Nutrition, Thymic T-Cell Production and control of HIV

Cancer Prevention Program

Nutrition, Thymic T-Cell Production and control of HIV

Does poor nutrition contribute to the high risk of viral cancer in HIV-infected adults in Uganda?

PI: Alan Kristal DrPH

Kaposi sarcoma (KS) is a cancer caused by human herpesvirus 8 (HHV-8). Most people infected with HHV-8 do not develop KS because their immunologic system can control the viral infection. However, if people are also infected with the Human Immunodeficiency Virus (HIV) they may not be able to control their HHV-8 infection, and in these people KS commonly develops. In the United States and in other resource-rich countries, KS was the most common cancer in HIV-infected persons. But after drugs to control HIV were developed and became widely used, KS became very rare.  The situation in Africa, however, is very different. In Uganda, a country in eastern Africa, nearly 80% of the population is infected with HHV-8.  KS occurred in adults and children prior to the HIV pandemic; however, once the HIV pandemic occurred, rates of KS increased dramatically. Now KS is the most prevalent cancer in the entire population of Uganda. When people develop KS, the disease is far more severe and much more likely to be fatal than in resource-rich countries.  This remains true despite to use of effective HIV medications and chemotherapy.   

It is well known that under-nutrition impairs the immune system.  Under-nutrition is a broad term, and includes deficiencies of specific nutrients (for example zinc or selenium), specific dietary patterns (for example, very low in protein) or simply too little food;  all of these can affect immune function.  Under-nutrition is far more common in Africa than in resource-rich countries, and we hypothesize that under-nutrition can explain the high risks of KS and mortality from KS in Uganda. 

The goal of this study is to do preliminary research that will allow us to test whether nutritional rehabilitation, using either food or nutritional supplements, can improve the response to HHV-8 treatment and reduce KS mortality in adults living in Uganda. We will first develop and test measures of nutritional status based on samples of body fat, hair and toenails. Many of the standard measures of nutritional status are based on blood tests, but these are not accurate when used in people who have active infections such as HIV or HHV-8.  However, many nutritional status measures can be based on the levels of nutrients in bodyfat, hair and toenails. We will then examine whether poor nutritional status in people infected with HHV-8 is associated with an inability to control HHV-8 infection. At the same time, we will evaluate the performance of blood tests used to measure immune system function, and then use these measures to examine the relationships among immune function, infection with HIV and HHV-8, and measures of under-nutrition. Finally, we will do a small pilot study to determine what types of food supplements will be most acceptable to Ugandan adults with KS.  Because KS often causes sores in the mouth and throat, it will be important to understand what types of foods and supplements people can and will use.

The results of the work conducted with the Synergy grant will allow us to properly design a randomized clinical trial to determine whether improving nutrition status can either prevent KS or improve KS treatment in Africa.