Tryptophan degradation in patients infected by human immunodeficiency virus

Tryptophan and kynurenine were measured retrospectively in sera of 11 male patients with advanced human immunodeficiency virus (HIV) infection (Walter Reed stages 4 and 6). Tryptophan levels are significantly reduced to less than 50% in patients with HIV infection and kynurenine levels significantly elevated when compared to sex and age matched controls. The decrease of tryptophan levels might contribute to neurologic symptoms often associated with HIV infection. Since interferon-gamma induces degradation of tryptophan via the kynurenine pathway, the present results may be consistent with enhanced endogenous production of interferon-gamma in advanced HIV infection.     

Polyamines in lymphocytes from patients infected by human immunodeficiency virus

Lymphocytes from patients with antibodies against the AIDS associated human immuno-deficiency virus (HIV-1) have elevated concentrations of polyamines. Spermidine and spermine are similar in amount in patients with Persistent Generalized Lymphadenopathy (PGL) and overt AIDS, while putrescine is much higher in the latter. Spermidine-acetyltransferase activity is also increased in lymphocytes from patients with PGL. Diamine-oxidase activity is decreased in serum of patients with PGL, but not in those with AIDS.     

Patterns of primary care of patients infected with human immunodeficiency virus.

To determine the patterns of care of patients infected with the human immunodeficiency virus (HIV), data from 2 sources were analyzed. Initial data obtained from the Washington State HIV/Acquired Immunodeficiency Syndrome (AIDS) Epidemiology Unit indicate that 46% of patients with class IV AIDS were seen by physicians who reported fewer than 5 patients with AIDS, and 68% of all Washington physicians who reported treating patients with AIDS have reported only 1 patient. Subsequent data obtained from a questionnaire distributed in 4 Northwest states suggest that 74% of primary care internists and 73% of family practitioners have some experience in caring for patients with HIV infection, but most of these physicians report fewer than 6 patients in the past 2 years. Although most providers seeing large numbers of HIV-infected patients in their practices were based in the region''s major metropolitan area, 59% of the internists and 55% of the family practitioners surveyed outside of the metropolitan area had seen at least 1 HIV-infected patient in their practices. These results suggest that primary care physicians with relatively little experience treating HIV infection are providing care for a large number of HIV-infected persons. Further study is needed to determine the extent and quality of care provided.     

A statistical characterization of consistent patterns of human immunodeficiency virus evolution within infected patients

Within-patient HIV populations evolve rapidly because of a high mutation rate, short generation time, and strong positive selection pressures. Previous studies have identified "consistent patterns" of viral sequence evolution. Just before HIV infection progresses to AIDS, evolution seems to slow markedly, and the genetic diversity of the viral population drops. This evolutionary slowdown could be caused either by a reduction in the average viral replication rate or because selection pressures weaken with the collapse of the immune system. The former hypothesis (which we denote "cellular exhaustion") predicts a simultaneous reduction in both synonymous and nonsynonymous evolution, whereas the latter hypothesis (denoted "immune relaxation") predicts that only nonsynonymous evolution will slow. In this paper, we present a set of statistical procedures for distinguishing between these alternative hypotheses using DNA sequences sampled over the course of infection. The first component is a new method for estimating evolutionary rates that takes advantage of the temporal information in longitudinal DNA sequence samples. Second, we develop a set of probability models for the analysis of evolutionary rates in HIV populations in vivo. Application of these models to both synonymous and nonsynonymous evolution affords a comparison of the cellular-exhaustion and immune-relaxation hypotheses. We apply the procedures to longitudinal data sets in which sequences of the env gene were sampled over the entire course of infection. Our analyses (1) statistically confirm that an evolutionary slowdown occurs late in infection, (2) strongly support the immune-relaxation hypothesis, and (3) indicate that the cessation of nonsynonymous evolution is associated with disease progression.     

