PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “HIV evolution”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 613 records · Page 34Linked to original sources

[HIV infection declines among intravenous drug addicts in Barcelona: 1987-1993].

BACKGROUND: The evolution of the prevalence of HIV infection in intravenous drug addicts who initiate hospital detoxication was analyzed. METHODS: Six hundred fifty intravenous drug addicts (535 males, 115 females) were analyzed for HIV and surveyed in regard to demographic variables and the use of drugs over a period of 7 years (1987-1993): age, sex, year of initiation of intravenous drug addiction, length of the habit and year of admission. RESULTS: Most of the subjects were men (82%) with a mean age of 19.7 years at the time of initiation to the use of i.v. drugs and an age of 25.9 years on admission to the unit. The mean time of i.v. drug addiction at admission was 74 months. The characteristics of the patients according to the year of admission were homogeneous in regard to age, length of drug addiction and male/female ratio. More than 50% of the subjects had initiated the use of i.v. drugs during the first half of the last decade. The global prevalence of HIV infection was of 66.3% with no differences being observed between sexes. The frequency of infection was shown to have globally decreased from 1987 to 1993 (p = 0.06) although the rates of HIV infection in women did not significantly modify (p = 0.08) in contrast to that of men (p = 0.05). CONCLUSIONS: The epidemia of HIV infection in intravenous drug addicts may have entered into remission following a decade characterized by a spread in the use of heroin and great diffusion of the disease.

Adult↗

Requirement of an additional Sam68 domain for inhibition of human immunodeficiency virus type 1 replication by Sam68 dominant negative mutants lacking the nuclear localization signal.

Human immunodeficiency virus type 1 (HIV-1) replication requires active nuclear export of unspliced and incompletely spliced HIV-1 RNA transcripts. This process is evolutionally made possible by expression of HIV-1 Rev, one of the three HIV-1 proteins encoded by completely spliced HIV-1 RNAs. Evidence has accumulated to suggest that Sam68 plays an important role in HIV-1 replication through HIV-1 Rev protein. In the present study, we further examined the structure-function relationship of Sam68 protein in relation to HIV-1 replication. We identified a Sam68 domain located between aa269 and aa321 to be involved in the HIV-inhibitory effects of Sam68 dominant negative mutants lacking the nuclear localization signal (NLS). Deletion of this domain abrogated inhibition of HIV-1 replication by these mutants. HIV-1 Rev protein appeared to mediate the HIV-inhibitory effects of these mutants and by this domain, as assessed by Rev-dependent chloramphenicol acetyltransferase reporter gene assay, in trans rev-defective HIV-1 complementation assay, and RNase protection assay. The HIV-inhibitory mutants containing this domain were further found to have diminished binding affinity to the wild-type Sam68 and to be associated with cytoplasmic retention of exclusively nuclear localized wild type Sam68. Taken together, these results further ascertain the important role of Sam68 in HIV-1 Rev function and viral replication, and suggest that the HIV-inhibitory effects of Sam68 dominant negative mutants directly result from their binding to endogenous Sam68 and their interference with nuclear localization of endogenous Sam68.

Adaptor Proteins, Signal Transducing↗

The growth and the control of human immunodeficiency virus in the lung: implications for highly active antiretroviral therapy.

In recent years, it has become apparent that the lung is an important niche for the proliferation of human immunodeficiency virus (HIV), which may have implications for highly active antiretroviral therapy (HAART). The lung itself is a major site for the opportunistic infections associated with the progression to acquired immune deficiency syndrome (AIDS), specifically Pneumocystis carinii, Myobacterium tuberculosis and pyogenic bacteria. These cases of active pulmonary complications are direct indicators of enhanced progression to AIDS-defining illness and increased morbidity and mortality. It is therefore essential that the interaction between the lung and HIV is fully understood. Recent research indicates the lung may be a major sanctuary for the virus, with distinct evolution and replication in contrast to other target organs for HIV. In this review, we will discuss the recent findings of HIV infection, evolution, host factors involved in the control of HIV within the lung and the impact this may have on current therapy.

AIDS-Related Opportunistic Infections↗

Directions in HIV/AIDS research. A Minnesota perspective.

