Human immunodeficiency virus (HIV) infection and arthritis

A variety of inflammatory arthritic conditions are observed in the setting of HIV infection. The epidemiology of these disorders is a point of current controversy, although it appears that several unique syndromes are clinically associated. The pathogenesis of these disorders remains unclear, but we hope that further work in this area will lend important insights into the mechanisms of both HIV-associated and non-HIV associated rheumatic disease. The overall management of such patients is based on recognizing the underlying HIV infection and the judicious use of antirheumatic drug therapy. Rheumatologists need to be aware of the natural history of HIV infection and its clinical manifestations.     

Live attenuated simian immunodeficiency virus (SIV)mac in macaques can induce protection against mucosal infection with SIVsm

OBJECTIVE: To investigate whether vaccination of macaques with attenuated simian immunodeficiency virus (SIV)macC8 could induce long-term protective immunity against rectal exposure to SIVsm and intravenous exposure to the more divergent HIV-2. DESIGN AND METHODS: Eight months after vaccination with live attenuated SIVmacC8, four cynomolgus monkeys were challenged with SIVsm intrarectally and another four vaccinated monkeys were challenged with HIV-2 intravenously. Sixteen months after SIVmacC8 vaccination, another two monkeys were challenged with SIVsm across the rectal mucosa. Two vaccinees shown to be protected against SIVsm were rechallenged 8 months after the first challenge. Ten naive animals were used as controls. Serum antigenaemia, virus isolation, antibody responses, cell-mediated immunity and CD4+ and CD8+ T-cell subpopulations were monitored. PCR-based assays were used to distinguish between virus populations. RESULTS: At the time of challenge, eight out of 10 vaccinees were PCR-positive for SIVmacC8 DNA but no virus could be isolated from peripheral blood mononuclear cells. After SIVsm challenge, three out of six vaccinees were repeatedly SIVsm PCR-negative. In one of the three infected monkeys, the challenge virus was initially suppressed but the monkey ultimately developed AIDS after increased replication of the pathogenic virus. Rechallenged monkeys remained protected. All HIV-2-challenged vaccinees became superinfected. All controls became infected with either SIVsm or HIV-2. At the time of challenge the vaccinees had neutralizing antibodies to SIVmac but no demonstrable cross-neutralizing antibodies to SIVsm or HIV-2. Titres of antigen-binding or neutralizing antibodies did not correlate with protection. Cytotoxic T-cell responses to SIV Gag/Pol and virus-specific T-cell proliferative responses were low. CONCLUSION: The live attenuated SIVmacC8 vaccine was able to induce long-term protection against heterologous intrarectal SIVsm challenge in a proportion of macaques but not against the more divergent HIV-2, which was given intravenously.     

Human immunodeficiency virus (HIV) antigen testing to detect HIV infection in female sex workers in Singapore

Human immunodeficiency virus (HIV) infection is characterised by seroconversion after a ?window? period of 2 to 3 months. After this period antibodies are usually detectable by screening tests (enzyme immunoassay or particle agglutination) confirmed by Western blot analysis. We studied 1000 newly enrolled female sex workers who had not been previously tested for HIV to assess the usefulness of HIV antigen testing to improve the efficacy of HIV infection detection. Blood was taken at enrollment for HIV antigen and HIV antibody testing. The Abbott HIVAG-1 test was used to detect antigen; antibody detection was by the Abbott recombinant HIV-1/HIV-2 3rd generation enzyme immunoassay (EIA) test, the Fujirebio Serodia-HIV particle agglutination (PA) test for screening, and the Diagnostic Biotechnology HIV Blot 2.2 Western blot (WB) test for antibody confirmation. Of the 1000 samples, 26 were positive for HIV antibody testing (26/26 for EIA, 25/25 for PA, 26/26 for WB), giving a prevalence rate of 2.6%, Of these 26 seropositive samples 1 was positive on HIV antigen testing. There were no samples which were antigen-positive and antibody-negative. HIV antigen testing does not add to increased efficacy of HIV detection among female sex workers in Singapore.     

