Decrease of CD4 cell number and function in HIV-seropositive hemophiliacs in a longitudinal study.

The Regional Hemophilia Center in St. Louis initiated a prospective study beginning in 1982 to measure sequentially T-cell subpopulations and in vitro lymphoproliferative responses in hemophilia A patients. In a cohort of 106 hemophiliacs, the prevalence of HIV-seropositivity increased from 46.7% in 1982 to 74.5% by 1987. There was a persistent gradual decline over time of T helper/inducer (CD4) cells in HIV-seropositive hemophiliacs (P less than .01). This was reflected by an increasing percentage of hemophiliacs with abnormally low CD4 cells (less than 2 standard deviations below the mean of normal individuals) from 6.7% in 1983 to 52.4% in 1987. Function of CD4 cells, as estimated by in vitro lymphoproliferative responses to phytohemagglutinin (PHA) and tetanus toxoid stimulations also demonstrated a decline over the same years. Lymphoproliferative responses to PHA by HIV-seropositive hemophiliacs' mononuclear cells (MNC) declined from a 90.2% normal response in 1983 to a 71.7% normal response in 1987 (P less than .05). Decreased responses to stimulation with the soluble antigen tetanus toxoid were also seen from 1983 compared with 1987 (P less than .05). This was due to an increased percentage of HIV-seropositive hemophiliacs' MNC, which were unresponsive to stimulation to tetanus toxoid (stimulation index less than 3.0) from 20.8% in 1983 to 41.0% in 1987. These findings indicate that HIV-infection was associated over time with a decline of CD4 number and function in a substantial portion of hemophiliacs.

Human immunodeficiency virus infection. Clinical diagnosis.

Primary care physicians are likely to see HIV-infected individuals well before they develop full-blown AIDS or even AIDS-related complex. The author presents an overview of the symptoms that may appear in so-called "asymptomatic" patients with human immunodeficiency virus infection.

Incidence and risk factors for human immunodeficiency virus seroconversion in a cohort of Sydney homosexual men.

By means of prospective cohort data from the Sydney AIDS Project, we report on 55 homosexual or bisexual men who have become infected with human immunodeficiency virus (HIV), as measured by the development of serum HIV antibodies (seroconversion). We have compared the sexual practices, recreational drug abuse, history of sexually-transmissible diseases, and antecedent immunological findings of the men who seroconverted with those of 588 subjects who persistently remained seronegative in the same time-period. The cumulative incidence rate of HIV infection over the three years of observation was 8.5%. The cumulative incidence rate ranged from less than 1% for the six months before August 1, 1984, to a peak of 5% in the six months before August 1, 1985. Of those subjects for whom we had data for the period of seroconversion, all but two of the subjects who seroconverted admitted to a recognized high-risk sexual practice in the six months before the first visit at which they were found to be seropositive. Univariate analysis found that men who seroconverted were significantly more likely to have had a greater number of recent sexual partners (relative risk per partner, 1.02; P less than 0.001), to have engaged in receptive anal intercourse (incidence rate ratio, 3.1; 95% confidence interval [CI], 1.3-7.6; P = 0.01) and to have used nitrite inhalant (incidence rate ratio, 2.6; 95% CI, 1.2-5.9; P = 0.02) and amphetamine (incidence rate ratio, 4.8; 95% CI, 2.2-10.5; P less than 0.001) drugs. The men who seroconverted were significantly (incidence rate ratio, 2.7; 95% CI, 1.2-6.1; P = 0.014) more likely to have antecedent T-suppressor-cell counts of greater than 800 cells/microL. Factors that retained significance in multivariate analysis were the number of recent sexual partners, recent amphetamine abuse and a T-suppressor-cell count of greater than 800 cells/microL.

Transmission of retroviruses by transfusion of screened blood in patients undergoing cardiac surgery.

