1% of patients at French hospital develop rash after starting treatment with atazanavir

Approximately 1% of patients who took the protease inhibitor atazanavir (Reyataz) at a major Parisian HIV treatment centre developed a skin rash, according to a series of case reports published in the May 2006 edition of AIDS. The rash developed within eleven days of treatment with the drug being initiated and in one case was severe enough for treatment with atazanavir to be discontinued.

Rash is a side-effect of antiretroviral medications most frequently associated with abacavir (Ziagen)from the nucleoside reverse transcriptase inhibitor class (NRTI) or nevirapine (Viramune) from the non-nucleoside reverse transcriptase inhibitor (NNRTI) group of antiretrovirals.

In the late summer of 2004, doctors at the Pitie-Salpetriere Hospital in Paris treated three patients who had recently started therapy with atazanavir for rash.

The first case involved a 40 year-old man who had been HIV-positive since 1991 and infected with hepatitis B virus since 2002. He had received numerous anti-HIV drugs in the past and in late August 2004 he replaced indinavir with atazanavir, which he took with 3TC (Epivir) and tenofovir (Viread). Ten days later he was admitted to hospital with a widespread red rash and jaundice. His bilirubin level was 28 mg/l but tests revealed that there were no other biological abnormalities. As his symptoms were mild, antiretroviral therapy was continued unaltered and the rash disappeared of its own accord.

A diffuse red rash and jaundice were also seen in the second patient, a 33 year-old man who was diagnosed with HIV in 1999 and hepatitis of unknown origin in 2003. Between 1999 and early 2004 he was treated with multiple antiretroviral drugs and commenced therapy with atazanavir, ddI and 3TC eleven days before presenting with a rash. Tests revealed that the man had elevated bilirubin (202 mg/l), a viral load of a little under 100,000 copies/ml and a CD4 cell count of 246 cells/mm³. The blood concentration of atazanavir was within normal range at 899 ng/ml. Although the individual’s rash disappeared within 48 hours, treatment with atazanavir was stopped because of persistent hyperbilirubinaemia and the pre-existing chronic hepatitis.

The final case also involved a man, aged 40, who was diagnosed with HIV in 1993. Once again, he had extensive prior experience of antiretroviral therapy and started treatment with atazanavir, lopinavir and 3TC after a rebound in his viral load. He was admitted to hospital nine days after starting this regimen with a generalised red rash. All his laboratory investigations were normal and an antihistamine was prescribed. However, the rash worsened and 48 hours later antiretroviral therapy was stopped. There was no rash or involvement of the mucous membranes.

“Clinicians must be aware of adverse cutaneous reactions to atazanavir, which may require treatment discontinuation”, conclude the investigators. However, they note that between March 2004 and the end of August 2004 over 330 patients at their centre developed a rash after commencing treatment with atazanavir “giving a prevalence rate of approximately 1%.”