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 less than or equal to200 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 less than or equal to20 copies/mL at all visits (uVL patients), whereas 68 patients had HIV RNA levels 120 copies/mL at greater than or equal to1 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.