Absolute quantification of HTLV-1 basic leucine zipper factor (HBZ) protein and its plasma antibody in HTLV-1 infected individuals with different clinical status.

BACKGROUND: Human T cell leukemia virus type 1 (HTLV-1) basic leucine zipper factor (HBZ), which is encoded by a minus strand mRNA, is thought to play important roles in the development of adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). However, a comprehensive analysis of HBZ, including mRNA and protein expression, humoral immunoreactivity against HBZ, and HTLV-1 proviral load (PVL), in HTLV-1-infected individuals with different clinical status has not been reported previously. RESULTS: In this study, using novel monoclonal antibody-based in-house enzyme-linked immunosorbent assay systems, we report the absolute quantification of HBZ protein and its plasma antibody in clinical samples from HTLV-1-infected individuals with different clinical status. The data were compared to both HBZ mRNA levels and PVL. The results showed that plasma anti-HBZ antibody was detectable only in 10.4 % (5/48) of asymptomatic carriers (ACs), 10.8 % (13/120) of HAM/TSP patients, and 16.7 % (7/42) of ATL patients. HBZ protein was detected in three out of five patients with acute ATL, but was not detected in patients with HAM/TSP (0/10) or ACs (0/4). Thus, an antibody response to HBZ was not associated with the PVL or the expression of HBZ (both at the mRNA and protein levels) or the clinical status of the infection. CONCLUSIONS: The present results emphasize the extremely low expression and immunogenicity of HBZ in natural HTLV-1 infection. However, there is a possibility that the low but distinct expression of HBZ protein in PBMCs is associated with the survival of HTLV-1-infected cells and the development of ATL.

HTLV-2 APH-2 expression is correlated with proviral load but APH-2 does not promote lymphocytosis.

We recently discovered the antisense protein of human T-cell leukemia virus (HTLV) type 2 (APH-2), whose messenger RNA is encoded by the antisense strand of the HTLV-2 genome. We quantified proviral load, level of tax, and APH-2 in a series of blood samples obtained from a cohort of HTLV-2 carriers. We determined whether APH-2 promotes cell proliferation. APH-2 was detectable in most samples tested and was correlated with proviral load. APH-2 levels were not correlated with lymphocyte count in vivo, consistent with the inability of APH-2 to promote cell proliferation in vitro. APH-2 does not promote cell proliferation and does not cause lymphocytosis.

New strain of human T lymphotropic virus (HTLV) type 3 in a Pygmy from Cameroon with peculiar HTLV serologic results.

A search for human T lymphotropic virus (HTLV) types 1 and 2 and related viruses was performed by serological and molecular means on samples obtained from 421 adult villagers from the southern Cameroon forest areas. One individual (a 56-year-old Baka Pygmy hunter) was found to be HTLV-3 infected; however, there was a low proviral load in blood cells. Complete sequence analysis of this virus (HTLV-3Lobak18) indicated a close relationship to human HTLV-3Pyl43 and simian STLV-3CTO604 strains. Plasma samples from Lobak18, the HTLV-3 infected individual, exhibited a peculiar "HTLV-2-like" pattern on Western blot analysis and were serologically untypeable by line immunoassay. These results were different from those for the 2 previously reported HTLV-3 strains, raising questions about serological confirmation of infection with such retroviruses.

Diagnosis of feline leukaemia virus infection by semi-quantitative real-time polymerase chain reaction.

In this paper the design and use of a semi-quantitative real-time polymerase chain reaction assay (RT-PCR) for feline leukaemia virus (FeLV) provirus is described. Its performance is evaluated against established methods of FeLV diagnosis, including virus isolation and enzyme-linked immunoassay (ELISA) in a population of naturally infected cats. The RT-PCR assay is found to have both a high sensitivity (0.92) and specificity (0.99) when examined by expectation maximisation methods and is also able to detect a large number of cats with low FeLV proviral loads that were negative by other conventional test methods.

Detection of feline leukemia virus RNA in saliva from naturally infected cats and correlation of PCR results with those of current diagnostic methods.

