Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glutathione (GSH), a cysteine-containing tripeptide, is essential for the viability and function of virtually all cells. In vitro studies showing that low GSH levels both promote HIV expression and impair T cell function suggested a link between GSH depletion and HIV disease progression. Clinical studies presented here directly demonstrate that low GSH levels predict poor survival in otherwise indistinguishable HIV-infected subjects. Specifically, we show that GSH deficiency in CD4 T cells from such subjects is associated with markedly decreased survival 2-3 years after baseline data collection (Kaplan-Meier and logistic regression analyses, P < 0.0001 for both analyses). This finding, supported by evidence demonstrating that oral administration of the GSH prodrug N-acetylcysteine replenishes GSH in these subjects and suggesting that N-acetylcysteine administration can improve their survival, establishes GSH deficiency as a key determinant of survival in HIV disease. Further, it argues strongly that the unnecessary or excessive use of acetaminophen, alcohol, or other drugs known to deplete GSH should be avoided by HIV-infected individuals.
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PMID:Glutathione deficiency is associated with impaired survival in HIV disease. 905 Aug 88

Human herpesvirus-8 (HHV-8) has been detected in Kaposi's sarcoma (KS) lesions of all types (AIDS-related, classical and endemic), in body-cavity-based B-cell lymphomas (BCBLs) and in lesions of multicentric Castleman's disease (MCD). We have identified a major gamma-herpesvirus-divergent locus (DL-B) in HHV-8 DNA encoding several HHV-8 unique open reading frames (ORFs), including a homologue of interleukin-6 (IL-6) and two homologues of macrophage inflammatory protein MIP-1. We show that the HHV-8-encoded IL-6 homologue (vIL-6) shares functional properties with endogenous IL-6 proteins and that both vIL-6 and vMIP-1 transcripts are present at high levels following butyrate induction of an HHV-8' BCBL cell line. Low amounts of constitutive vIL-6, but not vMIP-1, mRNA were also detected. The presence of a functional IL-6 homologue encoded by HHV-8 may provide a mechanistic model for the hypothesized role of HHV-8 in KS, MCD and BCBL that involves the mitogenic effects of vIL-6 on surrounding cells. MIP-1 proteins may enhance these effects through the chemotactic recruitment of endogenous cytokine-producing cells into affected tissues and could potentially influence HIV disease progression in coinfected individuals through interactions with the HIV co-receptor CCR-5.
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PMID:Kaposi's sarcoma-associated human herpesvirus-8 encodes homologues of macrophage inflammatory protein-1 and interleukin-6. 905 55

Dual infection with HIV and hepatitis B virus (HBV) is not an uncommon feature. Immunity impairment due to HIV infection can be the cause of a higher rate of HBV replication with less intensive liver damage and less effective immune response to HBV. Many HIV-infected patients have an elevated level of circulating immune complexes (CIC) in serum, throughout all stages of illness evolution. The aim of our study was to estimate p24 and HBsAg content of CIC in dually infected patients, and the prevalence of major classes of complexed antibodies (IgM and IgG). We examined 146 samples of sera from 105 HIV positive patients of the Institute for Infectious and Tropical Diseases during 1992 and 1993. On those sera we performed p24Ag and HbsAg detection, with and without prior dissociation of CIC, we determined serum level of CIC and immunoglobulin classes IgM and IgG level in sera and in polyethilenglycol (PEG) precipitates of sera. Acid dissociation of immune complexes revealed a high proportion of HIV antigen positive sera in all stages of HIV disease progression. HbsAg in serum of HIV positive patients was also found coupled in immune complexes much more frequently than in the HIV negative control group. In many instances both antigens were simultaneously found coupled in CIC. Immune complexes detected have been shown to contain both IgM and IgG immunoglobulins, while IgM antibodies were associated to immune complexes in higher proportion than IgG, compared to total serum immunoglobulins.
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PMID:Antigen/antibody content of circulating immune complexes in HIV-infected patients. 909 Oct 62

