Serum P24 Antigen Research Articles

Changes of Soluble CD16 Levels in Serum of HIV-Infected Patients: Correlation with Clinical and Biologic Prognostic Factors

The modulation of soluble CD16 titers in human immunodeficiency virus (HIV)-infected patients' serum, with an initial increase in Centers for Disease Control (CDC) clinical stage II and III patients followed by a dramatic drop in patients with AIDS (CDC clinical stage IV), is reported. These changes are statistically correlated with the CDC staging system, the number of CD4+ cells, the amount of p24 antigen in serum, and the anti-p24 antibody titers, indicating the potential value of soluble CD16 titer as an easily available serum marker of disease progression. To evaluate a possible link between this observation and the expression of membrane-associated CD16/FcRIII, flow cytometry immunofluorescence analysis was performed on peripheral blood lymphocytes from patients in three CDC stages; no specific changes in the number of natural killer cells expressing CD16+ antigens or in the total number of Leu19+ cells were found. However, there was a statistical correlation between the absolute number of T cells expressing CD16 antigens (CD3+/CD16+) and the modulated titers of soluble CD16 in HIV-infected serum.

CD4 lymphocyte counts and serum p24 antigen of no diagnostic value in monitoring HIV-infected patients with pulmonary symptoms

The diagnostic value of the CD4 cell counts and the HIV p24 antigen were evaluated in a consecutive series of 105 HIV-infected patients experiencing 128 episodes of pulmonary symptoms which required bronchoscopy. One-third of patients with opportunistic infection (OI) had CD4 counts greater than 0.200 x 10(9)/l, and 60% of patients without OI had CD4 counts less than 0.200 x 10(9)/l; 47 and 42% of patients with and without OI, respectively, had detectable p24 antigen in serum. Only 36% of the patients with OI presented the combination of CD4 cells less than 0.200 x 10(9)/l and p24 in serum. In conclusion, the CD4 cell counts and the presence of p24 antigen in serum had a very limited predictive value for the presence of OI in HIV-infected patients with pulmonary symptoms.

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.

Two‐year evaluation of clinical and laboratory variables of immune function in 117 hemophiliacs seropositive or seronegative for HIV‐1

Fifty-nine HIV-1 antibody positive and 58 antibody negative hemophiliacs were evaluated over a 2 year study period to gain insight into the natural history and prognosis of HIV-1 disease in members of this risk group. Mean CD4 (Leu 3+) cell counts calculated at 6 month intervals decreased gradually in seropositive patients (from 403 to 311/microliters) whereas CD8 (Leu 2+) counts remained stable but above the normal range. CD4 cell counts correlated closely with advancing CDC clinical stage; CD8 numbers showed no such association, but were markedly lower in the six patients with overt AIDS. Serum P24 antigenemia was associated with low CD4 cell counts and with advanced clinical stage (58% of antigenemic and 14% of non-antigenemic seropositive patients were in stage IV). In addition to CD4 cell counts, significant reductions in Leu 11+ natural killer cell (NK) subsets and in Leu 3 + 8 - cells occurred in seropositive patients over the study period; Leu 2 + DR + cells increased significantly. When expressed as a percentage of lymphocytes, the reduction in Leu 19 + NK cells was also significant, as were the increases in Leu 4 + DR + cells and Leu 12 + 8 + B cells. In summary, declining CD4 cell numbers and percentages are valuable markers of progressive HIV-1 disease in hemophiliacs, but may not always accurately reflect the degree of disease activity. Progressive changes in additional variables such as serum P24 antigen, and numbers and percentages of NK cell subsets and (as AIDS supervenes) CD8 cell numbers, may allow more precise monitoring of HIV-1 disease. This will, in turn, facilitate the design of optimal individualized strategies for therapeutic intervention.

CD4 Counts as Predictors of Opportunistic Pneumonias in Human Immunodeficiency Virus (HIV) Infection

