Abstract
BackgroundThe impact of immunosuppression despite virological suppression (immuno-virological discordance, ID) on the risk of developing fatal and non-fatal AIDS/non-AIDS events is unclear and remains to be elucidated.MethodsPatients in EuroSIDA starting at least 1 new antiretroviral drug with CD4<350 cells/µl and viral load (VL)>500 copies/mL were followed-up from the first day of VL< = 50 copies/ml until a new fatal/non-fatal non-AIDS/AIDS event. Considered non-AIDS events included non-AIDS malignancies, pancreatitis, severe liver disease with hepatic encephalopathy (>grade 3), cardio- and cerebrovascular events, and end-stage renal disease. Patients were classified over time according to whether current CD4 count was above (non-ID) or below (ID) baseline level. Relative rates (RR) of events were calculated for ID vs. non-ID using adjusted Poisson regression models.Results2,913 patients contributed 11,491 person-years for the analysis of non-AIDS. 241 pre-specified non-AIDS events (including 84 deaths) and 89 AIDS events (including 10 deaths) occurred. The RR of developing pre-specified non-AIDS events for ID vs. non-ID was 1.96 (95% CI 1.37–2.81, p<0.001) in unadjusted analysis and 1.43 (0.94–2.17, p = 0.095) after controlling for current CD4 count. ID was not associated with the risk of AIDS events (aRR 0.76, 95% CI 0.41–1.38, p = 0.361).ConclusionCompared to CD4 responders, patients with immuno-virological discordance may be at increased risk of developing non-AIDS events. Further studies are warranted to establish whether in patients with ID, strategies to directly modify CD4 count response may be needed besides the use of ART.
Highlights
Combination antiretroviral therapy mainly exerts its effect on the reduction of HIV related morbidity and mortality by suppressing HIV viral load which leads to an increase of CD4 cells [1,2]
A rapid increase of CD4 cells is important in the light of the fact that a significant proportion of patients continue to present for therapy when advanced immunodeficiency is present and their immediate risk of AIDS and death is high [3]
The aim of our analysis was to investigate whether a lack of any increase in CD4 count above levels observed prior to starting a suppressive regimen and despite evidence of sustained viral suppression was associated with adverse clinical progression
Summary
Combination antiretroviral therapy (cART) mainly exerts its effect on the reduction of HIV related morbidity and mortality by suppressing HIV viral load which leads to an increase of CD4 cells [1,2]. The inability to achieve an increase in CD4 count in the context of sustained virological suppression is known as immuno-virological discordance (ID) [8] and has been associated with increased mortality [9]. Previous work from the ClinSurv Study group showed an association between ID and the risk of AIDS and death [10]. This risk was greatly reduced with longer time spent with a suppressed viral load suggesting that maintaining a suppressed viral load is key for patients with immuno-virological discordance [10]. The impact of immunosuppression despite virological suppression (immuno-virological discordance, ID) on the risk of developing fatal and non-fatal AIDS/non-AIDS events is unclear and remains to be elucidated
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