A TRIAL COMPARING NUCLEOSIDE MONOTHERAPY WITH COMBINATION THERAPY IN HIV-INFECTED ADULTS WITH CD4 CELL COUNTS FROM 200 TO 500 PER CUBIC MILLIMETER

Background This double-blind study evaluated treatment with either a s ingle nucleoside or two nucleosides in adults infected with human immu nodeficiency virus type 1 (HIV-1) whose CD4 cell counts were from 200 to 500 per cubic millimeter. Methods We randomly assigned 2467 HIV-1-i nfected patients (43 percent without prior antiretroviral treatment) t o one of four daily regimens: 600 mg of zidovudine; 600 mg of zidovudi ne plus 400 mg of didanosine; 600 mg of zidovudine plus 2.25 mg of zal citabine; or 400 mg of didanosine. The primary end point was a greater than or equal to 50 percent decline in the CD4 cell count, developmen t of the acquired immunodeficiency syndrome (AIDS), or death. Results Progression to the primary end point was more frequent with zidovudine alone (32 percent) than with zidovudine plus didanosine (18 percent; relative hazard ratio, 0.50; P<0.001), zidovudine plus zalcitabine (20 percent; relative hazard ratio, 0.54; P<0.001), or didanosine alone ( 22 percent; relative hazard ratio, 0.61; P<0.001). The relative hazard ratios for progression to an AIDS-defining event or death were 0.64 ( P=0.005) for zidovudine plus didanosine, as compared with zidovudine a lone, 0.77 (P=0.085) for zidovudine plus zalcitabine, and 0.69 (P=0.01 9) for didanosine alone. The relative hazard ratios for death were 0.5 5 (P=0.008), 0.71 (P=0.10), and 0.51 (P=0.003), respectively. For zido vudine plus zalcitabine, the benefits were limited to those without pr evious treatment. Conclusions Treatment with zidovudine plus didanosin e, zidovudine plus zalcitabine, or didanosine alone slows the progress ion of HIV disease and is superior to treatment with zidovudine alone. Antiretroviral therapy can improve survival in patients with 200 to 5 00 CD4 cells per cubic millimeter.