A novel diagnostic test for feline leukemia virus (FeLV) RNA in saliva from naturally infected cats is described in this study. We evaluated different diagnostic tests and compared them with the widely used enzyme-linked immunosorbent assay (ELISA) for the detection of p27 in the diagnosis of FeLV. Blood samples from 445 cats were tested for the presence of provirus by real-time PCR and plasma and saliva specimens from those cats were tested for the presence of viral RNA by real-time reverse transcription (RT)-PCR and for the presence of p27 by ELISA. In comparison to conventional ELISA, the diagnostic sensitivity and specificity of the detection of salivary FeLV RNA by real-time RT-PCR were found to be 98.1 and 99.2%, respectively. Detection of viral RNA in saliva had a positive predictive value of 94.6% and a negative predictive value of 99.7%. The kappa value was 0.96, demonstrating an almost perfect agreement between both tests. Furthermore, we confirmed previous results showing that a number of cats which tested negative for the presence of p27 in plasma were in fact positive for the presence of DNA provirus in blood specimens (5.4%). However, 96.4% of these latently infected cats did not shed viral RNA in saliva; therefore, we assume that these cats are of relatively low clinical importance at the time of testing. This study shows considerable diagnostic value of the detection of saliva FeLV RNA in naturally infected cats. This new diagnostic method has advantages over the conventional ELISA, such as less invasive sample collection and no requirement for trained personnel.

Human foamy virus bel1 sequence in patients with autoimmune rheumatic diseases.

Since the association between human foamy virus (HFV) with rheumatic autoimmune diseases remains controversial, this study was designed to determine the relationship between HFV and systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), or progressive systemic sclerosis (PSS). The bel1 and Pol sequences of HFV were measured by reverse transcriptase-polymerase chain reaction (RT-PCR) in plasma and by PCR in peripheral blood mononuclear cells (PBMC) from patients with SLE, RA, and PSS. Antibodies against Bel1 and Pol were assessed by enzyme-linked immunosorbent assay. Active HFV infections were detected by a Bel1-responsive indicator cell line. The bel1 sequence was detected in the plasma (SLE 59, RA 32, and PSS 63%) and PBMC (SLE 54, RA 71, and PSS 57%). However, active HFV infection existed only in patients with the bel1 sequence in both plasma and PBMC. In SLE patients, antibodies against Bel1 (7.1%) and Pol (4.5%) were also detected. The results suggest a possible association between HFV infection and these autoimmune rheumatic diseases.

Demineralization for inactivation of infectious retrovirus in systemically infected cortical bone: in vitro and in vivo experimental studies.

BACKGROUND: Clinical and experimental studies have demonstrated viral transmission through the transplantation of fresh-frozen infected bone. While sterilization methods sufficient to inactivate the human immunodeficiency virus (HIV) have been shown to markedly alter osteoconductive and osteoinductive properties of bone allografts, the ability of a process for creating demineralized bone matrix to abrogate transmission of a retrovirus has not been investigated, to our knowledge. We hypothesized that a clinically accepted demineralization procedure would alter the nucleic acids of the feline leukemia virus (FeLV, a retrovirus with a structure and replication cycle similar to those of HIV), inactivating the virus in infected bone and rendering it noninfectious. METHODS: Bone infected with FeLV was demineralized with a method employed for creating demineralized bone matrix powder. The effects of demineralization on cellular and (pro)viral nucleic acids were examined with use of gel electrophoresis and quantitative polymerase chain reaction, respectively. To compare the infectivity of the demineralized bone matrix with that of mineralized bone particles in cell cultures and in animals in which they had been implanted, we measured FeLV p27 antigen and (pro)viral nucleic acids as well as antiviral antibodies. RESULTS: Demineralization of FeLV-infected bone appeared to inactivate the virus by degradation and fragmentation of the DNA, rendering it noninfectious in both in vitro and in vivo test systems. In contrast, untreated mineralized FeLV-infected bone contained intact nucleic acids and readily transmitted the virus in both test systems. CONCLUSIONS: The demineralization process inactivated infectious retrovirus in infected cortical bone, thereby preventing disease transmission.

Protection against oronasal challenge with virulent feline leukaemia virus lasts for at least 12 months following a primary course of immunisation with Leukocell 2 vaccine.

