THE SEQUENTIAL OCCURRENCE OF POL-215 AND POL-41 ZIDOVUDINE RESISTANCEMUTATIONS IS ASSOCIATED IN AN ADDITIVE FASHION WITH LOW CD4 CELL COUNTS AND HIGH PLASMA AND CELLULAR HIV VIRAL LOAD

We report on a cross-sectional study of virological and immunological surrogate markers of HIV infection in 115 patients for whom a determin ation of the pol 215 and pol 41 zidovudine (ZDV) resistance mutations had been described between January 1995 and February 1996. The patient s received ZDV alone or a combination of ZDV and zalcitabine or didano sine. A total of 55, 15 and 45 patients exhibited a wild (W), a mixed (MM) or a mutant (M) genotype at codon pol 215, respectively; 85, 10 a nd 20 patients exhibited a W, a MIX or a M genotype at codon pol 41, r espectively. Patients exhibiting the pol 215 M genotype had lower CD4 cells, higher plasma viral load and higher proviral burden than patien ts exhibiting the pol 215 W genotype. Patients who had variants exhibi ting both pol 215 M and pol 41 M or MIX: genotypes had significantly w orsened surrogate marker values than patients having variants only car rying the pol 215 M genotype. These observations demonstrate that the two mutations additively associate with pejorative surrogate markers. (C) 1998 Elsevier Science B.V. All rights reserved.