We determined the rates of seroconversion to human immunodeficiency virus type 1 (HIV-1) and human T-cell leukemia virus Type I (HTLV-I) in a cohort of patients receiving transfusions of blood components screened for antibody to HIV-1. Preoperative and postoperative serum samples were collected from 4163 adults undergoing cardiac surgery who received 36,282 transfusions of blood components. The postoperative samples from all patients were tested for serologic evidence of HIV-1 infection, and those that were positive were compared with the corresponding preoperative samples. One case of HIV-1 transmission by transfusion of screened blood components was identified; two preexisting HIV-1 infections were found. Samples from 2749 patients were tested similarly for serologic evidence of HTLV-I infection; these patients received 20,963 units of blood components. Five new cases and two preexisting cases of HTLV-I infection were detected. The observed risk of HIV-1 transmission by transfusion was 0.003 percent per unit; the risk of HTLV-I transmission was 0.024 percent per unit. We conclude that there is a very small risk of HTLV-I infection from transfused blood products that have been screened for antibodies to HIV-1, but that it is nearly 10-fold higher than the risk of HIV-1 infection.

Prevalence of HIV infection among intravenous drug users in the United States.

We reviewed 92 published and unpublished studies of the prevalence of infection with the human immunodeficiency virus (HIV) among intravenous drug users (IVDUs) in the United States. Human immunodeficiency virus seroprevalence among IVDUs in drug treatment programs in the United States ranged from 0% to 65%. Seroprevalence was highest in the Northeast (10% to 65%) and Puerto Rico (45% to 59%); lower in the South Atlantic (7% to 29%) and in the metropolitan areas of Atlanta, Ga (10%), Detroit, Mich (7% to 13%), and San Francisco, Calif (7% to 13%); and 5% or less in other areas of the West, the Midwest, and the South. Among IVDUs seen in drug treatment programs, risk of infection was not associated with gender or age but was associated with black and Hispanic ethnicity, male homosexual orientation, and certain intravenous drug-use practices. Cross-sectional and cohort studies indicated increases in seroprevalence of between 0% and 14% per year among IVDUs in treatment. We estimated that between 61,000 and 398,000 IVDUs in the United States were infected with human immunodeficiency virus, or 5% to 33% of the IVDU population. High rates of infection among IVDUs in treatment in the Northeast indicate the potential for rapid spread in regions where rates are currently low. An urgent need exists to monitor human immunodeficiency virus infection levels and trends more widely and to develop effective programs to reduce the further spread of human immunodeficiency virus infection among IVDUs.

["Occupational" infection caused by the human immunodeficiency virus in 6 members of a single family]. / Infección "ocupacional" por el virus de inmunodeficiencia humana en seis miembros de una misma familia.

The risk groups for AIDS have been defined and include homosexuals, bisexuals, polytransfused patients, drug addicts, sexual partners of any of the above groups and sons of infected fathers. We have previously proposed that paid donors should be considered also as high risk individuals. We report here a family in which six of its eight members had HIV infection without other risk factor than being paid blood donors.

Management of the oral surgery patient addicted to heroin.

A review of the clinical characteristics of heroin addiction and parameters surrounding outpatient and inpatient care of patients afflicted with heroin dependency is presented. A case report demonstrating the difficulties encountered when one elects to treat the heroin addict is included.

Spectrum of HIV infection and AIDS in a cohort of Italian hemophiliacs.

A group of 173 subjects affected by congenital clotting factor deficiencies was evaluated with regard to the impact of HIV infection. On the whole, 78 patients (45%) were found to be HIV Ab-positive. As of March, 1988, of the seropositive patients, 63 (80.8%) had an asymptomatic HIV infection (Group II/CDC), three (3.8%) had a persistent generalized lymphadenopathy (Group III/CDC). The 12 (15.4%) remaining patients could be classified in Group IV of the CDC classification due to their symptoms and signs; in particular, 10 came under surveillance case definition for AIDS. Assay for the HIV antigen was positive in 14 (17.9%) seropositive hemophiliacs. With regard to the immunological features, our data clearly show that a sharp decline in the number of CD4+ cells was associated with symptomatic forms of the disease. An evaluation of the time elapsed from seroconversion to the appearance of the symptomatic clinical condition showed an average incubation of 37 months.

