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Delayed Immunologic Deterioration among Patients Who Virologically Fail Protease Inhibitor-Based Therapy S. G. DEEKS1, J. D. BARBOUR2, J. N. MARTIN1, and R. M. GRANT2.
1San Francisco Gen. Hosp., CA; and 2Gladstone Inst. of Virology and Immunology, San Francisco, CA Background: CD4 preservation after virologic failure of protease inhibitor (PI)-containing regimens has been observed, although the duration of follow-up has been limited. We sought to determine the time to immunologic failure in patients receiving long-term PI-based therapy.
Methods: In this ongoing clinic-based observational cohort study, we analyzed patients who initiated a PI-based regimen prior to September, 1997, and who remained on therapy for at least 16 weeks. Virologic failure was defined as a confirmed HIV RNA > 500 copies RNA/mL at or after week 16. Immunologic failure was defined as return of CD4 cell count to the pre-therapy baseline. Patients experiencing virologic failure were censored at the time they initiated a successful salvage regimen (HIV RNA < 500 for > 16 weeks) or stopped therapy (for > 16 weeks). As an untreated comparison group we used the San Francisco Men's Health Study (SFMHS), a cohort of 304 HIV infected men observed in the pre-treatment era of the mid-1980s.
Results: This cohort of 479 PI-treated patients had a median pre-PI CD4 of 156 cells/mm3 and HIV RNA of 4.65 log copies/mL. The median duration of follow-up was 32.2 months. At 34 months of PI therapy, the probability of virologic failure was 59% while the probability of immunologic failure was 29 %. Among those experiencing virologic failure, the median time to immunologic failure from the first date of observed virologic failure was 35 months. The rate of CD4 cell T cell depletion (log10 transformed) at any given level of viremia was slower in treated subjects failing PI therapy than in untreated subjects from the SFMHS (p<0.05). There were 42 deaths among the PI-treated patients, most non-HIV related.
Conclusion: In patients who virologically fail a PI-based regimen, immune deterioration is delayed but does eventually occur in the majority of patients. The rate of CD4 T cell depletion in these patients is significantly lower than in untreated patients. These data suggest that the immunologic benefit of therapy persists long after virologic failure, but that patients can not be maintained indefinitely on virologically failing regimen.
Key Words: immunologic failure, protease inhibitors, virologic failure
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