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 1,063 records · Page 59Linked to original sources
PubMed2003

Early induction and maintenance of Env-specific T-helper cells following human immunodeficiency virus type 1 infection.

Mounting evidence points to a role for CD4+ T-helper (Th) cell activities in controlling human immunodeficiency virus type 1 (HIV-1) infection. To determine the induction and evolution of Th responses following acute infection, we prospectively analyzed Env- and Gag-specific Th responses longitudinally for 92 patients with acute (n = 28) or early (n = 64) HIV-1 infection (median, 55 days postinfection [DPI]). The probability of detecting HIV-1-specific lymphoproliferative responses was remarkably low, and when present, the responses were more likely to be Gag specific than Env specific (16 versus 5%). Env-specific responses were significantly more common in patients presenting at <30 DPI than in those presenting at 30 to 365 DPI (21 versus 0.5%, P = 0.001). By contrast, Gag-specific responses occurred with similar frequencies among subjects presenting at <30 DPI and 30 to 365 DPI (13 versus 17%, P = 0.6). After treatment, and regardless of the duration of infection before therapy, Gag-specific Th responses predominated. Furthermore, some acutely infected subjects lost detectable Env-specific Th proliferative responses, which failed to reemerge upon treatment. Detailed analysis for one such subject revealed Env-specific lymphoproliferation at 11 DPI but no detectable Env-specific lymphoproliferation or ex vivo gamma interferon (IFN-gamma) secretion at multiple subsequent time points. Env-specific CD4+ T-cell clones from 11 DPI recognized six epitopes in both conserved and variable regions within gp120 and gp41, exhibited major histocompatibility complex-restricted cytotoxicity, and secreted high levels of antiviral cytokines. T-cell receptor clonal transcript analyses and autologous virus sequencing revealed that Th cells induced during acute infection were maintained and there were no Th escape mutations. Subsequent analysis for this subject and six of seven others revealed detectable IFN-gamma-secreting cells, but only following in vitro gp160 stimulation. In summary, we conclude that Env-specific Th responses are elicited very early in acute infection and may precede Gag-specific responses. The inability to detect Env-specific Th responses over time and despite antiretroviral therapy may reflect low frequencies and impaired proliferative capacity, and viral escape is not necessary for this to occur.

Acute Disease↗
PubMed1999

Antiretroviral therapy in 1999 for antiretroviral-naive individuals with HIV infection.

The choice of initial antiretroviral regimen for treating people infected with HIV is crucial to successful long-term control of virus replication. Potent antiretroviral therapy substantially suppresses viral replication as measured by plasma HIV RNA levels to below limits of detection: the current standard of care is usually a combination of at least three drugs and frequently includes a protease inhibitor, or alternatively a non-nucleoside reverse transcriptase inhibitor (nnRTI). Patients who have low CD4+ cell counts (< or = 200 CD4+ cells/mm3) or high plasma HIV RNA levels (> or = 100,000 copies/ml) may not attain maximal suppression of HIV replication when treated with current regimens and may require more aggressive therapy. In contrast, patients with relatively normal CD4+ cell counts and low to non-measurable levels of plasma HIV RNA over prolonged periods (i.e., slow or non-progressors) may not require immediate antiretroviral therapy. These individuals should reconsider treatment when either the CD4+ cell count declines or the HIV RNA level increases. Early and potent antiretroviral therapy should provide more durable virological and clinical benefits for many patients, especially if they receive sufficient counselling and support to aid adherence to the treatment regimen. The optimum time to initiate antiretroviral therapy is not well established, but to maximise the recovery of the immune system and the virological and clinical benefits, initiation of therapy is generally recommended for individuals who have symptoms or those with plasma HIV RNA levels > 5000-10,000 copies/ml, or CD4+ cell counts < 500 cells/mm3. The current choice of initial antiretroviral regimens includes two nucleoside reverse transcriptase inhibitors (nRTI) with a potent, well-tolerated HIV-1 protease inhibitor or nnRTI. Recent short-term activity data (24-week comparative clinical trial data) indicate that regimens combining three nRTI, including abacavir, could also be considered. Other emerging combination regimens for consideration include two HIV-1 protease inhibitors with one or two nRTI, or a combination of drugs from all current categories (e.g., nRTI with a nnRTI and HIV-1 protease inhibitor). The goal of antiretroviral therapy is to maximise suppression of HIV replication and thereby prevent or delay viral resistance, restore immunological function and improve clinical outcome. Since evolution of the virus towards resistance can occur with plasma HIV RNA levels between 50 and 500 copies/ml, current standards for best suppression of HIV replication have shifted to declines in plasma HIV RNA to < 50 copies/ml. In addition, non-adherence to any regimen is associated with the greatest risk for virological failure. Therefore, both the decision to initiate therapy and the choice of initial therapy should be carefully weighted and balanced with the long-term implications of antiretroviral therapy.