To determine if circulating CD4+ lymphocyte counts are predictive of specific infectious or neoplastic processes causing pulmonary dysfunction. Retrospective, consecutive sample study. Referral-based clinic and wards. We studied 100 patients infected with human immunodeficiency virus (HIV) who had had 119 episodes of pulmonary dysfunction within 60 days after CD4 lymphocyte determinations. Circulating CD4 counts were less than 0.200 X 10(9) cells/L (200 cells/mm3) before 46 of 49 episodes of pneumocystis pneumonia, 8 of 8 episodes of cytomegalovirus pneumonia, and 7 of 7 episodes and 19 of 21 episodes of infection with Cryptococcus neoformans and Mycobacterium avium-intracellulare, respectively. In contrast, circulating CD4 counts before episodes of nonspecific interstitial pneumonia were quite variable: Of 41 episodes, 11 occurred when CD4 counts were greater than 0.200 X 10(9) cells/L. The percent of circulating lymphocytes that were CD4+ had a predictive value equal to that of CD4 counts. Serum p24 antigen levels had no predictive value. Pneumocystis pneumonia, cytomegalovirus pneumonia, and pulmonary infection caused by C. neoformans or M. avium-intracellulare are unlikely to occur in HIV-infected patients who have had a CD4 count above 0.200 to 0.250 X 10(9) cells/L (200 to 250 cells/mm3) or a CD4 percent above 20% to 25% in the 60 days before pulmonary evaluation. Patients infected with HIV who have a CD4 count below 0.200 X 10(9) cells/L (or less than 20% CD4 cells) are especially likely to benefit from antipneumocystis prophylaxis.

Predictive Markers for the Acquired Immunodeficiency Syndrome (AIDS) in Hemophiliacs: Persistence of p24 Antigen and Low T4 Cell Count

To investigate the predictive value of assays for human immunodeficiency virus (HIV) p24 antigen, p24 antibody, and gp120 antibody compared with T4 cell counts. Prospective cohort selected from persons who had HIV-antibody seroconversion. Eighty-seven persons with hemophilia with an actuarial cumulative acquired immunodeficiency syndrome (AIDS) incidence of 26% (CI, 12% to 40%), 8 years after HIV-antibody seroconversion. None. Human immunodeficiency virus p24 antigen was detected in 8 of 74 (11%) of the patients without AIDS and 7 of 13 (54%) of the patients with AIDS. The 2-year actuarial incidence of AIDS was 24% (CI, 0% to 48%) after detection of p24 antigen, 16% (CI, 0% to 34%) after loss of p24 antibody, 20% (CI, 0% to 45%) after loss of gp120 antibody, 31% (CI, 15% to 47%) after a T4 count of less than 200 cells/microL, and 67% (CI, 31% to 100%) after a T4 count of less than 200 cells/microL among those patients positive for p24 antigen. Very low numbers of T4 and T8 lymphocytes, presence of p24 antigen in serum, and absence of p24 antibody all had some predictive value. However, only p24 antigen (relative hazard 6.0, P = 0.008) and T4 counts (relative hazard 5.3, P = 0.002 with T4 count less than 200 cells/microL) independently predicted AIDS up to 12 months before diagnosis. Strong predictors of AIDS are p24 antigenemia or low T4 counts. Detection of p24 antigen is highly specific and complementary to the greater sensitivity of low T4 counts. These findings have important implications regarding prognosis, counseling, and the planning of clinical trials.

Serum 2-Microglobulin Decreases in Patients with AIDS or ARC Treated with Azidothymidine

Abnormally elevated serum beta 2-microglobulin has been associated with progression of human immunodeficiency virus (HIV) disease and could reflect in vivo HIV activity. We prospectively studied the effect of azidothymidine therapy on serum beta 2-microglobulin concentration in 41 patients with AIDS or AIDS-related complex. Median beta 2-microglobulin concentration decreased from 4.02 mg/L before therapy to 3.73 mg/L at week 24 of therapy (P = .016). Individual changes in beta 2-microglobulin during azidothymidine therapy correlated with changes in serum HIV p24 antigen (Spearman, r = .42, P = .007). Also, in a randomized placebo-controlled study, median beta 2-microglobulin concentration decreased after 16 w of therapy in 5 azidothymidine-treated patients compared with levels in 7 placebo-treated controls (P = .05). Serum beta 2-microglobulin appears to be a sensitive marker for in vivo antiretroviral drug activity and may be a better marker than serum p24 antigen for early intervention trials involving antiretroviral agents.

Suppression of p24 antigen in sera from HIV-infected individuals with low-dose α-interferon and zidovudine

On the basis of the observations that HIV antigenaemia indicates a high risk of progression to AIDS and that zidovudine and alpha-interferon act synergistically against HIV replication in vitro, we performed a pilot trial including 12 HIV-infected asymptomatic patients with detectable p24 antigen in serum. The patients received low-dose lymphoblastoid alpha-interferon alone for 4 weeks followed by a combination of interferon and low-dose zidovudine for a further 16 weeks. The median p24 antigen level decreased significantly (P less than 0.01), the decrease being most pronounced at week 5. Decreases in haemoglobin and neutrophil counts were observed. Four patients required reduction of the zidovudine dose and three patients were transfused. In conclusion, the drug combination was capable of reducing the serum level of HIV p24 antigen and it was tolerated by the patients. Further studies are required to evaluate the clinical implications of these observations.

