Future treatment strategies in HIV infection.

Effectiveness of early treatment with zidovudine: In terms of progression to AIDS-related complex, AIDS or death, clinical trials have not yet shown any long-term benefit for early compared with deferred treatment with zidovudine. The Concorde trial showed a short-term benefit, as did two of the AIDS Clinical Trials Group studies, but the number of deaths in these short-term trials was too small to draw definitive conclusions. Use of CD4 cell counts as a marker of AIDS: Most trials of zidovudine treatment have shown a slower decline in CD4 cell counts. However, it is still not clear whether these markers can predict long-term survival although they appear to have some value in predicting short-term benefits. Second-line therapy: In patients who are intolerant of or have failed to respond adequately to zidovudine, treatment with didanosine or zalcitabine has shown some short-term benefit, mainly in asymptomatic patients or those with AIDS-related complex. No substantial long-term benefit was observed. Zalcitabine appeared to show a slight increase in survival compared with didanosine. Future prospects: Treatment strategies still being developed include multidrug combinations, the combination of a nucleoside with a non-nucleoside reverse transcriptase inhibitor, or the use of a combination of drugs that affect different stages of the HIV life cycle, such as proteinase inhibitors. More sensitive assays, such as RNA polymerase chain reaction, may allow treatment to be tailored more closely to the needs of the individual patient.