Immunologic profile of HIV-positive patients during viral remission and relapse on antiretroviral therapy

Highly active antiretroviral therapies (HAART) potently suppress plasma human immunodeficiency virus (HIV) RNA levels. Many patients who achieve suppression, however, suffer viral relapse to detectable levels of the virus.

Current understanding of the relationship between viral and immune pathogenesis is based primarily on natural history studies and studies of treatment initiation. HIV disease progression is marked by a decline in both naive and memory CD4+ lymphocyte sub-populations. When antiretroviral therapy is initiated CD4+ lymphocytes rapidly increase, and this increase is restricted to the memory sub-populations, followed by slower increases in naive lymphocytes over a more prolonged period.

The current pilot 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, N.C.). The stable suppressed group included patients on therapy for three months, whose most recent plasma HIV RNA level was <500 copies/mL. Patients in the 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 from the study if they had an active AIDS-defining illness or other acute illness 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 was defined as “study entry.” Laboratory measurements included immunophenotyping, plasma HIV RNA levels (Amplicor; lower limit of detection, 400 copies/mL), and T cell receptor excision circle (TREC) analysis.

According to the authors, the study was small and included only 28 patients: “10 in the stable suppressed group and 18 in the viral relapse group. Although the viral relapse group had fewer men, 11 (61%) of 18, compared with 9 (90%) of 10, the groups were statistically similar with regard to sex, age, and race (P = .105, P = .999, and P = .283, respectively). The median age was 43.1 years (range, 22.3-56.7 years); 15 (54%) of 28 patients were black.

“The groups had similar antiretroviral treatment histories. Overall, 18 (64%) of 28 were receiving a protease inhibitor containing regimen, and 21 (75%) of 28 were receiving >3 antiretroviral medications.” Longitudinal analyses show that both groups had stable or increasing CD4+ cell counts.

According to the study results, “The rate of change in CD4+ cells/week was significantly lower in the viral relapse group, compared with that in the stable suppressed group (P = .043). At study entry, the viral relapse group and stable suppressed group had similar CD4+ lymphocyte counts (407 vs. 562 cells/mm; P = .175). However, the viral relapse group had significantly fewer CD4+ lymphocytes ( 20% vs. 32%; P = .015).”

While naive CD4+ lymphocyte phenotype and TREC levels were not significantly different in patients with virus suppression or in those who had relapsed, “CD8+ lymphocyte activation, including the number and percentage of activated cells and CD38 antibody- binding capacity, was significantly elevated during viral relapse, compared with that in suppressed patients. By multivariable regression analyses, CD8+ and CD4+ lymphocyte activation were associated significantly with increasing plasma HIV RNA levels.”

The authors assume that CD8+ lymphocyte activation in persons with viral relapse directly reflects increasing HIV replication in a manner similar to the relationship observed during an acute HIV infection. According to them, “Prior research has shown that increases in CD8+ lymphocyte activation do not coincide with immediate reductions in circulating CD4+ lymphocytes or progression to clinical AIDS-related events. However, over the longer term, increased CD8+ lymphocyte activation is associated with functional immune impairment and clinical disease progression.”

Wellons MF, Ottinger JS, Weinhold KJ et al. Journal of Infectious Diseases 2001; 183: 1522-1525.