Healthy Homosexuals Research Articles

Spectrum of opportunistic infections in relation to CD4 counts in HIV/AIDS patients admitted in the department of general medicine of a tertiary care hospital

Background: HIV/AIDS was first recognized in USA in 1981 when centre for disease control (CDC) reported unexplained occurrence of Pneumocystis carinii pneumonia in 5 healthy homosexuals. Soon it was recognized in drug abusers and blood transfusion recipients. The present study has been taken up with an aim to know the incidence of various opportunistic infections in HIV positive patients and to correlate different opportunistic infections (OIs) with the CD4+cellcount.Methods: Sample of 132 cases admitted in Gandhi hospital during the study period were taken. CD4+ counting of blood samples was done by Flow cytometry as per manufacturer’s instructions (FACS Calibur, Becton- Dickinson, Immunocytometry system). Correlation of CD4 cell counts was done with the respective opportunistic infections.Results: TB (50%) is the most frequent OI followed by candidiasis (49%), pneumocystis (16%) and others. The mean CD4 cell count in TB was 110.80/mL and in candidiasis 97.84/mL. Low values were observed in CMV (27/mL) and in toxoplasmosis (61.66/mL).Conclusions: In most of the patient’s respiratory system was the most common system involved by OIs and had CD4 T cell count below 200/mL. Early diagnosis and prompt treatment of opportunistic infections is important. This study helps the clinicians in proper guidance to come up before development of severe immunodeficiency to prevent serious and fatal outcome.

Pneumocystis Pneumonia—Los Angeles

This article describes 5 cases of Pneumocystis carinii pneumonia occurring in homosexual men in Los Angeles California. All 5 patients had previous or current cytomegalovirus and candidal mucosal infection. The men 2 of whom have died ranged from 29-36 years of age. The patients did not know each other and had no known common contacts or knowledge of sexual partners with similar illnesses. The 5 did not have comparable histories of sexually transmitted disease. 4 had serologic evidence of past hepatitis B infection but no evidence of current hepatitis B surface antigen. 2 of the men reported frequent homosexual contact with various partners. All 5 reported use of inhalant drugs. The 3 patients in whom lymphocyte studies were performed had profoundly depressed in vitro proliferative responses to mitogens and antigens. The occurrence of pneumocystosis in these 5 previously healthy men without a clinically apparent underlying immunodeficiency is unusual but seems to reflect some association with a homosexual lifestyle or disease acquired through sexual contact. Cytomegalovirus infection has been shown to induce transient abnormalities of in vitro cellular immune function in healthy homosexual men with and without antibody and a high prevalence of cytomegalovirus infections has been reported among male homosexuals. In additon there is some evidence that seminal fluid may be an important vehicle of cytomegalovirus transmission. Although the role of cytomegalovirus infection in the pathogenesis of pneumocystosis reamins unknown the possibility of P. carinii infection should be carefully considered in previously healthy homosexuals with dyspnea and pneumonia.

Immune response and epitope mapping of a candidate hiv‐1 p17 vaccine hgp30

A thirty amino acid synthetic peptide (HGP30) representing the conserved region of HIV-1 p17 induced high titer antibodies to the native p17 in rabbits. This immune sera neutralized HIV-1 replication in cell culture and one of the high titer antisera also inhibited CD4-dependent cell fusion. Pepscan analysis with overlapping nonapeptides derived from the sequence of HIV-1 p17 identified the sequence (KE) ALDKIEE (EQ) as the major antibody binding site. Sera of 9% of AIDS patients (7/76) and 18% of HIV-1 seropositive healthy homosexuals (40/223) were positive for HGP30 antibodies. Decline in HIV-1 p17 antibodies has been shown to be related to disease progression in both children and adults, suggesting that HIV-1 p17 antibodies may be protective. Hence, a synthetic HIV-1 p17 peptide, representing the immunodominant epitope, could be useful as a candidate vaccine for immunization of HIV-1 seronegative or seropositive healthy homosexuals.