Clinical and immunological aspects of HIV infection in drug addicts.

Intravenous drug users (IVDUs) account for more than 64% of the total AIDS cases in Italy. The IVDUs' seropositivity rate is greater than 70% in Milan and greater than 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.

Increased levels of soluble CD8 molecule in the serum of patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related disorders.

In this study we investigated the serological levels of the soluble form of the CD8 molecule (s-CD8) in 97 human immunodeficiency virus (HIV) seropositive patients. The control groups included 20 normal heterosexual subjects and 19 healthy seronegative subjects belonging to risk groups for AIDS. Our results show that patients with HIV infection have significantly higher levels of s-CD8 U/ml than the control groups. When the patients were further subdivided according to the Centers for Disease Control (CDC) classification, s-CD8 U/ml values were consistently increased in all HIV patients, irrespective of the CDC stages. No statistically significant correlation was found between the serological levels of s-CD8/ml and the absolute numbers of CD8 lymphocytes/mm3, in both HIV seropositive patients and control groups. Since in the more advanced stages of HIV infection (IV-A, IV-C1) the decrease in the absolute number of CD8+ cells was not followed by a decrease in s-CD8 levels, it is conceivable that an increased release and/or shedding of s-CD8 per cell might occur in these patients. In fact, when the results were expressed as s-CD8 units per CD8 positive cell (s-CD8/absolute number of CD8), the levels of s-CD8/cell were higher in patients belonging to the IV-A and IV-C1 CDC groups (1.94 U/cell +/- 0.33 and 3.39 U/cell +/- 0.5, respectively) compared to normal controls (P less than 0.001), HIV seronegative subjects at risk for AIDS (P less than 0.001), and the other patients' groups (II and III CDC groups, respectively, P less than 0.001 and P less than 0.001). The evidence herein provided that in patients with HIV infection s-CD8 levels are increased suggests a possible pathogenetic role of the cells involved in the release of this molecule.

Possible role of natural cytotoxic activity in the pathogenesis of AIDS.

In an attempt to assess the role of immune cytotoxic activity in the sequence of events leading to the acquired immunodeficiency syndrome (AIDS), natural cytotoxic activity was studied in 17 asymptomatic homosexual males, seropositive for anti-human immunodeficiency virus (HIV) antibodies, as compared to 16 of their seronegative counterparts and to 14 control healthy heterosexual individuals. Cell (contact)-mediated cytotoxicity (CMC) as well as cytotoxin (CTX) production by lipopolysaccharide (LPS)-stimulated, phytohemagglutinin (PHA)-stimulated, HeLa tumor cell-stimulated, and unstimulated peripheral blood mononuclear cells (PBMC) were determined using HeLa cell monolayer cultures, sensitized with cycloheximide, as targets. The CMC was markedly enhanced in the seropositive group (28 +/- 21 (mean +/- SD) lytic units/10(6) PBMC) as compared to the seronegative group (17 +/- 7; P less than 0.005) and to the heterosexual group (13 +/- 6; P less than 0.05). Likewise, CTX production by unstimulated PBMC from seropositive homosexuals (19 +/- 26 units/ml) was higher than that observed in the other groups (both 4 +/- 4 units/ml; P less than 0.05). CTX production by PHA-stimulated, LPS-stimulated, and HeLa cell-stimulated PBMC was significantly enhanced in both the seropositive and seronegative groups in comparison to the normal heterosexual controls. These results suggest that increased cytotoxic activity may be present in homosexuals prior to their exposure to HIV, and may be further enhanced after HIV infection.

Passive transfer of HIV antibody by hepatitis B immune globulin.

