Study of T cell subsets and IL-7 protein expression in HIV-1-infected patients after 7 years HAART.

OBJECTIVE: To study the changes in T cell subsets and IL-7 in HIV-1-infected patients after seven years of highly active antiretroviral therapy (HAART). METHODS: Seventy-five individuals were included in this study (25 with effective HAART, 18 with ineffective HAART, 17 untreated HIV+ patients, and 15 volunteers in the HIV negative control group). The counts of CD4+, CD8+, CD8/CD38+, and CD8/HLADR+ T cells as well as the IL-7 protein expression was measured at 5 time points during a period of seven years in patients starting HAART (baseline) and in the HIV negative control group. The expression of CD127 on CD3+ T cells was measured by flow cytometry at a single time point (after 7 years) in patients with HAART and was compared with untreated HIV+ patients and the HIV negative control group. RESULTS: At baseline CD4+ T cell counts of HIV-1-infected patients were lower than that in the control group (p < 0.01), whereas the CD8+, CD8/HLADR+ and CD8/CD38+ T cell counts were higher than those in the control group (p < 0.01). After seven years of effective HAART, the CD4+ T cell counts had increased and the CD8+ T cell count had decreased, although not to the normal levels (p < 0.05). Both the CD8/HLADR+ and CD8/CD38+ T cell counts had gradually approached those of the control group (p > 0.05). In the ineffective HAART group, the CD8/CD38+ T cell count had not decreased significantly, and CD8/HLADR+ T cell count gradually decreased. Before treatment, IL-7 serum levels of patients were significantly higher than that in the control group (p < 0.01). After seven years of effective HAART, IL-7 levels had gradually decreased, but were still higher than in the control group (p < 0.01). The CD127 expression on CD3+ CD8+ T cells in effective HAART patients was higher than in untreated HIV+ patients (p < 0.05), but was lower than that in the control group (p < 0.05). CD127 expression on CD3+ CD4+ T cells was not significantly different among the control group, untreated HIV+ patients and effective HAART group. CONCLUSION: After seven years of effective HAART, the quantity and capacity of T cell subsets and IL-7 in HIV-1-infected patients had been partially restored, and the abnormal immune activation has significantly diminished.

Does chemosensitivity-assay-directed therapy have an influence on the prognosis of patients with malignant melanoma stage IV? A retrospective study of 14 patients with malignant melanoma stage IV.

OBJECTIVE: To evaluate the efficacy of chemosensitivity-testing directed chemotherapy in comparison with empirically chosen therapy regimens in patients with malignant melanoma stage IV. PATIENTS AND METHODS: Retrospective study including 14 patients with histologically confirmed malignant melanoma and diagnosis of stage IV disease by routine diagnostic procedures. Patients in group A (n = 7) were treated according to their individual chemosensitivity testing results, whereas patients in group B (n = 7) received empirically chosen treatment regimens. Chemosensitivity testing was performed using a nonclonogenic ATP-TCA assay. For statistical analysis the Kaplan-Meier method was used to calculate survival curves. The log-rank test was performed to compare the overall survival according to treatment group, LDH level in serum and AJCC-category. To compare the distribution of sex, LDH level in serum and AJCC-category between the treatment groups, the Fisher exact test was used. RESULTS: The median overall survival of group A exceeded the median overall survival of group B by 8 versus 3 months, respectively with a median overall survival of 5 months for the whole study population. LDH level in serum at study entry showed a strong correlation with overall survival, with normal LDH levels leading to a statistically significant longer survival (p = 0.006 for the log-rank test, respectively). Moreover, stage AJCC M1a/b yielded to a better prognosis compared with stage AJCC M1c (log-rank test p = 0.066; not statistically significant). CONCLUSION: Chemosensitivity-assay directed therapy might be a useful tool in determining the optimized chemotherapeutic drug or drug combination in the individual patient and might contribute to a better prognosis in patients with metastatic melanoma stage IV.