Hepatitis C virus serology in parenteral drug users with chronic liver disease.

Chronic liver disease is a common complication of parenteral drug use, and liver cirrhosis is frequently seen in users of both parenteral drugs and alcohol. In 1978-83, we studied 88 parenteral drug users with sufficient evidence of chronic liver disease to warrant liver biopsy. Current alcohol abuse was noted in 63 (72%), and six (7%) were former alcohol abusers. Cirrhosis was found in 33 (38%). Hepatitis C antibody (anti-HCV) was detected in 86 (98%). Also, 40 of the anti-HCV positive sera were tested with recombinant immunoblot assay and all of these were reactive. All but one of the 31 patients with anti-HCV and cirrhosis were alcohol abusers. We conclude that parenteral drug users with chronic liver disease almost always have evidence of HCV infection.

Recovery of infectious HIV-1 from whole saliva.

Whole saliva and serum samples were collected from 75 HIV-infected homosexual or bisexual men. Thirty-eight percent of cultured sera were positive for cell-free, infectious virus while only 1 percent of the 218 cultured whole salivas contained cell-free, infectious virus. These data support previous studies suggesting unlikely potential transmissibility of HIV infection by saliva.

Prognostic significance of quantitative levels of HIV p24 binding capacity in HIV infection.

Human immunodeficiency virus, type 1 (HIV-1), produces a chronic infection with a long latency before clinical disease. We followed 214 untreated subjects for 12-42 months to study the natural history of HIV infection: 110 were classified as asymptomatic, 11 as AIDS-related complex (ARC), 15 as AIDS with Kaposi's sarcoma (KS), 31 as AIDS with opportunistic infections (AIDS/OI), and 47 were HIV-seronegative controls. The quantitative capacity of serum to complex HIV p24 antigen, termed the p24 binding capacity (p24 BC), and quantitative levels of HIV p24 antigen in serum were determined at regular intervals. For people in all diagnostic groups, a p24 BC below 31 ng/ml was more closely associated with progression to AIDS/OI than was p24 antigen positivity; 94% of AIDS/OI, 86% of ARC, 56% of AIDS/KS, and 19% of asymptomatic subjects had p24 BC less than 31 ng/ml during the study period, while 67% of AIDS/OI, 27% of ARC, 61% of AIDS/KS, and 20% of asymptomatic subjects were p24 antigenemic. Prospective analysis of 47 asymptomatic seropositive men followed for 3 years, who showed actuarial progression rates to ARC at 4%, 13%, and 23% and to AIDS at 5%, 8%, and 8% at 1, 2, and 3 years, indicated that entry levels of p24 BC below 31 ng/ml were as strongly associated with progression to ARC/AIDS as was p24 antigenemia (p = 0.0003 vs. p = 0.008). The p24 binding capacity assay is a new and convenient methodology to measure immunocomplexing antibody to HIV p24 and is a powerful indicator of progressive HIV disease.

Absence of antibody to human immunodeficiency virus in long-term, socially rehabilitated methadone maintenance patients.

Human immunodeficiency virus (HIV) infection has become widespread among parenteral drug abusers. We measured antibody to HIV and hepatitis B virus markers in 58 long-term, socially rehabilitated methadone-maintained former heroin addicts. None of the 58 had antibody to HIV, but one or more markers of hepatitis B virus infection were seen in 53 (91%). The duration of methadone maintenance was 16.9 +/- 0.5 years, and the median dose of methadone was 60 mg (range, 5 to 100 mg). Before methadone treatment, the patients had abused heroin parenterally for 10.3 +/- 1.7 years, and they had engaged in additional high-risk practices for HIV infection. We conclude that successful outcomes during methadone maintenance treatment are associated with sparing of parenteral drug abusers from HIV infection.

A diffuse infiltrative CD8 lymphocytosis syndrome in human immunodeficiency virus (HIV) infection: a host immune response associated with HLA-DR5.

