Clinical Outcome of HIV-Infected Patients with Discordant Virological and Immunological Response to Antiretroviral Therapy

Antiretroviral therapy (ART) has led to a dramatic reduction in AIDS related morbidity and mortality among human immunodeficiency virus (HIV)–infected patients [1–3]. The risk to develop AIDS clearly depends on immune reconstitution and viral suppression during therapy, and prognosis is best for patients who show both recovery of CD4+ cell counts and sustained viral suppression [4, 5]. Currently, up to 30% of patients still present late to HIV centers in Europe in advanced stages of immunodeficiency (CD4+ cell counts of <200 cells/μL) and are therefore at high risk to develop AIDS [6–10]. Results from observational studies suggest that at least 73.5% of patients initiating ART achieve complete virological suppression within 6 months [11], but 9%–45% of patients do not experience an appropriate increase in their CD4+ cell counts in the short term [12, 13]. This condition, commonly referred to as immuno-virological discordance, is associated with the CD4+ cell count nadir before initiation of ART, and the risk of progression to AIDS and death may be increased in this patient population [14–16]. However, detailed risk progression analyses are largely missing in patients with persisting immuno-virological discordance. Clinical observation suggests that the rate of new AIDS-defining events may be low in this subgroup of patients irrespective of CD4+ cell response. In contrast, some experts suggest to change ART regimen or to add immunomodifiers (eg, interleukin-2 or CCR5 antagonists) to ART regimens for those patients with immuno-virological discordance to augment CD4+ cell count increases and to prevent disease progression. In the present study, we evaluated patient characteristics associated with immuno-virological discordance and subsequently analyzed the risk of developing new AIDS-related events in patients with advanced stages of immunodeficiency who were receiving fully suppressive ART.