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Control of Viremia after Treatment Interruption F. LORI*1, A. FOLI1, R. MASERATI2, E. SEMINARI2, L. MINOLI2, F. ALBERICI3, and J. LISZIEWICZ1. 1Res. Inst. for Genetic & Human Therapy, Pavia, Italy, and Washington, DC; and 2Clin. Malattie Infettive, Policlinico S. Matteo, Pavia, Italy, and 3Piacenza, Italy HAART inhibits HIV replication in most patients; however, it impairs HIV-specific T helper and CTL responses (Pitcher, Nat Med, 1999; Ogg, J Virol, 1999). A rapid rebound of viremia is observed after HAART interruption. We have previously described a cohort of chronically infected patients treated with hydroxyurea and didanosine (PANDA cohort). Unlike HAART patients, PANDAs have low but detectable viremia and vigorous HIV-specific cellular immune responses (Lori, ARHR, 1999). To test whether in the presence of HIV-specific immune responses patients can control HIV during treatment interruption, PANDAs and a matched control group of HAART patients interrupted treatment for 8 weeks. Matching criteria before treatment interruption included length of previous treatment (>2 years in both groups), CD4 count (HAARTs=549+175, PANDAs=495+127), and CD8 count (HAARTs=874+203, PANDAs=805+335). Viremia before interruption, however, was significantly different between HAART patients (<50 copies/ml in 7/8 subjects) and PANDAs (<50 copies/ml in 1/9 subjects). Failure after treatment interruption was defined as viremia rebound >10,000 copies/ml or CD4 count decrease to <200 cells/mm3. 5/8 HAART patients failed by week 6 and had to restart therapy, whereas no PANDA had to restart treatment during the entire 8 weeks follow-up. Average viremia rebounded by week 6 from 97 to 16,863 copies/ml in HAART patients (+2.25 log). In contrast, PANDAs average viremia only changed from 843 to 1,596 copies/ml (+0.27 log). PANDAs CD4 and CD8 count remained stable during treatment interruption, while in HAART patients CD4 count decreased (average -208 cells/ mm3) and CD8 count increased (average +323 cells/ mm3). CD4/CD8 ratios also remained stable in the PANDAs (0.7); however, they significantly dropped below 0.3 in the HAART group by week 6. In conclusion, reconstitution of HIV specific cellular immune responses obtained during the treatment of chronically infected patients was associated with the control of viral rebound during treatment interruption. Key Words: hydroxyurea, immune control, therapy interruption |
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Conference on Retroviruses and Opportunistic Infections, |