Clinical Stage Of HIV Infection Research Articles

Affinity of anti‐GP41 antibody in patients infected with human immunodeficiency virus type I

Anti-gp41 antibody affinity was investigated prospectively in 25 patients with asymptomatic and symptomatic HIV-1 infection for a period of 9-42 months. Major differences in the processes of immune response maturation towards gp41 were observed among individual subjects, however, antibody affinity increased with time in all examined persons including patients with AIDS. Anti-gp41 affinity values were found to reflect both the duration and the clinical stage of HIV infection.

Serological responses to mycoplasmas in HIV-infected and non-infected individuals.

To assess the frequency of mycoplasma infections in HIV-antibody-positive and -negative individuals by studying the serological responses against mycoplasmas, especially Mycoplasma fermentans and M. pirum. An enzyme-linked immunosorbent assay (ELISA) was used to measure immunoglobulin G (IgG) class antibody concentrations against six mycoplasma species in sera of HIV-positive and HIV-negative individuals. Serum samples were obtained from 30 HIV-positive individuals (10 asymptomatics, 10 with lymphadenopathy syndrome and 10 with AIDS), 10 HIV-negative partners of HIV-positive individuals and 40 HIV-negative blood donors. Antibodies to M. fermentans strains incognitus and PG18, M. pirum, M. genitalium, M. pneumoniae and M. hominis were assessed by immunoblot or ELISA. Absorbance values were taken as a semiquantitative measurement for antibody concentration and an arbitrary cut-off value (0.8) was set to establish seroprevalence. There was no significant difference in the mean IgG concentrations of any of the six mycoplasmas between HIV-positive and HIV-negative groups. Antibody concentrations were also similar in different clinical phases of HIV infection. Antibody concentrations to different mycoplasma strains were compared with each other to reveal eventual cross-reactions caused by shared antigens; the strongest correlation (r = 0.836) was found between M. fermentans strains incognitus and M. pirum antibody concentrations. The correlation between M. fermentans strains incognitus and PG18 was also significant but weaker (r = 0.522). No shared antigens between M. fermentans strain incognitus and M. pirum were demonstrated by immunoblot. Antibodies against M. fermentans type strain PG18, strain incognitus and against M. pirum are detected infrequently and their presence does not correlate with HIV infection per se or with the clinical stage of HIV infection.

HIV and the brain: Evidence of early involvement and progressive damage

AIDS is often accompanied by progressive encephalopathy and 'subcortical' dementia, but there is uncertainty regarding how early the brain involvement may begin in the course of HIV infection. This study used a cognitive auditory 'oddball' paradigm to elicit sensory and cognitive event related potential (ERP) components from healthy controls and from patients at different stages of HIV infection. Sensory component latencies did not differ between groups, but cognitive components showed progressive delays corresponding to increasingly severe clinical stages of HIV infection. The earliest changes were found among asymptomatic HIV + patients, suggesting that this test is a sensitive indicator of early subclinical CNS damage. In contrast, neither frequency analysis nor nonlinear dynamical analysis of the EEG showed differences between healthy controls and patients.

Anti-IgG Autoantibodies in HIV-Infected Hemophilia Patients

Sera of 76 HIV-negative hemophilia patients, 103 HIV-positive (HIV+) hemophilia patients free of AIDS or AIDS related complex (ARC), and 32 HIV+ hemophilia patients with AIDS/ARC were tested for four different anti-IgG activities. IgG-anti-F(ab')(2γ), IgM-anti-F(ab')(2γ), and IgG-anti-Fcγ serum activities were significantly associated with the clinical stage of HIV infection, whereas IgM-anti-Fcγ was not. IgG-anti-F(ab')(2γ) activity was found to be caused by cross-reaction of anti-HIV antibody with an epitope within the constant CH1 domain of human IgG. HIV+ hemophilia patients with severe thrombocytopenia (<50,000/µI platelet counts) had significantly higher IgM- anti-IgG activity than patients with >50,000/µI platelets. Because anti-IgG antibodies possess immunoregulatory properties, our results may serve as a possible explanation for the frequent B cell disorders encountered in HIV- infected patients.

