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At least 793 records · Page 44Linked to original sources
PubMed1995

HIV infection and drug use: influence on cognitive function.

OBJECTIVE: To examine the involvement of cognitive function in HIV-seropositive drug users (DU) in a pre-AIDS state. DESIGN: Fifty-six HIV-positive DU were prospectively evaluated. They belonged to groups II, III and IV (subgroups A, C2 and E) of the 1987 Centers for Disease Control and Prevention classification, with anamnesis negative for neurological pathology. HIV-negative DU (n = 19) and non-DU (n = 27) were used as controls. Infection with HIV and use of toxic drugs were considered variables of influence on cognitive function. METHOD: Subjects underwent neuropsychological evaluation by tests designed to explore cortical and subcortical function. RESULTS: HIV-positive DU showed worse performance scores at the psychometric tests than HIV-negative non-DU, but there was no difference when compared with HIV-negative DU. Ex-DU showed better performance than active DU. No difference with regard to degree of disease evolution was observed among HIV-positive individuals (i.e., groups II and III versus group IV). CONCLUSIONS: There was no evidence of cognitive deficits in HIV-positive individuals in non-AIDS phases to indicate early involvement by HIV at the cerebral level. Progression of the disease, prior to the AIDS phase, did not determine a worsening of intellectual performance. Instead, cognitive function was affected by the chronic and current use of toxic substances. In HIV-positive DU, a decline in cognitive function was found to be attributable to the chronic use of toxic substances rather than HIV infection.

Cognition↗
PubMedDate not supplied

[Germinal tumor of the testis and acquired immunodeficiency syndrome].

Over the last few years a number of testicular tumours in seropositive patients or patients with AIDS-diagnostic factors have been described in the literature with no clear relationship having been established between both conditions. Most authors believe management should not differ from that being given to non-immunodeficient patients. The paper presents one case of non-seminomatous germinal tumour in a 41-year old homosexual patient, HIV positive, with unfavourable evolution in spite of the treatment received.

Acquired Immunodeficiency Syndrome↗
PubMed2002

Evolution of the cutaneous immune response to experimental Haemophilus ducreyi infection and its relevance to HIV-1 acquisition.

Haemophilus ducreyi causes the sexually transmitted disease chancroid, which facilitates HIV-1 transmission. Skin biopsies were obtained from subjects experimentally infected with H. ducreyi to study the evolution of the immune response and immunophenotypes relevant to transmission of HIV-1. Compared with peripheral blood, there was an enrichment of T cells and macrophages after 48 h of infection in the skin. Neutrophils became the predominant cell type by 7-9 days. By immunohistochemistry, macrophage-inflammatory protein-1alpha was not present early in infection, but was abundant at later stages. RANTES was present throughout the papular and pustular stages of experimental infection, but not present in uninfected control skin. Stromal cell-derived factor-1 was present at low levels in all samples examined. Macrophages in lesions had significantly increased expression of CCR5 and CXCR4 compared with peripheral blood cells, and CD4 T cells had significant up-regulation of CCR5. The magnitude of increased expression of these receptors was not replicated when PBMCs were incubated with H. ducreyi or H. ducreyi lipooligosaccharide in vitro. Together with the disruption of mucosal and skin barriers, the presence of cells with up-regulated HIV-1 coreceptors in H. ducreyi-infected lesions may provide an environment that facilitates the acquisition of R5 (CCR5), X4 (CXCR4), and dual-tropic HIV-1 strains.

Chancroid↗
PubMed2001

Gene flow in wild chimpanzee populations: what genetic data tell us about chimpanzee movement over space and time.

