Highly active antiretroviral therapy (HAART) often leads to increases in a patient’s CD4+ T-cell count of 100–200 cells/μl or more, even though individual re- sponses in cases of HIV-1 infection are quite variable [1, 2, 3]. The CD4+ T-cell responses are generally relat- ed to the degree of viral load suppression [1, 2]. How- ever, a substantial proportion of patients undergoing HAART have had persistently detectable viremia de- spite their strict adherence to treatment [4, 5]. What happens to those patients who remain highly viremic while undergoing HAART is not fully understood, though a sustained CD4+ T-cell response in patients taking protease inhibitor (PI)-based regimens has been reported [3, 4]. Diminished fitness of heavily mutated viruses (that is, reduced ability of resistant virus to rep- licate and deplete CD4+ T cells) could partly explain these observations [6]. The durability of these immunologic responses that occur despite failure of virological suppression is still unknown, though a 24-month benefit has been reported in patients continuing on PI-containing regimens [4]. We report the results of a 36-month observational study per- formed on 16 patients who had a sustained CD4+ T-cell response despite high-level viremia and extensive drug resistance while continuing combination antiretroviral therapy. The study population was selected from outpatients at the Infectious Diseases Unit of the Pistoia Hospital, Pi- stoia, Italy. The study design was single center, open- label, and observational. On the basis of available re- cords from a 3-year period, 16 (14 male and 2 female) patients (10% of all HIV patients regularly followed) be- tween the ages of 29 and 52 years (mean, 37 years) met the study purpose. At baseline, the mean±SD viral load was 4.36±1.05 log RNA copies/ml, and the mean CD4+ T-cell count was 400±353 cells/mm 3 . Seven patients were in CDC stage A (A2=4; A3=3); two in stage B (B1=1; B2=1); and seven in stage C (C2=1; C3=6) [7]. As starting treatment, 12 patients were given a PI plus two nucleoside reverse transcriptase inhibitors (NRTIs); two patients were given two PIs plus a NRTI; one patient received a non-nucleoside reverse transcriptase inhibitor plus two NRTIs; and one patient received two NRTIs. Regimens were assigned on the basis of the level of vire- mia, the degree of immunodeficiency, concurrent treat- ments, and the presumptive patient’s commitment to therapy and adherence. Study monitoring included coun- selling; monthly assessment of adherence to treatment by standardized questionnaire (graded as poor, good, or ex- cellent); measurement of virus load (median, 14 times/ patient: range, 9–20); the CD4+ T-cell count (median 12 times/patient: range, 4–18; and genotyping resistance testing (median, 4 times/patient: range, 2–7) as a guide for switching treatment. Virological failure was defined as a plasma HIV RNA rebound after initial suppression to undetectable levels or declines in HIV-RNA of <0.5 and <1.0 log, respectively, by 4 and 8 weeks from the start of treatment [3]. The plasma HIV-1 load was quantitated using the Roche Amplicor method (Roche Laboratories, Switzerland). The detection limit of the assay was 400 copies/ml. For genotypic antiretroviral resistance testing, RNA was extracted from plasma stored at –7°C using the QIAmp Viral RNA kit (Qiagen, Germany). The HIV-1 pol regions coding for RT amino acids 1–230 and for the whole protease were generated by reverse transcription- nested polymerase chain reaction amplification and di- rectly sequenced as described elsewhere [8]. Mutations conferring resistance to the different reverse transcrip- tase inhibitors and PIs were retrieved from available dat- abases, and drug susceptibility was inferred with use of a comprehensive set of rules [9]. D. Dionisio ( ✉ ) · A. Vivarelli · F. Esperti C. Fabbri · M. Giorgi · B. Menichini Infectious Diseases Unit, Pistoia Hospital, Piazza Giovanni XXIII, 51100 Pistoia, Italy e-mail: mpdioni@tin.it Tel.: +39-0573-352324/352078, Fax: +39-0573-352076 M. Zazzi Division of Microbiology, Department of Molecular Biology, University of Siena, Siena, Italy Eur J Clin Microbiol Infect Dis (2003) 22:69–71 DOI 10.1007/s10096-002-0845-7 BRIEF REPORT D. Dionisio · A. Vivarelli · M. Zazzi · F. Esperti C. Fabbri · M. Giorgi · B. Menichini Long-term CD4+ T-Cell Response in HIV-1-Infected Patients Continuing Combination Antiretroviral Therapy Despite High-Level Viremia and Drug Resistance Published online: 28 January 2003 © Springer-Verlag 2003