Chemokine receptors in HIV-1 and SIV infection

Glucose-6-phosphatase (G6Pase) activity and the rate of glucose cycling are increased in islets from animal models of Type II (non-insulin-dependent) diabetes mellitus. Glucocorticoid treatment further stimulates these processes and inhibits glucose-induced insulin release. To determine whether these effects result from a direct action of glucocorticoids on the beta-cells, we used isolated islets. The islets were from transgenic mice overexpressing the glucocorticoid receptor in their beta-cells to increase the cells' sensitivity to glucocorticoid. Islets from transgenic and non-transgenic control mice utilized and oxidized the same amount of glucose. In contrast, islet G6Pase activity was 70 % higher, glucose cycling was increased threefold and insulin release was 30 % lower in islets from transgenic mice. Hepatic G6Pase activity was the same in transgenic and control mice. Dexamethasone administration increased G6Pase activity and glucose cycling and decreased insulin release in both transgenic and control mouse islets. We conclude that glucocorticoids stimulate islet G6Pase activity and glucose cycling by acting directly on the beta-cell. That activity may be linked to the inhibition of insulin release.     

New mechanisms of viral persistence in primary human immunodeficiency virus (HIV) infection

Viruses, including the Human Immunodeficiency Virus (HIV), have evolved multiple strategies to overcome host immune defenses, allowing them to persist in the host. Molecular and cellular approaches were simultaneously used to provide sensitive and unbiased delineation of the diversity and dynamics of the immune response, and to study the relative compartimentalization of HIV-specific CTL clones in patients undergoing primary HIV infection. This approach revealed that some HIV-specific CTL clones can be deleted in presence of high levels of antigen, a phenomenon analogous to high-dose tolerance or clonal exhaustion described in murine models of persistent viral infections. Also, HIV-specific CTL clones were found to accumulate preferentially in peripheral blood as compared to lymph nodes, even though the large majority of viral replication during primary HIV infection takes place within lymph nodes. These two mechanisms may decrease the effectiveness of the host cell-mediated immune responses, and favor the establishment of virus persistence during primary HIV infection.     

Depressive syndromes and symptoms in subjects with human immunodeficiency virus (HIV) infection

The association between the infection produced by the human immunodeficiency virus (HIV) and syndromal or subsyndromal depression has been the topic of several studies in recent years. The results of the WHO Neuropsychiatric AIDS Study, conducted in the five geographical areas predominantly affected by the HIV epidemic, suggest that the symptomatic stages of HIV infection are associated with an increased prevalence of depressive symptoms, and, at least in some contexts in which the spreading of the infection is more recent and the social rejection of HIV-seropositive subjects is harsher, may also be associated with an increased prevalence of a syndromal diagnosis of depression.     

Role of macrophages in the pathogenesis of human immunodeficiency virus (HIV) infection

There are a number of machanisms by which HIV-infected macrophages contribute to the pathogenesis of the Acquired Immunodeficiency Syndrome (AIDS). Macrophage-tropic strains of HIV are present at the time of infection, and persist throughout the course of infection, despite the emergence of T cell tropic quasispecies. As HIV causes chronic infection of macrophages with only minimal cytopathology, these cells can provide an important viral reservoir in HIV-infected persons. Macrophages are more susceptible to HIV infection than freshly isolated monocytes. HIV-infected macrophages can contribute to CD4 T lymphocyte depletion through a gp120-CD4 dependent fusion process with uninfected CD4-expressing T cells. Increasing data support the role of HIV-infected macrophages and microglia in the pathogenesis of HIV-related encephalopathy and AIDS-related dementia through the production of neurotoxins. HIV infection of macrophages in vitro results in impairment of many aspects of their function. Reduced phagocytic capacity for certain opportunistic pathogens, including Toxoplasma gondii and Candida albicans, may be responsible for reactivation of these pathogens in persons with advanced HIV infection, although the mechanisms underlying reactivation of infections and susceptibility to disease from new infections are likely to be multifactorial. Our studies showing defective phagocytosis and killing provide additional information that contribute to our understanding of the pathogenesis of AIDS. Studies of in vitro efficacy of potential antiretroviral therapies should be performed in both primary lymphocyte and monocyte cultures, given the importance of both of these cell populations to HIV pathogenesis and their differing biology.     