Molecular characterization of human T-cell lymphotropic virus coinfecting human immunodeficiency virus 1 infected patients in the Amazon region of Brazil

The present work evaluated the epidemiology of human immunodeficiency virus 1/human T-cell lymphotropic virus (HIV-1/HTLV) coinfection in patients living in Belém (state of Pará) and Macapá (state of Amapá), two cities located in the Amazon region of Brazil. A total of 169 blood samples were collected. The sera were tested by enzyme-linked immunosorbent assay to determine the presence of antibodies anti-HTLV-1/2. Confirmation of infection and discrimination of HTLV types and subtypes was performed using a nested polymerase chain reaction targeting the pX and 5' LTR regions, followed by restriction fragment length polymorphism and sequencing analysis. The presence of anti-HTLV1/2 was detected in six patients from Belém. The amplification of the pX region followed by RFLP analysis, demonstrated the presence of HTLV-1 and HTLV-2 infections among two and four patients, respectively. Sequencing HTLV-1 5' LTR indicated that the virus is a member of the Cosmopolitan Group, Transcontinental subgroup. HTLV-2 strains isolated revealed a molecular profile of subtype HTLV-2c. These results are a reflex of the epidemiological features of HIV-1/HTLV-1/2 coinfection in the North region of Brazil, which is distinct from other Brazilian regions, as reported by previous studies.     

Cross-reactive T-helper responses in patients infected with different subtypes of human immunodeficiency virus type 1

Immunization with a recombinant glycoprotein 160 envelope immunogen derived from a virus of genetic subtype B induced strong specific T-helper cell responses in asymptomatic human immunodeficiency virus (HIV) carriers infected with subtypes B to G. This indicates that the HIV-specific T-helper immunity, which is the basis for development of antibodies and cytotoxic T lymphocytes, can be improved by both homologous and heterologous antigens. It also suggests that a particular immunogen can be effective against many different HIV strains.     

Immunological evaluation of human immunodeficiency virus infected individuals by flow cytometry

Human immunodeficiency virus (HIV) infection heavily compromises the immune system. The decrease of the T cell CD4+ subset along the evolution to acquired immunodeficiency syndrome has been considered as a hallmark of HIV infection. In this paper we review some aspects of the immunopathology of HIV infection and discuss the importance of the flow cytometry for the evaluation of the T lymphocyte subsets in the follow-up of HIV infected children and adults, and for the monitoring of the immune reconstitution upon antiretroviral therapy.     

Primary care physicians' refusal to care for patients infected with the human immunodeficiency virus.

We conducted a telephone survey of a random sample of office-based primary care physicians in Los Angeles County to determine their practice experiences with patients infected with the human immunodeficiency virus (HIV). Telephone interviews included questions related to the physicians'' experiences evaluating patients for HIV infection during the past 6 months and the presence of HIV-infected patients in their practices. Those without HIV-infected patients were asked if this was because they had not encountered such patients, because those patients had died, or because the physicians had chosen to refer these patients elsewhere or the patients had gone elsewhere for care. Of physicians who participated in the survey, 78% had evaluated a patient for HIV infection in the past 6 months; 34% were currently providing primary care for infected patients; and 36% had elected to refer HIV-infected patients elsewhere, or their patients had elected to find other physicians. In all, 48% of physicians in the sample had elected not to care for, or said they would not provide care for, patients with HIV infection. Among Los Angeles County primary care physicians, 36% have refused to provide continuing care for HIV-infected patients and another 12% indicated their unwillingness to do so should such patients present themselves for care. As of 1991, the reservoir of primary care physicians in Los Angeles not yet involved with but willing to care for HIV-infected patients is relatively small (15%).     

Rapid expression of human immunodeficiency virus following activation of latently infected cells

The host cell activation state impacts the nature of human immunodeficiency virus infection. Activated cells facilitate productive infections; quiescent cells enable the virus to enter a latent state, the major obstacle to viral clearance. We wanted to understand how these differences affected viral gene expression. In quiescent cells activated prior to infection, viral RNA was seen 12 h postinfection; when cells were stimulated postinfection, viral RNA was not seen until 36 h postinfection. Up-regulation of viral RNA in latently infected cells occurred within 2 h poststimulation. This hierarchy also held true for viral protein production. These results may explain the rapid reemergence of viremia following termination of therapy.     