Clinical studies involving HIV therapeutics are becoming ever more challenging because of the changing epidemiology of HIV infection, the rapid evolution of standard clinical practice, and a more difficult economic environment for research. Recent studies relating to HIV pathogenesis have provided novel insights into the interactions between HIV, the immune system, and antiretroviral therapies. Current dogma now suggests that the interaction of HIV and the immune system is an incredibly dynamic process. HIV is an intimidating pathogen capable of replicating quickly and mutating very rapidly in response to antiretroviral therapy. An important question being studied by Minnesota-based investigators is how well plasma analysis reflects HIV-immune system interactions in the lymphoid tissue where most virus and CD4+ (T-helper) cells are located. Most of the HIV clinical studies in Minnesota are conducted under the auspices of the AIDS Clinical Trials Group (ACTG) or the AIDS Research Consortium of the Twin Cities (ARCTiC). Much expertise is available in Minnesota addressing a wide range of topics, from epidemiology, to basic virology, to prevention. To optimize patient access to clinical studies, we recommend that physicians discuss available clinical studies with an HIV investigator soon after first seeing a new HIV-infected patient.

Acquired Immunodeficiency Syndrome↗

Women and HIV infection: a cohort study of 483 HIV-infected women in Bordeaux, France, 1985-1991. The Groupe d'Epidémiologie Clinique du SIDA en Aquitaine.

OBJECTIVES: To study the epidemiological trends, clinical patterns, evolution and prognosis of HIV infection in women. DESIGN: Cohort study of 1816 HIV-infected patients. RESULTS: Up to 1 January 1991, 483 (26.6%) of the patients reported to the Groupe d'Epidemiologie Clinique du SIDA en Aquitaine surveillance system were women. The male-to-female ratio has decreased progressively (3.4:1 in 1985; 2.7:1 in 1990) over time. Fifty per cent of HIV-infected women are or have been intravenous drug users (IVDU). The proportion of heterosexually acquired HIV infection increased from 11.6 to 34.6% over the last 5 years; 46.9% of the women infected through heterosexual intercourse reported sexual contacts with male IVDU. Excluding Kaposi's sarcoma, no significant difference was observed between men and women in the overall distribution of AIDS-defining events. The observed trend of a slower progression to AIDS in women, compared with men, disappeared when controlling for prognostic variables. However, female sex significantly enhanced survival after AIDS diagnosis in multivariate analysis (relative risk, 2.7; 95% confidence interval, 1.1-6.2). CONCLUSION: Early diagnosis of HIV infection in female patients and prevention of HIV infection among women is now a priority for public health interventions, both in industrialized and in developing countries.

AIDS-Related Opportunistic Infections↗

Procedures for reliable estimation of viral fitness from time-series data.

In order to develop a better understanding of the evolutionary dynamics of HIV drug resistance, it is necessary to quantify accurately the in vivo fitness costs of resistance mutations. However, the reliable estimation of such fitness costs is riddled with both theoretical and experimental difficulties. Experimental fitness assays typically suffer from the shortcoming that they are based on in vitro data. Fitness estimates based on the mathematical analysis of in vivo data, however, are often questionable because the underlying assumptions are not fulfilled. In particular, the assumption that the replication rate of the virus population is constant in time is frequently grossly violated. By extending recent work of Marée and colleagues, we present here a new approach that corrects for time-dependent viral replication in time-series data for growth competition of mutants. This approach allows a reliable estimation of the relative replicative capacity (with confidence intervals) of two competing virus variants growing within the same patient, using longitudinal data for the total plasma virus load, the relative frequency of the two variants and the death rate of infected cells. We assess the accuracy of our method using computer-generated data. An implementation of the developed method is freely accessible on the Web (http://www.eco.ethz.ch/fitness.html).

Anti-HIV Agents↗

Impact of tuberculosis on the course of HIV-infected patients with a high initial CD4 lymphocyte count.

