Human Immunodeficiency (human + immunodeficiency)

Distribution by Scientific Domains
Distribution within Medical Sciences

Terms modified by Human Immunodeficiency

  • human immunodeficiency virus
  • human immunodeficiency virus immunodeficiency syndrome
  • human immunodeficiency virus infection
  • human immunodeficiency virus patient
  • human immunodeficiency virus testing
  • human immunodeficiency virus type

  • Selected Abstracts

    Human immunodeficiency virus-associated diffuse non-Hodgkin's lymphoma in Venezuelan patients: treatment with full-dose cyclophosphamide-doxorubicin-vincristine-prednisone without routine use of granulocyte-colony stimulating factor

    D.E. HERNÀNDEZ md, phd
    The routine use of granulocyte-colony stimulating factor (G-CSF) for 10 days during full-dose cyclophosphamide-doxorubicin-vincristine-prednisone (CHOP) chemotherapy in HIV-associated diffuse non-Hodgkin's lymphoma (NHL) patients is very expensive in developing countries. We treated 22 HIV-associated diffuse NHL patients with standard-dose CHOP and used G-CSF after an episode of febrile neutropenia until neutrophil count reached 1000/mm3. The clinical response was: complete response (36%), partial response (32%), stable disease (14%) and progression (18%). There were no toxicity-related deaths. Grade 3 or 4 neutropenia was observed in 16% of cycles, but only 8% were complicated with febrile neutropenia. Seventeen patients died (median survival 15 months; range 2,70). There are five patients alive (median survival 24+ months; range 17,36+). Our experience showed that we can treat HIV-related NHL patients with full-dose CHOP, achieve good responses and have an acceptable toxicity profile, with the use of G-CSF as needed. [source]

    Role of the pro-inflammatory cytokines TNF-, and IL-1, in HIV-associated dementia

    N. A. C. H. Brabers
    Abstract Human immunodeficiency virus-1 (HIV-1)-infected and immune-activated macrophages and microglia secrete neurotoxins. Two of these neurotoxins are the pro-inflammatory cytokines tumour necrosis factor-, (TNF-,) and interleukin-1, (IL-1,), which are thought to play a major role in inducing neuronal death. Both TNF-, and IL-1, increase the permeability of the blood,brain barrier, through which subsequently HIV-infected monocytes can enter the brain. They both induce over-stimulation of the NMDA-receptor via several pathways, resulting in a lethal neuronal increase in Ca2+ levels. Additionally, TNF-, co-operates with several other proinflammatory mediators to enhance their toxic effects. Although most research has focused on the neurotoxic effects of TNF-, and IL-1, in HAD, there is also evidence that these cytokines can be neuroprotective. In this paper the effect of TNF-, and IL-1, on neuronal life and death in HAD is discussed. [source]

    Human immunodeficiency virus-associated progressive multifocal leucoencephalopathy: epidemiology and predictive factors for prolonged survival

    A. K. Drake
    We performed a retrospective review of cases of human immunodeficiency virus-associated progressive multifocal leucoencephalopathy in four hospitals (three in Australia and one in Hong Kong) between 1987 and 2003 in order to describe the local experience with this disease and to evaluate parameters impacting upon survival. Eighty-seven cases were identified and demographic details, baseline parameters and treatment methods and response were described. Survival was substantially increased in the post-highly active antiretroviral therapy (HAART) era with a median survival increase from 14 to 64 weeks. On multivariate analysis, variables associated with prolonged survival included a CD4 count of >100 cells/,l at diagnosis and the use of HAART post-diagnosis, with no significant additional advantage from the use of neuroactive antiretrovirals. [source]

    Change in pattern of skin disease in Kaduna, north-central Nigeria

    Husain Yahya MSc
    Background, We report our experience on the pattern of skin disease in Kaduna, north-central Nigeria over a 6-year period, and compare it with a similar survey conducted in the same area 30 years ago and with surveys from Nigeria and from other parts of Africa. Methods, The medical records of new patients attending the dermatology outpatient clinics of Barau Dikko Specialist Hospital and Habbat Medical Center from March 2000 to December 2005 were retrieved. Demographic data (age and sex) and the diagnoses of skin disease were extracted and analyzed. Results, A total of 5982 cases was seen. Forty-nine per cent were males and 51% were females. One-third of the patients were aged under 20 years, and three quarters were aged below 40 years. Eczematous dermatitis was the most common skin disorder seen, making up 35% of cases, and had replaced dermatophyte infections and scabies, which were the most dominant skin diseases 30 years previously (now constituting 6% and 1.4% of cases, respectively). Atopic dermatitis had more than doubled in frequency (13.8% vs. 5.2%), and contact dermatitis had tripled in frequency (5.8% vs. 1.8%). Acne vulgaris (6.7%), pigmentary disorders (3.9%), urticaria (3.6%), papular urticaria (3.6%), hair disorders (3.3%), lichen simplex chronicus (3%), viral warts (2.9%), and drug eruptions (2.7%) had also increased. Human immunodeficiency virus-related skin disease constituted 4.3% of cases, with pruritic papular eruption being the most common condition. Conclusion, These changes in skin disease can be attributed mainly to an increase in urbanization and improved socio-economic conditions. [source]

    Human immunodeficiency virus-associated neurocognitive disorders: Mind the gap

    ANNALS OF NEUROLOGY, Issue 6 2010
    Justin C. McArthur MBBS
    Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HANDs) remain among the most common disorders in people infected with HIV, even in an era when potent antiretroviral therapy is widely deployed. This review discusses the clinical features of HANDs and the implications for more effective treatment. With the improved survival of individuals treated with antiretrovirals, comorbid conditions are increasingly salient, including particularly coinfection with hepatitis C and the effects of aging. This review attempts to answer why there appears to be a therapeutic gap between the salutary effects of antiretroviral regimens and normalization of neurological function. A second gap is found in the understanding of the pathophysiology of HANDs. This review addresses this and discusses the animal models that have helped to elucidate these mechanisms. Although triggered by productive HIV infection of brain macrophages, aberrant and sustained immune activation appears to play a major role in inducing HANDs, and may explain the often incomplete neurological response to highly active antiretroviral therapy. Novel therapies aimed at persistent central nervous system inflammation will be needed to close this gap. ANN NEUROL 2010;67:699,714 [source]

    Clade-specific differences in neurotoxicity of human immunodeficiency virus-1 B and C Tat of human neurons: significance of dicysteine C30C31 motif