The duration of immunity provided by a feline leukemia virus (FeLV) vaccine, Leukocell 2, was determined. Kittens were vaccinated when 9 and 12 weeks of age and were challenged 12 months later with FeLV-A/Glasgow-1. An oronasal challenge protocol without corticosteroid enhancement was developed in order to induce a persistent viraemia in a high proportion of adult cats. Fourteen of 18 (80%) of the vaccinated cats challenged in this way remained non-viraemic while 9/15 (60%) of age-matched controls became persistently infected, a preventable fraction of 63%. This difference was statistically significant (P=0.038). For comparison, 10 of 12 (83%) 15-17-week-old kittens challenged in the same way became persistently infected, confirming the relative resistance of adult animals to FeLV. Tests for virus neutralising and anti-feline oncornavirus-associated cell membrane antigen (FOCMA) antibodies suggested that the former were more important than the latter in protection. Thus, Leukocell 2 protected a significant proportion of cats from FeLV challenge 1 year after primary vaccination as kittens.

Detection and characterization of porcine endogenous retrovirus in porcine plasma and porcine factor VIII.

The pig genome contains porcine endogenous retroviruses (PERVs) capable of infecting human cells. Detection of infectious retrovirus in porcine peripheral blood mononuclear cells and endothelial cells suggested to us that pig plasma is likely to contain PERV. Both PERV env sequences and viral reverse transcriptase (RT) activity were detected in all plasma samples isolated from four NIH minipigs. To detect infectious virus from plasma, we performed a culture assay using three cell lines of feline, swine, and human origin that had previously been shown to be permissive for PERV. Infectious virus was successfully cultured from all four NIH minipig plasmas on the swine cell line ST-IOWA. Using RT-PCR with env-specific primers, we could detect expression of PERV class C envelope in the supernatant of ST-IOWA cells that had been exposed to each pig plasma. We next examined a pig plasma derivative, Hyate:C (porcine factor VIII), and found evidence of PERV particles, since all six lots examined were positive for PERV RNA and RT activity. However, infectious virus could not be detected in clinical lots of Hyate:C, suggesting that the manufacturing process might reduce the load of infectious virus to levels below detectable limits of the assay. Detection of infectious virus in porcine plasma confirms and extends the previous findings that certain porcine cells express PERV when manipulated in vitro and clearly demonstrates that there are porcine cells that express infectious PERV constitutively in vivo.

Virus threshold determines disease in SIVsmmPBj14-infected macaques.

Simian immunodeficiency virus (SIV) variant SIVsmmPBj14 is unique in producing an acutely lethal enteropathic syndrome in pigtail macaques. To determine whether the nature of the PBj14 disease would be attenuated by decreasing virus input and to relate tissue virus burden to the severity of disease, we infected pigtail macaques with serial 10-fold doses of SIVsmmPBj14 clone bcl.3 spanning 10(-2) through 10(4)TCID50. The results revealed a strikingly narrow difference between minimum infectious and fatal disease-inducing doses and a close association between enteric lymphoid tissue virus burden and disease. All animals infected with as much as 10(4) TCID50 through as little as 100 TCID50 of virus died of the lethal PBj14 syndrome between 7 and 13 days postinfection. Animals receiving 10(-1) TCID50 became infected (PCR+) but did not develop clinical disease. Animals receiving 10(-2) TCID50 did not become infected. The clinical syndrome was surprisingly similar in all affected macaques, although the time to disease onset and total survival time increased slightly as virus input decreased from 10(4) to 10 degrees TCID50. Highest terminal virus loads in plasma, gut-associated lymphoid tissue (GALT), and lymph nodes and greatest lesion severity were attained at intermediate levels of virus input (10(1) to 10(2) TCID50), probably owing to optimal time for virus amplification in target tissues. The present study reinforces others on the PBj14 system, suggesting that once a threshold level of virus replication is attained in intestinal lymphoid tissues, the cascade of events precipitating the lethal PBj14 syndrome is triggered irreversibly.

Effect of complement consumption by cobra venom factor on the course of primary infection with simian immunodeficiency virus in rhesus monkeys.