OBJECTIVE: To assess the influence of tuberculosis (TB) on the progression of human immunodeficiency virus (HIV) infection in patients without immunological impairment. MATERIAL AND METHODS: In an observational study of retrospective cohorts, the evolution of 28 HIV-infected patients with TB and a CD4 lymphocyte count >500 x 10(6) cells/l was compared with 56 HIV-infected patients without TB. Each case was paired with two controls by CD4 lymphocyte count (+/-50 x 10(6)/l) and date of starting follow-up (+/-6 months). The progression of HIV infection was evaluated as: 1) immunological progression: time to CD4 lymphocyte count <200 x 10(6)/l; 2) clinical progression: time to development of acquired immune-deficiency syndrome (AIDS), excluding TB; 3) survival; and 4) global disease progression: time to the first defined event in 1, 2 and/or 3. The times to these events were estimated using Kaplan Meier curves. RESULTS: There were no significant differences between the cohorts for age, sex and risk group. Faster immunological impairment (RR 2.94; 95%CI 1.46-8.6; P < 0.01), greater progression to AIDS (RR 4.01; 95%CI 1.66-9.69; P < 0.01), lower survival (RR 3.89; 95%CI 1.53-9.87; P < 0.05) and higher global disease progression (RR 2.82; 95%CI 1.57-5.09; P < 0.01) were found in the cohort of TB patients. These associations were still significant after adjustment for CD4 lymphocyte counts. CONCLUSION: The diagnosis of TB in HIV-infected patients with a high initial CD4 lymphocyte count (>500 x 10(6)/l) was related to greater progression to AIDS and shorter survival.

Adult↗

Genetic and stochastic influences on the interaction of human immunodeficiency virus type 1 and cytotoxic T lymphocytes in identical twins.

Human immunodeficiency virus type 1 (HIV-1) evolves in vivo under selective pressure from CD8+ T-lymphocyte (CTL) responses, which are in turn determined by host and viral genetic factors, such as restricting major histocompatibility complex molecules and the available viral epitope sequences. However, CTL are derived stochastically through the random gene rearrangements to produce T-cell receptors (TCR), and the relative impact of genetic versus stochastic processes on CTL targeting of HIV and immune-driven viral evolution is unclear. Here we evaluate identical twins infected with HIV-1 as neonates from a common blood transfusion, with subsequently similar environmental exposures, thereby allowing controlled comparisons of CTL targeting and viral evolution. Seventeen years after infection, their CTL targeting of HIV-1 was remarkably similar. In contrast, their overall TCR profiles were highly dissimilar, and a dominant epitope was recognized by distinctly different TCR in each twin. Furthermore, their viral epitopes had diverged, and there was ongoing viral phylogenetic divergence between the twins between 12 and 17 years after infection. These results indicate that while CTL targeting is predominately genetically determined, stochastic influences render the interaction of HIV-1 and host immunity, and therefore viral escape and CTL efficacy, unpredictable.

Acquired Immunodeficiency Syndrome↗

Accurate reconstruction of a known HIV-1 transmission history by phylogenetic tree analysis.

Phylogenetic analyses are increasingly used in attempts to clarify transmission patterns of human immunodeficiency virus type 1 (HIV-1), but there is a continuing discussion about their validity because convergent evolution and transmission of minor HIV variants may obscure epidemiological patterns. Here we have studied a unique HIV-1 transmission cluster consisting of nine infected individuals, for whom the time and direction of each virus transmission was exactly known. Most of the transmissions occurred between 1981 and 1983, and a total of 13 blood samples were obtained approximately 2-12 years later. The p17 gag and env V3 regions of the HIV-1 genome were directly sequenced from uncultured lymphocytes. A true phylogenetic tree was constructed based on the knowledge about when the transmissions had occurred and when the samples were obtained. This complex, known HIV-1 transmission history was compared with reconstructed molecular trees, which were calculated from the DNA sequences by several commonly used phylogenetic inference methods [Fitch-Margoliash, neighbor-joining, minimum-evolution, maximum-likelihood, maximum-parsimony, unweighted pair group method using arithmetic averages (UPGMA), and a Fitch-Margoliash method assuming a molecular clock (KITSCH)]. A majority of the reconstructed trees were good estimates of the true phylogeny; 12 of 13 taxa were correctly positioned in the most accurate trees. The choice of gene fragment was found to be more important than the choice of phylogenetic method and substitution model. However, methods that are sensitive to unequal rates of change performed more poorly (such as UPGMA and KITSCH, which assume a constant molecular clock). The rapidly evolving V3 fragment gave better reconstructions than p17, but a combined data set of both p17 and V3 performed best. The accuracy of the phylogenetic methods justifies their use in HIV-1 research and argues against convergent evolution and selective transmission of certain virus variants.

