Clinical and immunological aspects of HIV infection in drug addicts
ABSTRACT Intravenous drug users (IVDUs) account for more than 64% of the total AIDS cases in Italy. The IVDUs' seropositivity rate is >70% in Milan and >50% in the main cities of Italy. The first evidence of seropositivity in this population dates back to 1979. In a cohort study performed in Milan the rate of progression to overt AIDS among IVDUs was 6% in 3 years (1984–1987). At presentation, more than 75% of the subjects had CD4+ cell counts higher than 400/mm3 (mean 631, median 528, mode 465). These values are significantly higher than those observed in the same population in New York, the only American city with HIV-infection spread comparable to that observed in Milan. The probability of having CD4+ cell counts lower than 400, 300, and 200/mm3 in relation to the length of follow-up was, respectively, 50, 40, and 2% after 36 months from presentation. At the same end point, subjects presenting less than 400 CD4+ cells at entry had 30% probability of falling under 200 cell/mm3. The pattern of CD4+ cells, as much as the low percentage of yearly progression to overt AIDS, is probably related to the recent, even if rapid, spread of infection among IVDUs in Italy. The clinical features of overt AIDS present some differences between IVDUs and other at-risk groups. Among U.S. IVDUs with AIDS, Kaposi's sarcoma is infrequent (2.9% vs 27.7% in homosexual men) while mycotic infections such as deep candidiasis and cryptococcosis are significantly more frequent. The same pattern has been observed in our case file in Milan: esophageal candidiasis represents the most frequent cause of diagnosis of overt AIDS. Mycotic infections, overall, are more frequent than in U.S. IVDUs. The increased rate of mycotic infections among IVDUs might be justified by altered functions of nonspecific immunity, such as PMNL killing and phagocytosis of Candida albicans spores, impaired in HIV-infected IVDUs, but generally normal in infected subjects belonging to the other at-risk groups.
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ABSTRACT: In Reply. —Dr Winkelstein raises the possibility of selection bias in our analysis of CD4 lymphocyte decline in the ALIVE cohort of IVDUs. This bias must always be a serious concern in any longitudinal study; for this reason and because the decline in CD4 lymphocytes in our cohort of IVDUs was lower than that reported by others, we looked for evidence of significant bias in our original analysis, as Winkelstein notes. However, we did not find such evidence, and we concluded that while the possibility of selection bias could not be completely excluded, a large bias did not appear likely, for the reasons already stated. We have recently updated the analysis of CD4 lymphocyte changes in our cohort based on an additional year of follow-up. Eighteen-month follow-up data are now available for 537 (85.7%) of the 627 cohort members, and the median rate of CD4 lymphocyte change is -7.4/μL perJAMA The Journal of the American Medical Association 03/1992; 267(12):1631-1636. DOI:10.1001/jama.267.12.1631 · 30.39 Impact Factor
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ABSTRACT: We report here on brain associated autoimmune features in opiate-dependent subjects. This study includes 107 (37 HIV + and 70 HIV -) hospitalized heroin-addicted subjects on a methadone maintenance program, and 45 healthy individuals. Human brain S100 protein, neuron specific enolase (NSE), myelin basic protein (MBF), and old tuberculin (OT) were used as antigens in the study. Serum autoantibodies to brain antigens S100, NSE and MBP were detected by ELISA, whereas delayed hypersensitivity skin reactions were evaluated after intradermal injection of S100, NSE, MBP and OT (control brain-irrelevant antigen). In drug-dependent subjects, 68.2% produced anti-S100, 56.1% anti-NSE and 20.5% anti-MBP autoantibodies, while the incidence of autoantibodies in control healthy individuals was 4.4%, 2.2% and 0%, respectively. Occurrence and amount of anti-S100 and anti-NSE autoantibodies were much higher in HIV + than in HIV - heroin-abusing adults. In drug abusers, the incidence of positive delayed hypersensitivity skin reactions were as follows: 67.2% to S100, 51.4% to NSE, 14.9% to MBP, and 94.3% to OT. In control subjects, the occurrence of hypersensitivity reactions to brain antigens was insignificant. Cutaneous reactions were more frequent in HIV - addicts. The incidence of both autoantibodies and delayed skin responses was positively related to the duration of drug abuse, worsening of HIV infection, and dementia. The high incidence of autoantibodies and delayed hypersensitivity skin reactions to S100 and NSE human brain antigens in heroin-abusers indicates that heroin dependence, as well as HIV infection, are associated with a hyperergy towards brain-related autoimmune phenomena. It has been suggested that the brain-associated autoimmune phenomena in HIV + heroin-addicts represent a hyperimmune phase which precedes immunodeficiency that occurs in the further development of HIV infection.International Journal of Neuroscience 06/1991; 58(1-2):113-26. DOI:10.3109/00207459108987188 · 1.53 Impact Factor
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ABSTRACT: The role of CD4+ lymphocytes in resistance of N:NIH(S) III bg/bg nu/+ mice to mucosal candidiasis was evaluated. Alimentary tract colonization with a pure culture of Candida albicans induced a population of lymphocytes in both the Peyer's patches and spleens of bg/bg nu/+ mice, but not bg/bg nu/nu mice, that proliferated and produced interleukin-2 (IL-2) in response to C. albicans antigens. The induction of candida-specific lymphocytes correlated with the clearance of C. albicans from the esophagus and tongue of resistant bg/bg nu/+ mice. Isogenic bg/bg nu/nu mice which do not develop candida-reactive lymphocytes were unable to clear C. albicans from their tongues and esophagi. Treatment of bg/bg nu/+ mice with anti-CD4+ monoclonal antibodies depleted their CD4+ lymphocytes and increased their susceptibility to mucosal candidiasis of the tongue and esophagus. In vivo treatment of bg/bg nu/+ mice with anti-IL-2, anti-gamma interferon (IFN-gamma), or both anti-IL-2 and anti-IFN-gamma monoclonal antibodies did not abrogate their resistance to mucosal candidiasis. Furthermore, treatment of C. albicans-susceptible bg/bg nu/nu mice with IFN-gamma and IL-2 did not protect them from mucosal candidiasis. Thus, CD4+ cells apparently play a critical role in resistance to mucosal candidiasis; however, we were unable to demonstrate a role for IL-2 and IFN-gamma in mediating resistance to mucosal candidiasis.Infection and Immunity 08/1991; 59(7):2447-55. · 4.16 Impact Factor