STUDY OBJECTIVE: To describe the clinical, immunologic, and immunogenetic features of a diffuse infiltrative lymphocytic disorder resembling Sjögren syndrome in persons infected with human immunodeficiency virus (HIV). DESIGN: Clinical case study. SETTING: University-affiliated hospitals and outpatient clinics. PATIENTS: Consecutive sample of 17 patients. MEASUREMENTS AND MAIN RESULTS: All of the 17 patients had bilateral parotid gland enlargement; 14 had xerostomia and 6 had xerophthalmia. Of the 17 patients, 14 had generalized lymphadenopathy, 10 had histologically proved lymphocytic interstitial pneumonitis, 4 had neurologic involvement, and 3 had lymphocytic infiltration of the gastrointestinal tract. Gallium scanning in all of 11 tested patients showed abnormal salivary gland uptake. Minor salivary gland biopsies showed more than 2 lymphocytic foci per 4 mm2 tissue in all of 11 tested patients, the infiltrate consisting predominantly of CD8 cells. Fifteen patients had circulating CD8 lymphocytosis; the principal phenotype of these cells was CD8+ CD29+. Rheumatoid factor and antinuclear antibodies were infrequent, and none of the patients had anti-Ro/SS-A or anti-La/SS-B antibodies. HLA-DR5 was significantly more frequent in the black patients (10 of 12) compared with controls (13 of 45). Only one patient developed an opportunistic infection during 544 patient-months of study, and none has died of AIDS. CONCLUSIONS: A distinct syndrome primarily characterized by parotid gland enlargement, sicca symptoms, and pulmonary involvement occurs in HIV infection. This disorder is associated with CD8 lymphocytosis and the presence of HLA-DR5, and appears to be a genetically determined host immune response to HIV.

Natural killer cell activity and lymphocyte subsets in parenteral heroin abusers and long-term methadone maintenance patients.

We studied natural killer (NK) activity and lymphocyte subsets in 11 active parenteral heroin abusers, 11 long-term methadone-maintained former heroin abusers and 11 apparently healthy individuals. All subjects were males aged 23 to 49 and none had active infectious or inflammatory diseases. All current or former heroin abusers were seronegative for antibody to human immunodeficiency virus. The methadone maintenance patients were socially rehabilitated and had not abused drugs parenterally for at least 10 years. NK activity was determined by a standard Cr-release cytotoxicity assay using K562 cells as targets, and lymphocyte subsets were determined by direct immunofluorescence using flow cytometry. At all three effector-target ratios (100:1, 50:1 and 25:1), NK activity was reduced significantly (P less than .01) in parenteral heroin abusers compared with methadone maintenance patients and apparently healthy individuals. The latter two groups did not differ from each other. Parenteral heroin abusers also had higher absolute numbers of CD2, CD3, CD4 and CD8-positive cells. These data support our hypothesis that significant abnormalities of cellular immunity in parenteral heroin abusers can be normalized by successful long-term methadone treatment.

Changes in the hypothalamic-pituitary-gonadal axis in human immunodeficiency virus-infected homosexual men.

Serum total testosterone, total 17 beta-estradiol, LH, FSH, and PRL concentrations were measured by RIA in 59 homosexual men infected with the human immunodeficiency virus (32 clinically healthy antibody-positive men (HH+), 20 men with acquired immune deficiency syndrome (AIDS), and 7 men with AIDS-related complex (ARC). The results were compared with those of 26 antibody-negative homosexual men (HH-) who served as controls. The mean serum total testosterone concentration was significantly lower in the men with AIDS [414 +/- 230 (+/- SD) ng/dL (14.5 +/- 8.0)] than in the HH- men [550 +/- 172 ng/dL (19.0 +/- 6.0 nmol/L); P less than 0.05]. The mean serum LH level was significantly higher in the men with AIDS (26 +/- 14 vs. 14 +/- 4 IU/L in HH- men; P less than 0.01) and slightly but significantly higher in the men with ARC (19 +/- 8 IU/L; 0.10 greater than P greater than 0.05). Serum FSH also was significantly higher in the men with AIDS (P less than 0.05). Serum PRL was significantly higher in the men with ARC (10 +/- 2 micrograms/L; P less than 0.05) and AIDS (16 +/- 10 micrograms/L; P less than 0.001) than in the HH- men (8 +/- 3 micrograms/L). Serum sex hormone-binding globulin levels were similar in HH- men and men with AIDS as were serum T responses to hCG administration for 2 days. These results suggest that alterations of the hypothalamic-pituitary-gonadal axis indicative of primary hypogonadism accompany human immunodeficiency virus infection in homosexual men.

