Efficacy and safety of combination therapy with delavirdine and zidovudine: a European/Australian phase II trial

The objective of the study was to investigate the safety and antiviral effe ct of three delavirdine dose regimens or placebo in combination with zidovu dine in patients who were already taking zidovudine. Eighty-nine symptomati c HIV-1 seropositive individuals with CD4(+) cell counts between 50 and 350 cells/mu l were included in this trial The influence of combination therap y on viral susceptibility to both zidovudine and delavirdine was investigat ed. Death or the occurrence, or re-occurrence of an AIDS-defining illness w as considered as a clinical endpoint. The addition of delavirdine to the an tiretroviral treatment regimen resulted in a significant, but transient, re duction in virus load, as determined by quantitative RNA measurements. CD4( +) cell count did not change significantly. Susceptibility to zidovudine re mained unchanged after 12 weeks of combination therapy, while 70% of the pa tients demonstrated a substantial decrease (> 10-fold) in sensitivity to de lavirdine. Two patients suffered from an AIDS-defining disease during the s tudy. No deaths occurred. Generally, the drug appeared to be safe. Skin ras h was the most frequently observed adverse event (52%). In most patients th e rash either resolved spontaneously or was treated successfully with a sho rt course of antihistamines. The definite place of the compound in the mana gement of HIV disease, in particular when given in combination with other a ntiretroviral agents, remains to be further explored. (C) 1999 Elsevier Sci ence B.V. and International Society of Chemotherapy. All rights reserved.