Amino Acid Sequence↗

Inferring frequency dependent selection from the molecular evolution of a rapidly evolving virus: a theoretical investigation.

Hypotheses have been put forward suggesting that immune selection generates much of the intra-patient genetic diversity of rapidly evolving viruses. A Monte Carlo simulation is presented which models sequence evolution in an HIV-like virus under selection from the immune system. Measurements of evolutionary change are then made from the resulting sequences, generating predicted outcomes for each scenario. Frequency dependent immune selection is shown by two statistical measurements to have a significant effect on viral sequence evolution. The use of drawing inferences about underlying evolutionary processes from samples of viral diversity in infected individuals is discussed.

Evolution, Molecular↗

Dual nucleoside analogue treatment in the era of highly active antiretroviral therapy (HAART): a single-centre cross-sectional survey.

Since limited literature exists regarding the outcomes of dual nucleoside analogue reverse transcriptase inhibitor (NRTI) treatment in the highly active antiretroviral therapy (HAART) era, a cross-sectional survey was carried out in a population of around 1000 HIV-infected patients in a single northern Italian university hospital, to assess the frequency, background and long-term evolution of anti-HIV treatment conducted with two NRTIs. An appreciable proportion (20.4%) of the 798 HIV-infected patients currently treated with antiretrovirals at our centre still take a dual NRTI combination, and the great majority of them (68.7%) have a stable disease course (characterized by a viral load <3.7 log(10) HIV RNA copies/mL, a maintained CD4(+) lymphocyte count and absence of HIV disease progression after at least 24 months of follow-up), regardless of the selected regimen, prior antiretroviral therapy use, and baseline virological and immunological situation. Further studies are warranted to establish whether dual NRTI regimens may have residual indications in the HAART era, and whether the shift to a triple antiretroviral combination is expected to lead to long-term advantages in patients with a low risk of disease progression while on dual NRTI treatment.

Anti-HIV Agents↗

Hyperthermic therapy for HIV infection.

The objective of this paper is to review what is known about the antiviral effects of fever and to highlight the scientific evidence supporting the hypothesis that hyperthermic therapy may prove to be a beneficial treatment modality for persons infected with HIV. Our hyperthermic hypothesis is based upon the mutant escape, quasispecies theory of HIV antigenic diversity. We propose that, if initiated during the asymptomatic stage of HIV infection, hyperthermia may prove to decrease the number of mutant HIV strains arising due to evolutionary pressures created by the patient's immune system, with a resultant prolongation of the asymptomatic period of infection. A review of the literature from three areas of investigation: the immune response to fever, heat as a tumor killing agent, and preliminary studies with fever and retroviral infections, strongly suggests that there is a good scientific basis for the use of hyperthermic therapy in a multimodal treatment approach to HIV infection.

Acquired Immunodeficiency Syndrome↗

HIV type 1 tat gene heteroduplex mobility assay as a tool to establish epidemiologic relationships among HIV type 1-infected individuals.

Molecular biology techniques are increasingly used to study the molecular epidemiology of infectious diseases. Most of these methods are expensive and labor-intensive. The human immunodeficiency virus (HIV) has substantial genomic variation, such that HIVs from different individuals are genetically diverse, although mutation rates differ for distinct regions of the genome. Most studies of HIV linkage and molecular evolution have focused on env or gag regions. We show that heteroduplex mobility analysis of the first exon of the HIV tat gene provides a simple, rapid, inexpensive, and reliable discriminatory tool for the molecular differentiation of shared versus distinct HIV-1 quasispecies when epidemiologic relations need to be defined. tat, as a relatively conserved region, appears to be a better region than the more variable env region to establish HIV-1 epidemiological linkages.

DNA, Viral↗

Mycoplasmas and HIV infection: from epidemiology to their interaction with immune cells.

