Existence and failure of T-cell homeostasis prior to AIDS onset in HIV-lnfected injection drug users

Abstract

Prior studies, based on populations of homosexual men, have shown that during HIV infection, levels of total circulating T-cells (CD3+ lymphocytes) remain constant for long periods of time after seroconversion. This suggested homeostatic phenomenon was observed to break down about 18 months prior to AIDS diagnosis with a quick loss of T-cells. The objective of this study was to determine whether (a) total T-cells are maintained at a constant level for long periods of time among HTV-infected injection drug users (IDUs) and (b) total T-cells decline before AIDS onset in this risk group and, if so, by how long. The design and setting was prospective follow-up, with semiannual clinic visits, of 646 HIV-infected IDUs who participate in the ALIVE study (Baltimore, MD). Among AIDS cases, T-cell levels remained quite stable at about 1500 cells/μl up to approximately 24 months prior to AIDS. However, a steep decline in CD3+ cell levels began approximately 24 months prior to AIDS diagnosis and was -17.5% per 6 months in the last 18 months before AIDS. Among seropositive IDUs without AIDS, a gradual decline of less than -4% per 6 months was observed. These trends remained virtually unchanged after accounting for current injection drug use, smoking, and HIV-related medications. IDUs, like homosexual men, exhibited T-cell homeostasis following HIV infection, as well as failure of this homeostasis about 2 years before AIDS. Although the mechanisms for the maintenance and later failure of the homeostasis of T-lymphocytes are not well understood, the observation has a potentially important prognostic value as well as biological interest.