The growing obesity epidemic

In Australia, as with many other countries, over two-thirds of the population is classified as overweight, and one-third is obese. Obesity is becoming an international health crisis, and people with HIV are not immune.

HIV treatments have dramatically improved in recent decades. Today’s medications are more effective, easier to take, and carry fewer risks of side effects, including metabolic disorders. However, an unsettling trend has emerged: weight gain and obesity are becoming more common among people with HIV. This presents concerns, as those who are overweight face an increased risk of metabolic issues and inflammation, in addition to the inflammation already caused by the virus.

HIV treatments and weight gain

Modern antiretroviral therapies (ART) have made HIV a manageable, chronic condition rather than a death sentence. These treatments, such as Integrase Inhibitors (IIs) like Dolutegravir (DTG) and Bictarvy (BIC), and the newer formulation of Tenofovir (TAF), have been groundbreaking in their ability to combat the virus with fewer side effects. In fact, they are often hailed for their convenience, requiring just one pill per day, with no food restrictions and a much lower risk of metabolic complications than older therapies.

But these newer drugs may also contribute to weight gain. Studies have indicated that patients taking these medications could experience up to five kilograms of weight gain within a year. While some experts argue that the association between HIV treatments and weight gain is clear, others remain sceptical, suggesting that the weight changes may be due to other factors, such as lifestyle or changes in the body’s metabolism over time.

The impact of older treatments

Interestingly, older treatments—such as Tenofovir Disoproxil Fumarate (TDF) and Efavirenz (EFV)—have been shown to have a weight-suppressive effect. For individuals on these regimens, switching to newer medications could lead to an increase in weight as the suppressive effect disappears. This change, combined with more efficient viral suppression from the newer therapies, might lead to unexpected weight gain even when lifestyle factors remain the same.

For many individuals who had been living with untreated HIV before beginning therapy, a phenomenon known as “return to health” could also be playing a role. This refers to the weight gain that occurs as the body recovers after starting HIV treatment. Before starting ART, many people with HIV lost weight due to the energy demands of the untreated virus, and once they start treatment, their body often returns to a more typical weight. While this effect still holds true for some, it’s unlikely to be the sole contributor to the rising rates of obesity among people living with HIV.

The role of appetite and metabolism

One theory surrounding weight gain in people with HIV relates to the melanocortin system (MCs), a network in the brain that controls appetite, metabolism, and eating behaviours. Studies suggest that certain HIV treatments, particularly Dolutegravir (DTG) and Bictegravir (BIC), may interfere with the MCs, leading to increased hunger and a reduced sense of fullness. This disruption in appetite regulation could lead to overeating, especially of calorie-dense, processed foods, making it harder for people to maintain a healthy weight.

Research is ongoing to understand the connection between HIV treatments and the MCs, and whether altering the functioning of this system is a significant factor in weight gain among people with HIV.

The influence of Tenofovir Alafenamide (TAF)

Tenofovir Alafenamide (TAF), a newer version of the widely used antiviral Tenofovir, has also been linked to weight gain. When combined with Integrase Inhibitors like Dolutegravir, TAF may contribute to noticeable increases in weight. Studies have shown that TAF is associated with weight gain in both HIV-positive and HIV-negative individuals, particularly in comparison to the older Tenofovir Disoproxil Fumarate (TDF). While the exact mechanism is still unclear, it appears that TAF’s impact on weight could be significant, with some studies also linking it to elevated blood pressure and changes in cholesterol and triglyceride levels.

Despite these concerns, TAF remains a crucial part of modern HIV treatment regimens, and its benefits in terms of viral suppression and long-term health should not be overlooked.

Exploring solutions: Treatment switches and weight loss medications

Given the growing concern over weight gain among people with HIV, some are exploring whether switching treatments could help. While large-scale studies specifically focused on weight loss through treatment switches are limited, a study known as the DOIT Study is currently underway in the United States. The research is exploring whether switching from Integrase Inhibitors (INSTIs) to Doravirine, an HIV treatment that is not associated with weight gain, can help people lose weight without causing other negative side effects.

In addition to treatment adjustments, weight loss medications are also being explored. One medication attracting attention is Ozempic (semaglutide), a GLP-1 agonist that helps regulate appetite and metabolism. Originally developed to treat type 2 diabetes, Ozempic has shown promise for weight loss, and research indicates that it could be an effective tool for people with HIV as well. In addition to helping with weight loss, GLP-1 agonists like Ozempic may offer other health benefits, including improved liver and kidney function, better cardiovascular health, and reduced inflammation.

While Ozempic and other weight loss drugs can be expensive, people with HIV who are struggling with weight gain may want to discuss these options with their healthcare provider, as there are clinical studies that offer these medications at no cost.

Conclusion

The rise in weight gain and obesity among people living with HIV is a complex issue influenced by a range of factors, including changes in HIV treatment regimens, altered metabolism, and lifestyle behaviours. While modern treatments have dramatically improved health outcomes, they may also contribute to weight gain for some individuals. As research into the mechanisms of HIV treatment-related weight gain continues, it’s crucial for patients to work closely with their healthcare providers to understand and address their individual concerns.

Whether it involves switching medications, adjusting lifestyle habits, or exploring weight loss medications, there are options available to help manage weight and promote overall health. With ongoing research and new treatment options on the horizon, the future looks promising for people living with HIV striving for a healthier, more balanced life.