Antibodies against HTLV-III, neopterin levels in blood and urine, TH/TS ratio and hepatitis marker were determined in 34 clinically symptom-free persons known to be intravenous drug abusers. 15 persons were positive in the ELISA and Western-blot tests. There was a strong reaction to protein p24 compared with that to protein p41. In 12 of 14 persons who were antibody-positive the neopterin level in morning urine was elevated; an abnormal TH/TS ratio was present in nine of 13 persons. In future, determination of neopterin and of antibodies against certain proteins of HTLV-III may make it possible to provide a simple way of prognosticating on the course of an HTLV-III infection.

This study followed 184 drug abusers. Examined in all of them were urinary neopterin levels, HBV, SGOT, and Luestest. Seventy-three percent of IV drug addicts showed elevated neopterin levels reflecting activated cellular immunity. Statistically, no correlation of neopterin levels with, eg, excessive alcohol consumption, duration of drug abuse, or studied laboratory parameters was found. Individuals using cocaine revealed higher neopterin levels than those not doing so. Twenty-one of twenty-two patients with no parenteral drug use had normal neopterin excretion. In 34 drug detoxification patients, we examined in addition: T-lymphocyte subsets (T4/T8 ratio) and serum neopterin levels. Thirty-eight of ninety-four parenteral drug addicts presented with anti-LAV/HTLV-III antibodies (ELISA + Western blot + IFT). Our data demonstrate an activated cellular immune status in parenteral drug addicts that cannot be attributed to LAV/HTLV-III infection in all cases. The development of AIDS seems to depend not only on the exposure to LAV/HTLV-III but also on activated cellular immunity, which is easily assessed by neopterin measurement.

Urinary neopterin levels are raised with a high incidence in all risk groups for AIDS. Neopterin elevations reflect activated cellular immunity in risk group members, in some cases independently of LAV/HTLV-III infection. Moreover, we are able to show that in patients receiving multiple blood transfusions at least a transient challenge of cell-mediated immunity occurs, which is indicated in part by increasing neopterin levels. We conclude that neopterin levels are a reliable index for assessment of susceptibility for AIDS when infection with LAV/HTLV-III occurs. Activated status of cell-mediated immunity might predispose infected persons to an overwhelming infection and secondary spreading of LAV/HTLV-III, thus leading to the development of full-blown AIDS or ARC. As a consequence of these observations, T-cell-stimulatory actions and agents should intentionally be avoided. Treatment of AIDS patients with immunosuppressants should be examined. The success of therapeutic regimens should be monitored by measurement of neopterin levels.

Elevated neopterin levels are indicative of activation of the cellular immune system. Studies on excretion of neopterin in patients with AIDS and ARC, as well as in members of risk groups have demonstrated repeated or permanent stimulation of the immune system. This stimulation can be observed in all risk groups independent of LAV/HTLV-III infection. Additionally, in vitro replication of LAV/HTLV-III has been observed to be quantitatively greatest in activated CD4+-lymphocytes. Hence, we conclude that activation of the cellular immune system represents the central cofactor for progressive LAV/HTLV-III infection. These findings seem to contrast with most reports in the literature to date, but observations of other authors corroborate them. As consequence of these studies, therapeutic regimens using immunostimulatory strategies should be prevented in AIDS and ARC patients. Immunosuppressive treatment should be considered.