297 Persistent Low Viral Load is Associated with Enhanced Th1 Responses to HIV-p24 Compared to Full Viral Suppression or Viral Failure Under Antiviral Therapy A. Samri*1, D. Costagliola2, N. Alatrakchi1, A.G. Marcelin2,3, A. Biligui2,4, R. Agher2,4, M. Astriti2,4, V. Calvez2,3, B. Autran1, C. Katlama2,4, C. Duvivier5 1Cell Immunology, INSERM U543; 2INSERM EMI 0214; 3Virology; 4Infectious Diseases; and 5Infectious Diseases Pitie-Salpetriere Univ Hosp, Paris, France
Background: The aim of the study was to evaluate whether a stable low level HIV replication in patients (pts) treated with antiviral therapy can 1) allow persistence of a stronger immunity to HIV; and 2) be deleterious for the hostís immune defenses against other pathogens compared to pts with controlled viremia or virological failure.
Methods: Cross-sectional comparative study of 3 groups (Gp) under combined therapy including at least 2 RT inhibitors: Gp1: 200 > VL < 10,000 cp/mL; Gp 2: VL > 10,000 cp/mL and Gp3: VL < 20 cp/ml since 18 months. Specific CD4+ responses were analyzed using an IFNg-ELISpot assay (Th1) and lymphocyte proliferation assay (LPA). Antigens tested were: HIV-1 p24, gp160, CMV, Tuberculin, and streptokinase. Statistical analysis used Chi2 test or Fisher test for qualitative data and the Mann-Whitney test for quantitative data. Comparison is Gp1 vs 2 and 1 vs 3.
Results: Median CD4 counts were 341/mm3 in Gp1 (n = 28) vs 53/mm3 in Gp 2 (n = 13) (p < 0.001) and 479/mm3 in Gp 3 (n = 29) (NS). Median HIV-1 RNA were 3.21 log10 cp/mL in Gp 1 vs 4.96 log10 cp/mL in Gp 2 (p < 0.001) and vs < 1.3 log10 cp/mL in Gp 3 (p < 0.001). CD4 Th1 cell frequencies were significantly higher in Gp1 (131 SFC/106 PBMC (0-1,600)) than Gp 2 (23 SFC/106 PBMC (0-940) (p = 0.047) and Gp 3 (47 SFC/106 PBMC [0-1320]) (p = 0.012). This observation was still significant when results are expressed as SFC/mL of blood despite lower CD4 counts. Numbers of detectable Th1 responses, but not of LPA responses, were significantly higher in Gp1 (20/28) than Gp 2 (4/13) (p = 0.014) and Gp3 (13/29) (p = 0.042). Although proliferative responses to CMV were higher in Gp3 than Gp1 (p = 0.005), Th1 responses directed against opportunist antigen did not differ between the 3 groups.
Conclusion: Persistent low HIV replication under antiviral therapy load is associated with an increase in Th1 responses (IFNg-production), but not in proliferative responses to HIV-p24 and has no deleterious effects on CD4 T-cell responses to opportunistic pathogens when compared to pts with full viral suppression or virological failure.