Both serum HIV type 1 RNA levels and CD4+ lymphocyte counts predict clinical outcome in HIV type 1-infected subjects with 200 to 500 CD4+ cells per cubic millimeter

To evaluate HIV-1 RNA and CD4(+) cell responses to therapy as predictors of clinical progression and to evaluate levels and trends of these markers prior to clinical failure, HTV-1 RNA measurements were retrospectively obtained on subjects who progressed to AIDS or death and a random sample of subjects who did not. Samples were taken from AIDS Clinical Trials Group Study 175, a randomized trial comparing nucleoside analog therapies in subjects with CD3(+) cell counts of between 200 and 500 cells/mm(3). HIV-1 RNA and CD3(+) cell count independently predicted clinical progression. Risk of subsequent progression is best captured by the change to the last measured value for CD4(+) cell count and the area under the curve minus baseline, a measure of viral replication over time, for HIV-1 RNA. Subjects who failed had lower CD4(+) cell counts, greater rates of CD4(+) cell decline, and higher HIV-1 RNA levels, but not greater rates of HIV-1 RNA increase than subjects who did not. Subjects who maintained more than 200 CD4(+) cells/mm3 and fewer than 10,000 copies of HIV-1 RNA per milliliter had low risk of progression. During the first few months of therapy, treatments are best monitored by regular HIV-1 RNA and less frequent CD4(+) cell measurements. Thereafter, both markers should be monitored on a similar schedule to identify rapidly declining CD4(+) cell counts, or adverse levels of either. These results further delineate the prognostic significance of HIV-1 RNA and CD3(+) cell count and should help to better define their utility in the practice setting.