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There are increasing reports supporting a role for Epstein-Barr virus (EBV) in AIDS; EBV-DNA has been detected in lymphomas and other pathologic lesions, oral hairy leukoplakia and lymphocytic interstitial pneumonitis, found in these patients. The present study expanded on the possible contribution of EBV to the development of AIDS and related disorders by determining the viral load in these patients. The results were compared to those from two control groups.
Beta 2-microglobulin levels were measured in the cerebrospinal fluid (CSF) and serum of 163 human immunodeficiency virus-positive (HIV+) persons with normal neurologic physical examinations. None were on antiretroviral therapy. Only 3% had a positive CSF HIV p24 antigen test. The CSF beta 2-microglobulin levels increased as the CD4+ T cell count decreased. Intrathecal production of beta 2-microglobulin was suggested by finding CSF concentrations greater than serum concentrations in 15% of patients. The CSF beta 2-microglobulin levels rose as in vitro T helper cell function deteriorated, independent of CD4+ T cell count. CSF beta 2-microglobulin levels paralleled CSF IgG, IgG index, and IgG synthesis. Higher CSF beta 2-microglobulin levels were found in persons with positive CSF oligoclonal bands. CSF beta 2-microglobulin concentration may serve as a marker for subclinical neurologic damage due to HIV. If this is established, defining the effect of anti-HIV interventions on CSF beta 2-microglobulin would be warranted.
Lumbar punctures were done on 114 consecutive active duty patients referred for evaluation of positive tests for antibodies to the human immunodeficiency virus (HIV). Eighty-eight percent of these patients appeared to have early HIV infections, as evidenced by intact delayed hypersensitivity, T helper lymphocyte counts greater than 400/mm3, and lack of constitutional symptoms. Forty-four (38.6%) of the patients met our criteria for abnormal cerebrospinal fluid (CSF); another 13 (11.4%) had borderline elevations of nucleated cells or protein and could not be definitely classified as having normal or abnormal CSF. No significant differences existed between the patients with normal and abnormal CSF with regard to age; sex; race; serum FTA-Abs; clinical staging; absolute T helper lymphocyte counts; or cytomegalovirus, Toxoplasma, or Epstein-Barr virus serologies. Seventy-two percent of the patients with abnormal CSF had evidence of possible viral infection of the central nervous system (CNS), as evidenced by increased CSF IgG, increased IgG synthesis rates, or the presence of oligoclonal bands. We found that a significant percentage of asymptomatic patients with apparent early HIV infections have abnormal CSF that is possibly due to CNS involvement by HIV.
EDITOR-It would appear from the article by Krilov et al.[1], on antibody-mediated enhancement of respiratory syncytial virus (RSV) infection that the authors, and presumably the referees of the Journal, were unaware of an earlier publication from my colleagues and me [2] in this area.We demonstrated that human sera containing RSV-specific antibodies enhanced the in vitro infection
Objective: To evaluate the prognostic significance of cutaneous delayed-type hypersensitivity (DTH) skin testing in persons infected with HIV. Design: Cohort study. Setting: United States Air Force (USAF) Medical Center. Patients: Consecutive sample of 889 HIV-infected USAF personnel or dependents undergoing their first staging evaluation from 1985 through August 1990 in the USAF HIV Natural History Study. Measurements: All patients were evaluated with DTH skin testing including purified protein derivative and four control skin test antigens: mumps, candida, tetanus toxoid, and trichophyton. In addition, all patients underwent CD4+ T-cell surface marker determinations. The relation between DTH skin test response at first evaluation and progression to Walter Reed stage 6 (presence of an AIDS-defining opportunistic infection) was evaluated using Kaplan-Meier survival analysis. Results: Patients with more than 400 CD4+T cells/mm3 are more likely than those having fewer than 400 CD4+T cells per mm3 to respond to at least one (94% compared with 67%, P < 0.001) or at least two (86% compared with 45%, P < 0.001) DTH skin tests. Mean CD4 counts are lower for anergic compared with nonanergic patients and for patients responding to a single control skin test compared with those responding to two or more skin tests (P < 0.05). The DTH skin test response at first evaluation was also found to predict progression to AIDS; the relative risk at 5 years of follow-up was 2.5 (95% CI, 1.2 to 5.2) for anergy compared with a single positive skin test and 3.0 (CI, 1.4 to 6.2) for a single compared with two or more skin test responses. The DTH skin test response at first evaluation was a predictor of progression (P < 0.001) when controlling for initial CD4 count and Walter Reed stage in a Cox proportional-hazards regression analysis. Conclusions: The DTH skin test response, a functional measure of cellular immunity, is an independent predictor of progression to AIDS in persons with HIV.
Summary In this study, we asked whether there is a difference in the number of CD4+ and CD4− peripheral blood monocytes as CD4+ T cells decrease during HIV-mediated immunodeficiency. Monocytes and T cells from 90 HIV-positive and 43 HIV-negative persons were analyzed by flow cytometry. The 90 HIV-positive patients represented the entire spectrum of CD4+ T-cell counts. We report that as CD4+ T cells decrease, the number of CD4+ monocytes decrease in parallel. Moreover, significantly higher CD4+ monocyte counts were observed in persons with early stage HIV disease, i.e., >800 CD4+ T cells/mm3, than in HIV-negative persons with >800 CD4+ T cells/mm3. Potential implications of these findings are discussed.
In this study, we compared sera from 159 human immunodeficiency virus type 1 (HIV-1)-infected individuals from Tanzania and 103 infected individuals from the United States for antibodies reactive with 10 HIV-1 gp160 epitopes defined by synthetic peptides. Our data indicate that the anti-gp160 antibody fine specificity differs between infected individuals from these two geographically diverse populations. For example, 50% of the Tanzanian sera contained antibodies reactive with an immunodominant HIV-1 gp41 epitope defined by peptide 600-611, whereas 91% of the sera from the United States were reactive. Differences in serologic reactivity between HIV-1-infected individuals from Tanzania and the United States were also observed with gp160 epitopes defined by peptides 503-528 and 846-860. Included among the peptides examined were four which corresponded to the V3 region of gp120. The majority of sera from either country contained antibodies reactive with peptide RP142, whose V3 sequence is based upon that of HIV-1 isolate MN. Further characterization of serologic reactivity suggested that sera from Tanzania were more likely to neutralize HIV-1 isolate IIIB or MN in vitro than were sera from the United States. These differences in antibody fine specificity between HIV-1-infected individuals from Tanzania and the United States suggest that regional isolates of HIV-1 may exist.
This report summarizes the results of neurologic and cerebrospinal fluid (CSF) study findings in over 400 of the 649 human immunodeficiency virus-infected US Air Force personnel, evaluated as of Dec 31, 1987. Eighty percent of these patients were entirely asymptomatic and immunologically normal, 13% had low T-helper lymphocyte counts and/or cutaneous anergy, and only 7% had opportunistic infection. Sixty-three percent of all patients had some CSF abnormality. Sixty percent of the asymptomatic group had at least one abnormal result, over 25% had three or four CSF abnormalities, and over 7% had five or six abnormal values. When patients with evidence of blood-brain barrier leak were excluded, significant differences were seen between disease groups with regard to CSF glucose, CSF IgG levels, and CSF IgG synthesis. No human immunodeficiency virus-related central nervous system abnormalities were found on neurologic examination in immunologically intact asymptomatic patients regardless of CSF findings. No clear-cut predictor of impending central nervous system complications has, as yet, been identified from the CSF parameters studied.
