Rare abacavir liver side-effects reported

Two cases of liver toxicity caused by the anti-HIV drug abacavir (Ziagen, also in the combination pill Kivexa) have been reported in the November 30^th edition of AIDS. Both cases involved young women who changed their HIV treatment to include abacavir. Tests showed that neither of the women was allergic to abacavir.

Liver side-effects occur in between 5% and 10% of patients taking antiretroviral therapy. Such side-effects are most associated with rarely used drugs from the NRTI class (d4T and ddI), the NNRTI nevirapine (Viramune) and some protease inhibitors.

Abacavir can cause a serious allergic reaction and minor changes in liver enzymes can be a symptom of this. However, there have hitherto been few reports of liver side-effects in patients who are negative for the gene (HLA-B*5701) associated with abacavir allergy.

However, investigators from Brighton in southern England have reported two cases of abacavir-induced liver toxicity in young HIV-positive women, neither of whom were allergic to the drug.

The first case involved a 26-year-old Zimbabwean woman who switched from an antiretroviral regimen of Combivir (AZT and 3TC) with nevirapine (Viramune) to one consisting of Kivexa (abacavir and 3TC) with nevirapine because of concerns about AZT-associated fat loss.

This treatment change occurred after the patient tested HLA-B*5701-negative. When therapy with abacavir was started, the women’s ALT level (a key marker of liver function) was 21 iu/l, and although this had increased to 36 iu/l six weeks later, this was still well within the normal range.

One month later, however, the patient contacted the clinic complaining of fatigue and muscle aches. She did not attend the clinic for a further two months at which time her ALT level was 433 iu/l. Tests for viral hepatitis were negative and excessive alcohol consumption was also ruled out as a possible cause of the side-effect.

A liver biopsy showed that the patient had severe inflammation of the liver with cell loss, likely to be treatment-induced. Therapy with Kivexa was stopped, the patient being maintained on Kaletra monotherapy. Within one month, the patient’s ALT levels had returned to normal and all her physical symptoms had resolved.

The second case involved a 34-year-old Spanish woman who also switched treatment from Combivir and nevirapine because of concerns about lipoatrophy.

After a negative HLA-B*5701 test, the patient started treatment with Kivexa and nevirapine. At this time, her ALT level was 10 iu/l and this was still normal six weeks later, being 21 iu/l. However, approximately three months after starting abacavir therapy, the woman’s ALT increased to 423 iu/l. Once again, the patient tested negative for viral hepatitis. The patient replaced Kivexa with Truvada (FTC and tenofovir) and her ALT level returned to normal within four weeks.

“Clinicians should be aware of the possibility that abacavir can cause impaired liver function and should remain alert for signs of hepatitis”, write the investigators. They conclude, “patients should be encouraged to report even mild symptoms at their onset and close monitoring of liver function tests is recommended.”