Genetic Test Could Reduce Number of HIV/AIDS Patients Who Experience Adverse Reactions to Abacavir
A genetic test may be able to predict which people are likely to experience a hypersensitivity reaction to the antiretroviral drug abacavir, according to two studies presented yesterday at the Ninth Conference on Retroviruses and Opportunistic Infections in Seattle, the Los Angeles Times reports. About 5% of people who use abacavir, marketed by GlaxoSmithKline under the brand name Ziagen, experience adverse side effects ranging from fever and vomiting to rash and shortness of breath. Symptoms generally subside when the patient stops taking the drug, but the reaction can be fatal in some instances, particularly if therapy is halted and then resumed (Maugh, Los Angeles Times, 2/27). In a study presented yesterday and appearing in the March 2 issue of the Lancet, a team of researchers from Australia's Royal Perth Hospital located three gene variants associated with hypersensitivity to the drug by comparing DNA from 200 patients who had received the drug. Eighteen of the patients exhibited hypersensitivity to the drug, which is typically used in combination with other antiretroviral drugs. Seventy-eight percent of the abacavir-sensitive patients had the gene HLA-B*5701, and 72% had a combination of two other genes, HLA-DR7 and HLA-DQ3. Overall, 72% of patients sensitive to abacavir had the three-gene combination. Further analysis revealed that those with HLA-B*5701 were more than 100 times more likely than those without the allele to experience an adverse reaction to the drug (Reuters Health, 2/27). Dr. Simon Mallal of Royal Perth Hospital said his practice now "routinely" screens for the genes before prescribing abacavir and has lowered the frequency of reactions to about 2.5%. "The really exciting thing for us is for the first time (we) have a good handle on hypersensitivity. We see a lot of other hypersensitivity reactions to other drugs but don't have enough patients to come to grips with the genetic causes," Mallal said (Haney, AP/Newsday, 2/27). A second study of 200 HIV/AIDS patients conducted by GSK researchers found similar results, concluding that the HLA-B*5701 allele was present in about 46% of patients with hypersensitivity to abacavir (Reuters Health, 2/27). Participants in both studies were mainly white, and researchers pointed out that the different findings may be due to "the genetic diversity of American Caucasians compared with Australian Caucasians" (Schoofs, Wall Street Journal, 2/28).
"It's a truly astonishing connection between a human genetic marker and the risk of a potentially fatal drug reaction," Dr. Charles Flexner of Johns Hopkins University said. Dr. Amalio Telenti and colleagues from the University Hospital in Lausanne, Switzerland, wrote in an accompanying commentary appearing in the Lancet that using the same technology, doctors should soon be able to screen patients for a host of genetic risk factors. "This projection may look far-fetched, with just a few relevant genes identified, but these are the first drops before a downpour," they stated. However, they warned that the high cost of such screening -- about $500 per patient -- could be a "major impediment." With approximately 5% of patients at risk of hypersensitivity, the cost per case detected amounts to between $10,000 and $50,000. However, as more screenings become available the costs should be reduced, they noted (Los Angeles Times, 2/28).
Several other studies were presented yesterday at the conference. Summaries of the some of the findings appear below:
- Triple Therapy Feasible in Developing Countries: Triple combination therapy "works well, is used properly by doctors and is eagerly embraced by patients" in developing countries if prices are kept in check, according to several studies presented yesterday. "It's comparable to what's going on in the United States," CDC epidemiologist and pharmacologist Paul Weidle, who studied triple therapy in Kenya, said. CDC researchers and their Kenyan counterparts studied the effects of triple therapy in 217 Kenyans with advanced-stage HIV infections who could afford therapy. Sixty percent of the participants had undetectable viral levels after six months, while 47% maintained that level after a year. Those rates are comparable to rates at a medical school-based AIDS clinic in Baltimore, the researchers noted. The study results poke holes in the argument that "complicated therapies are too difficult to implement and will do more harm than good" in poor resource settings, the Washington Post reports (Brown, Washington Post, 2/28).