T-Cell populations in liver and renal transplant recipients with infectious esophagitis

Individuals undergoing hepatic and renal transplants are susceptible to infections of the gastrointestinal tract, particularly the esophagus. The most common responsible agents are Candida and herpes simplex virus (HSV) with cytomegalovirus (CMV), Aspergillus, and other agents being regarded as unusual pathogens even in this unique population. Altered T-cell populations have been associated with CMV colitis in healthy homosexuals and in individuals with the acquired immunodeficiency syndrome (AIDS). Similarly, individuals with Epstein-Barr virus infections have altered T-cell populations. Whether these infections alter T-cell populations in infected individuals or the abnormalities in T-cell subpopulations occur first and enhance the likelihood of an infection in susceptible populations is as yet unknown. In this study peripheral blood T-cell populations in individuals before (19 patients) and after (47 patients) liver transplantation and after receiving a renal allograft (21 patients) were compared. Those individual having any symptoms related to esophageal disease underwent upper gastrointestinal endoscopy combined with mucosal biopsies, brushings, and cultures and were subdivided into those with and without infectious esophagitis. CMV esophagitis was found to be associated with an arithmetically decreased T-cell helper/suppressor (H/S) ratio principally due to an increase in the suppressor cell number. Such a reduction in the TH/S ratio and in the number of circulating suppressor cells was not found in esophagitis due to either HSV or Candida and was unrelated to the serum cyclosporine level or prednisone dosage prescribed.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of an Indirect Immunoperoxidase Assay for Specific IgG and IgA to Chlamydia trachomatis

Cell culture methods for detection of Chlamydia trachomatis are technically difficult, expensive, and yield results only two to four days later. Direct methods of C trachomatis antigen detection require sampling from infected sites and suffer from false-negative results. We have evaluated a new immunoperoxidase kit for detection of specific serum IgG and IgA to C trachomatis. The kit uses slide-fixed C trachomatis serotype L2 infected cells and contains stabilized liquid reagents and a stable chromogen/substrate. The assay is simple and reproducible; positive and negative results are quickly and easily determined. We tested serum samples from 228 patients and found positive results for current infection in ten of 11 patients whose cultures were positive for C trachomatis, all of nine patients with pelvicinflammatory disease, 15 of 29 patients with acquired immunodeficiency syndrome, 17 of 25 patients with lymphadenopathy syndrome, four of nine healthy homosexuals, 24 of 70 asymptomatic pregnant women, and 15 of 70 asymptomatic controls. This method may be useful in excluding infections in patients where sampling is difficult.

Anticardiolipin antibodies associated with HTLV-III infection.

Anticardiolipin antibody levels were determined in 73 homosexual men. Thirty of these patients had acquired immunodeficiency syndrome (AIDS), 16 patients had the AIDS-related complex (ARC) and 27 were healthy. Antibodies to human T-lymphotropic virus type III (HTLV-III) were detected in all patients with AIDS and ARC and in 11 of the healthy homosexuals. Eight patients with positive fluorescent treponemal antibody absorption test were excluded from the study. High levels of IgG-anticardiolipin antibodies were present in 23 of the 28 patients with AIDS; 12 of the 14 with ARC; five of the 10 HTLV-III positive healthy homosexuals; and none of the 13 HTLV-III negative healthy homosexuals. High levels of IgM-ACA were detected only in four patients with AIDS. The IgG-anticardiolipin levels were higher in the HTLV-III positive patients than in the HTLV negative group (P = 0.013). None of the patients with anticardiolipin antibodies exhibited venous thrombosis.

Antibody to Human Lymphotropic Virus Type III

Twenty homosexual men who reported having sexual contact with homosexual men who had the acquired immunodeficiency syndrome (AIDS) or the AIDS-related complex were examined to determine their clinical status, immunologic profiles, and the presence of antibody to the human T-cell lymphotropic virus type III (HTLV-III). Of the 20, eight men had one or more signs or symptoms of the AIDS-related complex and 12 were asymptomatic. Antibodies to HTLV-III were present in 14 (70%) of 20 of the sexual contacts as compared with four (10%) of 40 healthy homosexuals without known contact with a patient who had AIDS (P less than .0001). Seropositive contacts had significantly higher mean counts of suppressor lymphocytes and lower helper: suppressor ratios (P less than .05 and .005, respectively) and higher serum levels of IgG than seronegative contacts (P less than .05). It was not possible to determine significant differences in sexual practices, drug use, length of relationship, or numbers of different sexual partners between symptomatic and asymptomatic contacts or between seropositive and seronegative contacts in this study.