    ANNALS OF NEUROLOGY, Issue 3 2008
    Mamata Mishra MPhil
    Objective Human immunodeficiency virus-1 (HIV-1) causes mild to severe cognitive impairment and dementia. The transactivator viral protein, Tat, is implicated in neuronal death responsible for neurological deficits. Several clades of HIV-1 are unequally distributed globally, of which HIV-1 B and C together account for the majority of the viral infections. HIV-1,related neurological deficits appear to be most common in clade B, but not clade C prevalent areas. Whether clade-specific differences translate to varied neuropathogenesis is not known, and this uncertainty warrants an immediate investigation into neurotoxicity on human neurons of Tat derived from different viral clades Methods We used human fetal central nervous system progenitor cell,derived astrocytes and neurons to investigate effects of B- and C-Tat on neuronal cell death, chemokine secretion, oxidative stress, and mitochondrial membrane depolarization by direct and indirect damage to human neurons. We used isogenic variants of Tat to gain insights into the role of the dicysteine motif (C30C31) for neurotoxic potential of Tat Results Our results suggest clade-specific functional differences in Tat-induced apoptosis in primary human neurons. This study demonstrates that C-Tat is relatively less neurotoxic compared with B-Tat, probably as a result of alteration in the dicysteine motif within the neurotoxic region of B-Tat Interpretation This study provides important insights into differential neurotoxic properties of B- and C-Tat, and offers a basis for distinct differences in degree of HIV-1,associated neurological deficits observed in patients in India. Additional studies with patient samples are necessary to validate these findings. Ann Neurol 2007 [source]

    Highly Purified 1000-cSt Silicone Oil for Treatment of Human Immunodeficiency Virus-Associated Facial Lipoatrophy: An Open Pilot Trial

    Derek H. Jones MD
    Background. Among human immunodeficiency virus-infected individuals, facial lipoatrophy has become epidemic. Those affected are stigmatized, leading to psychological distress, social and career impediments, and impaired compliance to human immunodeficiency virus medications. Temporary treatment options are limited by excessive cost, necessity of frequent treatments, and lack of a natural look or feel beneath the skin. Affected patients require more persistent, affordable, safe, and effective treatment options. Objective. The objective was to evaluate the safety and efficacy of highly purified 1000-cSt silicone oil injected by microdroplet serial puncture technique for the treatment of human immunodeficiency virus-associated lipoatrophy. Methods. Data on 77 patients with a complete correction were analyzed to determine the number of treatments, amount of silicone, and time required to reach complete correction, relative to initial severity. Results. The volume of silicone, number of treatments, and time required to reach a complete correction were directly related to initial severity of lipoatrophy (p < 0.0001). Supple, even facial contours were routinely restored, with all patients tolerating treatments well. No adverse events were noted. Conclusion. In this pilot trial, we have demonstrated that highly purified 1000-cSt silicone oil is a safe and effective treatment option for human immunodeficiency virus facial lipoatrophy. Longer-term safety and efficacy in human immunodeficiency virus patients remain to be proven. [source]

    Intrastriatal administration of human immunodeficiency virus-1 glycoprotein 120 reduces glial cell-line derived neurotrophic factor levels and causes apoptosis in the substantia nigra

    Rachel L. Nosheny
    Abstract Uninfected neurons of the substantia nigra (SN) degenerate in human immunodeficiency virus (HIV)-positive patients through an unknown etiology. The HIV envelope glycoprotein 120 (gp120) causes apoptotic neuronal cell death in the rodent striatum, but its primary neurotoxic mechanism is still under investigation. Previous studies have shown that gp120 causes neurotoxicity in the rat striatum by reducing brain-derived neurotrophic factor (BDNF). Because glial cell line-derived neurotrophic factor (GDNF) and BDNF are neurotrophic factors crucial for the survival of dopaminergic neurons of the SN, we investigated whether gp120 reduces GDNF and BDNF levels concomitantly to induce apoptosis. Rats received a microinjection of gp120 or vehicle into the striatum and were sacrificed at various time intervals. GDNF but not BDNF immunoreactivity was decreased in the SN by 4 days in gp120-treated rats. In these animals, a significant increase in the number of caspase-3- positive neurons, both tyrosine hydroxylase (TH)-positive and -negative, was observed. Analysis of TH immunoreactivity revealed fewer TH-positive neurons and fibers in a medial and lateral portion of cell group A9 of the SN, an area that projects to the striatum, suggesting that gp120 induces retrograde degeneration of nigrostriatal neurons. We propose that dysfunction of the nigrostriatal dopaminergic system associated with HIV may be caused by a reduction of neurotrophic factor expression by gp120. © 2006 Wiley Periodicals, Inc. J Neurobiol, 2006 [source]

    Response to first-line antiretroviral treatment among human immunodeficiency virus-infected patients with and without a history of injecting drug use in Indonesia

    ADDICTION, Issue 6 2010
    Rudi Wisaksana
    ABSTRACT Background There is a common belief that injecting drug use (IDU) is associated with lower uptake, retention and success of antiretroviral treatment (ART) in human immunodeficiency virus (HIV)-infected patients. We examined this in an Indonesian setting, where IDU is the main risk factor for HIV infection. Methods Patient characteristics and response to ART were recorded for all patients diagnosed with HIV infection in the referral hospital for West Java (40 million people). Kaplan,Meier estimates and Cox's regression were used to compare mortality, loss to follow-up and virological failure between patients with and without a history of IDU. Result A total of 773 adult HIV patients (81.9% IDUs) presented between January 1996 and April 2008. IDUs had a median CD4 cell count of 33 [interquartile ratio (IQR), 12,111] cells/mm3 compared to 84 (IQR, 28,224) cells/mm3 in non-IDUs. Among patients with a history of IDU, 87.7% were coinfected with hepatitis C (HCV). Mortality was associated strongly with CD4 count; after 6 months of ART, 18.3, 20.3, 7.1 and 0.7% of patients with CD4 cell counts <25, 25,99, 100,199, respectively, ,200/mm3 had died (P < 0.0001). Mortality [adjusted for CD4; hazard ratio (HR) = 0.65; 95% confidence interval (CI) 0.35,1.23], loss to follow-up (HR = 0.85, 95% CI 0.51,1.41) and virological failure (HR = 0.47, 95% CI 0.19,1.13) were not significantly different in IDUs and non-IDUs. Conclusion Intravenous drug users (IDUs) in Indonesia with HIV/acquired immune deficiency syndrome tend to have more advanced disease but respond similarly to non-IDUs to antiretroviral therapy. [source]

