Update on Lipid Abnormalities and

Cardiovascular Complications in HIV Infection

San Diego is a beautiful city. The weather is great-cool and sunny and the city is clean and new. The fod so far is also great. I just returned from a pre-ICAAC symposium sponsored by Serono. The speakers at the symposium were Dr Don Kotler, of St Luke's-Roosevelt in NYC and Dr Kathleen Mulligan of UCSF in San Francisco. Having just heard Dr Kotler last week in Redondo Beach, I was familiar with his presentation which was posted on this web page two days ago. Both Mulligan and Kotler think that fat redistribution may not be a direct effect of Protease inhibitor (PI) therapy. Mulligan thinks Kotler's study data is good. The Redondo article discusses his data in detail. Kotler thinks the people who he sees experiencing fat redistribution are people whose CD4s were low and had good increases in CD4s and potent viral load suppression from HAART. Therefore, he thinks it is more likely to occur in individuals with more advanced HIV who do well on HAART. He suggests it may be due to partial immune reconstitution and it may be an autoimmune disease. Mulligan does not like calling it lipodystrophy, she prefers calling the syndrome fat redistribution.

Both Mulligan and Kotler think the syndrome may be due to the magnitude of viral load suppression from HAART. Both agreed strongly that we need to define the syndrome. Mulligan showed 7 studies of the incidence of fat redistribution and all 7 had widely varying percentages of people experiencing the syndrome: 2%, 12%, 14%, 24%, 25%, 64%, and 76%. Mulligan said this wide variable in incidence is because each study investigator defined the syndrome differently. Both agreed the first priority is to make a case definition of the syndrome. This may sound easy but it appears it's not so easy. In the ACTG there is a whole committee of researchers and community involved in trying to define the syndrome. Two important questions are- (1) is the syndrome directly or indirectly due to PI therapy? If it's due to high magnitude in viral load reduction and CD4 increases, that would be an indirect effect of PI therapy. It might also be caused by any therapy reducing viral load to undetectable. In fact, in a study conducted by Kotler and discussed in the Redondo Beach paper, his data suggests that there were no differences in fat redistribution between individuals taking PI therapy and those not taking PI therapy. But, individuals with HIV experienced fat redistribution while individuals without HIV did not; (2) is the syndrome due to partial immune reconstitution resulting from HAART?

At this symposium Mulligan started out by showing pictures of two individuals who experienced the syndrome. Neither one had taken a PI. Dr Mulligan made an interesting comment that I didn't have a chance to ask her about. Some individuals did not experience increased tryglicerides if they were taking 3TC with their PI therapy. She noted post-PI therapy higher levels of insulin and insulin resistance have been reported, diabetes is rare, and sugar and insulin in is increased but not if one is taking 3TC. She compared fat redistribution to Syndrome X which is described by Kotler in the Redondo Beach report (click here to link to that article). Kotler said it will take some time before we will be able to accumulate some hard and good data on this subject, maybe 1-2 years. Friday there is an entire session devoted to this syndrome, but I read the abstracts and there doesn't appear to me to be any new information. Like Kotler said, it may be a year or two before we have good solid data. Dr Kotler is conducting an open-label study of HGH (human growth hormone) for people with fat redistribution at CRIA in NYC. If you are interested in enrolling you can all Community Research Initiative for AIDS in Manhattan. There is a litlle bit of anecdotal and study (n=4) information suggesting that HGH might help with fat redistribution a little bit. As you can see I am trying to emphasize that there is very little to hang your hat on but this open-label study might give us some direction about HGH. Since it is open-label we might see some data fairly quickly. Kotler said that diet may help reduce the risk of heart disease and can also reduce your stomach fat. He suggests diet and exercise for that purpose. Before starting a new diet and exercise program you may want to speak to your doctor first. Also, low dose aspirin may help reduce the risk of heart disease that may occur due to elevated lipids. OK, it's 7pm and I'm off to dinner.