Impaired monocyte-to-macrophage maturation in patients with lymphadenopathy syndrome.

The in vitro maturation of monocytes from patients with lymphadenopathy syndrome (LAS) was studied by means of enzymatic activity performed during a 7-day incubation period. Monocytes from LAS patients, healthy homosexuals, and healthy heterosexuals were assayed for beta-galactosidase and beta-N-acetylglucosaminidase activity on days 3, 5, and 7 of culture. The LAS monocytes had significantly lower (P less than 0.01) absolute levels of both enzymes compared with controls or healthy homosexual subjects. All three groups showed a linear increase in enzyme activity over time. There was no statistical difference between the slopes of the curves of enzyme activity vs time for the three groups, indicating that the rate of increase in enzyme activity was similar for the groups. These results suggest that monocyte-to-macrophage maturation is impaired in LAS. LAS monocytes are initially less mature than those of healthy homosexuals or heterosexuals but retain their capacity to mature during incubation in vitro.

Epidemiologic and laboratory evaluation of homosexual males from an area of low incidence for acquired immunodeficiency syndrome (AIDS)

The northeastern Ohio area is currently one of low incidence for the acquired immunodeficiency syndrome (AIDS). From July through December 1983, 17 sexually active healthy homosexual males, 15 men with AIDS-related complex (ARC), and nine patients with AIDS were studied. In contrast to similar studies from high-incidence areas, healthy homosexuals did not have significant laboratory abnormalities, particularly of lymphocyte subpopulations, when compared with heterosexual controls. Epidemiologically, there were no significant differences detected based on travel to epidemic areas or sexual practices between healthy homosexuals and patients with ARC. Furthermore, ARC patients were significantly less sexually active than healthy homosexual controls. It appears that subclinical immunodeficiency is uncommon in areas of low attack rates for AIDS and that studies from low-incidence areas may shed light on the early events in the spread of AIDS.

Tumor-Associated Antigen Is Expressed on Lymphocytes from Patients with Acquired Immunodeficiency Syndrome

Monoclonal antibody BE2 recognizes an antigen found on malignant T4+ lymphocytes from cutaneous T-cell lymphoma patients (CTCL). Normal peripheral blood lymphocytes do not express detectable levels of BE2 antigen. Forty-eight percent of patients with the acquired immunodeficiency syndrome (AIDS) had lymphocyte populations that were reactive with monoclonal antibody BE2. Peripheral blood lymphocytes from healthy homosexuals, patients with classical Kaposi's sarcoma or viral syndromes, and healthy normal controls were BE2-. Double-labeling studies demonstrated that BE2+ cells were T lymphocytes. This observation demonstrates that some AIDS patients as well as CTCL patients have circulating cells that express a common lymphocyte abnormality.

The relationship of abnormalities of cellular immunity to antibodies to HTLV-III in homosexual men

A comprehensive evaluation of the cellular immune system (total T-cell, helper cell, suppressor cell, and natural killer cell numbers; in vitro interleukin-2 production, T-cell responses to mitogens and antigens, serum β 2 microglobulin levels, and delayed hypersentivity skin tests) was performed on 36 HTLV-III seronegative and 16 HTLV-III seropositive healthy homosexual men, 48 asymptomatic homosexual men with the chronic lymphadenopathy syndrome, 41 patients with AIDS, and 29 heterosexual controls without any known risk factors for AIDS. Our studies demonstrate that HTLV-III seronegative homosexual men have normal cellular immunity and are comparable to heterosexual controls. The abnormalities of lymphocyte subsets observed in HTLV-III seropositive healthy homosexual men are comparable to subjects with chronic lymphadenopathy. Assays of lymphocyte function, with the exception of delayed type hypersensitivity (DTH) skin tests, are similar in each group except patients with AIDS. Subjects with chronic lymphadenopathy were less responsive to DTH skin tests and HTLV-III seropositive healthy homosexuals were comparable to chronic lymphadenopathy subjects. We conclude that immunologic abnormalities in homosexual men are attributable to infection with HTLV-III.

