Abacavir - A review of its clinical potential in patients with HIV infection

Abacavir is a carbocyclic 2'-deoxyguanosine nucleoside analogue. It is meta bolised intracellularly to a T-deoxyguanosine nucleoside analogue which com petitively inhibits HIV reverse transcriptase and terminates proviral DNA c hain extension. In double-blind trials in antiretroviral therapy-experienced or -naive pati ents, reductions in HIV RNA levels were greater and more prolonged in patie nts receiving abacavir in combination with other antiretroviral drugs than in those receiving placebo in combination with the same agents. Furthermore , abacavir in combination with lamivudine and zidovudine reduced viral load to below detectable levels in a proportion of patients, and to a similar e xtent to the protease inhibitor indinavir in combination with lamivudine an d zidovudine. Greatest viral load reductions were seen in antiretroviral th erapy-naive patients. Preliminary results suggest that the viral suppression achieved with a prot ease inhibitor plus 2 nucleoside reverse transcriptase inhibitors (NRTIs) c an be maintained as effectively with abacavir in combination with 2 NRTIs a s it can be by continuing the protease inhibitor-containing treatment regim en. Initial virological data from studies of combination regimens including abacavir and protease inhibitors appear promising but larger controlled tr ials are required to confirm these observations. Nausea is the most frequently reported adverse event in patients receiving abacavir-containing combination therapy. Adverse events tend to be reported most frequently soon after starting treatment; thr majority of events are mild or moderate in intensity and transient. Other adverse events reported in >5% of patients include vomiting, malaise and fatigue, headache, diarrho ea, sleep disorders, cough, anorexia and rash. A major cause of abacavir tr eatment discontinuation is the development of a hypersensitivity reaction w hich has been reported in 3 to 5% of patients. The reaction usually occurs within 6 weeks of commencing treatment, shows evidence of multiorgan system involvement and typically includes fever and/or rash. Symptoms resolve rap idly after discontinuation of treatment. Continuing treatment or rechalleng e can result in more severe symptoms, life-threatening hypotension and even death. Conclusion: Abacavir used in combination with other antiretroviral drugs ef fectively reduces viral load in both adults and children with HIV infection . Although these responses are greatest in individuals with little or no pr evious antiretroviral treatment, useful responses are still sometimes achie ved in heavily pretreated individuals. Abacavir in combination with lamivud ine and zidovudine provides a simple and convenient dosage regimen which is generally well tolerated, able to produce sustained suppression of viral r eplication and has the advantage of sparing other classes of antiretroviral drugs for subsequent use. This triple combination represents an alternativ e antiretroviral regimen for patients intolerant to protease inhibitors or those wishing to retain the option of protease inhibitors for later use. Fu rther clinical studies are needed to define the activity of abacavir in com bination with protease inhibitors and non-nucleoside reverse transcriptase inhibitors.