Circulating p24 Antigen Levels and Responses to Dideoxycytidine in Human Immunodeficiency Virus (HIV) Infections

To determine the safety and efficacy of dideoxycytidine in patients with the acquired immunodeficiency syndrome (AIDS) or advanced AIDS-related complex. A partially randomized phase I and II outpatient, dose-ranging study. Four university medical centers involving government-supported referral AIDS Clinical Trial Units. Sixty-one patients with AIDS or advanced AIDS-related complex and 100 pg/mL or more serum p24 antigen titers. Dideoxycytidine was administered orally at 0.06, 0.03, 0.01, or 0.005 mg/kg body weight every 4 hours for 3 to 6 months depending on tolerance and benefit. In patients receiving 0.06 and 0.03 mg/kg, diffuse erythematous rash, fever, and aphthous stomatitis occurred in the first weeks of therapy, but resolved later. Hematopoietic suppression was rare. Peripheral sensory neuropathy occurred in patients receiving 0.06 mg/kg and 0.03 mg/kg and improved after discontinuation of therapy. Serum p24 antigen fell significantly (P less than 0.01) from baseline entry values in most of these patients. The CD4 lymphocytes rose transiently at the 0.03 mg/kg dosage. At the 0.005 mg/kg dosage, skin rash, fever, and aphthous stomatitis were mild or absent. Peripheral neuropathy, which occurred in all patients receiving 0.01 mg/kg was less severe than at higher dosages. At the 0.005 mg/kg dosage, peripheral neuropathy was occasionally seen. Significant suppression of serum p24 antigen was seen in most patients with AIDS-related complex receiving 0.01 mg/kg and less frequently in patients receiving 0.005 mg/kg. Less toxic regimens of dideoxycytidine merit clinical assessment for advanced anti-human immunodeficiency virus-1 (HIV) infection. Several studies alternating dideoxycytidine and zidovudine are in progress.

Tubuloreticular inclusions in skin biopsies from patients with HIV infection

Skin biopsies obtained from apparently normal skin from 15 HIV infected patients and 6 anti-HIV negative patients were examined by electron microscopy. Tubuloreticular inclusions (TRI) were detected within the cytoplasm of capillary endothelial cells in 5/5 AIDS patients and in 2/5 patients with AIDS related conditions. Biopsies from 5 asymptomatic HIV positive patients and the 6 control subjects were without ultrastructural alterations. The occurrence of TRI was related to low numbers of CD 4+ lymphocytes. 5/7 patients with TRI had elevated serum interferon activity, and in all of the patients without TRI, interferon activity was below detection level. The occurrence of TRI was not dependent on the presence of free p24 antigen in serum. It is concluded that the occurrence of TRI in entothelial cells of skin capillaries is associated with late stages of HIV infection and this may indicate a generalization of this change.

Hemophiliacs With HIV Antibody Are Actively Infected

Cultures of peripheral blood mononuclear cells for human immunodeficiency virus type 1 (HIV-1) and assays for the p24 antigen were performed for a group of 75 unselected hemophiliacs to determine whether patients positive for HIV-1 antibody are actively infected rather than immunized by viral proteins in non-heat-treated factor VIII or IX concentrates. Fifty-six (75%) of the 75 hemophiliacs were antibody positive and 55 (98%) of the 56 with antibodies also had positive cultures. The one culture-negative individual had detectable HIV-1 proviral DNA sequences in three separate samples of peripheral blood mononuclear cell DNA, as detected by a polymerase chain reaction assay. Detection of serum p24 antigen and the time to development of a positive culture were significantly more frequent and shorter, respectively, in symptomatic vs asymptomatic patients. None of the 19 hemophiliacs negative for HIV-1 antibody had positive cultures, detectable p24 serum antigen, or symptoms of HIV-1 infection. Moreover, latent HIV-1 infection was not detected in 16 female sexual partners of hemophiliacs positive for HIV-1 antibody using Western blot testing, assays for p24 antigen, HIV-1 cultures, and polymerase chain reaction assays, despite repeated unprotected sexual exposure. We conclude that antibody-positive hemophiliacs have been actively infected by HIV-1 and that a long period of latent HIV-1 infection prior to overt seroconversion is unlikely.