HIV infection is associated with relatively high levels of inflammation, and that may increase the risk for a range of health problems such as heart disease, cancer, and osteoporosis. In a discussion with 鶹ý at the recent annual Conference on Retroviruses and Opportunistic Infections (CROI), , of the University of California San Francisco, discusses the work he's done treating one of the root drivers -- even though it wasn't causing any symptoms -- in order to suppress these levels of inflammation in the body.
Following is a transcript of his remarks:
We've been working on why inflammation persists in a lot of people living with HIV despite controlling the virus on antiretroviral therapy, and [what] happens with most people living with HIV, and the degree of persistent inflammation really increases the risk of a lot of aging-associated diseases like heart disease, cancer, osteoporosis. We're really interested in coming up with interventions that suppress that low-level inflammation to improve the life expectancy and the quality of life for people living with HIV in the modern-treatment era.
One of the root drivers of the inflammatory state we think is another virus that almost everyone with HIV has called cytomegalovirus or CMV. While in the old, pretreatment era, we saw a lot of end-organ disease from CMV, like retinitis and colitis that can cause blindness or severe abdominal infections, we don't see that much anymore, but even though it's not causing any symptoms, it may contribute to low-level inflammation. We did a study many years ago among people on treatment who failed to recover normal CD4 counts on HIV therapy to see if treating that low-level CMV in the body that wasn't causing any symptoms might actually lower these levels of inflammation in the body.
We showed in that first study that some markers of immune activation went down, and that was promising. The drug we had at the time couldn't be carried forward because it had too many side effects. But there are new drugs that are now approved to treat CMV that are much less toxic, so we went back to those old samples from that initial study to see whether other immunologic pathways that we now know are strong predictors of heart disease, type 2 diabetes, and HIV might have been affected by treating CMV. We found massive effects on a lot of key inflammatory pathways that contribute to disease.
If we were to translate that into what it might mean for decreasing [the] risk of disease, it would be about a 22% reduced risk of heart disease and about a 50% reduced risk of type 2 diabetes, two things that are really strongly increased in the HIV-infected people living with HIV. We think the strategy is going to be really important, and there's a new trial that's now in development, an AIDS clinical trials group of a new CMV drug called letermovir that has far fewer side effects than the older drugs, and we're going to see if it not just reduces inflammation, but also decreases what we call surrogate markers of [the] risk of heart disease and also diabetes in a much longer-term study in a much larger number of people. If successful, it may eventually lead to a new clinical strategy where you don't just treat the HIV, but you also treat this other virus that's along for the ride that might be causing some of the inflammation.