Cobra venom factor (CVF)-induced consumption of complement proteins was used to investigate the role of complement in vivo in the immunopathogenesis of simian immunodeficiency virus of macaques (SIVmac) infection in rhesus monkeys. Repeated administration of CVF was shown to deplete complement to <5% of baseline hemolytic activity of serum complement for 10 days in a normal monkey. Three groups of SIVmac-infected animals were then evaluated: monkeys treated with CVF resulting in complement depletion from days -1 to 10 postinfection, monkeys treated with CVF resulting in complement depletion from days 10 to 21 postinfection, and control monkeys that received no CVF. CD8+ SIVmac-specific cytotoxic T lymphocyte (CTL) generation and CD4+ T lymphocyte depletion during primary infection were not affected by CVF treatment. Viral load, assessed by measurements of plasma p27gag antigen and viral RNA, was transiently higher during the first 4 weeks following infection in the CVF-treated monkeys and the subsequent clinical course in these treated animals was accelerated. These results suggest that complement proteins may participate in immune defense mechanisms that decrease virus replication following the initial burst of intense viremia during primary SIVmac infection. However, we cannot rule out that the observed increased virus replication was induced by immune activation resulting from the administration of a foreign antigen to these monkeys.

In vivo effects of thymostimulin treatment on monocyte polarization, dendritic cell clustering and serum p15E-like trans-membrane factors in operable head and neck squamous cell carcinoma patients.

Head and neck squamous cell carcinoma patients have been characterized by impairments in their cell-mediated immune system, particularly by decreased chemotactic function of monocytes and impairments in the function of the monocyte-derived dendritic cells (viz, a decreased capability to form cell "clusters"). These impairments are thought to be due to immunosuppressive factors of low molecular mass released by tumor, the so-called p15E-like factors. These suppressive effects of p15-like factors can be neutralized in vitro by thymic peptides, such as thymostimulin (TP1). In a randomized double-blind, placebo-controlled multicenter trial in the Netherlands, 41 patients with operable head and neck squamous cell carcinomas (HNSCC) were treated for 10 days prior to surgery with intramuscular TP1 in one of three dosages (0.5 mg/kg; 1.0 mg/kg or 2.0 mg/kg body weight) or treated with placebo. Assessment of monocyte chemotaxis, the capability of dendritic cells to form clusters and the presence of p15E-like low-molecular-mass factors (LMMFs) in serum was performed before TP1 treatment and on the day of surgery. Findings demonstrated that TP1 in a dose of 1.0 mg/kg and 2.0 mg/kg resulted in normalization of impaired monocyte chemotactic capability. Although the cluster capability of dendritic cells after TP1 treatment improved, values only reached statistical significance for the 0.5 mg/kg group. Serum p15E-like LMMF levels were not affected by TP1 treatment in any of the patient groups. Contrary to expectations we found no correlation between elevated immunosuppressive LMMFs and defective monocyte chemotaxis or cluster capability of dendritic cells. We conclude that treatment with TP1 can improve monocyte chemotaxis in HNSCC patients but an effect on the production of p15E-like factors by carcinoma cells could not be demonstrated.

Increased antiretroviral antibody reactivity in sera from a defined population of patients with systemic lupus erythematosus. Correlation with autoantibodies and clinical manifestations.

OBJECTIVE: The implied role of retroviruses in the pathogenesis of murine systemic lupus erythematosus (SLE) led us to study antiretroviral antibodies in a population-based SLE cohort. METHODS: Immunoassays using whole virus and synthetic peptides were performed on sera from 72 patients with SLE and 88 control subjects. RESULTS: Reactions with whole baboon endogenous virus occurred more frequently in patients with SLE, and correlated with the presence of anti-RNP and anti-Sm. Some retroviral env and gag peptides, several of which were similar to U1 small nuclear RNP, reacted more strongly in patients with SLE, and their presence was correlated with discoid rash, hematologic disorder, and other symptoms. CONCLUSION: These results provide circumstantial evidence for involvement of retroviruses in the pathogenesis of human SLE; further studies should be carried out using other techniques for measurement of retroviral expression.

The presence of immunosuppressive 'p15E-like' factors in the serum and urine of patients suffering from malign and benign breast tumours.

