Abacavir (ABC, Ziagen) is an important agent for the management of HIV infection. The greatest challenge with this agent is the potential for developing a hypersensitivity reaction (HSR). Although most studies have indicated that the abacavir HSR rate is in the 6 to 10 % range, the diagnosis is not always straightforward. Abacavir HSR can be quite severe, especially if the agent is restarted after a previous reaction. Deaths from abacavir HSR have been reported and this complication has tempered the enthusiasm for the use of abacavir, especially as alternative therapeutic options have expanded.

Study

This open-label trial involved participants with primary HIV infection who all received abacavir and lamivudine (3TC, Epivir) as their nucleoside backbone. In addition, they were randomized to 1 of 3 treatment arms that included either efavirenz (EFV, Sustiva, Stocrin), efavirenz plus indinavir (IDV, Crixivan), or ritonavir (RTV, Norvir) plus indinavir.

Although it is an area of strong research interest, there are limited data addressing the treatment of primary HIV infection. The appeal of early treatment is based on previous trials that suggested prompt therapy may lower the viral set point by preventing widespread dissemination of virus to tissue reservoirs. However, most trials reported thus far are hindered by their small numbers and limited follow-up.

Fifty people were enrolled in the trial and 9 (18%) were diagnosed with probable or definite abacavir HSR. Of these 9 subjects, 2 had HLA-B*5701 polymorphism versus 0/39 in the group without HSR (P = .032).

There were other significant differences between the people who developed abacavir HSR and those who did not. People with HSR commenced treatment later in the course of acute infection (103 days vs. 48 days) and also tended to have a lower HIV-RNA level and CD8+ lymphocyte percentage.

Comment

Previous studies have indicated that certain individuals with the genetic subtype HLA-B*5701 are more likely to develop abacavir HSR.¹ This association also held up in this small study of primary HIV infection. Unfortunately, there is limited potential for utilization of this test in clinical practice because of the cost of testing and the relatively low frequency of this subtype.

Although the total number of cases of abacavir HSR in this study was small, the surprisingly high rate of 18% may signify a magnified risk of the use of abacavir in patients with primary HIV infection. One potential explanation of this observation is that the presence of an intact immune system in primary HIV infection may heighten the risk of abacavir HSR.

Regardless of the cause, on the basis of these limited data, special caution should be exercised if abacavir is used in the management of patients with primary HIV infection.

Footnote

1. Mallal S, Nolan D, Witt C, et al. Association between presence of HLA-B*5701, HLA-DR7, and HLA-DQ3 and hypersensitivity to HIV-1 reverse-transcriptase inhibitor abacavir. Lancet. March 2, 2002;359(9308):727-732.