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Patterns of Plasma HIV RNA Responses in Antiretroviral Treatment Success and Failure W. HUANG1, V. DEGRUTTOLA1, M. FISCHL2, S. HAMMER3, D. D. RICHMAN4, D. HAVLIR4, and J. MELLORS*5 for the DACS 095 Study Team.
1Harvard/SDAC, Cambridge, MA; 2Univ. of Miami, FL; 3Columbia Univ., New York; 4Univ. of California, San Diego, VA Med. Ctr., La Jolla; and 5Univ. of Pittsburgh, VA Med. Ctr., PA Background: Identification of early virologic predictors of treatment failure in patients starting antiretroviral therapy could improve virologic outcome by triggering appropriate treatment changes (e.g., intensification).
Objective: The goal of this study was to characterize patterns of HIV RNA response associated with treatment success or failure, defined as whether or not plasma HIV RNA was suppressed to undetectable levels after 24 weeks of therapy.
Methods: HIV RNA datasets were analyzed from several ACTG studies of different antiretroviral regimens in naïve and experienced patients. New analytical methods combining failure time and transition models were used to estimate the probability that a patient would follow a pattern typical of treatment success or not. Results: Combined results from ACTG 343, 320 and 368 showed two types of HIV RNA response: 1) staying "on track" for suppression with biphasic HIV RNA decline, or 2) deviating from this pattern (i.e., going "off track"). Two patterns of going "off track" were noted: 1) in 10-20% of patients the initial decline in HIV RNA was significantly slower; and 2) in the majority of patients, sharp rebounds in HIV RNA occurred without prior evidence of going "off track". For patients who rebounded after being "on-track", baseline HIV RNA and initial slope were not predictive of time to rebound.
Conclusions: Only a minority of patients who experience treatment failure can be identified by slower initial declines in HIV RNA. Most failures are characterized by sharp, unexpected rebounds in HIV RNA after being "on-track" for suppression. This complicates the identification of appropriate patients for treatment modification to improve virologic response.
Key Words: Antiretroviral, HIV RNA, Viral Load
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