HIV/HCV coinfected patients who develop severe allergy to nevirapine have significantly increased risk of death

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People with hepatitis C and HIV coinfection who develop a hypersensitivity reaction to nevirapine (Viramune) have a seven-fold increase in their risk of death when compared to people without HCV, according to Canadian researchers writing in the July 31st edition of AIDS.Their findings add weight to current recommendations that nevirapine should not be used in people with HCV/HIV coinfection.

Nevirapine (Viramune) is a generally well-tolerated non-nucleoside reverse transcriptase inhibitor (NNRTI) but a number of side-effects are seen with this drug. Around 16% of patients will develop a mild to moderate rash while around 6.5% will suffer a more serious rash – usually within six weeks of taking it. But around one in ten patients have elevated liver enzymes while around five per cent will suffer symptomatic liver toxicity.

However, a potentially life-threatening hypersensitivity reaction can occur alongside rash and hepatitis. Women and patients with higher CD4 cell counts are at increased risk of hypersensitivity accompanied by liver toxicity, and because of this women with a CD4 cell count above 250 cells/mm3 and men with a CD4 cell count above 400 cells/mm3 should not start treatment with nevirapine.

Glossary

hypersensitivity

An allergic reaction.

rash

A rash is an area of irritated or swollen skin, affecting its colour, appearance, or texture. It may be localised in one part of the body or affect all the skin. Rashes are usually caused by inflammation of the skin, which can have many causes, including an allergic reaction to a medicine.

toxicity

Side-effects.

AIDS defining condition

Any HIV-related illness included in the list of diagnostic criteria for AIDS, which in the presence of HIV infection result in an AIDS diagnosis. They include opportunistic infections and cancers that are life-threatening in a person with HIV.

alanine aminotransferase (ALT)

An enzyme found primarily in the liver. Alanine aminotransferase may be measured as part of a liver function test. Abnormally high blood levels of ALT are a sign of liver inflammation or damage from infection or drugs.

People with hepatitis B or C coinfection, and individuals with raised liver enzymes (specifically ALT) are known to be at higher risk of developing a hypersensitivity reaction to nevirapine too. Instead, the risk of death appears to be elevated as a result of treatment interruption after the hypersensitivity reaction.

Researchers from the British Columbia Centre for Excellence in HIV/AIDS in Canada examined all cases of hypersensitivity in the province's patients who had started antiretroviral therapy with nevirapine between 1997 and 2003.

They identified 66 individuals out of 685 treatment-naïve patients starting a nevirapine-containing regimen between 1997 and 2003. Of these 66 people, 26 (53%) had a HCV co-infection and the researchers compared the risk of death between different groups. HIV-infected patients who developed a HSR to nevirapine and were coinfected with HCV were seven times more likely to die than those without the HSR or HCV coinfection (p

The causes of death were similar for both nevirapine-tolerant and hypersensitive patients and were mainly due to HIV disease progression. The authors say the influence of the nevirapine HSR on HCV infection and mortality was “unexpected” but shows it plays some sort of role in modifying the association between the virus and the risk of death. HIV-infected people who developed the HSR but were not HCV-infected had a small but not statistically significant increase in risk of death.

Hypersensitivity or liver failure caused by nevirapine was not the direct cause of death in any patient who experienced hypersensitivity reaction. The risk of death appeared to be elevated in patients with HCV coinfection and hypersensitivity due to treatment interruptions, with nine deaths in 13 patients who did not resume therapy dying during the follow-up period, compared to only one death among 22 patients who resumed therapy within six months of experiencing a hypersensitivity reaction.

A fourfold increase in the risk of death (due to non-AIDS-defining causes) in HIV/HCV coinfected patients was seen among those with HCV who interrupted their antiretroviral treatment in the SMART study, according to findings presented last month at the International AIDS Society conference in Sydney.

Several factors have been associated with increased risk of developing nevirapine HSR including CD4 cell counts of 250 cells/mm3 or above, being female, prolonged exposure to any antiretroviral drug and raised liver enzymes at start of treatment. No such risk factors could be identified in this study, possibly because the numbers studied were too small to reveal them.

However the authors say the results support the recommendation that nevirapine should not be used in people who are infected with both HIV and HCV.

References

Phillips E et al. Determinants of nevirapine hypersensitivity and its effect on the association between hepatitis C status and mortality in antiretroviral drug-naïve HIV-positive patients. AIDS 21: 1561-1568, 2007.