Presence Of HIV Antigen Research Articles

HIV infection

At a satellite meeting prior to the International AIDS Meeting in Washington DC in July, a great deal of discussion was focused on finding a “cure” for HIV infection [1]. While this objective has been discussed at various times over the past decade, the real incentive for this goal comes from the encouraging findings with Timothy Brown, also known as the “Berlin patient.” This HIV-infected man received hematopoietic stem cells from an HLA-matched donor whose genome naturally lacked CCR5, the major receptor for HIV. Five years after two transplants, Mr. Brown appears to be cured of HIV as well as leukemia [2]. Although potentially infected with both a virus that requires CCR5 for entry and a small population of viruses that can infect cells by another receptor, no infectious virus can be recovered from his blood and other tissues. This finding includes biopsies from the brain, bowel, and lymph nodes. Certainly his “cure” encourages approaches that could mimic this achievement in all HIV-infected individuals.

Methods of using interleukin 2 to enhance HIV-specific immune responses.

Interleukin 2 (IL-2) in combination with highly active antiretroviral therapy (HAART) can significantly increase CD4+ T cell counts but does not improve HIV-specific T cell-mediated immune responses that are associated with the control of viral replication. To characterize the immunomodulatory activity of IL-2 in HIV-infected individuals we studied the virus-specific immune response (VIR) by intracellular cytokine expression (interferon gamma, IFN-gamma) after mimicking HIV rebound in peripheral blood mononuclear cells (PBMCs). We found that the whole virus used as HIV antigen was able to activate HIV-specific T cells in the presence of a low concentration (50 IU/ml) of IL-2. Interestingly, increasing concentrations of IL-2 (400 or 1000 IU/ml) in combination with the same amount of HIV doubled the number of HIV-specific T cells. These cells were functionally intact because all of the IFN-gamma-producing CD8+ T cells contained perforin, a marker for cytotoxic T lymphocytes (CTLs). Induction of HIV-specific immune responses by IL-2 was not detected in the absence of HIV antigen both in vitro and in patients treated with HAART, indicating that IL-2 can amplify HIV-specific T cells in the presence of HIV antigen. Therefore, a combination of IL-2 with either structured treatment interruption, which results in a controlled viral load rebound, or with therapeutic vaccination is expected to improve HIV-specific T cell-mediated immune responses.

Prognostic value of adenosine deaminase compared to other markers for progression to acquired immunodeficiency syndrome among intravenous drug users

This study was designed to determine the prognostic value of erythrocyte adenosine deaminase (ADA) as a possible indicator of progression to AIDS, and compare this with other known cellular and serological markers. At the end of a 3-year study, a cohort of 114 human immunodeficiency virus-1 (HIV-1) seropositive intravenous drug users (IVDUs) from the five different Center for Disease Control (CDC) groups was examined in order to estimate the prognostic relevance with respect to the progression to acquired immunodeficiency syndrome (AIDS) of each of the following markers at baseline value: number and percentage of CD4+ T cells, number of CD8+ T cells, CD4+/CD8+ ratio, IgA and beta 2 microglobulin and ADA levels, and the presence of HIV antigens. Moreover, 57 IVDUs belonging to II and III CDC groups were analyzed in a follow-up study at 6-month intervals, in order to evaluate and compare the behavior of each marker over time. The prognostic significance of each marker was assessed by computing the survival distribution and the Cox analysis in a multivariate model providing the set of markers with greatest predictive value. The levels of ADA and the CD4+/CD8+ ratio showed a linear association with disease staging, whereas beta 2 microglobulin and CD4+/CD8+ ratio were the best predictors for AIDS progression. A highly significant increase in ADA and beta 2 microglobulin was observed during follow-up. The results obtained among HIV-positive IVDUs clearly indicate that the erythrocyte ADA may be considered a reliable marker of the development of HIV infection from the intermediate stages of the disease onwards.(ABSTRACT TRUNCATED AT 250 WORDS)

HIV Antigen and DNA in AIDS Spinal Cords Correlate with Macrophage Infiltration but not with Vacuolar Myelopathy

Since the relationship between vacuolar myelopathy (VM) and HIV infection of the spinal cord is unclear, we studied 74 cases of VM in AIDS patients for associated spinal cord and brain diseases, the presence of HIV antigens (n = 54) and amplified DNA (n = 7) and serum levels of vitamin B12 and folic acid (n = 6). Necrosis of the medial F. gracilis was present in 14%, HIV myelitis in 9%, cytomegalovirus myelitis in 3% and microglial nodules in 16%. HIV-immunoreactive macrophages were encountered in 6% of VM cords; they were in regions of gracile tract necrosis in two and in monocytes and multinucleated cells in spinal gray matter in one. Amplified HIV DNA was detected in 50% of cords and 70% of dorsal root ganglia (DRG) of cases with moderate or severe VM and 63% of cords and 75% of DRG in AIDS cases without VM. Six of the eight spinal cords with HIV DNA contained macrophages whereas all cords without HIV DNA (n = 6) were normal or contained only rare macrophages. There was no association between VM and HIV myelitis or opportunistic infections of the CNS, but there was a close association with HIV encephalitis which occurred in 80% of severe VM, 33% of moderate VM and 17% of mild VM. Vitamin B12 and folic acid levels were normal or elevated in all six AIDS with VM as well as in 12 AIDS without VM; all had received prophylactic vitamin therapy prior to death.(ABSTRACT TRUNCATED AT 250 WORDS)

Activation of cytotoxic cells in hyperplastic lymph nodes from HIV-infected patients