The isolation of phylogenetically distinct primate immunodeficiency viruses from at least seven wild-born, captive chimpanzees indicates that viruses closely related to HIV-1 may be endemic in some wild chimpanzee populations. The search for the chimpanzee population or populations harbouring these viruses is therefore on. This paper attempts to answer the question of whether or not such populations of chimpanzees are likely to exist at all, and, if so, where they are likely to be found. We summarize what is known about gene flow in wild populations of chimpanzees, both between major phylogeographical subdivisions of the species, and within these subdivisions. Our analysis indicates that hitherto undocumented reproductively isolated chimpanzee populations may in fact exist. This conclusion is based on the observation that, despite limited geographical sampling and limited numbers of genetic loci, conventional notions of the nature and extent of chimpanzee gene flow have recently been substantially revised. Molecular genetic studies using mitochondrial DNA sequences and hypervariable nuclear microsatellite markers have indicated the existence of heretofore undocumented barriers to chimpanzee gene flow. These studies have identified at least one population of chimpanzees genetically distinct enough to be classified into a new subspecies (Pan troglodytes vellerosus). At the same time, they have called into question the long-accepted genetic distinction between eastern chimpanzees (Pan troglodytes schweinfurthii) and western equatorial chimpanzees (Pan troglodytes troglodytes). The same studies have further indicated that gene flow between local populations is more extensive than was previously thought, and follows patterns sometimes inconsistent with those documented through direct behavioural observation. Given the apparently incomplete nature of the current understanding of chimpanzee gene flow in equatorial Africa, it seems reasonable to speculate that a chimpanzee population or populations may exist which both harbour the putative HIV-1 ancestor, and which have remained reproductively isolated from other chimpanzee populations over the time-scale relevant to the evolution of the SIVcpz-HIV-1 complex of viruses. Continued extensive sampling of wild chimpanzee populations, both for their genes and their viruses, should be performed quickly considering the high probability of extinction that many wild chimpanzee populations face today. The history of human-chimpanzee contacts is discussed.

Africa↗
PubMed2005

Detection of HIV-2 by PCR.

Genomes of human immunodeficiency virus type 2 (HIV-2), like those of HIV-1 or other retroviruses, are highly variable. These genetic variants have been classified into seven genetic subtypes. The average genetic divergence between different subtypes is about 20% in the gag gene, which is higher than those among HIV-1 group M subtypes. The current serological tests cannot distinguish the different subtypes from one another. To understand genetic variation, evolution, and subtype distribution of HIV-2, polymerase chain reaction (PCR) technology has been widely used. The PCR products that are amplified from highly conserved regions among all subtypes can be either cloned into plasmid vectors for sequence analysis or directly sequenced without a cloning step. Phylogenetic analysis of newly obtained sequences with reference sequences can determine the subtype classification or identify new subtypes if the sequences do not belong to any known subtypes.

DNA, Viral↗
PubMed2005

Genetic analysis of HIV by in situ PCR-directed laser capture microscopy of infected cells.

Behind the exponential expansion of the acquired immunodeficiency syndrome (AIDS) epidemic, there is a continuous and progressive molecular evolution of human immunodeficiency virus (HIV)-1. In this regard, the molecular analysis of viral strains infecting several anatomic compartments in humans has become critical to understanding AIDS-related pathologies and to improving emerging therapeutic protocols. Laser capture microdissection provides outstanding results in the genetic analysis of HIV-1 variants detectable in AIDS patients. The ability of the instrument to microdissect infected cells from a heterogeneous tissue compartment allows the investigator to obtain critical information regarding the genetic nature of a specific viral strain. To perform laser capture microdissection with better accuracy, a priori detection techniques may provide useful information about HIV distribution in the tissue specimen. An in situ polymerase chain reaction (PCR) assay on a serial slide results in a detailed map of the viral infection specific for the case under analysis. The knowledge of HIV distribution in the tissue section is critical for improving the dissection of infected cells by laser capture microscopy. This chapter describes laser capture microdissection and in situ PCR and its role in the analysis of the genetic nature of HIV-1 variants and quasispecies.

AIDS-Associated Nephropathy↗
PubMed2004

Modifications of haematological series in patients co-infected with human immunodeficiency virus and hepatitis C virus during treatment with interferon and ribavirin: differences between pegylated and standard interferon.

Therapy with interferon and ribavirin for hepatitis C virus (HCV) infection induces a decrease in several haematological population counts. It is unclear whether haematological toxicity is more severe in patients co-infected with HCV and human immunodeficiency virus (HIV). This study analysed the evolution of haematological population counts during and after interferon and ribavirin therapy for chronic HCV infection. Eleven patients co-infected with HIV and HCV and treated with pegylated interferon plus ribavirin, and ten treated with standard interferon plus ribavirin, were analysed. With reference to baseline values, neutrophil counts decreased by an average of 45% (range 18-67%), total lymphocytes by 50% (16-63%), CD4 lymphocytes by 54% (16-61%), haemoglobin by 9% (5-16%) and platelets by 31% (16-45%). The nadir of the decrease was reached in the first weeks of therapy and was maintained while patients were receiving treatment. The reduction in all series was higher with pegylated interferon. Patients recovered their baseline counts after finishing the treatment. No cases of haemorrhage or outstanding infection were detected during follow-up.

AIDS-Related Opportunistic Infections↗
PubMed2006

Modification of the Tet-On regulatory system prevents the conditional-live HIV-1 variant from losing doxycycline-control.

