The sequential occurrence of pol 215 and pol 41 zidovudine resistance mutations 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 determination of the pol 215 and pol 41 zidovudine (ZDV) resistance mutations had been described between January 1995 and February 1996. The patients received ZDV alone or a combination of ZDV and zalcitabine or didanosine. A total of 55, 15 and 45 patients exhibited a wild (W), a mixed (MIX) or a mutant (M) genotype at codon pol 215, respectively; 85, 10 and 20 patients exhibited a W, a MIX or a M genotype at codon pol 41, respectively. Patients exhibiting the pol 215 M genotype had lower CD4 cells, higher plasma viral load and higher proviral burden than patients exhibiting the pol 215 W genotype. Patients who had variants exhibiting both pol 215 M and pol 41 M or MIX genotypes had significantly worsened surrogate marker values than patients having variants only carrying the pol 215 M genotype. These observations demonstrate that the two mutations additively associate with pejorative surrogate markers.
Si Mohamed
A
A
Laboratoire de virologie, Hôpital Broussais, Paris, France.
Kazatchkine
M
M
Piketty
C
C
Cotigny
S
S
Gilquin
J
J
Weiss
L
L
Matta
M
M
Gutmann
L
L
Belec
L
L
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D015415:Biomarkers; D018791:CD4 Lymphocyte Count; D003430:Cross-Sectional Studies; D016049:Didanosine / Q000627:therapeutic use; D004352:Drug Resistance, Microbial / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009154:Mutation / Q000235:genetics*; D012367:RNA, Viral; D019562:Viral Load; D016047:Zalcitabine / Q000627:therapeutic use; D015215:Zidovudine / Q000627:therapeutic use
D019380:Anti-HIV Agents; D015415:Biomarkers; D012367:RNA, Viral; D015215:Zidovudine; D016047:Zalcitabine; D016049:Didanosine