Respuesta inmunológica discordante en pacientes con infección por el virus de la inmunodeficiencia humana no tratados previamente que inician terapia antirretroviral de gran actividad (TARGA): prevalencia, factores predictores y evolución clínica

Abstract

Since the introduction of highly active antiretroviral therapy the prognostic of patients with HIV infection has been improved significantly. We know that most patients who start HAART achieve a complete immunovirological response but about 10-30% of patients, according published studies, presents a poor CD4 T cell increment despite indetectable HIV viral load (discordant immunological response, DIR).The definition of DIR and the characteristics of patients included in published studies, are heterogeneous and it is difficult to reach a conclusion respect the prevalence, independent associated factors and clinical outcomes in patients with DIR. We included 272 naïve-antiretroviral HIV infected patients in a retrospective cohorts study, who started antiretroviral therapy with a HAART regimen in the HIV Unit of Hospital Universitario 12 de Octubre in Madrid between January 1997 and January 2003. The patients included presented a complete HIV viral load suppression at least in two consecutive determinations during the first year of follow-up and one of them at month 12. The selected patients had no any concomitant immunossupresor therapy. Epidemiolgy, clinical, biological and therapeutic variables were collected at baseline visit and the patients were followed-up every 4 months and the determinations of CD4 cell counts, HIV viral load and opportunistics diseases (CDC guidelines, Atlanta 1993) were specifically collected too. The patients were followed-up until 24 months on HAART were completed or until two consecutive HIV viral load were detectable, the suspension of HAART were necessary or the patient were lost during the follow-up or dead. DIR was defined as the increment in CD4 cell counts less or similar to 100cell/mm3 respect baseline count despite indetectable HIV viral load at month 12 on HAART. The study aims were to analyze the DIR prevalence at months 12 and 24, the independent associated factors to DIR and describe the clinical outcomes observed in patients with DIR. We analyzed the same goals in patients with less than 200 CD4 cell/mm3 counts at baseline. The prevalence of DIR was 33% at month12 and 18% at month 24. The independent associated factors to DIR were a minor baseline HIV viral load (RR=0.52, IC95%=0.33-0.81, p=0.004), HCV co-infection (RR=2.28, IC95%=1.24-4.19, p=0.008) and d4T versus AZT treatment (RR=0.48, IC95%=0.25-0.89, p=0.02) at month12 and a minor baseline HIV viral load (RR=0.48, IC95%=0.26-0.90, p=0.02), HCV co-infection (RR=2.81, IC95%=1.19-6.61, p=0.01) and a mayor baseline CD4 cell counts (RR=1.36, IC95%=1.09-1.69, p=0.005) at month 24. The opportunistic diseases incidence was 8.4% and there were no significant statistical differences between patients with and without DIR. The patients with severe baseline immunodepression had a prevalence of DIR of 33% and 11% at months 12 and 24 respectively; the independent associated factor to DIR was d4T versus AZT treatment (RR=0.41, IC95%=0.19-0.87, p=0.02) at month 12 and no independent associated factor were observed at month 24; the opportunistic diseases incidence was 8.7% and no significant statistical differences were observed between patients with and without DIR.