The Body Covers: The 35th Annual Meeting of the Infectious Diseases Society of America
The Effect of Virologic Control on Rates of Disease Progression: Findings from the CHORUS Cohort
November 19, 1999
Current treatment guidelines recommend suppression of HIV-1 replication to levels below the limit of detection by the most sensitive assays available. The rationale for these recommendations is based on the dynamics of HIV-1 replication and the high mutation rate of the virus. There is substantial evidence that in the absence of complete inhibition of virus replication drug-resistant virus inevitably emerges, with consequent treatment failure. However, the risk of clinical disease progression in patients with "low-level" virologic failure is poorly defined. In an attempt to study this question, investigators from the CHORUS Cohort studied rates of disease progression in patients with a stable clinical course, but different levels of plasma HIV-1 RNA.
The CHORUS project is a multicenter observational study of 4500 HIV-infected patients in four large outpatient practices. Patients with plasma HIV-1 RNA levels of <400, 400-20,000, or >20,000 copies/mL for at least six months were identified from the CHORUS database, and their subsequent clinical outcome determined. Patients with virus loads of <400 copies/mL or 400-20,000 copies/mL had a relatively low risk of clinical progression, whereas patients with virus loads >20,000 copies/mL had a significantly greater risk of progression to AIDS or death. The strongest predictor of disease progression was a low baseline CD4 count (p=0.0001). Patients with the highest virus loads (>20,000 copies/mL) were more than twice as likely to experience clinical progression as were patients with <400 copies/mL (p=0.0001), but no difference was found between patients with the lowest virus loads and those with 400-20,000 copies/mL. Wasting accounted for the majority of AIDS-associated condition in patients in the two lowest virus load cohorts, whereas opportunistic infections and deaths accounted for the majority AIDS endpoints in patients in the highest virus load cohort.
These results extend the findings of earlier studies and show that patients with the highest plasma HIV-1 RNA levels and lowest CD4 counts are at greatest risk of disease progression. These results also show that the risk of disease progression in patients with low but detectable plasma HIV-1 RNA levels (400-20,000 copies/mL) is not significantly greater than for patients with <400 copies/mL, and suggest that patients with "low-level" virologic failure are at low risk of disease progression over the short term. A likely explanation for this observation is that although patients in the middle stratum had detectable plasma HIV-1 RNA, antiretroviral therapy remained partially suppressive and patients had virus loads that remained significantly below baseline. However, this study does not address the longer term issues of emerging drug resistance and availability of future treatment options for those patients who continue an existing regimen in the setting of partial virus suppression. It is likely that patients in the CD4 cohort with 400-20,000 cells//mm3 will eventually experience a substantial increase in plasma HIV-1 RNA levels. Additional studies are needed to determine the response of these patients to subsequent treatment regimens at a time of rising virus loads.
Authored by: S. Raffanti, G. Fusco, W. Mangialardi, J. Fusco, B. Sherrill, N. Hansen, E. Igboko, and the CHORUS Project Team
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