Serine esterase B (SE B) is a protein contained in cytoplasmic granules of cytotoxic T lymphocytes and natural killer cells; SE B gene is transcribed upon activation of these cytotoxic cells. In order to show the in vivo interactions between HIV-infected cells and anti-HIV cytotoxic cells we analysed, by in situ hybridization, the expression of the SE B gene in eight hyperplastic lymph nodes from HIV-1-infected patients presenting with persistent generalized lymphadenopathy. We detected numerous cells expressing the SE B gene. The mean number of positive cells was 3.2 times higher in HIV lymph nodes than in six non-HIV hyperplastic lymph nodes studied in parallel (P less than 0.05). In control lymph nodes, the SE B gene was expressed only in interfollicular areas; virtually no cells expressed the SE B gene within follicles. In contrast, in HIV lymph nodes cells expressing the SE B gene were distributed either in interfollicular areas or within follicles. Expression of the SE B gene inside follicles was thus a specific feature of HIV lymph nodes (P less than 0.001) and was associated with the presence of HIV antigens and RNA at the same site. These results suggest that cytotoxic cells are activated in follicles of HIV lymph nodes and may be involved in the lysis of HIV-infected cells. Such a phenomenon may explain the development of follicle lysis, a specific feature of HIV lymph nodes. It may also inhibit the spreading of HIV infection.

Serological markers as prognostic criteria for the course of HIV infection

576 serum samples from 139 HIV infected patients were analyzed for the presence of HIV antigens, as well as anti-core, anti-env and neutralizing antibodies. The results were correlated with the clinical and immunological stages of the patients. While almost all sera were positive for anti-env antibodies, only two thirds of the same sera had antibodies to core proteins. The average antibody titres, particularly of anti-core antibodies, decreased with the onset of clinical symptoms. The presence of p24 antigen could be demonstrated in only 16% of the sera. A positive reaction for core antigen seemed to be correlated with the absence of anti-core antibodies. Env specific neutralizing antibodies were found to be present in all of the sera analyzed in the LC5-test with a maximum neutralizing capacity observed in sera from WR 4 patients. A useful serological marker must fulfil two criteria, namely positive reactivity in the majority of sera examined and a broad range of antibody titres. None of the above described parameters meet these demands. Here we describe the search for new antibody markers, for example antibodies directed against HIV regulatory proteins.

Intrathecal synthesis of anti-HIV antibodies in AIDS patients

We studied the production within the CNS of anti-HIV antibodies, of non-specific IgG, and the presence of HIV antigens in the serum and CSF of 28 HIV infected patients belonging to group IV in the Center for Disease Control classification. CSF and serum were diluted under optimal conditions to equalize their IgG content, to enable us to better interpret serum and CSF reactivity by means of Western blot and ELISA. Under these conditions, no patient displayed a limited immunological response profile in CSF as compared to serum. On the contrary, there was intrathecal synthesis (ITS) of anti HIV-antibodies in Western blot test in 21 patients for gp160 and ITS was demonstrable for env, gag, and pol products. ITS of anti-HIV antibodies occurred in 17 patients when measured by ELISA. ITS of non specific IgG and HIV-antigens in CSF were less frequent. A marked anti-HIV response is evident in the CSF-CNS compartment in the later phases of the HIV infection.

Independent clinical significance of HIV antigen determination and CD4 counts in anti-HIV positive patients.

HIV antigenemia was found in 52/243 HIV antibody positive individuals attending 2 AIDS-screening clinics, giving a prevalence of 13, 25 and 76% in CDC groups II, III and IV, respectively. No correlation was found to decreased CD4 lymphocyte values in the individual groups. HIV antigen therefore identified a separate subpopulation. For 138 asymptomatic patients followed prospectively both laboratory parameters predicted HIV-related events, the relative risk factor being 4 for low CD4 value and 6 for presence of HIV antigen. Individuals presenting with HIV antigen and decreased CD4 count all developed disease within 18 months, the relative risk factor being 24. Thus the 2 markers, when measured together, effectively separated asymptomatic HIV-infected patients into 1 of 3 risk categories.

HIV-serology and lymphocyte subsets in relation to therapy and clinical development in haemophiliacs.

389 Swedish patients with haemophilia A, B or von Willebrand's disease were examined for HIV-1 antibodies. T-cell subsets were measured in 260 of them. HIV-1 antibodies were found in 98 of these patients. Of the 199 patients with severe or moderate haemophilia A, 44% were seropositive. They had seroconverted between 1979 and 1983. HIV-1-seropositive patients had significantly decreased numbers of CD4 cells and increased numbers of CD8 cells. The seronegative haemophilia A patients had significantly increased numbers of CD8 cells. The T-cell subsets were followed for a median of 40 months in 73 seropositive patients. All groups of patients, at different clinical stages, showed decreasing numbers of CD4 cells. The most pronounced decrease was seen in the patients who developed AIDS, followed by the group which developed HIV-related signs or symptoms. HIV antigen in serum and antibody pattern in Western blot and ELISA were followed in 89 patients. HIV-1 antigen was present and p24 antibodies were lacking in 11% and 13% of asymptomatic subjects, in 13% and 20% of patients with persistent generalized lymphadenopathy, in 33% and 38% of patients with other HIV-related signs or symptoms and in 5/6 of the AIDS patients, respectively. In conclusion, the decrease of CD4 cells and the presence of HIV antigen and/or absence of p24 antibodies were found to be prognostic markers for HIV disease.