March 17, 2011
Nelson Vergel, B.S.Ch.E., M.B.A., is a leading HIV treatment advocate, author and founder of the Body Positive Wellness Center in Houston, Texas.
With the recent approval of tesamorelin (Egrifta), the daily injectable growth hormone-releasing factor shown to moderately decrease visceral fat, there may be a renewed interest in a field that has been neglected in the past few years due to a frustrating lack of accessible management options. It is an expensive drug at around $2,000 a month, and requires daily subcutaneous injections to attain a 15%-19% decrease in visceral fat in 26 weeks. It seems well tolerated and it has not been studied in combination with diet and exercise. I am monitoring its insurance reimbursement and patient assistance program now through my online network of patients, and will report about this in future writings. Some companies are starting to deny reimbursement since they consider this to be a cosmetic-related treatment that has not yet been shown to improve clinical outcomes.
We are also pretty certain that there is no regimen visceral fat "friendlier" than another, no matter what effect each regimen has on lipids (we used to believe that more lipid-friendly drugs also meant more body-friendly ones). What we have not proven after 16 years of highly active antiretroviral therapy (HAART) is whether or not starting at higher CD4+ cell counts protects patients against more pronounced visceral fat gains. There is a belief that the lower the CD4+ cell count at baseline, the more the immune reconstitution-related "return to health" gain in weight.
Unlike where we are with fat accumulation, we are now pretty certain that stavudine (d4T, Zerit) and zidovudine (AZT, Retrovir) are the main drugs linked to lipoatrophy. However, access to the two products approved by the FDA to correct facial lipoatrophy, poly-L-lactic acid (Sculptra, New-Fill) and calcium hydroxylapatite (Radiesse, Radiance), is still very limited. Over a year ago, Medicare approved reimbursement for facial reconstruction of HIV-infected patients with lipoatrophy-related depression. However, this decision has not helped access since it pays a very low fee for doctors to inject the products (an average of three to six initial sessions and yearly touch-ups are required for each since they are not permanent). The companies' patient assistance programs have also started to cut back with the belief that the approval by Medicare would take care of many patients who lacked access before. There is still no permanent option for HIV lipoatrophy treatment in the U.S., although we have one approved for cosmetic purposes (Artefill) that is cost prohibitive in the volumes required for facial lipoatrophy correction.
Buttock lipoatrophy is an unchartered market that is already attracting foreign companies that carry permanent products such as polymethyl-methacrylate (PMMA) for studies in the U.S. PMMA has also been used successfully as a permanent option for facial lipoatrophy for several years in Latin America and Europe.
So progress has been slow, but promising. A lot of patient advocacy is still needed in this area. You can learn more on the Web site FacialWasting.org.
We have spent the last few years reviewing cohorts for incidence data on bone loss, vitamin D deficiency, cognitive dysfunction, immune system aging, and other aging-related issues. But little to no intervention data have been generated to date. When searching for aging-related studies at ClinicalTrials.gov, there are only eight that are enrolling. None of the studies uses any therapies.
This is probably the hottest vitamin in HIV research at present. It is made by the body after our skin is exposed to sufficient amounts of sunshine, but the liver and kidneys need to transform it into the "active" form, known as 25-OH vitamin D, which is the form that helps our bones and immune system.
Vitamin D may be involved in increasing the ability of immune cells to kill invaders in our bodies. It also seems to help those with tuberculosis have less severe disease symptoms and progression. It can also mediate inflammation by decreasing tumor necrosis factor alpha levels. In addition, in a review of seven past studies in HIV-uninfected people, five of the studies found a correlation between low vitamin D levels and higher cardiovascular risk (although the studies were not very similar, so it is difficult to compare apples and oranges).
The general population commonly suffers from vitamin D deficiencies, especially now that most of us try to avoid the sun to minimize skin cancer risk. People with darker skin, those who live in northern latitudes, those in winter time and the elderly tend to have more vitamin D deficiency. And HIV in itself, as well as the medications used to treat it, seem to also be risk factors.
It is not completely clear if low vitamin D in HIV-infected people is due to inflammatory responses caused by HIV. Emerging data point to the likelihood that HIV-infected people using efavirenz (Sustiva, Stocrin) may have lower vitamin D levels due to this drug's acceleration of the degradation of the vitamin in the liver (it lowered vitamin D levels by 4.5% in 26 weeks). Other small studies have shown that tenofovir (Viread) may also affect the metabolism of vitamin D into its active metabolite in the kidneys.
There is a large study looking at the long-term effects of vitamin D plus fish oils in 20,000 HIV-uninfected people to see if fractures and other health issues are improved by these supplements. However, results will not be available until five years from now.
The CHARTER cohort in the U.S. included HIV-infected people with an average of 43 years of age (relatively young) and found that almost half of them had some sort of mild cognitive decline. In a conference call with private investigators, I asked them how this compares with a similar HIV-uninfected population. They said that mild cognitive declines would be expected to be present in 10%-20% of HIV-uninfected people, so HIV almost doubles the rate. It seems that CD4+ nadir was one of the strongest predictors of cognitive decline.
The Multicenter AIDS Cohort Study (MACS) showed that after adjusting for most important factors, frailty was higher in HIV-infected men compared to HIV-uninfected men. In fact, it was reported that the frailty of a 55-year-old HIV-infected man may be similar to that of a 65-year-old HIV-uninfected man.
So, as a patient and research advocate, I have generated a list of treatment studies that could be considered for those looking for research ideas that may attract patient enrollment:
HIV activists with the Coalition for HIV and Aging Research and Policy Advocacy (CHARPA) are demanding that the U.S. National Institutes of Health (NIH) devote more attention and resources to the issue of aging and HIV. Will the NIH respond, and will it respond in time?
With patient community support and involvement, guidelines geared toward managing aging-related issues in HIV are currently being considered by different groups such as the U.S. Department of Health and Human Services treatment guidelines panel.
The accelerated-aging model that HIV presents in a younger population that is used to clinical study participation may be attractive to experts in gerontology. So, we will definitely see more data on this research area, even if it is slowed down by research budget cuts.
Cure activism is gathering momentum. Advocacy groups such as Treatment Action Group (TAG), Project Inform, amfAR and, last but not least, the AIDS Policy Project are presently trying to initiate community-driven approaches to advocate for more research funding of innovative investigators, researcher collaboration, and community education for study enrollment. The next few years will be exciting and challenging as interest in the cure reaches the predicted tipping point in an era of budget cuts.
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