Background: Immunological non-response (INR) despite virological suppression is associated with AIDS-defining events/death (ADE). Little is known about its association with serious non-AIDS-defining events (nADE). Methods Patients highly-active antiretroviral therapy (HAART) with <200 CD4+/μl and achieving HIVRNA <50 copies/ml within 12 (±3) months were categorized as INR if CD4+ T-cell count at year 1 was <200/μl. Predictors of nADE (malignancies, severe infections, renal failure-ie, estimated glomerular filtration rate <30 ml/min, cardiovascular events and liver decompensation) were assessed using multivariable Cox models. Follow-up was right-censored in case of HAART discontinuation or confirmed HIV-RNA>50. Results: 1221 patients were observed for a median of 3 (IQR: 1.3-6.1) years. Pre-HAART CD4+were 77/μl (IQR: 28-142) and 56% of patients had experienced an ADE. After 1 year, CD4+ increased to 286 (IQR: 197-387), but 26.1% of patients were INR. Thereafter, 86 nADE (30.2% malignancies, 27.9%infectious, 17.4%renal, 17.4%cardiovascular, 7% hepatic) were observed, accounting for an incidence of 1.83 events (95%CI: 1.73-2.61) per 100 PYFU. After adjusting for measurable confounders, INR had a significantly greater risk of nADE (HR 1.65; 95%CI: 1.06-2.56). Older age (per year, HR 1.03; 95%CI: 1.01-1.05), hepatitis C co-infection (HR 2.09; 95%CI: 1.19-3.7), a history of previous nADE (HR 2.16; 95% CI: 1.06-4.4) and the occurrence of ADE during the follow-up (HR 2.2; 95%CI: 1.15-4.21) were other independent predictors of newly diagnosed nADE. Conclusions: Patients failing to restore CD4+ to >200 cells/μl run a greater risk of serious nADE, which is intertwined or predicted by AIDS progression. Improved management of this fragile population and innovative therapy able to induce immune-reconstitution are urgently needed. Also, our results strengthen the importance of earlier diagnosis and HAART introduction
Risk of severe non AIDS events is increased among patients unable to increase their CD4 + T-cell counts >200+/μl despite effective HAART / G. Lapadula, L. Chatenoud, A. Gori, F. Castelli, S. Di Giambenedetto, M. Fabbiani, F. Maggiolo, E. Focà, N. Ladisa, L. Sighinolfi, M. Di Pietro, A. Pan, C. Torti, G. Carosi, E. Quiros, P. Nasta, G. Paraninfo, R. Cauda, M. Colafigli, A. Scalzini, F. Castelnuovo, I. El Hamad, F. Mazzotta, S. Locaputo, P. Pierotti, N. Marino, C. Blè, F. Vichi, G. Angarano, N. Ladisa, L. Monno, P. Maggi, S. Costarelli, M. Puoti, P. Viale, V. Colangeli, M. Borderi. - In: PLOS ONE. - ISSN 1932-6203. - 10:5(2015), pp. e0124741.1-e0124741.15. [10.1371/journal.pone.0124741]
Risk of severe non AIDS events is increased among patients unable to increase their CD4 + T-cell counts >200+/μl despite effective HAART
A. Gori;
2015
Abstract
Background: Immunological non-response (INR) despite virological suppression is associated with AIDS-defining events/death (ADE). Little is known about its association with serious non-AIDS-defining events (nADE). Methods Patients highly-active antiretroviral therapy (HAART) with <200 CD4+/μl and achieving HIVRNA <50 copies/ml within 12 (±3) months were categorized as INR if CD4+ T-cell count at year 1 was <200/μl. Predictors of nADE (malignancies, severe infections, renal failure-ie, estimated glomerular filtration rate <30 ml/min, cardiovascular events and liver decompensation) were assessed using multivariable Cox models. Follow-up was right-censored in case of HAART discontinuation or confirmed HIV-RNA>50. Results: 1221 patients were observed for a median of 3 (IQR: 1.3-6.1) years. Pre-HAART CD4+were 77/μl (IQR: 28-142) and 56% of patients had experienced an ADE. After 1 year, CD4+ increased to 286 (IQR: 197-387), but 26.1% of patients were INR. Thereafter, 86 nADE (30.2% malignancies, 27.9%infectious, 17.4%renal, 17.4%cardiovascular, 7% hepatic) were observed, accounting for an incidence of 1.83 events (95%CI: 1.73-2.61) per 100 PYFU. After adjusting for measurable confounders, INR had a significantly greater risk of nADE (HR 1.65; 95%CI: 1.06-2.56). Older age (per year, HR 1.03; 95%CI: 1.01-1.05), hepatitis C co-infection (HR 2.09; 95%CI: 1.19-3.7), a history of previous nADE (HR 2.16; 95% CI: 1.06-4.4) and the occurrence of ADE during the follow-up (HR 2.2; 95%CI: 1.15-4.21) were other independent predictors of newly diagnosed nADE. Conclusions: Patients failing to restore CD4+ to >200 cells/μl run a greater risk of serious nADE, which is intertwined or predicted by AIDS progression. Improved management of this fragile population and innovative therapy able to induce immune-reconstitution are urgently needed. Also, our results strengthen the importance of earlier diagnosis and HAART introduction
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