Abacavir: a review of its clinical potential in patients with HIV infection.
Abacavir is a carbocyclic 2'-deoxyguanosine nucleoside analogue. It is metabolised intracellularly to a 2'-deoxyguanosine nucleoside analogue which competitively inhibits HIV reverse transcriptase and terminates proviral DNA chain extension. In double-blind trials in antiretroviral therapy-experienced or -naive patients, reductions in HIV RNA levels were greater and more prolonged in patients 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 extent to the protease inhibitor indinavir in combination with lamivudine and zidovudine. Greatest viral load reductions were seen in antiretroviral therapy-naive patients. Preliminary results suggest that the viral suppression achieved with a protease inhibitor plus 2 nucleoside reverse transcriptase inhibitors (NRTIs) can be maintained as effectively with abacavir in combination with 2 NRTIs as it can be by continuing the protease inhibitor-containing treatment regimen. Initial virological data from studies of combination regimens including abacavir and protease inhibitors appear promising but larger controlled trials 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; the 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, diarrhoea, sleep disorders, cough, anorexia and rash. A major cause of abacavir treatment discontinuation is the development of a hypersensitivity reaction which 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 rapidly after discontinuation of treatment. Continuing treatment or rechallenge can result in more severe symptoms, life-threatening hypotension and even death.


CONCLUSIONS
Abacavir used in combination with other antiretroviral drugs effectively reduces viral load in both adults and children with HIV infection. Although these responses are greatest in individuals with little or no previous antiretroviral treatment, useful responses are still sometimes achieved in heavily pretreated individuals. Abacavir in combination with lamivudine and zidovudine provides a simple and convenient dosage regimen which is generally well tolerated, able to produce sustained suppression of viral replication and has the advantage of sparing other classes of antiretroviral drugs for subsequent use. This triple combination represents an alternative antiretroviral regimen for patients intolerant to protease inhibitors or those wishing to retain the option of protease inhibitors for later use. Further clinical studies are needed to define the activity of abacavir in combination with protease inhibitors and non-nucleoside reverse transcriptase inhibitors.
Hervey
P S
PS
Adis International Limited, Mairangi Bay, Auckland, New Zealand.
Perry
C M
CM
D000818:Animals; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D015224:Dideoxynucleosides / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D000099227:Abacavir
D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D018894:Reverse Transcriptase Inhibitors; D000099227:Abacavir