Objective: To determine the HIV RNA and CD4 cell response to both initial and salvage therapy with protease inhibitor-based therapy, and to examine the relationship between the virological response and pre-therapy characteristics.
Design: Observational cohort.
Setting: University-based public hospital AIDS clinic.
Patients: HIV-infected adults who received at least 16 continuous weeks‚ therapy with a potent protease inhibitor (indinavir, ritonavir or nelfinavir)-based regimen, and who have had at least 48 weeks of follow-up.
Main outcome measures: Plasma HIV RNA and CD4 cell count response at week 48 of therapy for patients receiving their first protease inhibitor-containing regimen, and at week 24 of therapy with a salvage regimen.
Results: Of the 337 patients analysed, 170 (50.2%) had a successful outcome (HIV RNA <500 copies/ml after 48 weeks of treatment). Independent predictors of virological failure were higher baseline HIV RNA level, lower baseline CD4 cell count and failure to initiate at least one new nucleoside analog simultaneously at the time protease inhibitor therapy was initiated. The risk of failure increased incrementally across most HIV RNA and CD4 cell strata, with significant increases as the HIV RNA increased above 4.5 log10 copies/ml and the CD4 cell count fell below 100 cells/mm3 (P£0.01). The CD4 cell count remained above baseline to week 48 in most patients, regardless of the HIV RNA response. Of the 99 patients who experienced virological failure and switched to a salvage regimen, only 22 (22%) achieved an undetectable HIV RNA level 24 weeks after initiating salvage therapy. Independent predictors of failure with salvage therapy included an HIV RNA greater than 4.0 log10 RNA copies/ml at the time of the switch and failure to use a non-nucleoside reverse transcriptase inhibitor (NNRTI) in the salvage regimen.
Conclusion: Failure of potent protease inhibitor therapy to suppress HIV RNA levels below detectable levels is common in clinical practice, and can often be explained by their suboptimal use. CD4 T cell counts remain above baseline for at least one year in most patients experiencing virological failure. Successful salvage therapy, which was uncommon, was associated with a low plasma HIV RNA at the time of the switch and the use of a new class of antiretroviral agents (NNRTI) in the salvage regimen.
From the *University of California, San Francisco and San Francisco General Hospital, San Francisco, CA, USA; and †Gladstone Institute of Virology and Immunology, San Francisco, CA, USA.
Sponsorship: This work was supported in part by grants from the National Institutes of Health, University of California, San Francisco, Center for AIDS Research, P30 AI27763, and the Universitywide AIDS Research Program, University of California, San Francisco AIDS Clinical Research Center, CC95-SF-123.
This study was approved by the Institutional Review Board of the University of California, San Francisco, CA, USA.
Correspondence to: Steven G. Deeks, MD, Assistant Clinical Professor of Medicine, UCSF, UCSF AIDS Program, 995 Potrero Avenue, San Francisco General Hospital, San Francisco, CA 94110, USA. Tel: +1 (415) 476-4082 (extn 404); fax: +1 (415) 476-6953; e-mail: email@example.com
Date of receipt: 10 November 1998; revised: 11 January 1999; accepted: 21 January 1999.