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. 2015 May 28;10(5):e0124741.
doi: 10.1371/journal.pone.0124741. eCollection 2015.

Risk of Severe Non AIDS Events Is Increased among Patients Unable to Increase their CD4+ T-Cell Counts >200+/μl Despite Effective HAART

Giuseppe Lapadula  1 , Liliane Chatenoud  2 , Andrea Gori  1 , Francesco Castelli  3 , Simona Di Giambenedetto  4 , Massimiliano Fabbiani  4 , Franco Maggiolo  5 , Emanuele Focà  3 , Nicoletta Ladisa  6 , Laura Sighinolfi  7 , Massimo Di Pietro  8 , Angelo Pan  9 , Carlo Torti  10 ; Italian MASTER Cohort
Collaborators, Affiliations

Risk of Severe Non AIDS Events Is Increased among Patients Unable to Increase their CD4+ T-Cell Counts >200+/μl Despite Effective HAART

Giuseppe Lapadula et al. PLoS One. .

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 HIV-RNA <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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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Proportion of patients remaining free from severe non AIDS-related event.
List of abbreviations: AIDS, acquired immunodeficiency syndrome; HAART, Highly-active antiretroviral therapy.
See this image and copyright information in PMC

References

    1. Paredes R, Mocroft A, Kirk O, Lazzarin A, Barton SE, van LJ, et al. (2000) Predictors of virological success and ensuing failure in HIV-positive patients starting highly active antiretroviral therapy in Europe: results from the EuroSIDA study. Arch Intern Med 160: 1123–1132. - PubMed
    1. Marimoutou C, Chene G, Mercie P, Neau D, Farbos S, Morlat P, et al. (2001) Prognostic factors of combined viral load and CD4+ cell count responses under triple antiretroviral therapy, Aquitaine cohort, 1996–1998. J Acquir Immune Defic Syndr 27: 161–167. - PubMed
    1. Dronda F, Moreno S, Moreno A, Casado JL, Perez-Elias MJ, Antela A (2002) Long-term outcomes among antiretroviral-naive human immunodeficiency virus-infected patients with small increases in CD4+ cell counts after successful virologic suppression. Clin Infect Dis 35: 1005–1009. - PubMed
    1. Loutfy MR, Genebat M, Moore D, Raboud J, Chan K, Antoniou T, et al. (2010) A CD4+ cell count <200 cells per cubic millimeter at 2 years after initiation of combination antiretroviral therapy is associated with increased mortality in HIV-infected individuals with viral suppression. J Acquir Immune Defic Syndr 55: 451–459. - PubMed
    1. van Lelyveld SF, Gras L, Kesselring A, Zhang S, De WF, Wensing AM, et al. (2012) Long-term complications in patients with poor immunological recovery despite virological successful HAART in Dutch ATHENA cohort. AIDS 26: 465–474. 10.1097/QAD.0b013e32834f32f8 - DOI - PubMed

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