Evaluation of cytotoxic T-lymphocyte responses in human and nonhuman primate subjects infected with human immunodeficiency virus type 1 or simian/human immunodeficiency virus

Cytotoxic T-lymphocyte (CTL) responses have been implicated as playing an important role in control of human immunodeficiency virus (HIV) infection. However, it is technically difficult to demonstrate CTL responses consistently in nonhuman primate and human subjects using traditional cytotoxicity assay methods. In this study, we systematically evaluated culture conditions that may affect the proliferation and expansion of CTL effector cells and presented a sensitive method for detection of cytotoxicity responses with bulk CTL cultures. We confirmed the sensitivity and specificity of this method by demonstration of vigorous CTL responses in a simian-HIV (SHIV)-infected rhesus macaque. The expansion of epitope-specific CTL effector cells was also measured quantitatively by CTL epitope-major histocompatibility complex tetramer complex staining. In addition, two new T-cell determinants in the SIV gag region are identified. Last, we showed the utility of this method for studying CTL responses in chimpanzee and human subjects.     

Abnormal sweat electrolytes in symptomatic human immunodeficiency virus infection in a child.

A 3 1/2 year old girl presented with failure to thrive and a five month history of diarrhoea and recurrent cough. The results of sweat sodium tests suggested a diagnosis of cystic fibrosis; but atypical organisms were found (Haemophilus influenzae, Candida albicans, but no Staphylococcus aureus), she failed to respond to treatment, and her sweat sodium concentrations fell in response to fludrocortisone. She also had hyperglobulinaemia, neutropenia, and reduced numbers of T4 lymphocytes, which prompted the performance of a test for antibody to human immunodeficiency virus (HIV). This proved positive, and she was treated with co-trimoxazole, zidovudine, and human immunoglobulin. Both parents and two siblings were also positive for HIV, though all had normal sweat sodium concentrations. Children with symptoms suggestive of cystic fibrosis but who also show atypical features, as in this case, should have their HIV state checked.     

Fuzzy modeling in symptomatic HIV virus infected population

This paper introduces a model for the evolution of positive HIV population and manifestation of AIDS (acquired immunideficiency syndrome). The focus is on the nature of the transference rate of HIV to AIDS. Expert knowledge indicates that the transference rate is uncertain and depends strongly on the viral load and the CD4+ level of the infected individuals. Here, we suggest to view the transference rate as a fuzzy set of the viral load and CD4+ level values. In this case the dynamic model results in a fuzzy model that preserves the biological meaning and nature of the transference rate λ. Its behavior fits the natural history of HIV infection reported in the medical science domain. The paper also includes a comparison between the fuzzy model and a classic Anderson’s model using data reported in the literature.     

A possible method for detecting T-lymphocytes infected by the human immunodeficiency virus

A radioimmune method of AIDS diagnostics is proposed. Diphenylhydantoin sodium (diphenine sodium) is used as haptene in a probe. It binds to the T-cell membrane and has nonspecific influence on the cell surface. As a result the HIV receptor is blocked.     

Activation of complement on the surface of cells infected by human immunodeficiency virus

Cells were infected with HIV-1 and tested for C activation using a flow cytometric assay for bound C3 fragments. HIV-infected H9 cells bound increased levels of C3 using normal human serum as a C source only after cells were first incubated with serum containing anti-HIV antibody. Uninfected H9 cells or infected cells incubated with HIV-antibody negative sera did not bind C3. Although C3 bound quickly and was maximal within 10 min, modulation of bound C3 was slow with about 50% loss after 4 h. C3 binding required specific anti-HIV antibody, was blocked by EGTA, and did not occur in C2-deficient serum suggesting that binding was via the classical pathway. The HTLV-1-infected MT-4 cell line also bound high levels of C3 after coinfection with HIV. C3 binding in HIV-infected MT4 cells was also mediated via the classical pathway because it was not observed in Mg-EGTA chelated or C2-deficient sera. However, this classical pathway activation appeared to be antibody independent because it was also detected in HIV-antibody negative serum and a-gamma-globulinemic serum. This indicates that coinfection with HTLV-1 and HIV-1 can produce novel C activating conditions. No cytotoxic effect of human C for antibody-treated HIV-infected cells was observed in a chromium release assay. However, rabbit C was cytotoxic for HIV-infected cells in the absence of anti-HIV antibodies. Our results suggest that C can be activated in vivo by infected cells via specific anti-HIV antibody. The resultant C3 deposition on infected cells could have profound effects on interaction with CR-bearing cells.     