Mucosal antibody expression following rapid SIV(Mne) dissemination in intrarectally infected Macaca nemestrina

The early kinetics of antibody expression following transmucosal infection by SIV(Mne) were examined in several mucosal compartments in Macaca nemestrina. Five male-female pairs of macaques were inoculated intrarectally with SIV(Mne) E11S, a biological clone, and serially euthanized at 1, 2, 4, 8, and 12 weeks postinoculation. Plasma, tears, saliva, rectal secretions, and vaginal washes were collected serially and just prior to euthanasia. Both total and SIV-specific IgG and IgA levels were measured by immunoglobulin isotype-specific quantitative enzyme-linked immunosorbent assays (ELISAs), and were further examined by conventional and enhanced chemiluminescence (ECL) immunoblots. Virus coculture, polymerase chain reaction, and in situ hybridization assays revealed the systemic spread of virus as early as 1 week postinoculation in 8 of 10 animals. ECL immunoblots detected SIV-specific antibodies in mucosal samples collected 1 week postinoculation. The most dramatic increases in both total and SIV-specific IgA levels were detected in rectal secretion samples. In contrast, plasma and nonrectal mucosal samples from the same time points increased only slightly, suggesting that the most robust antibody response occurred at the portal of infection. Our results show that the SIV-infected macaque is an excellent model for studies designed to assess mucosal immune responses to primate lentivirus infections. Additional studies will assess the correlation between the antiviral protection afforded by candidate vaccines and mucosal antibody responses.     

Allergic diseases and infection with human immunodeficiency virus (HIV)-AIDS in pediatric patients

During an infection with human immunodeficiency virus (HIV) the immune system is deregulated, even before real immunodeficiency, lymphopenia and AIDS occur. The immunologic alterations that have been described are a differentiation of a T-lymphocyte subclass, Th1 to Th0. Immunologic stimulation of these Th0 cells afterwards, makes them mature into Th2 cells. This causes a imbalance between the Th1 and Th2 cells, in favor of the second group. The clinical expression of this imbalance is an elevated risk of HIV-seropositive patients for allergies and for autoimmune disease, specially those autoimmune disease in which the production of autoantibodies prevails. Sometimes of differential diagnosis with systemic lupus erythematosus is difficult. There has been describes a major prevalence of allergic diseases, especially allergic rhinitis, in adult patients infected by HIV. Reports in pediatric patients are still sporadic, and the prevalence of allergies in children infected with HIV-AIDS is unknown. Only after recognizing the allergic nature of some symptoms, the treatment will be complete, reducing morbidity and infectious complications.     

Bacteremia and fungemia in patients with advanced human immunodeficiency virus (HIV) infection in Taiwan

To understand the etiology and clinical outcome of bacterial and fungal sepsis in patients with advanced human immunodeficiency virus (HIV) infection in Taiwan, we conducted a prospective study of nonmycobacterial bacteremia and fungemia in HIV-infected patients with fever who were admitted to a university hospital in Taiwan during a 42-month period. Of 210 patients, 41 (19.5%) had a total of 52 episodes of sepsis due to nonmycobacterial bacteria or fungi, or both (15.5% of 336 episodes of fever). All but one patient had acquired immunodeficiency syndrome (AIDS), and the mean CD4 lymphocyte count was 29/microL (range, 0-321/microL). A total of 57 pathogens (39 bacteria and 18 fungi) were isolated from blood; polymicrobial sepsis due to both bacteria and fungi occurred in four episodes. Nontyphoid Salmonella (NTS) was the most common cause of community-acquired bacteremia (24/30, 80%). Staphylococcus aureus bacteremia was diagnosed in three episodes while Streptococcus pneumoniae bacteremia was found in only one. Cryptococcus neoformans was the most common cause of fungemia and was responsible for 12 episodes, while fungemia due to Penicillium marneffei and Histoplasma capsulatum, two emerging fungi in Taiwan, were diagnosed in four cases and one case, respectively. Nine episodes, eight of bacteremia and one of candidemia, were nosocomial. The overall in-hospital mortality was 29%, and nosocomial sepsis was associated with a higher mortality rate (56%, p = 0.02). The mean duration of survival after recovery from initial sepsis was 426 days. We conclude that NTS bacteremia was the most common cause of sepsis in patients with advanced HIV infection in Taiwan and clinicians caring for such patients should watch for emerging fungal infections. Nosocomial sepsis was associated with a high mortality rate. The mean survival duration after recovery from sepsis of our patients was short.     