    Cover Picture: Electrophoresis 15/2008

    ELECTROPHORESIS, Issue 15 2008
    Article first published online: 24 JUL 200
    Regular issues provide a wide range of research and review articles covering all aspects of electrophoresis. Here you will find cutting-edge articles on methods and theory, instrumentation, nucleic acids, CE and CEC, miniaturization and microfluidics, proteomics and two-dimensional electrophoresis. Selected topics of issue 15 are: The application of perfluorooctanoate to investigate trimerization of the human immunodeficiency virus-1 gp41 ectodomain by electrophoresis Metabolic fingerprinting of schistosoma mansoni infection in mice urine with capillary electrophoresis Supercritical fluid extraction as an on-line clean-up technique for determination of riboflavin vitamins in food samples by capillary electrophoresis with fluorimetric detection A two-step electro-dialysis method for DNA purification from polluted metallic environmental samples. [source]

    The application of perfluorooctanoate to investigate trimerization of the human immunodeficiency virus-1 gp41 ectodomain by electrophoresis

    ELECTROPHORESIS, Issue 15 2008
    Chi-Hui Lin
    Abstract The transmembrane glycoprotein gp41 of human immunodeficiency virus has been proposed to form trimer-of-hairpin during virus-cell membrane fusion. To investigate its oligomerization propensity under soluble and membrane-mimic conditions, sodium salt of perfluorooctanoate (PFO) was applied. A recombinant gp41 ectodomain devoid of disulfide linkage was overexpressed in Escherichia coli and characterized by MS and circular dichroism spectropolarimetry in PFO solution in comparison to SDS. The helical content of this ectodomain in PFO is higher than that in SDS. Notably, PFO employed in PAGE clearly conduced to the formation of trimer under the optimized condition as visualized in the gel. In addition, the proteins expressed from the two mutants in the heptad repeat (HR) domains of gp41, I62P, and N126K, were also examined by the PFO-PAGE analysis for functional ramification of molecular organization. Remarkably, the I62P mutation completely abolished the gp41 trimer formation, whereas the N126K mutation resulted in a more stable trimer. The data suggested that PFO-PAGE analysis is appropriate for evaluating the effect of mutations on the trimerization of gp41 and other fusion proteins which may be implicated in the alteration of their fusogenicity. [source]

    Quantitation of reduced glutathione and cysteine in human immunodeficiency virus-infected patients

    ELECTROPHORESIS, Issue 10-11 2004
    Elena Sbrana
    Abstract Plasma viral load (VL) values and CD4+ cell count are employed clinically for initiation of therapy in the treatment of patients infected with human immunodeficiency virus (HIV), as previous clinical studies have shown a marked prevalence of acquired immunodeficiency sydrome (AIDS) development in seropositive individuals with VL values over 30,000 copies/mL. Many studies have shown that reduced glutathione (GSH) and cysteine (Cys) deficiency play an important role in the infection. We have developed capillary zone electrophoresis (CZE)-based assays and have used them to investigate the relationship between plasma and intracellular thiol levels and HIV-1 viremia in plasma. Blood samples from healthy volunteers and seropositive patients undergoing different antiretroviral regimes were analyzed in the study. The VL assay was based on CZE-UV detection of viral RNA at 260 nm. Determination of endogenous reduced Cys and GSH was achieved by CZE-UV detection of their mercurial complexes at 200 nm. We found that a decrease in GSH and Cys levels may be associated with disease progress. In fact, reduced GSH and Cys levels appear progressively reduced with increasing VL. [source]

    The impact of alcohol use on depressive symptoms in human immunodeficiency virus-infected patients,

    ADDICTION, Issue 9 2008
    Lynn E. Sullivan
    ABSTRACT Aims To examine the impact of alcohol use on depressive symptoms in human immunodeficiency virus (HIV)-infected patients. Design Data were collected at 6-month intervals and analyzed to evaluate the association between alcohol dependence and consumption on depressive symptoms using longitudinal mixed-effects regression models controlling for specified covariates. Measurements The two independent variables were current alcohol dependence assessed using the Composite International Diagnostic Interview (CIDI) and past month consumption (heavy versus not heavy drinking) using a validated calendar-based method. The primary outcome was depressive symptoms as measured by the Center for Epidemiologic Studies Depression Scale (CES-D). Participants HIV-infected adults with current or past alcohol problems. Findings Alcohol dependence and heavy alcohol use were significantly associated with higher CES-D scores in unadjusted models. In adjusted analyses, the association of current alcohol dependence persisted [mean difference in CES-D was 3.49 for dependence versus non-dependence; 95% confidence interval (CI): 1.76,5.22]; however, the effect of heavy drinking was no longer statistically significant (mean difference in CES-D was 1.04 for heavy versus not heavy drinking; 95% CI: ,0.24,2.32). Conclusions Alcohol use is associated with more depressive symptoms in HIV-infected patients with alcohol problems. This association remains significant after adjusting for potential confounders only when alcohol use meets the criteria for alcohol dependence. [source]

    Human immunodeficiency virus-associated progressive multifocal leucoencephalopathy: epidemiology and predictive factors for prolonged survival

    A. K. Drake
    We performed a retrospective review of cases of human immunodeficiency virus-associated progressive multifocal leucoencephalopathy in four hospitals (three in Australia and one in Hong Kong) between 1987 and 2003 in order to describe the local experience with this disease and to evaluate parameters impacting upon survival. Eighty-seven cases were identified and demographic details, baseline parameters and treatment methods and response were described. Survival was substantially increased in the post-highly active antiretroviral therapy (HAART) era with a median survival increase from 14 to 64 weeks. On multivariate analysis, variables associated with prolonged survival included a CD4 count of >100 cells/,l at diagnosis and the use of HAART post-diagnosis, with no significant additional advantage from the use of neuroactive antiretrovirals. [source]

    Emerging clinical concerns in the ageing haemophilia patient

    HAEMOPHILIA, Issue 6 2009
    B. A. KONKLE
    Summary., The availability of safe replacement clotting factor concentrates together with effective antiviral drugs to treat human immunodeficiency and hepatitis C viruses and the provision of care at designated haemophilia treatment centres have resulted in a new phenomenon in haemophilia management , the ageing patient. Today, increasing numbers of persons with haemophilia (PWH) are middle-aged and older, and they face the same age-related health issues as the general population. The impact of these risks on PWH is unclear, however, and there is a paucity of information about how to manage comorbidities in this patient population. This review focuses on five comorbidities that uniquely affect older PWH: cardiovascular disease, liver disease, cancer, renal disease and joint disease. Available research is summarized and potential management approaches are suggested. [source]

