Does Genvoya make you gain weight?

Q: Does Genvoya make you gain weight?

Genvoya does not have weight gain listed as a side effect in the product labeling. However, a large study suggests some of the newer HIV treatments, including integrase strand inhibitors such as elvitegravir (found in Genvoya), can be linked with significant weight gain.

Official answer

by Drugs.com

Key Points

The HIV treatment medicine Genvoya (elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide) does not have weight gain listed as a side effect in the product labeling.

However, a large study suggests some of the newer HIV treatments, including integrase strand inhibitors such as elvitegravir (found in Genvoya), can be linked with significant weight gain.

The exact mechanisms by which integrase inhibitors may cause weight gain are not fully known. Based on a meta-analysis study, weight gain may be due to a variety of related reasons, such as:

baseline CD4 counts

weight before treatment initiation

a return to health and an improved appetite following HIV treatment

overall food choices.

What’s in Genvoya?

Genvoya (elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide), from Gilead Sciences is an oral prescription medicine used to treat human immunodeficiency virus (HIV) in adults and children who are at least 12 years old and who weigh at least 55 pounds (25 kilograms). HIV-1 is the virus that causes AIDS (Acquired Immune Deficiency Syndrome).

Genvoya is considered a complete, one pill regimen for HIV treatment. It is taken once-a-day with food and you do not need to use other HIV-1 medicines with Genvoya. It contains 4 different types of drugs:

Table 1: Drugs found in Genvoya

Ingredient	Class	Mechanism of Action
Elvitegravir	Integrase strand transfer inhibitor (INSTI)	Blocks the action of the integrase (an enzyme) that facilitates insertion of the HIV virus into the cell.
Emtricitabine (Emtriva)	Nucleoside analog reverse transcriptase inhibitor (NRTI)	Blocks the action of reverse transcriptase and inhibits viral replication.
Tenofovir alafenamide (TAF) - (Vemlidy)	Nucleoside analog reverse transcriptase inhibitor (NRTI)	Blocks the action of reverse transcriptase and inhibits viral replication.
Cobicistat (Tybost)	CYP3A inhibitor pharmacokinetic enhancer (booster)	Given to help increase blood levels of other HIV medications, such as elvitegravir. Does not treat HIV.

Research on weight gain with Genvoya

Recent studies have suggested that newer HIV treatments, including ones that contain integrase strand inhibitors (INSTIs) such as bictegravir, dolutegravir or elvitegravir, may be linked with weight gain in patients living with HIV. Elvitegravir is one of the medicines found in Genvoya.

A 2019 meta-analysis published in Clinical Infectious Diseases reported on weight gain with INSTIs. Investigators looked for an association between demographic factors, antiretroviral therapy (ART), disease-specific variables, and weight gain in previously untreated (treatment-naïve) people living with HIV. The group included roughly 5,600 patients who received treatment between 2003 and 2015. The study population was 88% male and 62% white.

Drugs evaluated included:

tenofovir disoproxil fumarate (TDF) in combination with emtricitabine and or the newer formulation tenofovir alafenamide (TAF)

efavirenz

INSTIs such as dolutegravir, elvitegravir (found in Genvoya) and bictegravir

atazanavir and ritonavir

rilpivirine

When looking at all treatments, researchers found each study group showed some weight gain. The overall median weight gain of 2 kg (4.4 lbs) occurred primarily in the first year of treatment (48 weeks) in 12.8% of treatment-naïve patients. Over a 2 year period, 17.3% of participants gained weight but 30.2% had weight loss.

Statistically significant risk factors linked to weight gain (over about one year) included:

Lower baseline CD4 cell count.

No injection drug use.

Lower baseline weight at study entry.

Presenting with HIV / AIDS symptoms at baseline.

Race and sex, with black women being at highest risk of weight gain.

Genvoya weight gain

Elvitegravir (and other integrase inhibitors) as well as tenofovir alafenamide (TAF), both components of Genvoya, were associated with weight gain in this analysis.

Integrase inhibitors dolutegravir and bictegravir were associated with similar weight gain, but more than elvitegravir / cobicistat.

Overall, people on integrase inhibitors gained significantly more weight (3.24 kg [7.1 lbs]) than did people taking either a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor.

Patients who had a lower CD4 count at study entry had more weight gain. Researchers also reported that weight gain can be linked to a “return to health” effect in patients who had active HIV disease for years.

Other studies have also found a risk of weight gain with integrase inhibitors with a median weight gain of between 1 kg (2.2 lbs) and 4 (8.8 lbs) kg over one to two years of follow-up.

Table 1: Weight Gain with Integrase Inhibitors

Integrase inhibitor	Mean weight gain (at 96 weeks)
*Table adapted from Sax, et al. 2019
bictegravir (BIC)	4.24 kg [9.2 lbs] (95% CI, 3.71–4.78 kg)
dolutegravir (DTG)	4.07 kg [9 lbs] (95% CI, 3.51–4.62 kg)
cobicistat-boosted elvitegravir (EVG/c)	2.72 kg [6 lbs] (95% CI, 2.45–3 kg)

Does tenofovir alafenamide (TAF) cause weight gain?

Stribild contains elvitegravir, emtricitabine, and the original form of tenofovir known as tenofovir disoproxil fumarate (TDF). When TDF was compared with the newer tenofovir alafenamide (TAF), more weight gain was seen with TAF (4.2 kg) than with TDF (2 kg) at 96 weeks.

Elvitegravir / cobicistat was also associated with a significantly higher odds of more than a 10% weight gain (OR 1.32, 1.04-1.78, p=0.026) when compared to efavirenz.

However, investigators did not find a link between >10% weight gain and metabolic effects such as increased blood sugar (hyperglycemia) or type 2 diabetes. In addition, obesity at study entry was not found to be a risk factor for weight gain in the meta-analysis.

Bottom Line

Genvoya is not noted to cause weight gain in the manufacturer’s package insert. However, a large meta-analysis study suggests all integrase inhibitors such as elvitegravir (found in Genvoya) may be linked with some weight gain. Over 96 weeks, elvitegravir was associated with a mean weight gain of 2.72 kg [6 lbs] (95% CI, 2.45–3 kg).

When looking at drug classes, integrase inhibitor use was associated with more weight gain than were protease inhibitors or non-nucleoside reverse transcriptase inhibitors (NNRTIs).

Weight gain is frequently seen in HIV treatment clinical trials, and may have many causes in addition to drug treatment. Mechanisms for weight gain are not well-defined, but may involve improved overall health, increased appetite, better gastrointestinal tolerability with newer ART treatments, or baseline weight prior to ART initiation.

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