Gene May Determine Why HIV Drugs Are Less Effective in Some Ethnic Groups
A mutation in the P-glycoprotein (PGP) gene, also known as the "multi-drug resistance protein," may enable doctors to more effectively tailor HIV drug regimens to specific patients according to ethnic group, Reuters Health reports. A study published in the Aug. 4 issue of the Lancet shows that the mutation, which increases the amount of PGP -- a protein that "pumps" certain drugs like antiretrovirals out of cells, causing the drugs to lose their effectiveness -- is more widely found among West Africans and African Americans than among whites and Asians. A team from the Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology in Stuttgart, Germany, tested samples from 142 Ghanians, 41 African Americans, 537 whites and 50 Japanese volunteers and found that 83% of the Ghanians and 61% of the African Americans carried two copies of the mutation, or a double allele, while only 26% of the whites and Japanese carried two copies (Reuters Health, 8/3).
Benefits of the Mutation
A double allele is associated with increased production of PGP in the cells of the stomach. The increase in PGP, which is "quite similar" to the antiretroviral medications used to treat HIV, means that "it might be difficult for the drug proteins to find vacant receptors on the cells they need to target for the medication to work," BBC News reports. Although the researchers are uncertain why some populations have a higher incidence of the double mutation, they theorized that the PGP mutation may "naturally" protect these populations from certain gastrointestinal disorders (BBC News, 8/3). According to the study's authors, bacterial and viral gastroenteritis is "endemic in tropical countries" such as the nations of West Africa and has been linked with "substantial infant morbidity and mortality." A "higher frequency" of the mutation may afford these groups a "selective advantage against gastrointestinal infections," the authors theorized (Schaeffeler et al., Lancet, 8/4).
Not an Excuse
AIDS activists said that the possibility of decreased effectiveness of some antiretroviral drugs in African populations "should not influence any arguments over" making drug treatment available in Africa and other parts of the developing world. A spokesperson for the Terrence Higgins Trust Lighthouse, a British HIV/AIDS charity, said there are a "wide variety" of drug combinations available to treat HIV and if one combination is unsuccessful, "there is likely to be another which is more effective," adding, "Everybody responds differently to treatment" (BBC News, 8/3). Dr. Matthias Schwab, one of the researchers, cautioned that more research is needed to "directly measure" drug response in subjects with two copies of the mutation before the findings can have clinical applications (Reuters Health, 8/3).