Factors influencing the emergence of resistance to indinavir: role of virologic, immunologic, and pharmacologic variables.
A major problem with the use of human immunodeficiency virus type 1 (HIV-1) protease inhibitors as monotherapy has been an unacceptably high rate of emergence of resistance. To examine possible influences on the time to emergence of resistance, 24-week data were examined from five studies in which indinavir had been administered as monotherapy or as a component of combination therapy. Monotherapy data indicated a correlation between the level of HIV-1 RNA achieved and the risk of emergence of resistance: the lower the level, the lower the risk. When combination and monotherapy regimens were compared, the group receiving indinavir + lamivudine + zidovudine had a significantly lower risk of resistance, even after adjusting for the minimum HIV-1 RNA level achieved. The findings indicate that if at all possible, HIV-1-infected patients should receive combination chemotherapy to minimize the emergence of resistance to the protease inhibitor portion of the regimen. The goal of therapy should be to decrease the HIV-1 RNA load to a less-than-detectable level.
Albany Medical College, New York 12208, USA. GLDRUSANO@AOL.COM
G L
GL
Drusano
J A
JA
Bilello
D S
DS
Stein
M
M
Nessly
A
A
Meibohm
E A
EA
Emini
P
P
Deutsch
J
J
Condra
J
J
Chodakewitz
D J
DJ
Holder
D019380:Anti-HIV Agents / Q000627:therapeutic use*; D004352:Drug Resistance, Microbial; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D019469:Indinavir / Q000627:therapeutic use*; D008297:Male
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D019469:Indinavir