Certain types of tumours are capable of producing factors inhibiting mononuclear phagocyte chemotaxis which may contribute to defects in immunosurveillance. In head and neck cancer these factors are said to be related to the retroviral protein p15E. This study examines the presence of p15E-like factors in serum and urine of patients with malign and benign breast tumours. Thirty patients with breast cancer, 29 patients with benign breast masses, and 28 healthy controls were tested blindly with the monocyte polarization assay, using N-formyl-methionyl-leucylphenylalanine as chemo-attractant. The low molecular weight fractions prepared of sera of the malign tumour patients inhibited the monocyte polarization significantly (mean inhibition 34%, s.d. = 12) compared with those of benign tumour patients (15%, s.d. = 7) and of controls (14%, s.d. = 6). The observed inhibitory effects on the monocyte polarization could be compensated by MoAbs reactive to p15E-related antigens. The mean difference between the polarization inhibition with and without anti-p15E adsorption (the 'p15E-like factor-induced inhibition') was 25% (s.d. = 13) in the breast cancer group, compared with 7% (s.d. = 5) in the benign tumour patients and 5% (s.d. = 4) in the healthy control group. Surgical removal of the tumours resulted in a restoration of the monocyte polarization in 20/23 (87%) patients of the breast cancer group. Results testing preoperative urine samples correlated well with those of corresponding sera. These data give additional support to the concept that tumour-derived p15E-like factors are responsible for the inhibitory effect on monocyte chemotaxis in breast cancer patients, and that these factors can be found in serum as well as in urine.

Retroviral p15E-related serum factors and recurrence of head and neck cancer.

Surgical removal of head and neck squamous cell carcinoma (HNSCC) restores the defective monocyte polarization found in patients with HNSCC. Since HNSCC contain p15E-like low molecular weight factors < 25 kD (LMWF) capable of suppressing N-formyl-methionyl-leucylphenylalanine (fMLP)-induced monocyte polarization, it is likely that HNSCC removal eradicates the production site of p15E-like factors. This report describes a prospective follow-up study on the levels of bioactive p15E-like serum factors for a period of 2 years in nine patients with HNSCC who had no recurrence and 11 patients with HNSCC who showed residual or recurrent disease after treatment. In the group of patients without recurrent disease p15E-like bioactivity gradually decreased and eventually became negative. In patients with recurrent/residual disease p15E-like bioactivity remained high or even became positive before or at the time of diagnosing tumour recurrence. This study strongly supports the concept that HNSCC tumours are the production site of p15E-like immuno-suppressive factors and indicates that serum p15E-like factors may be used for future studies on early serum markers for recurrent/residual disease developing in the first year after treatment.

Defects in cellular immunity in chronic upper airway infections are associated with immunosuppressive retroviral p15E-like proteins.

Partial defects in cell-mediated immunity have been shown in patients with chronic purulent rhinosinusitis. These defects, ie, impaired delayed-type hypersensitivity (type IV) skin reactions on commensal microorganisms of the upper respiratory tract and impaired chemotactic responsiveness of monocytes, are associated with the presence of immunosuppressive retroviral p15E-like proteins in the serum of these patients. In this study, we tested whether partial defects in cellular immunity could also be demonstrated in other groups of patients with chronic upper airway infections. Therefore, three well-characterized groups of patients with chronic upper airway infections were investigated: (1) patients with primary ciliary dyskinesia, a congenital disorder of respiratory cilia, resulting in absence of mucociliary clearance and, as a consequence, in chronic respiratory infections; (2) patients with chronic rhinosinusitis, with normally functioning cilia and with nasal polyps; and (3) patients with chronic rhinosinusitis, with normally functioning cilia but without nasal polyps. Our results show that in all three groups, most patients (87%) had defects in cellular immunity associated with the presence of p15E-like proteins in their serum. These results indicate that during chronic infections of the upper respiratory tract, immunosuppressive retroviral p15E-like proteins are found, which are probably responsible for the partial immune defects found in these patients.

Defects in monocyte polarization and dendritic cell clustering in patients with Graves' disease. A putative role for a non-specific immunoregulatory factor related to retroviral p15E.

A depressed chemotactic responsiveness of monocytes and a depressed cluster capability of dendritic cells have been found in diseases such as chronic purulent infections of the respiratory tract and in various types of malignancies. These impairments in monocyte and dendritic cell function could be ascribed to the action of a low molecular weight factor (LMWF; less than 25 kDa) circulating in the serum of the patients. The factor, which seems to be a non-specific immunoregulatory factor, shares a structural homology with p15E, the capsular protein of murine and feline leukaemogenic retroviruses. In order to study the chemotactic responsiveness of monocytes and the cluster capability of dendritic cells of Graves' patients, monocytes were isolated from the peripheral blood and dendritic cells were prepared from these peripheral blood monocytes by exposure to metrizamide. Monocytes were studied for their chemotactic responsiveness measuring their capability to polarize (morphological changes determined by light microscopy) after stimulation with the chemoattractant fMLP. Dendritic cells were studied for their capability to form clusters with allogeneic lymphocytes. A defective fMLP-induced monocyte polarization was found (16 vs 37% in healthy controls), whereas the dendritic cells showed a defective clustering (60 clusters vs 151 clusters in healthy controls). The effect of fractions of less than 25 kDa prepared from the serum of Graves' patients on healthy donor monocytes and dendritic cells was studied to test the presence of p15E-like factors. The serum fractions had a significant inhibitory effect on monocyte polarization and dendritic cell clustering.(ABSTRACT TRUNCATED AT 250 WORDS)

