More evidence that HIV integrase inhibitor treatment is associated with weight gain, and that people gain more weight after beginning treatment with an integrase inhibitor than people taking other drug classes, was presented this week at the Conference on Retroviruses and Opportunistic Infections (CROI 2019) in Seattle.
Weight gain on integrase inhibitor treatment was first flagged up in late 2018 and, since the first reports, other research groups have been looking at weight gain in a wider range of patient groups.
The form of weight gain seen in people starting integrase inhibitor treatment is not the same as the fat redistribution syndrome, or lipodystrophy, observed when the first generation of protease inhibitors was used in combination with nucleoside reverse transcriptase inhibitors (NRTIs) or when non-nucleoside reverse transcriptase inhibitors (NNRTIs) were used in combination with older NRTIs, especially stavudine (d4T).
Whereas lipodystrophy involved accumulation of central abdominal or visceral fat, and loss of subcutaneous fat, weight gain on modern antiretroviral treatment consists of general fat gain – both subcutaneous and central fat – with an increase in waist circumference.
Weight gain after starting antiretroviral treatment is a common event; gaining a modest amount of weight is normal, especially in people with more advanced HIV disease or low body mass prior to treatment. It’s been dubbed 'return to health' weight gain.
However, what has been seen with some drug regimens – not just integrase inhibitors, but some protease inhibitors too – is more substantial weight gain. Some clinicians have raised concerns that weight gain might eventually increase cardiovascular disease risks, blood pressure and type 2 diabetes in populations which already have a high prevalence of obesity and other risk factors for cardiovascular disease. The VACS study showed that gaining five pounds (2.26kg) after starting treatment increased the risk of diabetes by 14%, while the D:A:D cohort found that every unit of body mass increase after starting antiretroviral treatment raised the risk of diabetes by 13%.
But is this weight gain caused by antiretroviral drugs or is it a product of environments that encourage people to eat unhealthily and be physically inactive? Moderating a discussion on weight gain after starting treatment, Jane O’Halloran of Washington University, St Louis, pointed out that up to half of adults starting antiretroviral therapy in the United States may already be obese. Weight gain after starting treatment may be occurring in adults who already have diets and lifestyles that predispose them to further weight gain.
On the other hand, asked Carl Fichtenbaum of University of Cincinatti, what if weight gain on regimens other than integrase inhibitors is being blunted by effects of certain drugs on fat deposits?
Studies presented at CROI this week attempted to shed more light on the problem, specifically: whether integrase inhibitors cause more weight gain than other drugs; how much weight is being gained and over what period; who might be at greater risk; and whether there is any difference between integrase inhibitors.