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Immunological predictors of CD4+ T cell decline in antiretroviral treatment interruptions.

Seoane E, Resino S, Moreno S, de Quiros JC, Moreno A, Rubio R, Gonzalez-García J, Arribas JR, Pulido F, Muñoz-Fernández MA - BMC Infect. Dis. (2008)

Bottom Line: The common response to stopping anti-HIV treatment is an increase of HIV-RNA load and decrease in CD4+, but not all the patients have similar responses to this therapeutic strategy.Patients on stable highly active antiretroviral therapy (HAART), with CD4+ count > 600/microL, and HIV-RNA < 50 copies/ml for at least 6 months were offered the option to discontinue antiretroviral therapy.Patients with a CD4+ nadir of < 200 cells/microL had a greater risk of restarting therapy during the follow-up (RR (CI95%): 3.37 (1.07; 10.36)).

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratorio de Inmuno-Biología Molecular, Hospital General Universitario Gregorio Marañón, Madrid, Spain. meseoane.hdoc@salud.madrid.org

ABSTRACT

Background: The common response to stopping anti-HIV treatment is an increase of HIV-RNA load and decrease in CD4+, but not all the patients have similar responses to this therapeutic strategy. The aim was to identify predictive markers of CD4+ cell count declines to < 350/microL in CD4-guided antiretroviral treatment interruptions.

Methods: 27 HIV-infected patients participated in a prospective multicenter study in with a 24 month follow-up. Patients on stable highly active antiretroviral therapy (HAART), with CD4+ count > 600/microL, and HIV-RNA < 50 copies/ml for at least 6 months were offered the option to discontinue antiretroviral therapy. The main outcome was a decline in CD4+ cell count to < 350/microL.

Results: After 24 months of follow-up, 16 of 27 (59%) patients (who discontinued therapy) experienced declines in CD4+ cell count to < 350/microL. Patients with a CD4+ nadir of < 200 cells/microL had a greater risk of restarting therapy during the follow-up (RR (CI95%): 3.37 (1.07; 10.36)). Interestingly, lymphoproliferative responses to Mycobacterium tuberculosis purified protein derivative (PPD) below 10000 c.p.m. at baseline (4.77 (1.07; 21.12)), IL-4 production above 100 pg/mL at baseline (5.95 (1.76; 20.07)) in PBMC cultured with PPD, and increased IL-4 production of PBMC with p24 antigen at baseline (1.25 (1.01; 1.55)) were associated to declines in CD4+ cell count to < 350/microL.

Conclusion: Both the number (CD4+ nadir) and the functional activity of CD4+ (lymphoproliferative response to PPD) predict the CD4+ decrease associated with discontinuation of ART in patients with controlled viremia.

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Related in: MedlinePlus

Kaplan-Meier for decreases in CD4+ T-cells (A) and rebound of viral load (VL) (B) in HIV-infected patients after treatment interruption.
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Figure 1: Kaplan-Meier for decreases in CD4+ T-cells (A) and rebound of viral load (VL) (B) in HIV-infected patients after treatment interruption.

Mentions: Figure 1A shows the proportion of HIV-1-infected patients who experienced a decrease in CD4+ 24 months after treatment interruption. A decrease in the CD4+ count was observed in all the patients, 23 (85%) patients experienced declines in CD4+ cell count to < 500/μL, 19 (70%) in CD4+ to < 400/μL, and 16 (59%) in CD4+ to < 350/μL. The patients who experienced declines in CD4+ cell count < 350/μL restarted HAART. Figure 1B shows details on the proportion of HIV-1-infected patients who experienced an increase in VL during follow-up. An increase in the VL was observed in all the patients. Twenty two (81%) patients had VL > 30,000 copies/mL and 13 (48%) patients had VL > 100,000 copies/mL. Interestingly, the patients with high HIV-RNA load when starting HAART had a high likelihood to achieve a HIV-RNA load rebound of both > 30,000 copies/mL (RR: 1.85 per log10; CI95%: 1.02; 3.35; p = 0.04) and > 100,000 copies/mL (2.45; 1.12; 5.36; p = 0.02) after ART interruption.


