Register TodayEarn Free CME Credits by reading the latest medical news in your specialty.Sign UpKUALA LUMPUR -- A higher percentage of Malay people experienced treatment-limiting toxicity with the non-nucleoside reverse transcriptase anti-HIV drug nevirapine compared with other groups, and genetic differences may be the reason, researchers reported here.
"Malays had the highest incidence of treatment-limiting nevirapine toxicity amongst the different racial groups," said Joyce Yeap, MS, a clinical pharmacist at Sungai Buloh Hospital in Selangor, Malaysia. Malays had an incidence of treatment-limiting toxicity of 38.4%, compared with Indians, who had the lowest incidence of treatment-limiting nevirapine toxicities at 23.6% (P=0.016), she told MedPage Today.
It is difficult to understand why there should be a racial difference even after performing adjustments for age, sex, HIV transmission category, nadir CD4-positive cell counts, hepatitis B or C virus co-infection and other concomitant medication, Yeap said in her poster presentation at the International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention.
However, outcomes at 12 months were not different between the patients who developed toxicities and were switched to other regimens and those who did not have dose-limiting adverse events (P=0.456), Yeap said.
"Malays are 1.7 times more likely than Chinese or Indians or other ethnicities to develop treatment-limiting nevirapine toxicities," she noted. The researchers performed various logistic regression analyses and determined that toxicities to nevirapine were more frequent in the Malay population of Malaysia which has a polyglot of different races, including several indigenous peoples.
"We did not have resources to perform genome studies," she said, "but it could be due to some type of gene sub-types that makes the Malays more sensitive to nevirapine toxicity."
Yeap said that when treating Malays, physicians need to factor in sex and CD4 counts as well. "We might be more cautious in giving nevirapine to these individuals," she suggested.
While other treatment regimens are possible for HIV-infected individuals, Yeap noted that for a developing country with limited resources, nevirapine is one of the most cost-effective therapies available.
The average age of the 662 HIV-infected patients in her study was 37.4 years, and 75.8% of the patients were men. Their average nadir CD4 cell counts were 134.8 cells/mm3. The researchers identified 34.6% of the patients as Malay; 42.1% were Chinese; 10.9% were Indian; and 9.2% were foreigners.
Rash was the nevirapine treatment-limiting adverse event among 156 patients; flu-like illnesses were observed in 130 patients; hepatotoxicity was seen in 44 patients. She said 102 patients presented with rash, flu-like illness and liver toxicity.
A possible explanation for the treatment-limiting toxicity might have to do more with clinical observation rather than genetics, suggested Graeme Moyle, MBBS, director of research at Chelsea and Westminster Hospital, London.
"There are studies here that look at the genetic linkage between adverse events and specific drugs," Moyle told MedPage Today as he reviewed the poster presentation. "There appear to be certain alleles that are associated with nevirapine toxicity, especially the cutaneous toxicities. It may be due to allele variations across certain ethnic populations."
He said that another possibility that is often discussed is that among black patients nevirapine-associated rash appeared more severe. He said that may be caused by the fact that the rash may be more difficult to observe among darker-skinned individuals. Since the rash is non-itchy, the skin color may mask the rash until it reaches a more severe level, Moyle suggested.
"When you have darker skin you don't recognize early rash that can lead to discontinuation when the rash is mild," he said. "People continue to take therapy and the rash continues to a more severe event."
Yeap had no disclosures.
Moyle has reported commercial interests with Gilead, Ardea Biosciences, Abbott Laboratories, Bristol-Myers Squibb, GlaxoSmithKline, Merck, Tobira Therapeutics, Panacos Pharmaceuticals, Pfizer and Tibotec.
Primary source: International AIDS Society
Source reference:
Yeap J, et al "Incidence and risk factors for treatment-limiting toxicities in patients starting nevirapine-containing antiretroviral therapy" IAS 2013; Abstract MOPE092.
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