Figure 1: Proportion of patients  achieving Weight changes of >10% and 5%–10% at Month 12

BMI Changes

• Median BMI change at Month 12
  • CAB + RPV LA: -0.13 kg/m²
  • BIC/FTC/TAF: +0.01 kg/m²

Figure 2 : Shifts in BMI categories in patients  in CAB + RPV LA and BIC/FTC/TAF

Anthropometric Parameters:

• Median changes in waist circumference (WC) and hip circumference (HC):
  • CAB + RPV LA: WC +0.06 cm, HC +0.00 cm
  • BIC/FTC/TAF: WC +1.14 cm, HC +0.13 cm
• No clinically relevant changes in waist-to-height ratio (WHtR) or waist-to-hip ratio (WHR)

Metabolic Syndrome and Insulin Resistance:

• Prevalence of metabolic syndrome at baseline and Month 12:
  • CAB + RPV LA: 17%
  • BIC/FTC/TAF: 17%
• Insulin resistance prevalence at baseline and Month 12:
  • CAB + RPV LA: 42%
  • BIC/FTC/TAF: 43%

Lipid Changes:

• Minimal percentage changes in fasting lipid values from baseline at month 12 :
  • Total cholesterol: CAB + RPV LA +5.02%, BIC/FTC/TAF +0.52%
  • HDL cholesterol: CAB + RPV LA +3.41%, BIC/FTC/TAF -1.61%
  • Triglycerides: CAB + RPV LA +0.36%, BIC/FTC/TAF +3.43%

Conclusion

The study concluded that switching to CAB + RPV LA Q2M resulted in similar weight and metabolic profiles compared to continuing BIC/FTC/TAF, with no clinically significant changes in weight, BMI, or metabolic health parameters over 12 months. This supports the use of CAB + RPV LA Q2M as a viable maintenance treatment for PWH.

Reference

J Acquir Immune Defic Syndr 2025;98:401–409