Progression to AIDS in patients with lymphadenopathy or AIDS-related complex: reappraisal of risk and predictive factors.

PURPOSE: In 1985, we reported that acquired immunodeficiency syndrome (AIDS) developed in 14 of 81 (17%) men with generalized lymphadenopathy followed prospectively for an average of 13 months. The presence of oral thrush or constitutional symptoms, or both, or severely impaired T4+ cell responses to specific antigen (interferon-gamma production) accurately identified patients at immediate risk for AIDS. The purpose of the current report is to describe the progress of these 81 patients during the three and a half years since enrollment and to include new data on initial serum levels of beta 2 microglobulin and human immunodeficiency virus (HIV) p24 antigen. PATIENTS AND METHODS: The mean age of the 81 patients was 35.4 years; 79 were homosexuals and two were drug abusers. Immunologic testing was performed once at the time of enrollment in all patients. Seventy-seven of the 81 patients were seropositive for HIV antibody. Frozen samples of serum, also obtained at initial study, were assayed in 1988 for beta 2 microglobulin and HIV p24 antigen. The clinical status of patients was determined six, 14, and 36 months after enrollment was closed (June 1984) by either interview and examination or telephone contact with private physicians. RESULTS: After three and a half years of follow-up, 42 patients have developed AIDS, including (1) 77% who had had thrush or symptoms, or both, (2) 80% to 88% of those who originally demonstrated marked immunologic abnormalities (skin test anergy, less than 200 T4+ cells/mm3, T4/T8 cell ratio of less than 0.5, severely impaired interferon-gamma production [less than 25 U/mL], or elevated serum beta 2 microglobulin level [greater than 3.0 mg/L], and (3) 95% of patients with HIV p24 antigenemia. However, AIDS also developed in 51% of patients who had had more apparently benign initial manifestations (lymphadenopathy alone, herpes zoster), in 41% to 54% despite normal initial results for either T4+ cell number, interferon-gamma secretion, beta 2 microglobulin, or skin testing, and in 44% of those whose sera did not contain HIV antigen. CONCLUSION: These updated results demonstrate the remarkably poor prognosis of patients with generalized lymphadenopathy or AIDS-related complex irrespective of initial clinical, immunologic, and serologic findings, and suggest that essentially all such persons may be candidates for antiviral therapy.

Effect of azidothymidine (AZT) on P24 antigen levels in patients with AIDS-related complex and AIDS.

Circulating HIV P24 antigen levels at baseline and following AZT therapy were measured in 9 patients with ARC and 11 patients with AIDS. Eight of these patients had no detectable levels of P24. The P24 antigen levels in the remaining 12 patients decreased significantly after AZT treatment. Following discontinuation of AZT treatment in 2 patients, the P24 antigen levels went up. These results clearly demonstrate the efficacy of AZT in reducing P24 antigen levels in circulation.

[Neopterin--a prognostic marker in HIV infection]. / Neopterin--ein prognostischer Marker bei der HIV-Infektion.

28 HIV-infected persons (19 stadium II, 5 stadium III, 4 stadium IV) were investigated for CD4+ lymphocytes, HIV p24 core antigen and urinary neopterin. Monitoring the course of infection repeated estimations were done. Urinary neopterin was found elevated in 26 out of 28 infected people (p less than 0.001). There is an increase in urinary neopterin levels associated with clinical progression in the course of HIV-infection. An inverse correlation to CD4+ lymphocyte count exists. High levels of neopterin early indicate a clinical progression to disease, as well as a decrease of CD4+ lymphocytes below 0.4 or 0.2 Gpt/l, respectively, and a reappearance of HIV p24 core antigen. The course of 5 cases is presented. In HIV-infection urinary neopterin is a suitable marker of activity and progression.