    Liver damage underlying unexplained transaminase elevation in human immunodeficiency virus-1 mono-infected patients on antiretroviral therapy,

    HEPATOLOGY, Issue 2 2009
    Patrick Ingiliz
    Liver damage associated with chronic unexplained high serum transaminases in human immunodeficiency virus (HIV)-infected patients under combined antiretroviral therapy is unknown. Liver histology was prospectively investigated in patients presenting serum transaminase elevation for more than 6 months, after exclusion of alcohol abuse, hepatitis C virus (HCV) or hepatitis B virus (HBV) infection, autoimmune, and genetic liver diseases. In a subgroup of patients, liver mitochondrial activities were measured by spectrophotometry and mitochondrial DNA (mtDNA) by real-time polymerase chain reaction (PCR). Thirty patients were included with median values of alanine aminotransferase (ALT) levels: 80 U/L, age: 46 years, body mass index: 23 kg/m2, HIV RNA: 200 copies/mL, CD4 count: 365/mm3, duration of HIV infection: 13 years, and duration of treatment exposure: 118, 41, and 53 months for nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, and protease inhibitors, respectively. Histological anomalies were found in 22 of 30 patients. Steatosis was present in 18 patients, severe in nine patients, and associated with inflammation in 16 patients with a diagnosis of non-alcoholic steatohepatitis (NASH). Fibrosis was found in 18 patients, severe in six patients and associated with steatosis in 13 patients. Significant liver respiratory complex I defect, contrasting with high complex IV activity and normal mitochondrial DNA content, was observed in the group of patients compared with controls. The presence of NASH was correlated with high fasting glycemia and insulin levels, not with liver mitochondrial function or mitochondrial DNA content. Conclusions: HIV-infected patients on combined antiretroviral therapy with chronic transaminase elevation of unknown origin have a high rate of liver lesions, mostly consistent with NASH related to insulin resistance. (HEPATOLOGY 2008.) [source]

    Altered distribution of natural killer cell subsets identified by CD56, CD27 and CD70 in primary and chronic human immunodeficiency virus-1 infection

    IMMUNOLOGY, Issue 2 2008
    Kehmia Titanji
    Summary Human natural killer (NK) (CD3, CD56+) cells can be divided into two functionally distinct subsets, CD3, CD56dim and CD3, CD56bright. We analysed the distribution of NK cell subsets in primary and chronic human immunodeficiency virus-1 (HIV-1) infection, to determine if HIV infection stage may influence the subset distribution. In primary infection, contrary to chronic infection, the CD3, CD56dim subset was expanded compared to healthy controls. We also studied the effect of antiretroviral therapy administered early in infection and found that NK cell subset distribution was partially restored after 6 months of antiretroviral therapy in primary infection, but not normalized. Recently, NK cells have been divided into CD27, and CD27+ subsets with different migratory and functional capacity and CD27-mediated NK cell activation has been described in mice. We therefore investigated whether CD27 and/or CD70 (CD27 ligand) expression on NK cells, and thus the distribution of these novel NK subsets, was altered in HIV-1-infected patients. We found up-regulated expression of both CD27 and CD70 on NK cells of patients, resulting in higher proportions of CD27high and CD70high NK cells, and this phenomenon was more pronounced in chronic infection. Experiments conducted in vitro suggest that the high interleukin-7 levels found during HIV-1 infection may participate in up-regulation of CD70 on NK cell subsets. Imbalance of NK cell subsets and up-regulated expression of CD27 and CD70 initiated early in HIV-1 infection may indicate NK cell activation and intrinsic defects initiated by HIV-1 to disarm the innate immune response to the virus. [source]

    Impact of class A, B and C CpG-oligodeoxynucleotides on in vitro activation of innate immune cells in human immunodeficiency virus-1 infected individuals

    IMMUNOLOGY, Issue 4 2007
    Jeffrey A. Martinson
    Summary Oligodeoxynucleotides (ODN) with unmethylated deoxycytidyl-deoxyguanosine dinucleotides (CpG-ODNs) stimulate Toll-like receptor 9 (TLR9) in plasmacytoid dendritic cells (pDC) and B cells and activate innate and adaptive immunity. Three classes of synthetic CpG-ODNs, class A, B and C, activate cells through TLR9; our goal was to evaluate their effect on cells from human immunodeficiency virus (HIV)-1+ individuals. We compared the frequencies and the unstimulated activation status of immune effector cells in HIV-1+ and HIV-1, individuals. Fewer pDC, myeloid dendritic cells (mDC), B cells, natural killer (NK) cells and invariant natural killer T cells (iNKT) were present in HIV-1+ peripheral blood mononuclear cells (PBMC) and their baseline activation status was higher than HIV-1, PBMC. Exposure of HIV-1+ PBMC to all classes of CpG-ODNs led to activation and maturation of pDC based on CD86, CD80, and CD83 expression similar to that of cells from HIV-1, individuals. The percentage of CpG-ODN stimulated pDC that express CD40 was dramatically higher when cells were obtained from HIV-1+ than from HIV-1, individuals. B-lymphocytes were activated similarly in HIV-1+ and HIV-1, individuals. mDC, NK and iNKT cell, which lack TLR9, were indirectly activated. Interferon-, (IFN-,) and interferon inducible protein 10 (IP-10) secretion was induced by class A or C but not class B CpG-ODN, but the concentrations were less than those produced by HIV-1, PBMC. HIV-1 infected individuals have fewer innate effector cells that are chronically activated, but these cells can be further activated by CpG-ODN, which suggests that synthetic CpG-ODNs could be used to enhance the immune system in HIV-1 infected individuals. [source]

    Effects of human interleukin-18 and interleukin-12 treatment on human lymphocyte engraftment in NOD-scid mouse

