Restoration of cellular immunity against tuberculosis in patients coinfected with HIV-1 and tuberculosis with effective antiretroviral therapy: Assessment by determination of CD69 expression on T cells after tuberculin stimulation

Whether immunity against opportunistic pathogens can be fully restored by c ontrol of HIV-1 replication remains open to question. This longitudinal stu dy was conducted to measure anti-tuberculosis (TB) cellular immunity in 13 HIV-1/TB-coinfected patients effectively treated by highly active antiretro viral therapy (HAART) in a period of 12 months. In this study, anti-TB cell ular immunity was assessed by determining the frequencies of CD 69 expressi on an CD4(+) and CD8(+) T cells in response to purified protein derivative (PPD) stimulation (abbreviated as %CD4(+)CD69 to PPD and %CD8(+)CD69 to PPD ). Here, we show that %CD4(+)CD69 to PPD correlated with the results of tub erculin skin tests and interferon-gamma (IFN-gamma) production from PPD-sti mulated CD4(+) T cells, and %CD8(+)CD69 to PPD also correlated with CD8(+) T cell-mediated PPD-specific cytolysis. In overall analysis for these 13 pa tients, both %CD4(+)CD69 to PPD and %CD8(+)CD69 to PPD increased significan tly during the 12 months (p = .003 and p < .001, respectively). However, we found %CD4(+)CD69 to PPD or %CD8(+)CD69 to PPD failed to increase substant ially in some patients (i.e., immunolgic nonresponders). A significantly hi gher proportion of patients whose baseline CD4(+) count was <50 cells/mm(3) were considered to be CD4(+) nonresponders compared with those whose basel ine CD4(+) count was >50 cells/mm(3). Furthermore, baseline CD4(+) cell cou nt in nonresponders is significantly lower than that in responders, althoug h the effectiveness of HAART did not differ between them. Our results indic ate that PPD-specific frequencies of CD69 expression may be used as surroga te markers of anti-TB cellular immunity. By this method, we show that full reconstitution of anti-TB cellular immunity in HIV-1/TB coinfected patients may not necessarily be achieved by "successful" HAART and may be influence d by the baseline immune status when HAART is started. These data suggest t hat the decision to discontinue secondary prophylaxis for opportunistic inf ections should be cautiously made, even when the CD4(+) cell count has sign ificantly increased.