Human Immunodeficiency Virus Type 1 Protease Cleavage Site Mutations Associated with Protease Inhibitor Cross-Resistance Selected by Indinavir, Ritonavir, and/or Saquinavir

doi:10.1128/JVI.75.2.589-594.2001

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Journal of Virology, January 2001, p. 589-594, Vol. 75, No. 2
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.2.589-594.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Human Immunodeficiency Virus Type 1 Protease Cleavage Site Mutations Associated with Protease Inhibitor Cross-Resistance Selected by Indinavir, Ritonavir, and/or Saquinavir

Hélène C. F. Côté, Zabrina L. Brumme, and P. Richard Harrigan^*

British Columbia Centre for Excellence in HIV/AIDS, St. Paul's Hospital, Vancouver, British Columbia, Canada V6Z 1Y6

Received 18 May 2000/Accepted 11 October 2000

We examined the prevalence of cleavage site mutations, both within and outside the gag region, in 28 protease inhibitor (PI)cross-resistant patients treated with indinavir, ritonavir, and/orsaquinavir compared to control patients treated with reverse transcriptaseinhibitors. Three human immunodeficiency virus protease cleavagesites within gag (p2/NC, NC/p1, and NC/TFP) showed considerablein vivo evolution before and after therapy with indinavir, ritonavir,and/or saquinavir. Another gag cleavage site (p1/p6^gag) showed a trend compared to matched controls. The other eightrecognized cleavage sites showed relatively little differencebetween PI-resistant cases and controls. An A $right-arrow$ V substitution atthe P2 position of the NC/p1 and NC/TFP cleavage sites was themost common (29%) change selected by the PIs used in thisstudy.

^* Corresponding author. Mailing address: B.C. Centre for Excellence in HIV/AIDS, St. Paul's Hospital, 613-1081 Burrard St.,Vancouver, BC V6Z 1Y6, Canada. Phone: (604) 806-8281. Fax: (604)806-8464. E-mail: lab{at}hivnet.ubc.ca.

Journal of Virology, January 2001, p. 589-594, Vol. 75, No. 2
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.2.589-594.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

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