    IMMUNOLOGY, Issue 2 2002
    Hidenobu Senpuku
    Summary NOD/LtSz- prkdcscid/prkdcscid (non-obese diabetic-severe combine immunodeficiency; NOD-scid) mice grafted with human peripheral blood lymphoid cells have been used as an in vivo humanized mouse model in various studies. However, cytotoxic human T cells are induced in this model during immune responses, which gives misleading results. To assist in grafting of human lymphocytes without the induction of cytotoxic human T cells, we investigated the effects of T helper type 1 (Th1) and Th2 cytokines on human lymphocyte grafting and migration, as well as the production of immunoglobulin deposited in glomeruli and human immunodeficiency virus-1 (HIV-1) infection using NOD-scid mice. Administration of interleukin-18 (IL-18) and IL-12 enhanced the grafting of human CD4+ and CD8+ T cells in the mice, whereas co-administration prevented grafting due to interferon-,-dependent apoptosis. Immunoglobulin A (IgA) deposits were observed in mice treated with IL-18 alone, but not in those given phosphate-buffered saline, IL-12 alone, or IL-18 + IL-12. A high rate of HIV infection was also observed in the IL-18-treated group. Together, these results indicate that IL-18 may be effective for the grafting and migration of CD4+ and CD8+ T cells, except for the induction of apoptosis and regulation of class-switching IgA. IL-18-administered NOD-scid mice provide a useful small humanized model for the study of HIV infection and IgA nephropathy. [source]

    Analysis of the mechanism for extracellular processing in the presentation of human immunodeficiency virus-1 envelope protein-derived peptide to epitope-specific cytotoxic T lymphocytes

    IMMUNOLOGY, Issue 1 2000
    Y. Nakagawa
    Summary An immunodominant epitope of human immunodeficiency virus-1 (HIV-1) gp160 recognized by Dd class I major histocompatibility complex (MHC) molecule-restricted, CD8+ cytotoxic T lymphocytes (CTL) was originally identified as a peptide composed of 15 amino acids (P18IIIB: RIQRGPGRAFVTIGK). However, further study has indicated that a 10-mer peptide, I-10 (RGPGRAFVTI), within P18IIIB is the minimal-sized epitope and the trimming step(s) of two carboxyl terminal amino acids (GK) is essential to produce I-10 from P18IIIB. In the processing, angiotensin-1-converting enzyme (ACE), found in sera, plays a central role in generating I-10. Target cells could be sensitized with I-10 under conditions where ACE activity in the sera was abrogated. In contrast, in the case of P18IIIB, requiring further processing to delete the C-terminus of two amino acids in order to act, sensitization of target cells was completely abrogated under the conditions. Pretreatment of target cells with brefeldin A (BFA), preventing the presentation of endogenous antigens from the class I MHC molecule pathway, did not inhibit the presentation of P18IIIB. Moreover, glutaraldehyde-fixed cells, which can not process native protein, though they could present the exogenously added peptides, were also sensitized by P18IIIB. These results clearly demonstrate that the fine processing to produce I-10 occurred in the extracellular milieu. Furthermore, our result suggests that the longer P18IIIB can bind to the class I molecules on the cell surface, and then be trimmed by ACE while it is bound. The mechanisms behind the extracellular processing outlined in this paper will offer important information for designing peptide-based vaccines to elicit MHC molecule-restricted effectors. [source]

    Interleukin-8 fails to induce human immunodeficiency virus-1 expression in chronically infected promonocytic U1 cells but differentially modulates induction by proinflammatory cytokines

    IMMUNOLOGY, Issue 1 2000
    C. T. Tiemessen
    Summary This study addresses the role of interleukin (IL)-8, a CXC-chemokine, the level of which is reported to be raised in the peripheral circulation of human immunodeficiency virus-1 (HIV-1)-infected individuals, during the induction of HIV-1 expression from latency and during cytokine-mediated HIV-1 up-regulation. IL-8 at the higher concentrations tested (, 100 ng/ml) was unable to induce HIV-1 expression in the chronically infected promonocytic U1 cell line, as measured by p24 antigen enzyme-linked immunosorbent assay (ELISA), whereas at lower concentrations of 1 and 10 ng/ml, constitutive HIV-1 expression was only marginally reduced. HIV-1 replication in acutely infected U937 cells was also significantly reduced by IL-8. The potent up-regulation of HIV-1 expression in U1 cells by tumour necrosis factor-, (TNF-,) remained unaffected by the addition of IL-8. HIV-1 induction by IL-1,, IL-6 and TNF-,, cytokines grouped here as intermediate HIV-1 inducers, was suppressed by IL-8 at concentrations of 1 and 10 ng/ml. However, IL-8 at 100 ng/ml did not significantly alter the effect of IL-1,, synergized with IL-6 in enhancing, and marginally suppressed TNF-,-induced HIV-1 expression. IL-8 suppressed granulocyte,macrophage colony-stimulating factor (GM-CSF) and enhanced interferon-, (IFN-,)-induced HIV-1 expression in a dose-dependent manner. Pretreatment of U1 cells with IL-8 did not alter the IL-8-mediated effects on cytokine-induced HIV-1 expression, suggesting that this chemokine exerts its effect at the time of HIV-1 induction or at a postinduction stage. Furthermore, IL-8 was itself induced by cytokines that up-regulate HIV-1 expression in U1 cells and the levels produced correlated directly with the levels of p24 antigen produced, suggesting common pathways for cytokine induction of both HIV-1 and IL-8. These results show that IL-8, typically a non-inducer, can differentially modulate HIV-1 expression in U1 cells and that this is dependent on the inducing cytokine and on the concentration of IL-8. [source]

    ,, T-cell anergy in human immunodeficiency virus-infected persons with opportunistic infections and recovery after highly active antiretroviral therapy

    IMMUNOLOGY, Issue 4 2000
    F. Martini
    Summary ,, T lymphocytes recognize non-peptidic microbial antigens without antigen processing and major histocompatibility complex (MHC) restriction, representing an early defence mechanism against invading pathogens. As a defective response to non-peptidic antigens was observed in human immunodeficiency virus-positive (HIV+) persons, the aims of this study were twofold: to analyse the incidence of ,, T-cell anergy in HIV+ patients with opportunistic infections/co-infections (HIV-OIC), and to investigate the role of highly active antiretroviral therapy (HAART) on ,, T-cell functions. Peripheral ,, T-cell distribution and in vitro reactivity to a non-peptidic mycobacterial antigen, isopentenyl pyrophosphate (IPP), were analysed. ,, T-cell subset distribution was altered more in HIV-OIC patients than in asymptomatic HIV+ subjects (HIV-ASY). Specifically, the V,2/V,1 ratio was inverted as a consequence of a decrease in V,2 T-cell number. Moreover, IPP-stimulated V,2 T cells from the HIV-OIC group displayed a major defect in interferon-, (IFN-,) production. Interestingly, HAART induced a sustained recovery of naive CD45RA+ and CD62L+ T cells and restored ,, T-cell function. Accordingly, in vitro CD45RA depletion resulted in ,, T-cell hyporesponsiveness. Altogether, the incidence of ,, T-cell anergy was increased in HIV-OIC patients and dependent on CD45RA helper function. Moreover, HAART was able to restore ,, T-cell reactivity, extending the immune recovery to non-peptidic microbial antigens. [source]