Hepatitis D virus and human immunodeficiency virus antibodies in parenteral drug abusers who are hepatitis B surface antigen positive.

We studied unselected, hepatitis B surface antigen (HBsAg)-positive parenteral drug abusers for antibody to hepatitis D virus (anti-HD) and antibody to human immunodeficiency virus (HIV). The prevalences of anti-HD and antibody to HIV were 67% and 58%, respectively, and there was no association between positivity for these two markers. In a logistic regression model, anti-HD was associated with older age (P = .001), longer duration of drug abuse (P = .045), and the presence of liver disease (P = .002). Antibody to HIV was associated with a younger age (P = .003) and increased serum globulin levels (P less than .001). In patients infected with HIV, the severity of hepatic dysfunction remained correlated with anti-HD. In anti-HD-positive patients, most indices of hepatic dysfunction were similar whether or not antibody to HIV was present, but serum aspartate aminotransferase levels were significantly higher in patients with both anti-HD and antibody to HIV. (124 +/- 16 vs. 74 +/- 11, P less than .05).

Herpes zoster ophthalmicus in patients at risk for the acquired immune deficiency syndrome (AIDS).

In a prospective investigation of 54 consecutive cases of herpes zoster ophthalmicus, conducted over a two-year period, immunologic evaluations included enumeration of T lymphocyte subsets and serum immunoglobulin levels. Herpes zoster ophthalmicus occurred with frequent ocular complications in a subgroup of adults distinguishable by their young age, the presence of AIDS-risk factors, alterations in T-cell subpopulations, and polyclonal increases of serum gammaglobulin. Over the study duration, 21% (three of 14) of the AIDS-risk subgroup patients have developed AIDS with a 14% (two of 14) mortality. Herpes zoster ophthalmicus in AIDS-risk group members appeared to be an early clinical marker for the immune deficiency induced by AIDS retroviral infection.

The bone marrow in AIDS. A histologic, hematologic, and microbiologic study.

During one year, 55 bone marrow biopsies from 49 patients with CDC-defined acquired immune deficiency syndrome (AIDS) were studied. Eighty-three percent were normocellular or hypercellular; 17% were hypocellular. Marrow plasma cells were increased in 83% of patients, most showing polyclonal hypergammaglobulinemia. Forty percent of patients showed peripheral neutropenia, 29% thrombocytopenia, and 79% lymphopenia with markedly reduced T4+ lymphocytes. Eighty-five percent of patients were anemic, with iron studies showing a pattern consistent with the anemia of chronic disease. Mycobacterium avium-intracellulare (MAI) grew from ten (20%) biopsies, four with granuloma and six without granuloma (five of these six also showed marrow hypocellularity). Small poorly formed granuloma (70-150 micron) were seen in eight (16%) patients (four AFB-culture positive, 4 negative). Three of four granuloma-positive, culture-negative cases eventually grew MAI from autopsy material. Five (10%) patients had lymphoplasmacytic aggregates; later, one developed lymphoma, another, markedly atypical lymphoid hyperplasia. Two additional patients showed marrow B-cell lymphomas. Of these findings, only marrow MAI meets the CDC definition of AIDS. However, in this series, small ill-defined granulomas, lymphoplasmacytic aggregates, and B-cell lymphomas also were found. The authors conclude that these latter findings, when seen in high-risk patients, particularly those with lymphopenia, anemia, and/or hypergammaglobulinemia, also strongly suggest the diagnosis of AIDS.

Intraepithelial carcinoma of the anus in homosexual men.

Anal warts (condylomata acuminata) from seven homosexual men revealed intraepithelial carcinoma (carcinoma in situ) within the condylomatous tissue or in adjacent anal mucosa. All lesions displayed morphologic evidence of papillomavirus infection and two of the seven revealed histologic changes characteristic of herpes simplex infection. This association of viral infection with malignant transformation indicates that persistent or recurrent anal warts should be excised and thoroughly examined by histologic techniques. Since four of the seven patients had histories suspicious for or diagnostic of the acquired immunodeficiency syndrome (AIDS), we further suggest that homosexual men with persistent or recurrent perianal lesions be evaluated for the presence of the syndrome.