- Discovery of New SIV Reignites Debate Over HIV's Origins: The discovery of a new type of simian immunodeficiency virus in 19 greater spot-nose monkeys in Cameroon has reignited the debate over the origins of HIV, Agence France-Presse reports. Researchers from the Research Institute for Development in France identified in 19 of the monkeys a virus variant they call SIVgsn, which is similar to the chimpanzee virus SIVcpz and HIV-1. "The fact that 'chimpanzees eat these little white-nosed monkeys' indicates [chimps] are not, in fact, natural hosts of HIV-1 as was believed" and may have received the virus via the smaller monkey, IRD lead researcher Eric Delaporte told the conference. He added that there is a slight risk of the virus jumping to humans because the spot-nose monkeys are "highly sought" for their meat (Agence France-Presse, 2/28).
- Organ Transplants in HIV-Positive People Have Comparable Success: Preliminary results from a multi-site University of California-San Francisco study demonstrate that HIV-positive organ transplant recipients have success rates comparable to HIV-negative transplant recipients one year after transplant, according to findings presented at the conference. Ninety-five percent of HIV-positive individuals undergoing kidney transplants and 84% receiving liver transplants had survived one year after their transplants. Rates were also comparable for HIV-positive patients receiving organ grafts; 89% of kidney grafts and 84% of liver grafts were functioning one year after surgery (UCSF release, 2/27).
- Higher Frequency of Mutant Gene in Caucasian Population May Explain Lower Heterosexual HIV Transmission Rates: The higher frequency of the "mutant gene" delta-32 -- which, in its homozygous form, causes a mutation on the CCR5 receptor that renders it useless to HIV and may render some protection against HIV in its heterozygous form -- in the Caucasian population may explain why heterosexual transmission rates are lower for whites, Newsday reports. Dr. Harold Burger of the New York State Wadsworth Laboratory and colleagues examined the DNA of 2,047 HIV-positive women and 558 race- and age-matched HIV-negative women in the United States and found that white women carry the heterozygous form of delta-32 "far more frequently" than other women; about 1.2% of HIV-negative white women have the gene versus only 0.2% on HIV-negative African-American women. "This supports mathematical predictions that having a low frequency of delta-32 in non-Caucasians may render those populations vulnerable to far greater and more explicit HIV epidemics. And it may explain, in part, the rapid epidemics we see unfolding in Asia and Africa," Burger said (Garrett, Newsday, 2/28).
- Use of Hormonal Birth Control May Lead to "More Aggressive" HIV Infection: Women who used hormonal birth control at the time they became infected with HIV appear to be five to seven time more likely to develop a "more aggressive" HIV infection, according to a study by researchers from the Fred Hutchinson Cancer Research Center. Researchers studied 115 HIV-positive commercial sex workers in Mombasa, Kenya, who were on hormonal birth control -- largely oral contraceptives -- at the time of their infection, and found that the women had a five- to seven-fold increased risk of being infected with multiple strains of HIV, which leads to faster disease progression, than women who had not taken hormonal birth control. It is not clear why the women on hormonal birth control were more susceptible, but researchers think the hormones may have thinned the lining of the vagina, leaving them more susceptible to the virus (Sommerfeld, MSNBC.com, 2/27).
- HIV Can Be Transmitted Through Biting: HIV can apparently be transmitted through biting, although instances remain "extremely rare," according to the CDC. Brazilian researchers reported that a 31-year-old man infected his mother with the virus when he bit her while he was having a seizure. Doctors performed a DNA test of the woman's virus and confirmed that it matched her son's virus. Dr. Harold Jaffe, head of the CDC's Division of HIV, STDs and TB, said two similar incidents had been recorded in the United States but noted that there has never been a case attributable to saliva alone, as blood is usually present in the mouth (Laino, MSNBC.com, 2/27).