Plasma viraemia as a marker of viral replication in HIV-infected individuals

Two hundred and twenty-eight blood samples from 154 HIV-seropositive subjects were investigated for the presence of HIV in peripheral blood mononuclear cells (PBMC) and plasma (without prior ultracentrifugation or filtration), using normal PBMC as the target for replication. HIV was recovered from PBMC and plasma in 80.5 and 19.5% of the patients, respectively. Plasma viraemia was significantly associated with clinical manifestations of HIV infection, indicating that HIV replication increased as disease progressed. This was confirmed by the statistically significant correlations between plasma viraemia and low CD4 cell counts (P less than 0.01) and low anti-p24 antibody titers (P less than 0.01). On patient follow-up, detection of HIV in plasma was transient. p24 antigenaemia was only detected in 13.6% of cases and was also associated with advanced clinical stages of the disease. When HIV RNA detection by polymerase chain reaction (PCR) was compared with plasma viraemia, HIV RNA was detected in plasma in all symptomatic cases and in 53.8% (seven out of 13) of asymptomatic patients [Centers for Disease Control (CDC) stages II and III], confirming that PCR was far more sensitive than plasma culture. These results indicate that cell-free virus production is associated with the clinical stage of HIV infection and may serve as a marker for disease progression. Detection of HIV RNA by PCR appears to be the most sensitive method to detect viraemia.

Severe Anemia Is an Important Negative Predictor for Survival with DisseminatedMycobacterium avium-intracellularein Acquired Immunodeficiency Syndrome

Disseminated Mycobacterium avium-intracellulare (MAI) in patients with the acquired immunodeficiency syndrome (AIDS) is usually unresponsive to antimycobacterial therapy. We examined clinical and laboratory characteristics of MAI organisms and their relationship to the length of survival. We studied factors influencing survival and compared these in 76 patients with AIDS with and without MAI. Serum levels of p24 antigen and erythropoietin, and CD4-positive helper T-lymphocytes in blood were assessed in 36 additional patients with various clinical stages of HIV infection. In patients with MAI infection, survival was significantly related only to total lymphocyte count, hematocrit, platelet count, and sex. Of these, hematocrit and total lymphocyte count were the only linear predictors of survival. Anemia was significantly more profound in patients with AIDS and MAI than in the other patients. This anemia in patients with MAI could not be ascribed to increased peripheral destruction of red cells, deficient nutritional factors, or erythropoietin production, HIV viral or bacterial load, or a general effect on other blood elements such as neutrophils or platelets. The influence of MAI on survival in patients with AIDS did depend upon whether the MAI occurred as an index infection or was preceded by other opportunistic infections. Patients with other preceding opportunistic infection lived for a much shorter duration from the time of diagnosis of MAI.

Human immunodeficiency virus infection and the intestine

HIV is a retrovirus infecting CD4-positive cells causing profound immunosuppression, eventually clinically manifest as AIDS. The cells principally infected by HIV are T4 lymphocytes (helper) and macrophages. The eventual loss of helper cell function is the prime reason for immunodeficiency which renders the individual susceptible to opportunistic infections. HIV infection was first described in male homosexuals. However, the trend now is for seroprevalence to rise rapidly in intravenous drug abusers in the West. In addition, African AIDS is thought to be almost exclusively heterosexual in nature, a paradox which is not yet fully explained in comparison with the relatively low but increasing incidence in heterosexuals in the Western world. Virtually every organ system in the body can be affected clinically during the course of HIV infection. The gastrointestinal tract is a major target, and the physiological sequelae are an important cause of morbidity and mortality. The pathophysiology of intestinal infection is not yet fully understood, however two main mechanisms have been postulated. The first is reduced intestinal immunity resulting in chronic opportunistic infections, which themselves cause altered intestinal function. The second is that HIV itself affects the intestinal mucosa, causing malfunction. The mechanisms by which the latter occurs are controversial but may result from either direct infection of mucosal epithelial cells or macrophages within the mucosa. Reports have documented the presence of HIV genome in both epithelial argentachromaffin cells and macrophages. In addition, profound degeneration of intrinsic jejunal autonomic neurones has been demonstrated, but the functional significance of such denervation is as yet unknown. The clinical stage of HIV infection at which intestinal mucosal immunity fails is by definition when opportunistic infection occurs (that is, clinical progression to stage IV disease), namely AIDS, however a detailed knowledge of the mechanisms of intestinal immune failure are lacking.

