Combination antiretroviral therapies potently suppress plasma human immunodeficiency virus (HIV) RNA levels, although many patients who initially achieve suppression below the limits of detection experience viral relapse to detectable levels. Despite virologic relapse, many HIV‐infected patients continue to benefit clinically and can maintain CD4+ lymphocyte counts above pretreatment baseline values for prolonged periods.
Our current understanding of the relationship between viral and immune pathogenesis is based primarily on natural history studies and studies of treatment initiation. Lymphocyte activation has been correlated with an increased risk for disease progression and is more predictive for the development of AIDS and death than are plasma HIV RNA levels or CD4+ lymphocyte counts. In patients initiating antiretroviral therapy, markers of immune activation decrease dramatically and have been associated with restoration of functional immunity, as measured by response to neo and recall antigens.
HIV disease progression is marked by a decline in both naive and memory CD4+ lymphocyte subpopulations. When antiretroviral therapy is started, the number of CD4+ lymphocytes rapidly increases. This increase is initially restricted to the memory subpopulations and is followed by slower increases in naive lymphocytes over a more prolonged period. This increase in naive lymphocytes is observed only in patients who experience the greatest reductions in plasma HIV RNA levels [9, 10] and may reflect ongoing or renewed thymopoiesis.
Here we report on patients experiencing viral relapse while receiving stable antiretroviral regimens and compare them with patients who maintain virus suppression. We hypothesized that patients experiencing relapse would have immunologic profiles distinct from those maintaining virus suppression, particularly with respect to markers of lymphocyte activation and maturation.
Study design. This pilot cross‐sectional study assessed HIV‐infected patients receiving antiretroviral therapy with stable suppressed virus (stable suppressed group) and patients experiencing viral relapse (viral relapse group). All patients were recruited from the Duke University Adult Infectious Diseases Clinic (Durham, NC). The stable suppressed group included patients who were on therapy for 3 months and whose most recent plasma HIV RNA level was <500 copies/mL. Patients in the viral relapse group had 1 plasma HIV RNA level <500 copies/mL while receiving antiretroviral therapy. In addition, their most recent plasma HIV RNA level was >500 copies/mL. Patients were excluded if they had an active AIDS‐defining illness or other acute illness at enrollment or if they had any change in antiretroviral therapy since last achieving a plasma HIV RNA level <500 copies/mL. Blood samples were obtained from patients at a single time point, which we defined as “study entry.” Laboratory measurements at study entry included immunophenotyping, plasma HIV RNA levels (Amplicor; lower limit of detection, 400 copies/mL), and T cell receptor excision circle (TREC) analysis.
Viagra super force
Longitudinal characterization of study patients. Although this was primarily a cross‐sectional study, longitudinal information was obtained to further define the study cohort. Plasma HIV RNA levels, CD4+ lymphocyte counts, and antiretroviral therapy were abstracted from medical records. Change in CD4+ lymphocyte count over time was calculated, beginning with the date the patient achieved a plasma HIV RNA level <500 copies/mL and ending at study entry. In the stable suppressed group, the duration of viral remission was defined as the elapsed time between the patient’s first plasma HIV RNA level <500 copies/mL and study entry. In the viral relapse group, the duration of viral relapse was defined as the elapsed time from the patient’s last plasma HIV RNA level <500 copies/mL and study entry. Adherence to therapy was not assessed.