Thrombocytopenia in HIV infection

Thrombocytopenia commonly occurs in individuals with HIV disease. However, profound thrombocytopenia, occurring in only 1.5% of cases, is relatively rare. The mechanisms of thrombocytopenia appear to be multifactorial: profound thrombocytopenia in HIV disease is related to an immune destruction either by antiplatelet antibodies or by immune complexes. In addition, a defect in platelet production is quite frequent both in immune thrombocytopenia (ITP) and in mild thrombocytopenia. This impaired platelet production may be due to an HIV infection of megakaryocytes that express a functional CD4 molecule. Treatment of HIV-associated thrombocytopenia is quite similar to that of non-HIV ITP. However, zidovudine increases the platelet count without correlation with its antiviral effect. In animal models and HIV patients, this enhancement of platelet count appears to be due to a stimulation of platelet production, the precise mechanism of which remains unknown. Splenectomy is as effective in severe HIV thrombocytopenia as in non-HIV ITP and has no significant adverse effects on HIV disease.     

Macroamylasemia in HIV infection

A case of macroamylasemia was seen in a 40-year-old HIV-positive bisexual male treated at the Fort Worth-Tarrant County Health Department (Ryan White Clinic). Macroamylasemia is a rare condition encountered sometimes in persons with HIV infection. Apart from the setting of HIV infection and acquired immunodeficiency syndrome, macroamylasemia is seen also in various conditions including liver disease, diabetes, cancer, malabsorption, and autoimmune disorders. Although this biochemical phenomenon requires no therapy, it should be considered in the differential diagnosis of patients who have persistently high levels of serum amylase and yet do not exhibit any clinical symptoms of pancreatitis or salivary gland inflammation.     

Risk for human immunodeficiency virus (HIV) infection among persons with severe mental illnesses

Individuals diagnosed with a severe mental illness are at significantly enhanced risk for infection with the human immunodeficiency virus (HIV). To better understand elevated seroprevalence in this population, we review the research literature that has investigated HIV-related risk behavior among adults who have a severe and persistent mental illness. This review indicates that 54%-74% of adults report that they have been sexually active in the last year with approximately one third reporting two or more partners. Among those who were sexually active, condom use was inconsistent. A significant minority (4%-35%) of adults also reported a history of injection drug use. Overall, the data indicate that the severely mentally ill engage regularly in practices known to involve increased risk for HIV transmission. We introduce and modify Fisher and Fisher's (1992) theoretical model to organize the possible determinants of HIV-related risk taking among severely mentally ill adults, and encourage use of this model in the design of behavioral epidemiological and risk reduction studies. We also identify several methodological challenges to HIV-related research, including problems associated with the use of self-report measures; diagnostic imprecision; and participant recruitment and retention.     

Toxoplasma gondii infection in advanced HIV infection

OBJECTIVE: To study Toxoplasma encephalitis (TE) in advanced HIV infection, including predictive factors, possible prophylactic regimens and impact on survival. DESIGN: Epidemiological analysis of data collected prospectively during the Alpha study, a double-blind, randomized clinical trial, comparing two doses of dideoxyinosine in patients with advanced HIV disease. PATIENTS: First episode of TE occurred in 75 out of 499 patients participating in the trial. METHODS: Kaplan-Meier estimates and semi-parametric Cox's model were used. RESULTS: A low CD4 cell count and a positive Toxoplasma serology were strongly predictive of the occurrence of TE. In patients with CD4 counts < 100 x 10(6)/l and a positive Toxoplasma serology at entry to the study, the 12-month TE incidence was 25.4%. Patients who were receiving at entry any of the following potentially antitoxoplasmic drugs: trimethoprim-sulphamethoxazole, pyrimethamine, dapsone, pyrimethamine-sulphadoxine or sulphadiazine, had a lower TE incidence than those who were not; 6.2 versus 18.8%, respectively (P < 0.001). The rate of survival 12 months after TE was 29.6%. Even after adjusting the major prognostic covariates, TE was predictive of death (P < 0.001; relative risk, 1.8). CONCLUSIONS: The high HIV incidence, morbidity and mortality in high-prevalence areas suggests that primary prophylaxis should be given in patients at high risk for toxoplasmic reactivation.