Susceptibility to HIV infection and AIDS in Italian haemophiliacs is HLA associated

We compared the frequencies of HLA antigens in two matched groups of 31 HIV-seronegative and 31 HIV-seropositive haemophiliacs, exposed during the years 1981-85 to comparable amounts and batches of presumably infectious clotting factor concentrates. The frequency of A2 was significantly higher in HIV-seropositive than in seronegative haemophiliacs, with a relative risk (RR) of seroconversion of 3.92, whereas both Bw52 and DR4 were negatively associated with it. We also studied the distribution of HLA antigens in a larger group of 76 HIV-seropositive haemophiliacs, who were at different clinical stages of HIV infection (CDC classes II-IV) but were comparable for age and time elapsed since seroconversion. DR3 and DQw2 antigens were, particularly when concomitantly present, associated with a high risk of developing symptomatic HIV infection (RR = 11.79 and 25.33). Our data suggest that the HLA region controls susceptibility to infection with HIV and its progression to symptomatic disease in Italian haemophiliacs.

Expansion of activated T lymphocytes (CD3+HLA/DR+) detectable in early stages of HIV-1 infection

The phenotypic characterization of lymphocyte subsets in relation to different clinical stages of HIV infection has mainly focussed on CD4 and CD8 cells. Some reports focus on expansion of activated T lymphocytes in AIDS patients. Yet there is no detailed knowledge whether such changes occur also in earlier stages of HIV infection. In order to describe the kinetics and possible pathogenetic meaning of this subset when related to all distinct chronologic stages, we performed two-color flow cytometric lymphocyte differentiation in 173 HIV-infected patients and 30 healthy controls. All subjects were classified according to the Walter Reed (WR) system. Our results show that a significant increase of activated T lymphocytes (CD3 + HLA/DR +) occurs early, in WR1 and WR2, thus preceding the clinically relevant CD4 depletion. This increase is paralleled by an expansion of CD8 + Leu7 + cytotoxic cells. We conclude, that early changes of lymphocyte subsets are detectable in addition to inversion of the CD4/CD8 ratio. The possible pathogenetic meaning including the question of possible autoimmune mechanisms is discussed.

Four Different Markers for Activated Cell Mediated Immunity Compared with the Clinical Stages of HIV Infection

Summary Activated cell-mediated immunity, as defined by four markers, has been studied in HIV-infected patients, and compared with the clinical stages of HIV infection. All the values obtained with such markers (interferon-y expressed on lymphocytes, soluble CD8, soluble IL-2 receptor, and serum neopterin) were observed to increase with the progressive stages of HIV infection, with the highest figures occurring in stage IV-C patients. Since the replication of HIV depend strictly on the stimulation of infected cells, T-cell activation in vitro might contribute to a further spread of HIV-1 in infected subjects. Thus permanent or multiple stimulation of the cellular immune system could be an important cofactor in the progression of this syndrome.