    Reintroducing antituberculosis therapy after Stevens,Johnson syndrome in human immunodeficiency virus-infected patients with tuberculosis: role of desensitization

    Mahendra M. Kura MD
    First page of article [source]

    Pathogen-reduction methods: advantages and limits

    H. G. Klein
    Pathogen-reduction (inactivation) provides a proactive approach to reducing transfusion-transmitted infection. Pathogen-reduction technologies have been successfully implemented by plasma fractionators resulting in no transmission of human immunodeficiency, hepatitis C, or hepatitis B viruses by US-licensed plasma derivatives since 1987. Fractionation technologies cannot be used to treat cellular blood components. Although blood donor screening, deferral and disease testing have drastically reduced the incidence of transfusion-transmitted diseases, the threat of new or re-emerging pathogens remains. Of particular concern is the silent emergence of a new agent with a prolonged latent period in which asymptomatic infected carriers would donate and spread infection. The ultimate goal of pathogen-inactivation is to reduce transmission of potential pathogens without significantly compromising the therapeutic efficacy of the cellular and protein constituents of blood. The acceptable technology must not introduce toxicities into the blood supply nor result in neoantigen formation and subsequent antibody production. Several promising pathogen-inactivation technologies are being developed and tested, and others are currently in use, but all of them have limits. Pathogen-reduction promises an additional ,layer of protection' from infectious agents and has the potential to impact the safety of blood transfusions worldwide. [source]

    Determinants of perceived barriers to condom use among HIV-infected middle-aged and older African-American men

    Christopher Lance Coleman
    Abstract Title.,Determinants of perceived barriers to condom use among HIV-infected middle-aged and older African-American men Aim., This paper is a report of a study to describe which determinants best predict perceived barriers to condom use during sexual encounters among human immunodeficiency virus human immunodeficiency virus-infected African-American men, middle-aged and older, living in the United States of America. Background., While the global epidemic of acquired immunodeficiency syndrome infection is a well-documented phenomenon with national and international implications, prevalence statistics indicate that middle-aged and older African-American (non-Hispanic) men have not benefited from the prevention efforts implemented during the past two decades. Method., A cross-sectional design using a survey and convenience sampling was adopted between September 2003 and July 2004 to recruit n = 130 middle-aged human immunodeficiency virus-infected African-American men from infectious disease clinics from the Mid-Atlantic region in the United States of America. The survey covered demographics, perceived health beliefs, spiritual well-being and symptoms related to human immunodeficiency virus. Findings., Stepwise multiple regression showed having fewer human immunodeficiency virus-related symptoms associated with the human immunodeficiency virus (P = 0·004) and being single (P = 0·05) were perceived as barriers to condom use during sexual encounters (R2 = 0·029, P = 0·046). Conclusion., Tailored interventions are needed for African-American men, middle-aged and older, infected with human immunodeficiency virus nationally and worldwide that are designed to decrease perceived barriers in order to increase condom use. [source]

    In vitro effect of oral antiseptics on human immunodeficiency virus-1 and herpes simplex virus type 1