A combination of three beta, or C-C, chemokines, as well as IL-16, have been shown to inhibit HIV replication in vitro. Cellular antiviral factor is a more potent agent, and acts on all HIV strains. All are mainly, but not exclusively, produced by CD8+ T cells, both in HIV+ and healthy subjects. We studied the production of these HIV-suppressive factors in patients with HIV infection at different stages of disease. No difference in production by PBMC stimulated with PHA has been observed in asymptomatic HIV+, long-term nonprogressors (LTnP), and AIDS patients. When T cell line supernatants from these three groups were studied, no significant difference was found for C-C chemokines or IL-16 production, and viral suppression. However, T cell clones from LTnP secreted higher levels of all three chemokines, IL-16, and exerted a stronger inhibition on HIV replication. CD8+ clones showed a higher production than CD4+ clones. These clones were able to produce all antiviral factors irrespective of the secretion of type 1 or type 2 cytokines. The antiviral activities were not correlated, implying that viral suppression did not depend solely on C-C chemokines or IL-16. We postulate that all factors are needed to prevent HIV disease progression.
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PMID:C-C chemokines, IL-16, and soluble antiviral factor activity are increased in cloned T cells from subjects with long-term nonprogressive HIV infection. 912 15

The use of DHEA for the treatment of AIDS shows some promise, although controlled trials have not been performed to evaluate its efficacy. Low serum concentrations of DHEA have been correlated with states of decreased immune function in humans, since concentrations are lowest in early childhood, late adulthood, and as HIV disease progresses. DHEA appears to possess immunomodulating effects, perhaps by enhancing the secretion of IL-2 from activated T cells as demonstrated in a murine model. A decline in DHEA concentrations, particularly when initially less than 2.01 micrograms/L, might also prove to be a predictor of HIV disease progression. It is also plausible that a decrease in DHEA concentrations can be used to predict a decline in overall health status. Although the role of DHEA in the treatment of AIDS has not yet been determined, the drug appears to show potential for clinical benefit that should be evaluated in large, randomized, controlled trials.
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PMID:The role of dehydroepiandrosterone in AIDS. 916 64

Based on 392 infected children enrolled in two European prospective studies of infants born to HIV-infected women, with similar standard protocols, HIV disease progression in the first 6 years of life is described, using the 1994 CDC paediatric HIV classification. Most children had developed minor (A) or moderately severe (B) illness in the first 4 years of life, although usually it was transient in nature. Progression to U.S. Centers for Disease Control and Prevention (CDC) group C disease or HIV-related death is an estimated 20% (95% confidence interval 16-24%) during the first year of life, and 4.7% (3.3-6.5%) per year thereafter, giving a cumulative incidence of 36% (30-43%) by 6 years. The mortality rate at 6 years is 26% (20-32%). Two thirds of the children alive at 6 years had only minor symptoms, and one third had a CD4+ cell distribution of > 25% despite previous clinical manifestations and a transient period of moderate immune deficiency. Differences in zidovudine monotherapy between the two cohorts were not associated with the mortality rate. However, the risk of severe bacterial infections was lower in the French cohort, in which the use of antibacterial prophylaxis was more common. The early, severe form of HIV disease affects approximately 20% of infants, and after 6 years 75% of infected children are still alive. This has important implications for health-care planning.
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PMID:Morbidity and mortality in European children vertically infected by HIV-1. The French Pediatric HIV Infection Study Group and European Collaborative Study. 917 Apr 19

This paper presents recommendations on the care of HIV infected adults based upon the authors' personal experience with close to 700 patients in a multiprofessional pilot center. This medical care has 5 main objectives: 1) Promotion of good health (through standard recommendation of hygiene, health habits and regular checkups); 2) prevention of infectious complications (through detection of latent pathogens, chemoprophylaxis, vaccination and avoidance of risky exposures); 3) Treatment of complications (mainly infectious, through early diagnosis and proper treatment); 4) Delay of HIV disease progression (through timely and properly chosen antiretroviral therapy); 5) Reduction of HIV infection spread from index case to others (through promotion of responsible behavior and avoidance of pregnancy and HIV exposure to others). Studies for evaluating global health and immunologic status and carriage of potential pathogens are discussed as well as the criteria and timing for chemoprophylaxis for tuberculosis and P carinii pneumonia (PCP). Algorithms for the management of major clinical syndromes are presented: Diarrhea (afebrile, mostly parasitic, versus febrile, frequently bacterial); Pneumonia (lobar mostly bacterial versus interstitial, frequently PCP especially if lymphopenic and not receiving PCP prophylaxis); Brain mass lesion (most commonly toxoplasmosis). Finally, the evaluation and diagnostic possibilities of febrile patients is presented, based upon the immunologic status and associated symptoms.
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PMID:[HIV infection: recommendations for the management of asymptomatic adults and of various clinical syndromes]. 919