Plasma Viremia in Human Immunodeficiency Virus Infection

To determine which markers of human immunodeficiency virus type 1 (HIV) replication correlate most closely with progressive disease, we compared the following: (1) the frequency of isolation of HIV from peripheral-blood mononuclear cells (PBMC), (2) the frequency of isolation of the virus from cell-free plasma (plasma viremia), (3) the presence and titer of p24 antigen in plasma, and (4) the presence and titer of antibody to p24 antigen. We studied 213 persons who were positive for HIV antibody and 71 who were negative. HIV was isolated from PBMC from 207 of the 213 antibody-positive patients (97 percent), regardless of the clinical stage of the infection. Plasma viremia, in contrast, was correlated with the clinical stage of the infection. It was detected in 11 of 48 patients (23 percent) with asymptomatic infection, 32 of 71 (45 percent) in Class IVa of the Centers for Disease Control (those with AIDS-related complex), and 75 of 92 (82 percent) in Class IVc (those with AIDS) (P less than 0.01). Plasma HIV titers ranged from 10(0) to 10(4.3) and rose from a mean of 10(1.4) in asymptomatic patients to 10(2.5) in those with AIDS (P less than 0.02). Only 45 percent of patients with plasma viremia had HIV p24 antigen in either serum or plasma, and no correlation was found between the amount of p24 antigen in plasma and the plasma HIV titers. Follow-up tests indicated that plasma viremia was associated with a more marked decline in the CD4-lymphocyte cell count and the development of symptomatic disease (P = 0.034). We conclude that plasma viremia is a more sensitive virologic marker of the clinical stage of HIV infection and viral replication than the presence of p24 antigen or antibody in plasma. Not only whole blood but cell-free plasma from HIV-infected patients should be considered potentially infectious.

Characterization of GP120 binding to CD4 and an assay that measures ability of sera to inhibit this binding.

There is evidence that the initial interaction between HIV-1 and the host that is essential for infection is the specific binding of the viral envelope glycoprotein, gp120, to the CD4 molecule found on certain T cells and monocytes. Most individuals infected with HIV develop antibodies against the gp120 protein. Although in vitro treatment of CD4+ T cells with mAb to a specific epitope of the CD4 molecule (T4a) blocks virus binding, syncytia formation, and infectivity, it is unclear if antibodies to gp120 from an infected individual that can inhibit the binding of gp120 to CD4 is in any way related to the clinical course of disease. Our present study characterizes the binding of 125I-labeled rgp120 to CD4+ cells, and describes an assay system that measures a potentially relevant form of immunity to HIV infection, i.e., the blocking of HIV binding to CD4+ cells. Optimal binding conditions included a 2-h incubation at 22 degrees C, 4 x 10(6) CD4+ cells, and 1 nM gp120. The dissociation constant (KD) for gp120 binding to cell surface CD4 was 5 nM, and was inhibited by soluble CD4 and by mAb to T4a but not to T3 or T4. For the binding inhibition assay, negative controls included healthy seronegatives, seronegatives with connective tissue diseases, patients with HTLV-1 disease, and patients infected with HIV-2. In studying over 100 sera, the assay was highly sensitive (98%) and specific (100%). The majority of HIV+ sera could inhibit binding at dilutions of 1/100 to 1/1000. No correlation was noted between binding inhibition (BI) titer in this assay and clinical stage of HIV infection. In addition, there was no correlation between BI titer and HIV neutralizing activity. The BI titer was correlated with the titer of anti-gp160 (r = 0.63) and the titer of anti-gp120 (r = 0.52) antibodies determined by Western blot dilution. As with neutralizing antibodies and other forms of immune response to HIV, it is unclear what role antibody blocking of HIV binding to CD4+ cells may play in active immunity to HIV in infected individuals. This activity may prove to have some value in protection against initial HIV infection and, thus, the assay may be of use in monitoring vaccine trials.

High Prevalence of Serum Antibodies to Reverse Transcriptase in HIV-1-Infected Individuals

The HIV immunoblot profiles of 700 HIV-antibody-positive sera were examined to determine the frequency of antibody reactivity with p66/p51, the reverse transcriptase of HIV. We report a remarkably high seroprevalence of antibodies to p66/p51, detected in 79% of the sera. Only gp41 is recognized more frequently in these assays. The level of anti-p66/p51 seroreactivity varies only slightly among the clinical stages of HIV infection.