    A. A. M. A. Baqui
    Abstract Aim: The antiviral effectiveness of widely used commercial mouthrinses has not been well studied. A project was undertaken to evaluate and compare the in vitro antiviral effectiveness of essential oil-containing mouthrinses (LA & TLA) and chlorhexidine mouthrinses (PX & CHX) on 2 different enveloped viruses, human immunodeficiency virus (HIV-1) and Herpes simplex virus (HSV-1) McIntyre strain. Method: HIV-189.6 (1×105/ml) and HSV-1 (1×106/ml) in RPMI-1640 medium were treated with two commercially available forms of LA & TLA (tartar control LA), and 2 formulations of chlorhexidine [(PX), 0.12% chlorhexidine & (CHX), 0.2% chlorhexidine] for 30 sec. The antiviral effect was estimated by inhibition of the syncytia formation or the cytopathic effect (CPE) for HIV-1 on MT-2 cells and by inhibition of the plaque formation for HSV-1 on Vero cell monolayers. Results: Undiluted LA, TLA, PX and CHX completely inhibited both HIV-189.6 and HSV-1 McIntyre strain. PX and CHX inhibited HIV-1 up to 1:4 dilution, whereas, LA and TLA inhibited HSV-1 up to 1:2 dilution. The antiviral effects of LA and TLA were found to be similar and also the antiviral effect of PX and CHX were also found to be comparable. Conclusions: The methods used in this investigation allow easy and reproducible evaluations of antiviral efficacy. The anti-HIV-1 and anti-HSV-1 effects of LA, TLA, PX and CHX as evidenced in our in vitro study suggest that we should investigate potential in vivo effects during the use of essential oil-containing or chlorhexidine containing products when used by patients as mouthrinses. If the clinical studies confirm the in vitro data, pre-procedural use by clinicians may be beneficial in reducing viral contamination of bio-aerosols during the delivery of dental care. Zusammenfassung Ziel: Die antivirale Effektivität von breit genutzten kommerziellen Mundwässern wurde bisher nicht gut untersucht. Ein Projekt wurde deshalb aufgenommen, um den in vitro antiviralen Effekt von ätherischen Öl enthaltenden Mundwässern (LA & TLA) und Chlorhexidin Mundwässern (PX & CHX) auf 2 unterschiedlich entwickelte Viren, das menschliche Immundefizienz Virus (HIV-1) und das Herpes simplex Virus (HSV-1) McIntyre Stamm zu evaluieren und zu vergleichen. Methoden: HIV-189.6 (1×105/ml) und HSV-1 (1×106/ml) in RPMI-1640 Medium wurden mit 2 kommerziellen Formen von LA & TLA (Tartarkontrolle LA) und 2 Arten von Chlorhexidin [(PX), 0.12% Chlorhexidin & (CHX), 0.2% Chlorhexidin] für 30 Sekunden behandelt. Der antivirale Effekt wurde durch Inhibition der Syncytiumbildung oder des cytopathischen Effektes (CPE) für HIV-1 auf MT-2 Zellen und durch Inhibition der Plaquebildung für HSV-1 auf Vero Zellmonolayers bestimmt. Ergebnisse: Unverdünntes LA, TLA, PX und CHX inhibierte sowohl HIV-189.6 und HSV-1 McIntyre Stamm. PX und CHX inhibierte HIV-1 bis zu einer 1:4 Verdünnung, während LA und TLA HSV-1 bis zu einer 1:2 Verdünnung inhibierte. Die antiviralen Effekte von LA und TLA wurden gleichwertig gefunden und auch der antivirale Effekt von PX und CHX waren vergleichbar. Zusammenfassung: Die genutzten Methoden in dieser Untersuchung erlaubten leicht und reproduzierbar die Evaluation von antiviralen Effekten. Die anti-HIV-1 und anti-HSV-1 Effekte von LA, TLA, PX und CHX, die in unserer in vitro Studie evident waren, suggerieren, daß wir das Potential der in vivo Effekte während des Gebrauches von ätherischen Öl enthaltenden oder Chlorhexidin enthaltenden Produkten untersuchen sollten, wenn die Patienten dies als Mundwässer benutzen. Wenn die klinischen Studien die in vitro Ergebnisse bestätigen, kann der vorherige Gebrauch durch die Kliniker die virale Kontamination von Bioaerosolen während der durchgeführten zahnäztlichen Behandlung reduzieren. Résumé But: L'efficacité antivirale des bains de bouches largement commercialises n'a pas été bien étudiée. Notre projet a évalué et comparé l'efficité antivirale in vitro de bains de bouche aux huiles essentielles (LA et TLA) et à la chlorexhidine (PX et CHX) sur 2 virus à envelopes, le virus de l'immunodéfiscience acquise 1 (HIV1) et la souche McIntyre du virus de l'Herpes simplex de type 1 (HSV1). Méthode: HIV1896 (1×105/ml) et HSV1 (1×106 ml) dans un milieu RPMI-1640 furent traits avec 2 formes disponibles sur le marché de LA et TLA, et 2 formules de chloxhexidine (PX, 0.12% chlorexhidine et CHX, 0.2% chlorexhidine) pendant 30 s. L'effet antiviral fut estimé par l'inhibition de la formation de syncitia ou par l'effet cytopathique (CPE) pour HIV1, sur des cellules MT2 et par l'inhibition de la formation de plaque pour HSV1 sur des monocouches cellulaires Vero. Résultats: CHX, LA, TLA et PX non dilués inhibaient complètement à la fois HIV1896 et la souche McIntyre HSV1. PX et CHX inhibaient HIV1 jusqu'à une dilution par 4 alors que LA et TLA inhibaient HSV1 jusqu'à une dilution par 2. Les effets antiviraux de LA et TLA étaient similaires, et les effets antiviraux de PX et CHX étaient aussi comparables. Conclusions: Les methodes utilisées pour cette recherche permettent une évaluation facile et reproductible de l'efficacité antivirale. Les effets anti-HIV1 et anti-HSV1 de LA, TLA, PX et CHX trouvés ici in vitro suggèrent que nous recherchions des effects potentiels in vivo lors de l'utilisation de produits contenant des huiles essentielles ou de la chlorexhidine utilisés comme bains de bouches par les patients. Si les études cliniques confirment les données in vitro, l'utilisation préclinique par les praticiens pourrait leur être bénéfique en réduisant la contamination virale des bioaérosols lors des soins dentaires. [source]

    A service evaluation to determine the effectiveness of current dietary advice in treating human immunodeficiency virus-associated weight loss and to highlight potential service improvements

    C.A. Hunt
    Background:, Weight loss and muscle wasting are experienced by many patients with human immunodeficiency virus (HIV) (Grinspoon et al., 2003). Malnutrition is an important predicator of morbidity and mortality; people who are malnourished who received antiretroviral treatment are six times more likely to die than those who are adequately nourished (Paton et al., 2006). The physical manifestations of muscle wasting can have significant psychosocial implications for HIV patients (Power et al., 2003; Sattler, 2003). The aim of this study to evaluate provision of dietetic care to patients referred for acute weight loss advice and identify areas for potential service improvement. Methods:, The data were gathered from the departmental dietetic activity statistics in 2007, diagnosis code ,HIV , acute weight loss'. Fifty-nine cards were located and baseline weight, height and body mass index (BMI) were recorded (two female, 57 male). Qualitative data on dietetic intervention were extracted from record cards , little and often eating approach, food fortification (FF), high energy high protein oral nutritional supplement (ONS) prescribed. Data were collected on body image, exercise and weight at follow-up visits during 2007. Results:, Forty-three percent of the patients referred for ,HIV-acute weight loss' were lost to follow-up. Forty-seven percent of the remaining patients had a BMI <20 kg m,2. Following their initial dietetic intervention, 81% of these patients had gained weight at the first follow-up. All had received nutritional counselling on little and often eating approach and FF; 75% had ONS prescribed. Average weight gain with nutritional counselling alone was 1.3 kg (2.1 kg) and for nutritional counselling plus supplementation was 2.1 kg (1.8 kg). This represented 2.5% (4.1%) and 3.9% (3.4%) weight gain, respectively. Discussion:, This evaluation has highlighted that patient follow-up frequency is an area for service improvement. Fifty-three per cent of patients (excluding those lost to follow up) had a BMI ,20 kg m,2 and were inaccurately recorded in the statistics as being referred for ,HIV-acute weight loss'. Fifty-two percent of these patients reported lipodystrophy and body image concerns, similar to findings of other studies. Fifty-six percent reported weight improvements following dietetic consultation. Body image is a frequent referral trigger, therefore improvements should be made to identify and treat patients with body shape issues. Conclusions:, Dietitians are effective at achieving weight gain in HIV positive patients with a BMI <20 kg m,2 using nutritional counselling methods with or without oral nutritional supplementation; these patients experienced a 3.3% weight gain. Strategies need to be implemented to reduce the number of patients lost to follow-up, as weight loss is a key morbidity and mortality indicator in HIV. References, Grinspoon, S. & Mulligan, K. (2003) Weight loss and wasting in patients infected with HIV. Clin. Infect. Dis.36 (Suppl. 2): 69,78. Nerad, J., Romeyn, M., Silverman, E., Allen-Reid, J., Dieterich, D., Merchant, J., Pelletier, V., Tinnerello, D. & Fenton, M. (2003) General nutritional management in patients infected with HIV. Clin. Infect. Dis.36 (Suppl. 2): 52,62. Ockenga, J., Grimble, R., Jonkers-Schuitema, C., Macallan, D., Melchior, J.C., Sauerwein, H.P., Schwenk, A. & Suttmann, U. (2006) ESPEN guidelines on enteral nutrition: wasting in HIV and other chronic infectious diseases. Clin. Nutr.25, 319,329. Paton, N.I., Sangeetha, S., Earnest, A. & Bellamy, R. (2006) The impact of malnutrition on survival and the CD4 count response in HIV-infected patients starting antiretroviral therapy. HIV Med.7, 232,330. Power, R., Tate, H.L., McGill, S.M. & Taylor, C. (2003) A qualitative study of the psychosocial implications of lipodystrophy syndrome on HIV positive individuals. Sex. Transm. Infect.79, 137,141. Sattler, F. (2003) Body habitus changes related to lipodystrophy. Clin. Infect. Dis36 (Suppl. 2): 84,90. [source]