In light of new evidence suggesting that maternal human immunodeficiency virus (HIV) infection produces at least a three-fold increase in the number of early spontaneous abortions, it is important to search for factors that may predispose to fetal wastage. Immunological factors are thought to play an important role in permitting the HLA-disparate fetus to continue to term, despite powerful maternal immune forces capable of rejection. In the context of a heightened incidence of spontaneous abortion in HIV infection, evidence is now accumulating that implicates an imbalance in immune factors in contributing to this fetal loss. Soluble immune factors, such as cytokines, have been suggested as contributing agents to recurrent spontaneous abortions. Inflammatory cytokines-interleukin 1beta, interleukin 6 and tumor necrosis factor alpha-have been measured in isolated placental trophoblastic cells in HIV-infected and non-infected pregnant women in an attempt to explore this hypothesis. These inflammatory cytokines and their messenger RNAs were significantly elevated before and after stimulation in HIV-infected women, supporting the belief that HIV-infected women present their fetuses a milieu of imbalanced immune factors capable of contributing to immunological rejection. In addition, these elevated inflammatory cytokine levels may contribute to HIV disease progression in fetuses by virtue of activation of HIV gene transcription factors similar to what has been demonstrated in in vitro systems. We therefore propose that HIV infection in pregnant women produces an altered state of certain soluble immune factors, which in concert with other immune factor abnormalities, such as loss of immune selection in the fetal thymus, predisposes the fetus to advanced HIV infection and possible spontaneous abortion.
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PMID:Role of placental cytokines and inflammation in vertical transmission of HIV infection. 924 Aug 55

The thymus is thought to play a major role in the immunopathogenesis of human immunodeficiency virus (HIV) infection, particularly in maternal-to-fetal HIV transmission. Characteristic lesions of the HIV-infected thymus include a prominent CD4+ CD8+ T lymphocyte depletion at the corticomedullary junction, the region of the thymus where immune selection occurs. At least threefold excess early spontaneous abortions were noted in a cohort of 124 HIV-infected pregnant women. In these 13 abortuses a very high rate (54%) of HIV vertical transmission was documented, with the thymus gland particularly affected. It is possible that the thymic insult in HIV-infected fetuses contributes to immune rejection of the fetus, possibly by an imbalance of maternal and fetal T1- and T2-type cytokines, known to be important in HIV disease progression. We propose, therefore, that the early spontaneous abortions occurring in HIV-infected pregnant women are due, at least in part, to abnormal immune forces created by HIV infection of the thymus.
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PMID:Early spontaneous abortions and fetal thymic abnormalities in maternal-to-fetal HIV infection. 924 Aug 60

Despite a decade of human immunodeficiency virus (HIV) seropositivity, a few individuals termed as long-term nonprogressors (LTNPs) maintain a stable CD4+ T-cell count for a period of time. The aim of this study was to establish, through the sequential determination of all known predictors of HIV disease, the proportion of such patients having stringent criteria of true long-term nonprogression. Among 249 individuals who were HIV-infected and prospectively followed up over a 10-year period (1985 to 1995), 12 having a CD4+ T-cell count greater than 500/microL (LTNP I group) and 9 having a CD4+ T-cell count less than 500 but stable over time (LTNP II group) after at least 10 years of infection without intervention of antiviral therapy, were studied over the entire follow-up period. The plasma HIV RNA copy number and the serum concentrations of p24 antigen, each anti-HIV antibody, neopterin, beta-2-microglobulin, Immunoglobulin (Ig) G and IgA were determined every 18 months over the study period. Cellular and plasma viremias were cross-sectionaly assayed in all 21 patients. Only two patients had strictly no marker of progression over the follow-up period. They were the only ones who had, over the 10-year period, a viral copy number too low to be detected. The other patients had a viral copy number higher than 400/mL at at least one visit and increasing over the follow-up period, and they evidenced one or more markers of virological or immunological deterioration. Cellular viremia was positive in all patients but two, while plasma viremia was negative in all but one. The population of individuals termed as LTNPs is not virologically and immunologically homogeneous. The majority present biological signs of HIV disease progression. A new pattern of true LTNP can be drawn through stringent criteria based on the whole known predictors. This pattern appears to be rare in HIV-positive population.
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PMID:Even individuals considered as long-term nonprogressors show biological signs of progression after 10 years of human immunodeficiency virus infection. 924 45


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