Flow cytometric analysis of lymphocyte phenotypes in AIDS using monoclonal antibodies and simultaneous dual immunofluorescence

Simultaneous dual immunofluorescence and flow cytometry was used to study sixteen lymphocyte phenotypes in 209 men including: healthy heterosexuals, healthy homosexuals, lymphadenopathy patients (LAN), and AIDS patients. Significant differences between the distribution of lymphocytes in healthy homosexuals and healthy heterosexuals were decreased percentages of helper/inducer T cells (Leu 3), increased cytotoxic/suppressor T cells (Leu 2), and consequently a decreased Leu 3 Leu 2 ratio. The increased Leu 2 cells were identified as functionally cytotoxic subset Leu2 +15 − phenotype rather than suppressor cells which are Leu 15 +. Leu 2 and Leu 3 bearing cells exhibited an excess of membrane-bound immunoglobulins which were easily elutable at 37°C. An increased percentage of an HLA-DR framework determinant bearing T cells were also detected. Within the NK cell family, Leu 7 cells were moderately increased and the functionally unidentified Leu 2 +7 + population was strikingly elevated. LAN or AIDS patients were compared to healthy homosexual controls. Lower percentages of Leu 3 cells and higher percentages of Leu 2 cells were evident in LAN patients. These subsets were similar in LAN and AIDS patients. The increase in Leu 2 + cells was due to the Leu 2 +15 − cytotoxic subset. Fewer T cells had immunoglobulin in LAN and AIDS. A definite increase in Leu 2 + DR + cells but not Leu 3 +DR + cells occurred in AIDS compared to LAN or healthy controls. NK cell changes already present in healthy homosexuals persisted in LAN and AIDS patients. No differences in the distribution of B cells was detected in any intergroup comparisons. Changes in monocytes or pan-T cells were relatively insensitive measures of immunologic alterations among any of the groups. These results indicate many of the changes in lymphocyte subsets seen in AIDS and LAN subjects are already present in a carefully screened population of healthy homosexuals in San Francisco. Many of the changes in Leu 2 and NK family of cells suggest a possible adaptive response to viral or neoplastic challenge. Whether these interesting phenotypic alterations relate to functional changes in response to such challenge of the identified subsets waits further investigation.

Cytomegalovirus viremia increases with progressive immune deficiency in patients infected with HTLV-III.

Cytomegalovirus (CMV) viremia was studied in 15 homosexual patients [two healthy, nine with the acquired immune deficiency syndrome (AIDS), five with the AIDS-related complex (ARC)], in one patient with transfusion-related AIDS, and in four individuals with cancer or connective tissue disorders. While CMV viremia was absent in the latter patients, in the healthy homosexuals, and in three stable ARC patients, it was present in clinically-deteriorating ARC patients and in all nine AIDS patients. Some CMV isolates caused limited proliferation of fibroblasts in the culture medium. The rapidity and ease of CMV isolation from leukocytes of patients at different stages of infection with human T-lymphocytotropic virus type III (HTLV-III) indicate that the CMV titer in leukocytes increases as immune deficiency worsens. In ARC patients CMV viremia may be predictive of clinical complications in the next 3 months. In AIDS patients CMV viremia at high titer was an unfavorable prognostic sign.

Activated interferon system in healthy homosexual men

More than 50% of a group of healthy homosexuals in Israel were found to have an activated interferon (IFN) system as evidenced by markedly elevated blood IFN levels, increased in vitro production of IFN by unstimulated peripheral blood mononuclear cells and HuIFN-α and HuIFN-γ production by appropriately stimulated cells, and a surprisingly high incidence of an antiviral state of cells. This pattern resembles that found in persons with acute viral illness, and is unlike that found in normal healthy controls. The type of IFN in the blood was found to be unusual in that it was mainly HuIFN-α, pH 2-labile, a type of IFN found in certain collagen diseases as well as in homosexual men suffering from Kaposi's sarcoma or lymphadenopathy. Natural killer (NK) cytotoxic activity was found to be somewhat lower than that found in normal controls, although no correlation was found between blood IFN levels and NK activity. Mean (2′–5′)-oligoisoadenylate synthetase levels in cell extracts were intermediate between normal controls and patients with viral illness. Likewise no correlation was found between enzyme levels and blood IFN levels. The highly activated IFN system found in certain homosexuals, as well as the increased spontaneous production of IFN by unstimulated mononuclear cells, suggest the possibility of the presence of a virus, active or latent, in these individuals. This virus could be a retrovirus such as HTLV-III or LAV which have recently been isolated from AIDS patients. The special type of IFN present could be the response to a novel virus in an unusual situation. On the basis of recent reports, we speculate that homosexuals with highly activated IFN systems who produce pH 2-labile HuIFN-α could be at increased risk for developing AIDS.