    Molecular characterization of the env gene of two CCR5/CXCR4-independent human immunodeficiency 2 primary isolates,

    Quirina Santos-Costa
    Abstract Human immunodeficiency virus 2 (HIV-2) infection is characterized by a slower disease progression and lower transmission rates. The molecular features that could be assigned as directly involved in this in vivo phenotype remain essentially unknown, and the importance of HIV-2 as a model to understand pathogenicity of HIV infection has been frequently underestimated. The early events of the HIV replication cycle involve the interaction between viral envelope glycoproteins and cellular receptors: the CD4 molecule and a chemokine receptor, usually CCR5 or CXCR4. Despite the importance of these two chemokine receptors in human immunodeficiency virus 1 (HIV-1) entry into cells, we have previously shown that in some HIV-2 asymptomatic individuals, a viral population exists that is unable to use both CCR5 and CXCR4. The goal of the present study was to investigate whether possible regions in the env gene of these viruses might account for this phenotype. From the molecular characterization of these env genes we could not detect any correlation between V3 loop sequence and viral phenotype. In contrast, it reveals the existence of remarkable differences in the V1/V2 and C5 regions of the surface glycoprotein, including the loss of a putative glycosilation site. Moreover, in the transmembrane glycoprotein some unique sequence signatures could be detected in the central ectodomain and second heptad repeat (HR2). Some of the mutations affect well-conserved residues, and may affect the conformation and/or the dynamics of envelope glycoproteins complex, including the SU,TM association and the modulation of viral entry function. J. Med. Virol. 81:1869,1881, 2009. © 2009 Wiley-Liss, Inc. [source]

    Investigation of pre-diagnostic virological markers for progressive multifocal leukoencephalopathy in human immunodeficiency virus-infected patients

    Mary K. Grabowski
    Abstract Progressive multifocal leukoencephalopathy (PML) is a severe neurological disorder due to JC virus (JCV) infection. Pre-diagnostic biological markers and risk factors for PML are not well understood. We conducted a case,control study nested within the Multicenter AIDS Cohort Study to examine the association between JCV viruria and viremia and serum antibody to JCV capsids, in relation to subsequent PML diagnoses, 5 months to 12 years later. Other demographic and immunologic factors were also examined. The study population included 28 incident cases of PML, 26 matched HIV-positive controls, and 50 HIV-negative controls. Prevalence of JCV viruria was 37% in cases, 42% in HIV-positive controls, and 28% in HIV-negative controls (P,=,0.43). Among persons with JCV viruria, persistent viruria was more common in cases (89%) than in HIV-positive controls (33%) (P,=,0.02). Presence of JCV viruria was not related to the time to PML diagnosis (OR: 1.03, 95% CI: 0.8,1.4); however, the urinary concentration of JCV DNA increased with proximity to the date of PML diagnosis in cases. JCV seropositivity did not differ between cases or controls (P,=,0.42). Four cases tested JCV seronegative, including one case only 5 months prior to diagnosis with PML. JCV DNA was detected in the serum of one HIV-positive control. Smoking was the only demographic variable analyzed associated with an increased risk for PML (MOR: 9.0, 95% CI: 1.2,394.5). The results suggest that persistent JCV viruria and increasing urinary concentration of JCV DNA may be predictive of PML for some patients. J. Med. Virol. 81:1140,1150, 2009. © 2009 Wiley-Liss, Inc. [source]

    Intracellular and cell-free (infectious) HIV-1 in rectal mucosa

    Mariantonietta Di Stefano
    Abstract The intestinal mucosa contains most of the total lymphocyte pool and plays an important role in viral transmission, but only slight attention has been given to the immunological and virological aspects of human immunodeficiency virus-1 (HIV-1) infection at this site. In this study, before initiating or changing antiretroviral therapy, paired blood samples and rectal biopsies (RB) were obtained from 26 consecutive HIV-infected subjects. HIV-1 isolation and biological characterization, DNA, and HIV-1 RNA titration were assessed, as were in vitro tumor necrosis factor-alpha (TNF-,) and interleukin-, (IL-1,) spontaneous production. The rate of HIV-1 isolation from peripheral blood mononuclear cells (PBMCs) and RBs was 75% and 58%, respectively. All RB-derived isolates were nonsyncytium inducing (NSI), independent of the phenotype of blood-derived isolates. Proviral DNA and detectable HIV-1 RNA levels were measured in 100% and 77% of RBs, respectively. A statistical correlation was observed between HIV-1 DNA and HIV-1 RNA levels in rectal mucosa (P,=,0.0075), whereas no correlation was found between these levels in blood samples (P,>,0.05). Antiretroviral treatment did not seem to influence HIV-1 detection in RBs. Higher levels of in vitro proinflammmatory cytokine production were found in the RBs of most infected patients when compared with healthy controls. Therefore, the rectal mucosa is an important HIV-1 reservoir that demonstrates a discordant viral evolution with respect to blood. Both the virus type and the mucosa pathway of immunoactive substances might have important implications for therapeutic decision-making and monitoring and could influence the bidirectional transmission of HIV-1 in mucosal surfaces. J. Med. Virol. 65:637,643, 2001. © 2001 Wiley-Liss, Inc. [source]