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Exploring weight changes with different integrase inhibitors

Researchers from 30 clinics in Spain conducted a study called Paso Doble. In this study, participants with HIV who were taking HIV treatment (antiretroviral therapy, ART) and who had a suppressed viral load were randomly assigned to receive one of the following regimens:

  • dolutegravir + 3TC (Dovato) – 277 people
  • bictegravir + TAF + FTC (Biktarvy) – 276 people

Pre-study regimens included drugs such as efavirenz (85%) and tenofovir DF. No participant had previously used bictegravir- or dolutegravir-containing regimens. None had hepatitis B virus coinfection. 

Researchers assessed weight changes, and future analyses will explore changes to fat cells with biopsies, scans of the liver for fat accumulation, metabolic issues and premature aging.

At the start of the study, the average profile of participants was as follows:

  • age – 50 
  • 27% were female at birth and 73% were male at birth
  • length of time on ART – 12 years
  • duration with a suppressed viral load (less than 50 copies/mL) – 100 months
  • CD4+ count – 700 cells/mm3 (9% of participants had less than 300 CD4+ cells/mm3)
  • overweight or obese – 50%

Results

There have been previous clinical trials of this combination that focused on effectiveness. In such studies, Dovato was found to have similar effectiveness to Biktarvy (the technical statistical term for this is non-inferior). 

In the present study, results were similar. The proportions of participants with a suppressed viral load (less than 50 copies/mL) at week 48 were as follows:

  • Dovato – 93%
  • Biktarvy – 90%

Blips

Sometimes after viral suppression is achieved, viral load will temporarily increase a small but detectable amount due to infections (such as cold, flu, sexually transmitted infections), vaccination or seasonal allergies. After a time, viral loads generally return to undetectable. This temporary rise in viral loads is called a blip.

The proportions of participants with a blip (defined as a viral load between 50 and 199 copies/mL) were distributed as follows:

  • Dovato – 6%
  • Biktarvy – 9%

This difference was not statistically significant.

Only one person developed virological failure (a persistent viral load greater than 200 copies/mL) and that person was taking Biktarvy.

There were no significant changes in CD4+ cell counts.

Adverse effects

Adverse effects were reported, as follows, but they were generally mild to moderate and temporary:

Soreness of muscle/bone

  • Dovato – 20%
  • Biktarvy – 19%

Gastrointestinal issues

  • Dovato – 14%
  • Biktarvy – 9%

Neuropsychiatric issues

  • Dovato – 10%
  • Biktarvy – 13%

Premature departures from the study were distributed as follows:

  • Dovato – 1 person experiencing general discomfort and muscle/bone soreness
  • Biktarvy – 2 people with sleeping problems

Weight

Overall, participants gained weight, which was distributed as follows:

  • Dovato: +1 kg
  • Biktarvy: +2 kg

Readers should note that ART does not have the same effect on every person; some people can gain weight, while others can lose weight, and still others have no change in weight. 

Here are the proportions of participants who gained 5% of their initial body weight by week 48:

  • Dovato – 20% of participants
  • Biktarvy – 30% of participants

Researchers found that people who used abacavir or TDF in their pre-study regimen and who were given Biktarvy were more likely to gain 5% or more of their pre-study body weight. This effect was not seen in people who previously used abacavir or TDF and who were given dolutegravir + 3TC.

Researchers found that the proportions of people who were overweight or obese did not change among those who were taking dolutegravir + 3TC; however, the proportions increased among people who were taking Biktarvy.

Bear in mind

Both study regimens are highly effective and generally well tolerated over time. Overall weight gain with Biktarvy was modest (2 kg) and was linked to the use of previous medicines (abacavir or TDF). On average, people taking dolutegravir + 3TC gained about 1 kg.

Researchers analyzed previous use of ART and did not find relationships between past use of efavirenz and an increased risk of weight gain when they were switched to Biktarvy.

Additional analyses are needed to assess abdominal fat accumulation, particularly around the liver. The researchers collected information from participants about diet and exercise but have not yet analyzed them.

—Sean R. Hosein

REFERENCE:

Ryan P, Blanco JL, Masia M, et al. Non-inferior efficacy and less weight gain when switching to DTG/3TC than when switching to BIC/FTC/TAF in virologically suppressed people with HIV (PWH): the PASO-DOBLE (GeSIDA 11720) randomized clinical trial. 25th International Conference on AIDS, Munich, Germany, 22-26 July 2024. Abstract OAB3606LB