Mycoplasmas are possible HIV cofactors, contributing to the evolution of AIDS. Our knowledge about mycoplasma prevalence in HIV-infected subjects has considerably increased due the development of specific detection assays. A new mycoplasma, Mycoplasma penetrans, has been identified and has been shown to be associated with HIV infection, at least among individuals with homosexual practices. We and others investigated the properties of M. fermentans and M. penetrans concerning cell colonization, cell invasion and cytopathogenicity. The molecular components which are involved in the interaction between these bacteria and immune cells are beginning to be identified and characterized. Membrane lipoproteins of these wall-less prokaryotes are key components in their interaction with B cells and surface capsular material may contribute to their defense from the host immune response.

HIV↗

Immigration, HIV infection, and antiretroviral therapy in Italy. An epidemiological and clinical survey.

Epidemiological, clinical, and therapeutic features of 77 consecutive HIV-infected non-European Union immigrants were compared according to gender. Immigrants (from Sub-Saharan Africa in around 60% of cases) represented 7.9% of our patient cohort at the end of 2002. Compared with male patients, females were more numerous, significantly younger (p.0001), and experienced sexual exposure versus drug addiction (p.02), while no difference was observed according to place of origin. A negative HIV serology preceding immigration was available for five women and four males only, while HIV disease was known before migration in 14 men versus 7 women (p.04). The tendency towards a shorter known history of HIV infection (p.05) of females versus males may be responsible for a lower incidence of AIDS among women (p.02). The use of antiretroviral treatment was matched by time and selected regimens, but compliance proved significantly greater in females versus males (p.0001), and women had less need of a regimen switch due to poor tolerability or refusal (73.2% versus 61.1%); the latter could be responsible for a greater mean CD4+ count (p.02), and lower mean plasma viremia (p.0001), although no difference was found when considering viral suppression rate (70.7% among women, 52.8% among men). Surveillance studies and prospective therapeutic trials are strongly warranted, in order to have a reliable assessment of HIV-infected immigrated people, to check the efficacy of preventive measures, obtain validated data about the clinical, virologic, and immunological evolution and outcome of HIV infection undergoing HAART, and to evaluate the frequency and role of eventual untoward effects of pharmacologic treatment.

Adult↗

HIV-1 infection among non-intravenous drug user female prostitutes in Spain. No evidence of evolution to pattern II.

OBJECTIVES: To assess the prevalence of HIV-1 infection among non-intravenous drug user (IVDU) female prostitutes in Spain and to determine risk factors for HIV-1 infection in this population. DESIGN: Cross-sectional seroepidemiological study of 519 non-IVDU prostitutes. SETTING: Four university hospitals. METHODS: All participants completed a questionnaire and provided a serum sample. Serum samples were tested for antibodies against HIV-1, hepatitis C virus (HCV) and Treponema pallidum. RESULTS: Twelve out of the 519 (2.31%) participants were HIV-1-seropositive. HIV-1 infection was associated with the presence of both HCV and T. pallidum antibodies, multiple sex partners, longer history of prostitution, history of genital ulcers and anal intercourse. Condom use was associated with HIV-1 seronegativity. CONCLUSIONS: The prevalence of HIV-1 infection in non-IVDU prostitutes in Spain remains relatively low. Risk increases with a higher rate of sexual exposure and practices such as anal intercourse and unprotected coitus.

Adolescent↗

[Chronic hepatitis C in HIV co-infected patients. Study of 55 cases with liver biopsy].

BACKGROUND AND OBJECTIVE: To study the evolution of chronic hepatitis in HIV-HCV co-infected patients and the factors conditioning this evolution. PATIENTS AND METHOD: 55 intravenous drug users with HIV-HCV co-infection were studied. We performed a clinical and laboratory study determining the age at the time of HCV infection and the date of liver biopsy, HIV stage, CD4 cell count, viral load, and time under antiretroviral treatment. Moreover, we analyzed the HCV genotype, HCV viral load, ALT plasmatic level, and liver biopsy. Univariate and multivariate analyses were made. RESULTS: 55 patients with HIV-HCV co-infection were evaluated. In the multivariate analysis, gender (p = 0.034; 95% confidence interval [CI], 1.306-1082.625), lowest level of CD4+ lymphocytes (p = 0.021; 95% CI, 1,693-653,484) and highest viral load value (p = 0.022; 95% CI, 1366-53,817) were significantly correlated with liver disease progression. CONCLUSIONS: Both a male sex and a poor immune system situation are associated with a worse evolution of chronic hepatitis C.

Adult↗