Two newborns of mothers carrying hepatitis B and at high risk for human immunodeficiency virus (HIV) infection developed HIV-positive test results by enzyme-linked immunosorbent assay and Western blot tests after birth. Both had been administered hepatitis B immune globulin within 48 hours of birth. Serological tests detected HIV antibody as long as 17 days after birth. Both newborns had received lots of hepatitis B immune globulin containing antibody to HIV. While hepatitis B immune globulin cannot transmit HIV infection to recipients, physicians should be aware that administration of older lots of this preparation may result in transiently positive tests for HIV antibody in the recipients. Lots manufactured from screened plasma do not contain antibody to HIV.

Women and the acquired immunodeficiency syndrome. An interview.

SPECIAL EDITOR'S NOTE: Constance B. Wofsy, MD, is Co-Director of AIDS Activities at San Francisco General Hospital and Medical Center, as well as Associate Clinical Professor of Medicine at the University of California, San Francisco; Assistant Chief, Infectious Diseases, San Francisco General Hospital; and Principal Investigator, Project AWARE (Association for Women's AIDS Research and Education). Although she was not able to contribute an article for WOMEN AND MEDICINE on this very important subject, she kindly agreed to an interview. Both physicians and nonphysicians were asked what questions they had about the acquired immunodeficiency syndrome (AIDS) and the human immunodeficiency virus (HIV) in women.

Decline in CD4+ cell numbers reflects increase in HIV-1 replication.

Changes in CD4+ cell numbers were studied in relation to the presence of HIV-1 antigen (HIV-1-Ag) in serum from homosexual men followed prospectively. During 30 months of follow-up the mean CD4+ cell number (x 10(9) per liter) was stable in 134 at entry HIV-1 antibody (HIV-1-Ab) seropositives, who remained HIV-1-Ag negative (from 0.59 to 0.62) and declined in 38 at entry HIV-1-Ab seropositives who were persistently HIV-1-Ag positive (from 0.43 to 0.34). In sera of 9 of 65 HIV-1-Ab seroconverters HIV-1-Ag was detected only once, 3 months before or concomitantly with antibody seroconversion. Another 11 men became persistently HIV-1-Ag positive with antibody seroconversion or 2-6 weeks thereafter. A decline in CD4+ cell numbers was seen between 6 months before and the moment of HIV-1-Ab seroconversion, independently of duration and level of antigen expression. This indicates initial HIV-1 replication in both HIV-1-Ag negatives and positives. Following antibody seroconversion, HIV-1-Ag negatives had higher CD4+ cell numbers than HIV-1-Ag positives. Similarly to those who were HIV antigenemic from entry of the study, the HIV-1-Ab seroconverters who concomitantly with seroconversion or shortly thereafter became HIV-1 antigenemic showed a steady and significant (p = 0.01) decline in CD4+ cell numbers. In those who remained HIV-1-Ag negative after antibody seroconversion, CD4+ cell numbers were stable during follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Immune changes in male homosexuals--predisposing factors for HIV seroconversion.

Israel is still a low incidence country for AIDS and thus the temporal relationships between various cofactors and HIV infection can be more easily determined. We have studied a cohort of 243 asymptomatic male homosexuals (MHS) during the last 4 years. At the beginning of the study, 40% had significant decreases in the peripheral blood lymphoid populations, signs for reactivation of CMV and EBV infections, and elevated serum levels of interferon. There was no difference in the prevalence of these immune derangements between seropositive and seronegative individuals. In the course of 4 years' follow-up, the prevalence of these immune derangements has remained the same though being significantly more severe in the HIV seropositive subjects. HIV seroconversion did not exceed 8% (about 2% annually) and was related to the immune impairments found when first seen at the beginning of the study. The results suggest that immune impairments are common among asymptomatic MHS, precede HIV infection, and probably contribute to the increased risk for AIDS among male homosexuals.