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Instability of Delayed-type Hypersensitivity Skin Test Anergy in Human Immunodeficiency Virus Infection

Waleska T. Caiaffa, MD, MPH, ScD; Neil M. H. Graham, MB, BS, MD, MPH; Noya Galai, PhD; Rosetta T. Rizzo, RN, MMS; Kenrad E. Nelson, MD; David Vlahov, PhD
Arch Intern Med. 1995;155(19):2111-2117. doi:10.1001/archinte.1995.00430190107015.
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Objective:  To evaluate stability of delayed-type hypersensitivity (DTH) skin test over time in human immunodeficiency virus (HIV)—seropositive and HIV-seronegative injecting drug users.

Method:  A community-based cohort of injecting drug users who had serial skin testing with purified protein derivative tuberculin, mumps, and Candida albicans antigen. Delayed-type hypersensitivity anergy was defined as a skin test result of less than 3 mm for all three antigens; DTH positivity was a skin test result of 3 mm or greater for at least one antigen (Centers for Disease Control and Prevention, Atlanta, Ga, 1993).

Results:  At baseline, 36% of HIV-seropositive subjects (n=401) were anergic as compared with 14% of HIV-seronegative subjects (n=552; P<.001). During follow-up, fewer HIV-seropositive subjects remained DTH positive (42%) and more remained anergic (19%) than of HIV-seronegative subjects (67% and 7%, respectively). Twenty-four percent of HIV-seropositive subjects who were initially DTH positive became anergic as compared with 15.3% of the HIV-seronegative subjects. However, the proportion changing from anergy to DTH positivity was greater among HIV-seropositive subjects (15%) than HIV-seronegative subjects (12%). In comparison to those who remained DTH positive, HIV-seropositive subjects with CD4 cell counts of less than 0.50×109/L (odds ratio=6.4) and less than 0.35×109/L (odds ratio=11.2) were more likely to remain anergic than those who had CD4 cell counts above 0.50×109/L or were HIV seronegative.

Conclusions:  Although the prevalence and incidence of DTH anergy were higher in HIV-seropositive subjects, high rates of change in DTH status occurred in both directions. This suggests that instability of DTH skin testing is substantial and only partially dependent on HIV status. Although a single test may be an unreliable indicator of HIV-induced immunosuppression, two consecutive anergic readings were strongly associated with a CD4 cell count below 0.50×109/L and particularly below 0.35×109/L. For determining false negativity of tuberculin tests, persistent DTH anergy is more reliable than a single test among HIV-seropositive injecting drug users. Anergy testing appears to be unnecessary with CD4 cell counts greater than 0.50×109/L.(Arch Intern Med. 1995;155:2111-2117)

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