BACKGROUND: We have previously constructed a doxycycline (dox)-dependent HIV-1 variant by incorporating the Tet-On gene regulatory system into the viral genome. Replication of this HIV-rtTA virus is driven by the dox-inducible transactivator protein rtTA, and can be switched on and off at will. We proposed this conditional-live virus as a novel vaccine approach against HIV-1. Upon vaccination, replication of HIV-rtTA can be temporarily activated by transient dox administration and controlled to the extent needed for optimal induction of the immune system. However, subsequent dox-withdrawal may impose a selection for virus variants with reduced dox-dependence. RESULTS: We simulated this on/off switching of virus replication in multiple, independent cultures and could indeed select for HIV-rtTA variants that replicated without dox. Nearly all evolved variants had acquired a typical amino acid substitution at position 56 in the rtTA protein. We developed a novel rtTA variant that blocks this undesired evolutionary route and thus prevents HIV-rtTA from losing dox-control. CONCLUSION: The loss of dox-control observed upon evolution of the dox-dependent HIV-1 variant was effectively blocked by modification of the Tet-On regulatory system.

Binding Sites↗
PubMedDate not supplied

[Dynamic study of anti-HIV antibody avidity after cellular immunity restoration under antiretroviral treatment].

We have studied the evolution of the avidity of anti-HIV antibodies, in 14 infected patients with Aids, including 11 patients with severe immunodeficiency at Aids stage and under active antiretroviral therapy (HAART), and 3 non-treated patients with moderate immunodeficiency. These patients have been followed up to 4 years, every 4 months the first year and every 6 months the three others, with HIV1 RNA viral load, CD4 and CD8 cells dosages and anti-HIV avidity measurements (Axsym HIV-1/2), using 1 M guanidine denaturation. A rapid decrease of the viral load was observed under Haart, inducing immune restoration with CD4 and CD8 cells increases (10 and 2-fold respectively). The decrease of anti-HIV avidity (- 20%) has been observed after 5 to 8 months under Haart, with a return to baseline value (84%). The quick restoration of CD4 cells with a persistence of viral antigens at the beginning of treatment has facilitated the selection of novel naive B lymphocytes producing low-affinity antibodies, measured by the decrease of global anti-HIV avidity. The reduction or even clearance of viral antigens under Haart could secondarily induce the selection of B lymphocytes with higher antibody affinity and therefore higher anti-HIV avidity. Thus, this avidity measurement could be used to assess the functional activity of CD4 cells restoration in HIV infected patients under Haart.

Acquired Immunodeficiency Syndrome↗
PubMed1993

A prospective four-year follow-up of neuropsychological function in HIV seropositive and seronegative methadone-maintained patients.

The evolution of central nervous system (CNS) impairments associated with human immunodeficiency virus (HIV) infection was assessed by a prospective, longitudinal study of patients in a methadone maintenance clinic. At a mean of 47 months after baseline testing, which included physical exams, HIV antibody testing and a neuropsychological (NP) screening battery, 121 subjects received a second NP assessment. Forty subjects (33%) who were seropositive at baseline showed statistically significant declines in NP function over the 4 years compared with 81 seronegatives, on the Finger Tapping and Trail Making B tests. This relatively long-term follow-up suggests that subtle cognitive deficits develop over time and can be identified early, but their course is slow and appears generally to parallel that of non-CNS symptoms/signs of HIV infection.

AIDS Dementia Complex↗
PubMed1999

Human immunodeficiency virus infection in Haiti.

This article reviews human immunodeficiency virus (HIV) infection in Haiti. The evolution of the epidemic in Haiti, its spread from urban to rural areas, its varied clinical manifestations, and the attitudes of Haitian people toward HIV infection provide important lessons on understanding and managing this infection in a developing country. The heterosexual spread of HIV, particularly among the poor, is well-documented as is the role of other sexually transmitted diseases along with tuberculosis. Coinfection of HIV and tuberculosis have led researchers to study the effects of six-month supervised intermittent tuberculosis therapy both in controlling tuberculosis and slowing the progression of HIV. Various surveys and discussion groups about acquired immunodeficiency virus knowledge and beliefs demonstrate a large deficit in HIV education despite campaigns to educate the population. The great impact of HIV disease on morbidity and mortality in Haiti indicates that a great deal of work still needs to be accomplished and demonstrates the frustration in fighting the infection in countries with inadequate resources and infrastructure. Advances in HIV vaccine research seem to be the most promising option for developing countries such as Haiti.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Inhibiting HIV-1 entry with fusion inhibitors.