Prevalence of GB virus type C in urban Americans infected with human immunodeficiency virus type 1

Human T-lymphotropic virus type 1 (HTLV-1) and HTLV-2 were among the first human retroviruses discovered in the early 1980's. The International Retrovirology Association is an organized effort that fostered the efforts of scientists and clinicians to form interdisciplinary groups to study this group of retroviruses and their related diseases. The Association promotes excellent science, patient education, and fosters the training of young scientists to promote "bench-to-bedside" research. The International Conference on Human Retrovirology: HTLV and Related Viruses sponsored by the Association supports clinicians and researchers in the exchange of research findings and stimulation of new research directions. This years conference will be held from June 22 to 25, in Montego Bay, Jamaica http://www.htlvconference.org.jm/. Since its inception in 1988, these conferences have provided a highly interactive forum for the global community of HTLV scientists. This is of particular importance as HTLV research enters its third decade and a new generation of scientists takes over this important work. Many of the scientists attending the meeting will be from developing countries where HTLV is endemic, consistent with the history of international collaborations that have characterized HTLV research. The International Conference on Human Retrovirology provides a unique opportunity for researchers of all disciplines interested in HTLV infections to meet their peers and to address the questions facing clinicians and scientists who study retroviruses, like HTLV.     

Hepatitis B virus exposure in human immunodeficiency virus seropositive Cuban patients

In order to estimate the prevalence of serological markers of exposure to Hepatitis B Virus (HBV), 295 subjects were selected at random from the National Registry of human immunodeficiency virus positive subjects. Evidence of exposure to HBV was defined as: testing Hepatitis B surface antigen (HBsAg) and anti-Hepatitis B core antigen (anti-HBc) positive or anti-HBc positive only. Overall, 133 (45.5%) were positive for anti-HBc and 15 (5.1%) resulted positive to HBsAg. Significant statistical association was found between male sex and exposure to HBV (p<0.01). Homosexual or bisexual behavior was found to be strongly associated to HBV exposure (p<0.001). In conclusion, the prevalence of HBV serological markers is higher in Cuban HIV positive subjects compared to the Cuban general population.     

Recommendations for fungal opportunistic infections prevention in persons infected with human immunodeficiency virus

Fungal infections have become important causes of morbidity and mortality in immunocompromised hosts, including those with the acquired immune deficiency syndrome (AIDS). Although significant therapeutic advances are being made in the field of antiretroviral therapy, parallel advances must be attained in the management of secondary infections, including those due to fungi. As increasing numbers of people with HIV infection come in to medical attention, the problem of fungal infections will also increase, requiring innovative approaches toward understanding the pathogenesis of these infections and developing new diagnostic and therapeutic modalities. A better understanding is required for the immunopathogenesis of fungal infections. Improved understanding of new and established antifungal agents in conjunction with ART agents as well as immune modulators, should yield important advances in prevention, control and treatment of fungal infections of HIV infected people.     

Development of AIDS in a chimpanzee infected with human immunodeficiency virus type 1.

The condition of a chimpanzee (C499) infected with three different isolates of human immunodeficiency virus type 1 (HIV-1) for over 10 years progressed to AIDS. Disease development in this animal was characterized by (i) a decline in CD4+ cells over the last 3 years; (ii) an increase in viral loads in plasma; (iii) the presence of a virus, termed HIV-1JC, which is cytopathic for chimpanzee peripheral blood mononuclear cells; and (iv) the presence of an opportunistic infection and blood dyscrasias. Genetic analysis of the V1-V2 region of the envelope gene of HIV-1JC showed that the virus present in C499 was significantly divergent from all inoculating viruses (> or = 16% divergent at the amino acid level) and was suggestive of a large quasispecies. Blood from C499 transfused into an uninfected chimpanzee (C455) induced a rapid and sustained CD4+-cell decline in the latter animal, concomitant with high plasma viral loads. These results show that HIV-1 can induce AIDS in chimpanzees and suggest that long-term passage of HIV-1 in chimpanzees can result in the development of a more pathogenic virus.