Pathophysiology

A number of markers of immune dysfunction have been described in IVDUs separate from those produced by coincident HIV infection, other viral infections, or liver disease:

1. Exaggerated lymphocytosis and atypical lymphocytosis

2. Diminished lymphocyte responsiveness to mitogenic stimulation

3. Immunoglobulin G (IgG) and IgM hypergammaglobulinemia and increased opsonin production

4. A higher incidence of false-positive complement fixation tests for syphilis and febrile agglutinins

The use of IV drugs continues to play a major role in the acquisition and spread of HIV. In the United States, the proportion of AIDS cases directly attributable to IV drug use is estimated to exceed 30 percent, and HIV seroprevalence rates in IVDUs are as high as 10 to 50 percent.6 In addition to transmission among IVDUs, HIV also can be spread to their sex partners and offspring. Transmission of HIV infection in IVDUs accelerated dramatically in the 1980s, largely due to the widespread use of injectable cocaine. Cocaine, by virtue of its highly addictive properties and short duration of effect, encourages frequent injections and widespread sharing of injection paraphernalia.

The prevalence of HIV in IVDUs has expanded the spectrum of diseases associated with IV drug use to include those typically associated with HIV infection. 7 HIV

infection dramatically increases the probability of activation of latent Mycobacterium tuberculosis infection in IV drug users.8 In addition, new tuberculosis infection is more likely to progress to active disease in HIV-infected drug users. AIDS-defining illnesses that present in IV drug users are similar in spectrum to those in non-IV drug users, but the distribution of such diseases appears to be different. IVDUs have proportionally more cryptococcal disease, Pneumocystis carinii pneumonia, tuberculosis, and wasting syndrome, and significantly less cytomegalovirus (CMV) infection, non-Hodgkin's lymphoma and Kaposi's sarcoma. 9 HIV-positive IVDUs also appear to be at increased risk of acquiring bacterial infections, such as skin abscesses, pneumonia, and endocarditis. «Hand12 It has been hypothesized that HIV infection, even in the early stages, leads to early loss of regulation of immunoglobulin production, resulting in an ineffective response to bacterial infections. Greater immunosuppression, as defined by lower CD4 counts, is associated with both an increased risk of developing and dying from endocarditis. In those studies specifically comparing endocarditis in HIV- and non-HIV-infected IV drug users, there was no detectable differences in types of infecting organisms, frequency of right- and left-sided valve involvement, and duration of fever.

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