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Objective: Inadequate CD4 cell count recovery despite full HIV RNA control occurs in 30% of HAART-treated HIV-infected patients. A better understanding of the relationship between T-cell dynamics and the HIV intracellular reservoir in HIV-infected patients failing to recover CD4 cell count following long-term HAART, is required., Methods: In a cross-sectional study T-cell turnover and homeostatic parameters featuring discordant responses were investigated in 27 immunologic non-responders (INR; CD4 count, < or = 200 cells/microl; HIV RNA, < or = 50 copies/ml), 15 virological non-responders (VNR; CD4 count, > or = 350 cells/microl; HIV RNA, > or = 10 000) and 22 full responders (FR; CD4 count, > or = 500 cells/microl; HIV RNA, < or = 50 copies/ml)., Results: INR displayed significantly higher activated CD38CD8 than FR (P < 0.05) and was comparable to VNR (P > 0.05). As compared with VNR and FR, INR displayed the highest level of proliferating Ki67CD4 and apoptotic CD4 cells (P < 0.05). VNR presented lower proliferation and apoptosis than FR and INR. INR displayed the lowest levels of naive T cells (P < 0.05) and a predominant memory pattern. Despite the memory/activated/apoptotic phenotype, INR showed a statistically non-significant reduction in T-cell receptor excision circles (TREC) compared to FR (P > 0.05), and substantially heightened interleukin (IL)-7 (P < 0.05), while VNR showed higher naive T-cell counts and TREC. Moreover, the reservoir of infected CD4 cells was increased in INR, with a trend toward highest intracellular HIV DNA within total, naive and memory CD4 cells., Conclusions: The lack of CD4 cell count recovery in INR seems to reflect a highly activated apoptotic T-cell compartment, with elevated IL-7 and thymic impairment. High levels of intracellular HIV-DNA in INR could be strictly involved in the lack of T-cell reconstitution. Immune correlates of an ultimate direction of the response to HAART, could be exploited in clinical practice for the most effective management of discordant patients, to amend immune imbalances and to improve clinical outcome.

Background: Emerging evidence indicates that CD4 and CD8 T cell recovery is differentially regulated during HIV infection. The hallmark of interleukin-2 (IL-2)-induced immune reconstitution is the selective outgrowth of CD4 through undefined mechanisms., Objective: To delineate the effect of IL-2 on T cell homeostasis by analysing the differential impact of IL-2 immunotherapy on CD4 and CD8 dynamics., Design: A randomized trial of 15 HIV-positive patients, eight receiving IL-2 immunotherapy with highly active antiretroviral therapy (HAART) and seven with HAART alone. Patients were followed for a 48-week period following three IL-2 cycles (overall, 10 weeks in duration)., Methods: CD4 and CD8 count, naive and memory immunophenotype, proliferation by Ki67, and CD8+CD38+ activated pattern were measured longitudinally by flow cytometry. Thymic output contribution to both CD4 and CD8 was evaluated by measurement of T cell receptor excision circles (TREC). Wilcoxon test was used to compare results., Results: Compared with changes seen with HAART alone, IL-2 induced a more significant rise in CD4 than CD8 T cell count (P < 0.01), associated with a significant increase in Ki67-proliferating CD4 (P < 0.05), whereas no changes were seen in CD8+Ki67+ (P > 0.05). Furthermore, IL-2 administration was associated with CD4 TREC increase, whereas CD8 TREC remained stable (P > 0.05). Modifications in CD4 and CD8 T cells seen in patients taking only HAART were not associated with changes in CD4 and CD8 TREC., Conclusions: By showing a differential impact on CD4 and CD8 homeostasis, the study suggests that IL-2-associated immune reconstitution results from protean interactions between T cell compartments; this has significant implications for the correct planning of immunotherapeutic strategies.

Objective: To describe an outbreak of multidrug-resistant tuberculosis (MDR-TB), amongst HIV-infected patients, spread from one hospital in Milan to another., Design: Descriptive epidemiological investigation and molecular typing., Methods: All cases identified by intensive case-finding were described in terms of clinical characteristics, previous nosocomial exposure to an infectious MDR-TB patient, previous stays in other institutional settings where exposure to MDR-TB could have occurred, and restriction fragment length polymorphism (RFLP) pattern., Results: Between October 1991 and July 1995, 116 cases of MDR-TB were identified (85 at hospital A and 31 at hospital B). A single case patient, infected at hospital A, introduced the strain into hospital B. Eighty-two of the 92 strains available for fingerprinting revealed an identical pattern; 10 strains had unique RFLP patterns. Nosocomial exposure to an infectious MDR-TB patient was ascertained for 39 of the 56 patients with the 'outbreak' RFLP strain at hospital A (69.6%) and for 24 of the 26 patients at hospital B (92.3%). The median duration of exposure was 32 days at hospital A and 40 days at hospital B. For eight patients with the outbreak strain, exposure was determined to have probably occurred in other hospitals, in the community or in prison., Conclusions: This is the largest nosocomial outbreak of MDR-TB reported in Europe. Exposure to MDR-TB cases in other institutions caring for HIV-infected patients probably contributed to the spread of this epidemic. Strict control measures should be immediately adopted in order to prevent the spread of TB amongst HIV-infected patients in institutional settings in Europe.