HTLV-III-neutralizing antibodies in patients with AIDS and AIDS-related complex.

The isolation of the human T-cell leukaemia (lymphotropic) virus type III (HTLV-III or lymphadenopathy-associated virus) from cells of many patients with acquired immune deficiency syndrome (AIDS) presented the first evidence that the virus was the aetiological agent of the disease. Subsequent seroepidemiological studies have shown the presence of HTLV-III-specific antibodies in the serum of most patients with AIDS and AIDS-related complex (ARC), and in the serum of many individuals at risk for AIDS. Despite these extensive studies, there are no reports of protective effects of HTLV-III antibodies. In contrast, neutralizing antibodies specific for HTLV-I and -II have been identified previously. Therefore, we investigated whether HTLV-III-exposed individuals possess antibody activities capable of inhibiting viral infection. Here, we report that natural antibodies capable of neutralizing HTLV-III infection of H9 cells were detected in most adults AIDS and ARC patients but in no normal healthy heterosexual controls. Geometric mean antibody titres in ARC patients were double those in AIDS patients, and were even higher in two antibody-positive healthy homosexuals. This suggests that virus neutralizing antibodies may exert an in vivo protective effect. The presence of these antibodies indicates an immunological response to HTLV-III which potentially may be manipulated for therapeutic advantage. The methodology used here will be useful in monitoring future vaccine approaches.

Major glycoprotein antigens that induce antibodies in AIDS patients are encoded by HTLV-III.

Antibodies from the serum of patients with the acquired immune deficiency syndrome (AIDS) or with the AIDS-related complex and from the serum of seropositive healthy homosexuals, recognize two major glycoproteins in cells infected with human T-cell lymphotropic virus type III (HTLV III). These glycoproteins, gp160 and gp120, are encoded by the 2.5-kilobase open reading frame located in the 3' end of the HTLV-III genome, as determined by amino terminus sequence analysis of the radiolabeled forms of these proteins. It is hypothesized that gp160 and gp120 represent the major species of virus-encoded envelope gene products for HTLV-III.

β2-Microglobulin and the Acquired Immunodeficiency Syndrome in a Low-Incidence Area

To the Editor.— The study of Zolla-Pazner et al 1 is important in the search for useful clinical tests for diagnosis and management of persons at high risk for the acquired immunodeficiency syndrome (AIDS). They have demonstrated that β 2 -microglobulin (β 2 M) is a highly sensitive and specific test for AIDS and AIDS-like illnesses. Furthermore, they have shown it to be of prognostic value with six of seven healthy homosexuals with elevated levels progressing to some form of clinical disease. We would like to draw attention to the fact that sensitivity and specificity data, derived from areas where the incidence and prevalence of clinical and subclinical disease are high, may not be totally relevant in areas with a lower incidence and prevalence of clinical and subclinical disease. The northeastern Ohio area contains approximately 3.5 million people, and as of Jan 1,1984, has reported 15 cases of AIDS. From

Defective in vitro T cell colony formation in the acquired immunodeficiency syndrome.

Depressed T cell immunity is a universal characteristic of the acquired immunodeficiency syndrome (AIDS). In the present study, 25 patients with AIDS and opportunistic infections, 22 individuals with AIDS-related complex (ARC, or chronic lymphadenopathy syndrome), and 20 healthy homosexuals were evaluated by means of the T cell colony assay. Forty-seven healthy heterosexual controls showed an average of 3964 +/- 319 colonies/7.5 X 10(5) cells, with a range of 880 to 9340. The mean in the 20 healthy homosexuals (3173 +/- 483) did not differ significantly from the controls; in this group, only three patients had values less than 1000 colonies/plate. By contrast, all AIDS patients and 14 ARC patients had colony counts less than 1000. The mean value for the AIDS patients was only 24 +/- 15 (p less than 0.0005 compared with either controls or healthy homosexuals); values in the ARC group were intermediate (1180 +/- 360). The addition of interleukin 2 to the plates promoted correction of the proliferative abnormality in ARC patients. This interleukin increased colony scores in the AIDS group, but the mean value was still significantly less than controls. Comparison indicated that the colony assay is a more sensitive indicator for detecting proliferative abnormalities than responses to PHA, Con A, or pokeweed mitogen in suspension cultures.