Immunological predictors of CD4+ T cell decline in antiretroviral treatment interruptions.

Seoane E, Resino S, Moreno S, de Quiros JC, Moreno A, Rubio R, Gonzalez-García J, Arribas JR, Pulido F, Muñoz-Fernández MA - BMC Infect. Dis. (2008)

Kaplan-Meier for decreases in CD4+ T-cells (A) and rebound of viral load (VL) (B) in HIV-infected patients after treatment interruption.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2291054&req=5

Figure 1: Kaplan-Meier for decreases in CD4+ T-cells (A) and rebound of viral load (VL) (B) in HIV-infected patients after treatment interruption.
Mentions: Figure 1A shows the proportion of HIV-1-infected patients who experienced a decrease in CD4+ 24 months after treatment interruption. A decrease in the CD4+ count was observed in all the patients, 23 (85%) patients experienced declines in CD4+ cell count to < 500/μL, 19 (70%) in CD4+ to < 400/μL, and 16 (59%) in CD4+ to < 350/μL. The patients who experienced declines in CD4+ cell count < 350/μL restarted HAART. Figure 1B shows details on the proportion of HIV-1-infected patients who experienced an increase in VL during follow-up. An increase in the VL was observed in all the patients. Twenty two (81%) patients had VL > 30,000 copies/mL and 13 (48%) patients had VL > 100,000 copies/mL. Interestingly, the patients with high HIV-RNA load when starting HAART had a high likelihood to achieve a HIV-RNA load rebound of both > 30,000 copies/mL (RR: 1.85 per log10; CI95%: 1.02; 3.35; p = 0.04) and > 100,000 copies/mL (2.45; 1.12; 5.36; p = 0.02) after ART interruption.

Bottom Line: The common response to stopping anti-HIV treatment is an increase of HIV-RNA load and decrease in CD4+, but not all the patients have similar responses to this therapeutic strategy.Patients on stable highly active antiretroviral therapy (HAART), with CD4+ count > 600/microL, and HIV-RNA < 50 copies/ml for at least 6 months were offered the option to discontinue antiretroviral therapy.Patients with a CD4+ nadir of < 200 cells/microL had a greater risk of restarting therapy during the follow-up (RR (CI95%): 3.37 (1.07; 10.36)).

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratorio de Inmuno-Biología Molecular, Hospital General Universitario Gregorio Marañón, Madrid, Spain. meseoane.hdoc@salud.madrid.org

ABSTRACT

Background: The common response to stopping anti-HIV treatment is an increase of HIV-RNA load and decrease in CD4+, but not all the patients have similar responses to this therapeutic strategy. The aim was to identify predictive markers of CD4+ cell count declines to < 350/microL in CD4-guided antiretroviral treatment interruptions.

Methods: 27 HIV-infected patients participated in a prospective multicenter study in with a 24 month follow-up. Patients on stable highly active antiretroviral therapy (HAART), with CD4+ count > 600/microL, and HIV-RNA < 50 copies/ml for at least 6 months were offered the option to discontinue antiretroviral therapy. The main outcome was a decline in CD4+ cell count to < 350/microL.

Results: After 24 months of follow-up, 16 of 27 (59%) patients (who discontinued therapy) experienced declines in CD4+ cell count to < 350/microL. Patients with a CD4+ nadir of < 200 cells/microL had a greater risk of restarting therapy during the follow-up (RR (CI95%): 3.37 (1.07; 10.36)). Interestingly, lymphoproliferative responses to Mycobacterium tuberculosis purified protein derivative (PPD) below 10000 c.p.m. at baseline (4.77 (1.07; 21.12)), IL-4 production above 100 pg/mL at baseline (5.95 (1.76; 20.07)) in PBMC cultured with PPD, and increased IL-4 production of PBMC with p24 antigen at baseline (1.25 (1.01; 1.55)) were associated to declines in CD4+ cell count to < 350/microL.

Conclusion: Both the number (CD4+ nadir) and the functional activity of CD4+ (lymphoproliferative response to PPD) predict the CD4+ decrease associated with discontinuation of ART in patients with controlled viremia.

Show MeSH
Related in: MedlinePlus