The effect of AZT on in vitro lymphokine-activated killer (LAK) activity in human immunodeficiency virus type-1 (HIV-1) infected individuals

Human immunodeficiency virus type-1 (HIV-1)-infected individuals exhibit functional impairment in various forms of cell-mediated cytotoxicities (CMC) at all stages of disease. The purpose of this study was to determine (i) if peripheral blood mononuclear cells (PBMC) obtained from HIV-1-infected patients could be stimulated in vitro to yield lymphokine-activated killer (LAK) activity; (ii) if non-MHC-restricted gp120-specific CMC could be preserved; and (iii) what effect zidovudine (AZT) would have on LAK activity. Fourteen asymptomatic HIV-1 seropositive adults and five healthy seronegative adults (controls) were evaluated. PBMCs were isolated and incubated in media or supplemented with IL-2 for 4 or 72 hr. Lysis of the NK resistant target cell line, Daudi, was similar for the control and experimental group. The increase in activity after stimulation was elevated to a similar degree in both seronegative and seropositive groups (P less than 0.001). LAK activity was significantly decreased (P = 0.011) when AZT was added to LAK cultures. In addition, virus production may not have been completely inhibited by AZT in LAK cultures. Thus, PBMCs from asymptomatic HIV-1-infected patients could be stimulated to yield LAK activity. However, AZT can impair LAK generation. It is unclear if LAK activation results in virus production that cannot be inhibited by AZT in this system. Further definition in other patient populations is required prior to applying this information to clinical trials.