IAS 2013: Genetic Testing Lowers Risk of Nevirapine Skin Rash

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Screening for genetic mutations could substantially reduce the risk of hypersensitivity reactions involving skin rash among people starting nevirapine, according to a late-breaker report at the 7th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2013) this month in Kuala Lumpur.

Nevirapine (Viramune and generic equivalents) is an effective non-nucleoside reverse transcriptase inhibitor that is widely used in resource-limited settings due to its low cost and general good tolerability.

But nevirapine can cause hypersensitivity reactions in susceptible individuals -- estimated at approximately 15%-20% -- including skin reactions and liver inflammation, ranging from mild to severe. The risk is higher for people with stronger immune function, and the Viramune product label states that it is not recommended for women with CD4 counts above 250 cells/mm3 or men with more than 400 cells/mm3.

Sasisopin Kiertiburanakul and Somnuek Sungkanuparph from Mahidol Universityin Bangkok and colleagues conducted a study to assess whether advance genetic screening could help determine which individuals are likely to develop nevirapine-associated skin reactions among people starting HIV treatment in Thailand during 2009-2012.

Prior research has shown a link between nevirapine skin reactions and genetic variations of the major histocompatibility complex, which enables the immune system to distinguish the body's own cells from foreign invaders. These include an allele known as HLA-B*35:05 and single nucleotide polymorphisms (SNPs) of the CCHCR1 gene. A previous study by Sungkanuparph'steam found the HLA-B*35:05 variant in 18% of Thai patients who developed rash after starting nevirapine, compared with just 1% of those who were nevirapine-tolerant.

This prospective, randomized study included 1103 people with HIV at 9 hospitals in Thailand who were starting antiretroviral therapy (ART) for the first time. About 60% were men, the median age was 37 years, and the median CD4 count was 116 cells/mm3. Participants were stratified by sex and CD4 count above or below 250 cells/mm3 for women or 400 cells/mm3 for men.

Half of participants were randomly assigned to receive advance genotypic testing for HLA-B*35:05 and CCHCR1 SNPs before starting treatment, and those found to carry the suspect variations started on efavirenz (Sustiva) rather than nevirapine. The control group did not undergo advance genetic screening and started on nevirapine according to the local standard of care.

Results

"Point-of-care genotypic testing is [an] effective preventive intervention for [nevirapine cutaneous adverse reactions]," the researchers concluded.

"Nevirapine can be initiated safely" for those who are less likely to develop nevirapine skin reactions based on the results of genetic testing, they continued. "Our results support the use of genotypes-based screening in a clinical setting" to prevent nevirapine skin reactions among treatment-naive Thai HIV patients.

At a press conference prior to the presentation, Sungkanuparph said the next step is to confirm these findings in other ethnic populations, especially those in which HLA-B*35:05 is common. The researchers noted that this variant is "not common in populations except Southeast Asians and Southern Americans" (by which it is not clear whether they mean people in South America or the U.S. south).

If confirmed, "personal prescription" using HLA-B*3505 and CCHCR1 SNPs genetic screening could play a role similar to that of the HLA-B*5701 test for hypersensitivity to abacavir (Ziagen, also in the Epzicom coformulation), allowing the drug to be widely used with more confidence.

This prospect gains importance given new World Health Organization treatment guidelines released at the conference recommending treatment at higher CD4 counts that would be considered a contraindication to using nevirapine.

7/15/13

Reference

S Kiertiburanakul, S Mahasirimongkol, N Rajatanavin, S Sungkanuparph, et al. HLA-B*35:05 and CCHCR1 screening reduces nevirapine-associated cutaneous adverse reactions in Thailand: a prospective multicenter randomized controlled trial. 7th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention. Kuala Lumpur, June 30-July 3, 2013. Abstract WELBB04.