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Session 24 Oral Abstract Session Antiretroviral Chemotherapy: Pathogenesis of Primary HIV Infection Session Time: Wednesday, 10 am - 12:30 pm Room 6A-B

10:30   93. Are Episodes of Transient Viremia ("Blips" in HIV RNA) Predictive of Virologic Failure in Heavily Treatment-Experienced Patients? D. Havlir*1, R. Bassett2, V. DeGruttola2, S. Hammer3, R. Gulick4, and J. Mellors5 for the ACTG 359 and 398 Teams 1Univ. of California, San Diego; 2Harvard Sch. of Publ. Hlth., Boston, MA; 3Columbia Univ, New York, NY; 4Cornell Univ, New York, NY; and 5Univ. of Pittsburgh, PA Background: In treatment naïve patients or those with limited prior antiretroviral experience, achieving plasma HIV RNA<50 copies/mL with IDV+ZDV+3TC, blips in plasma HIV RNA > 50 copies/mL were associated with a higher steady state of plasma viremia but not virologic failure. We have now examined whether blips in plasma HIV RNA predict virologic failure in highly treatment-experienced patients on salvage therapy containing both Pis and NNRTIs. Methods: Cox proportional hazards models were used to evaluate the relationship between HIV RNA blips (HIV RNA >50 copies/mL with subsequent HIV RNA <50 copies/mL) and virologic failure (2 consecutive RNA >200 copies/mL) in ACTG 398 ( PI- [100%] and NNRTI- [44%] experienced patients randomized to amprenavir + a second PI in combination with abacavir, efavirenz, and adefovir). Higher thresholds for blip ( RNA >500 copies/mL ) and failure (RNA>1000 copies/mL) were also examined in ACTG 398 and in ACTG 359 (IDV- and NRTI-experienced patients randomized to nelfinavir/saquinavir vs ritonavir/saquinavir with either adefovir, delavirdine, or both). Results: In ACTG 398, 25% (41/161) of patients who achieved RNA <50 copies/mL had subsequent blips in HIV RNA. CD4 cell count increases at week 48 were no different between patients who did (+81) and did not exhibit blips (+64). Blips were not associated with virologic failure: RR 1.13 95% CI (0.42, 3.05). There was no association between baseline drug resistance (phenotypic sensitivity score) and HIV RNA blips (RR 0.56, 95% CI 0.20, 1.60, p=0.28). Consistent with other studies, failure to achieve HIV RNA nadir < 50 copies/mL in ACTG 398 was predictive of viral rebound (RR=3.13, 95% CI 1.91, 5.14, p<0.001). Analyses of patients enrolled in ACTG 359 (n=129) also showed no significant association between RNA blips >500 copies/mL and virologic rebound >1000 copies/mL (RR=1.40, p=0.51, 95% CI 0.52, 3.82). Conclusions: Even in highly treatment-experienced patients on multidrug salvage regimens, transient increases in HIV RNA do not predict virologic failure (within 38 weeks) in patients who have achieved plasma HIV-1 RNA <50 copies/mL on at least 1 occasion. Defining virologic failure by the occurrence of 1 or more episodes of HIV RNA > 50 copies/mL, after initial suppression to < 50 copies/mL is too stringent. These observations have implications for clinical practice and endpoints in clinical trials.

©2002 9th Conference on Retroviruses and Opportunistic Infections