In recent years, tremendous progress has been made in understanding the HIV-1 entry process in which the viral and cellular membranes are fused, resulting in the subsequent delivery of the viral genome into the host cell. The mechanistic insight gained from these studies has led to the formulation of exciting new approaches for therapeutic intervention. One of the first and clinically most advanced drugs to emerge from this effort is the fusion inhibitor T20. T20 acts by freezing a transient structural intermediate of the HIV-1 fusion process, thus blocking an essential step in viral entry. With phase III clinical trials already well underway, the success of T20 indicates that targeting of the viral entry process will soon be an important component of antiretroviral therapy. This review addresses this rapidly developing area of HIV research, with a focus on the mechanistic role of fusion inhibitors targeted to the HIV-1 gp41 transmembrane glycoprotein. We will review the results of recent clinical trials with T20 and discuss possible mechanisms of viral escape through the evolution of drug-resistant HIV-1 variants. We will also discuss ongoing research on fusion inhibitor susceptibility testing and the development of new improved fusion inhibitors.

Clinical Trials as Topic↗
PubMed2006

Model selection for mixtures of mutagenetic trees.

The evolution of drug resistance in HIV is characterized by the accumulation of resistance-associated mutations in the HIV genome. Mutagenetic trees, a family of restricted Bayesian tree models, have been applied to infer the order and rate of occurrence of these mutations. Understanding and predicting this evolutionary process is an important prerequisite for the rational design of antiretroviral therapies. In practice, mixtures models of K mutagenetic trees provide more flexibility and are often more appropriate for modelling observed mutational patterns. Here, we investigate the model selection problem for K-mutagenetic trees mixture models. We evaluate several classical model selection criteria including cross-validation, the Bayesian Information Criterion (BIC), and the Akaike Information Criterion. We also use the empirical Bayes method by constructing a prior probability distribution for the parameters of a mutagenetic trees mixture model and deriving the posterior probability of the model. In addition to the model dimension, we consider the redundancy of a mixture model, which is measured by comparing the topologies of trees within a mixture model. Based on the redundancy, we propose a new model selection criterion, which is a modification of the BIC. Experimental results on simulated and on real HIV data show that the classical criteria tend to select models with far too many tree components. Only cross-validation and the modified BIC recover the correct number of trees and the tree topologies most of the time. At the same optimal performance, the runtime of the new BIC modification is about one order of magnitude lower. Thus, this model selection criterion can also be used for large data sets for which cross-validation becomes computationally infeasible.

Bayes Theorem↗
PubMed2004

Evidence for positive epistasis in HIV-1.

Reproductive strategies such as sexual reproduction and recombination that involve the shuffling of parental genomes for the production of offspring are ubiquitous in nature. However, their evolutionary benefit remains unclear. Many theories have identified potential benefits, but progress is hampered by the scarcity of relevant data. One class of theories is based on the assumption that mutations affecting fitness exhibit negative epistasis. Retroviruses recombine frequently and thus provide a unique opportunity to test these theories. Using amino acid sequence data and fitness values from 9466 human immunodeficiency virus 1 (HIV-1) isolates, we find in contrast to these theories strong statistical evidence for a predominance of positive epistasis in HIV-1.

Amino Acid Sequence↗
PubMed2006

The XIVth International HIV Drug Resistance Workshop, Quebec City, Canada, June 2005.

This report summarizes research advances that further our understanding of the evolution, mechanisms and clinical impact of HIV drug resistance presented at the XIVth International HIV Drug Resistance Workshop held in Quebec City, Canada from June 7-11, 2005. The topics that were discussed included the clinical implications of resistance in mother-to-child transmission, breakthroughs in technologies for studying resistance, resistance to new antiretroviral agents, mechanisms of HIV drug resistance, epidemiological trends, and HIV fitness and pathogenesis.

Animals↗
PubMed2003

When it comes to contact notification, HIV is not TB.

HIV partner notification can help patients, partners, and disease control efforts in the community. The emphasis on HIV partner notification has varied widely in the United States. Stigma, denial, and competing priorities have limited the use of partner notification in many areas. Ongoing HIV transmission after the infection is diagnosed suggests a need for ongoing partner notification, but there is little evidence that this is occurring. The forces driving the evolution of partner notification for HIV are quite different from those acting on contact tracing for TB. Understanding these forces will help predict where partner notification is headed and may help make it more effective. In this paper we review partner notification for HIV, discuss effectiveness, and outline changes over time. A comparison with contact tracing for TB leads us to conclude that partner notification for HIV is very different from contact tracing for TB.

Contact Tracing↗