Changes in cellular virus load and zidovudine resistance of syncytium-inducing and non-syncytium-inducing human immunodeficiency virus populations under zidovudine pressure: a clonal analysis.
Zidovudine treatment preferentially benefits persons with only non-syncytium-inducing (NSI) human immunodeficiency virus type 1 (HIV-1) variants. To understand this differential efficacy, changes in cellular virus load, clonal composition of HIV-1 populations, and development of resistance-conferring reverse transcriptase mutations were studied in 17 persons initiating zidovudine therapy. Zidovudine treatment resulted in larger and more sustained decreases in cellular virus load in persons with NSI variants only compared with persons also carrying syncytium-inducing (SI) variants. Although the former group had a delayed emergence of resistance mutations, differences in initial responses between the 2 groups were independent of the emergence of resistance mutations. Changes in virus load in subjects also carrying SI variants were due mainly to loss of coexisting NSI virus. Resistance mutations emerged at similar rates in both coexisting variants. Data suggest that mechanisms other than drug resistance are necessary to completely explain the phenotype-dependent benefit of zidovudine.
van 't Wout
A B
AB
Department of Clinical Viro-Immunology, Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam, Netherlands.
de Jong
M D
MD
Kootstra
N A
NA
Veenstra
J
J
Lange
J M
JM
Boucher
C A
CA
Schuitemaker
H
H
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000821:virology; D019380:Anti-HIV Agents / Q000494:pharmacology*; D004351:Drug Resistance; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008297:Male; D009154:Mutation; D015215:Zidovudine / Q000494:pharmacology*
D019380:Anti-HIV Agents; D015215:Zidovudine