Immunoglobulin subclasses of antibodies to human T-cell leukemia/lymphoma virus I-associated antigens in acquired immune deficiency syndrome and lymphadenopathy syndrome.

Immunoglobulin G (IgG) and IgM antibodies to human T-cell leukemia/lymphoma virus-I (HTLV-I)-associated membrane antigens (HTLV-I-MA) were assayed by indirect cytospin immunofluorescence, and IgG and IgM antibodies to purified HTLV-I were assayed by enzyme-linked immunosorbent assay in sera from 119 immunologically well-characterized promiscuous male homosexuals in The Netherlands, of whom 9 suffered from acquired immune deficiency syndrome (AIDS), 18 suffered from lymphadenopathy syndrome (LAS), and 5 suffered from gay bowel syndrome. Antibodies to HTLV-I-MA were present in four of nine AIDS patients, including one patient with antibodies to purified HTLV-I. Antibodies to HTLV-I-MA were present in 6 of 18 LAS patients, including 3 patients with antibodies to purified HTLV-I. Of five patients with gay bowel syndrome, one had IgG and IgM antibodies to HTLV-I-MA. Of the four HTLV-I seropositive AIDS patients, two had IgG and IgM antibodies to HTLV-I or HTLV-I-MA, one had only IgG antibodies, and one had only IgM antibodies. Of the six HTLV-I seropositive LAS patients, four had IgG and IgM antibodies to HTLV-I or HTLV-I-MA, and two had only IgM antibodies. In the sera from 27 healthy homosexuals with and 60 without T-cell subset imbalances, no antibodies to HTLV-I or HTLV-I-MA were detected.

Diminished interleukin 2 production and receptor generation characterize the acquired immunodeficiency syndrome

The Acquired Immunodeficiency Syndrome (AIDS) is a disease found primarily in homosexual men, consisting of opportunistic infections and tumors, and is due to an acquired T-cell defect. In the present report, we studied various T-cell functions which might serve to distinguish homosexuals with a symptom complex including lymphadenopathy from those with AIDS. T lymphocytes from the lymphadenopathy and AIDS patients had markedly depressed proliferative responses in the autologous (auto) and allogeneic (allo) mixed lymphocyte reaction (MLR) compared to healthy homosexuals or heterosexual controls ( P < 0.001). Since proliferation in the MLR depends upon interleukin 2 (IL-2), a T-cell growth factor, we studied the production of and response to IL-2 in various groups of homosexuals and heterosexual controls. IL-2 production was markedly depressed in the lymphadenopathy and AIDS patients, 1.0 and 0.1 U/ml, respectively, compared to the healthy homosexual or heterosexual controls, both 5.0 U/ml ( P < 0.05 and ifP < 0.01, respectively). Although the auto MLR of the lymphadenopathy patients rose to control values with the addition of exogenous IL-2, the auto MLR of the AIDS patients did not ( P < 0.01). This lack of responsiveness to IL-2 in the AIDS group was due to their inability to generate IL-2 receptors as shown by the absence of IL-2 absorption by activated cells and the absence of the Tac antigen (IL-2 receptor) on these same cells. The T4 + and T8 + T-cell subsets from the AIDS patients each demonstrated depressed IL-2 production and responsiveness following activation with autologous cells or mitogen, as well as the absence of Tac antigen. The diminished T-cell proliferation in the auto MLR in the lymphadenopathy group is associated with one defect, low IL-2 production, while the depressed proliferation in the AIDS group is associated with two defects, low IL-2 production and a lack of IL-2 receptor generation. These studies demonstrate that IL-2 receptor generation helps distinguish homosexuals with lymphadenopathy from those with AIDS, and that in addition to T-cell defects in the OKT4 + T-cell subset there are significant abnormalities in the OKT8 − T-cell subset in AIDS patients.