Low-Level Viremia and Proviral DNA Impede Immune Reconstitution in HIV-1-Infected Patients Receiving Highly Active Antiretroviral Therapy

Background. Immunological and virological consequences of low-level viremia in human immunodeficiency virus (HIV) type 1-infected patients receiving highly active antiretroviral therapy (HAART) remain to be determined. Methods. For 24 months, 101 HAART-treated, HIV-1-infected patients with HIV RNA levels ⩽200 copies/mL were followed prospectively: HIV RNA level and CD4 and CD8 cell counts were investigated every 3 months, and proviral DNA and T cell subsets were investigated every 6 months. Results. During follow-up, 33 patients had HIV RNA levels ⩽20 copies/mL at all visits (uVL patients), whereas 68 patients had HIV RNA levels >20 copies/mL at ⩾1 visit (dVL patients) (median increase, 81 copies/mL [interquartile range, 37–480 copies/mL]). dVL patients had higher concentrations of CD8 cells, activated and memory T cells, and proviral DNA, compared with uVL patients (P < .05). A higher HIV RNA level was independently associated with reduced CD4 gain (P < .001). A higher HIV RNA level also was associated with increases in activated CD8+CD38+ and CD8+HLA-DR+ cells (P < .05), and a higher level of activated CD8+CD38+ cells was independently associated with reduced CD4 gain (P < .05). A higher proviral DNA level was associated with increases in CD4+CD45RA−CD28− effector cells and reductions in naive CD4+CD45RA+CD62L+ and CD8+CD45RA+CD62L+ cells (P < .05). Higher levels of activated CD4+HLA-DR+ and early differentiated CD4+CD45RA−CD28+ cells predicted increased risk of subsequent detectable viremia in patients with undetectable HIV RNA (P < .05). Conclusion. These findings indicate that low-level viremia and proviral DNA are intimately associated with the immunological and virological equilibrium in patients receiving HAART.