Anti-HIV Agents↗
PubMed1997

[HIV infection and pericardial disease invasion in Africa].

The number of cases with pericardial disease has been increasing in Africa and particularly in Zäire, after AIDS was defined. To investigate a possible link between HIV infection and risen incidence of pericardial effusions, 64 patients randomly selected (32 HIV carriers and 32 HIV-seronegative as controls), with suspected pericardial disease were studied in a longitudinal trial from January 1991 to December 1994. Central and accessory cells of immune system were measured in conjunction with blood screening, electrocardiogram (ECG), chest X-ray and cardiac ultrasound. Haematological examination included also microscopical examination of blood films after May-Grünwald-Giemsa staining. There were significant decreases of hemoglobin, CD4 cells, and basophils in HIV-seropositive patients. Pericardial disease was estimated 8.8% of in-hospital prevalence, in which 70% of cases were related to HIV infection. The HIV related pericardial disease had an incidence of 1.8% per year. Etiology of pericardial disease depends on evolution and immunodepression level; 90.5% of pericardial effusions related to HIV are caused by tuberculosis as shown at the second pericardiocenthesis.

AIDS-Related Opportunistic Infections↗
PubMed1995

Fatty acids and plasma antioxidants in HIV-positive patients: correlation with nutritional and immunological status.

OBJECTIVE: To investigate red blood cell (RBC) and plasma fatty acids (FA) in HIV-positive patients in relation to oxidative stress and nutritional or immunological status. DESIGN AND METHODS: FA, plasma selenium, vitamins A and E were measured in 95 patients divided into four groups according to CD4 cells. RESULTS: Poly- and di-unsaturated FA (PUFA, DUFA) decreased and saturated FA (SFA) increased in RBC in the patients below 400/mm3 and in plasma in the patients below 50/mm3. RBC SFA correlated to CD4 cells, PUFA to MDA. Unlike vitamin E, plasma vitamin A and selenium decreased in most groups. Plasma SFA and MUFA correlated negatively to selenium and PUFA and DUFA to vitamin E. No correlation was found between PUFA and nutritional markers. CONCLUSION: FA seem to be modified during HIV infection by oxidative stress and disease evolution, but not by denutrition.

Adult↗
PubMed2001

Substitution model of sequence evolution for the human immunodeficiency virus type 1 subtype B gp120 gene over the C2-V5 region.

Phylogenetic analyses frequently rely on models of sequence evolution that detail nucleotide substitution rates, nucleotide frequencies, and site-to-site rate heterogeneity. These models can influence hypothesis testing and can affect the accuracy of phylogenetic inferences. Maximum likelihood methods of simultaneously constructing phylogenetic tree topologies and estimating model parameters are computationally intensive, and are not feasible for sample sizes of 25 or greater using personal computers. Techniques that initially construct a tree topology and then use this non-maximized topology to estimate ML substitution rates, however, can quickly arrive at a model of sequence evolution. The accuracy of this two-step estimation technique was tested using simulated data sets with known model parameters. The results showed that for a star-like topology, as is often seen in human immunodeficiency virus type 1 (HIV-1) subtype B sequences, a random starting topology could produce nucleotide substitution rates that were not statistically different than the true rates. Samples were isolated from 100 HIV-1 subtype B infected individuals from the United States and a 620 nt region of the env gene was sequenced for each sample. The sequence data were used to obtain a substitution model of sequence evolution specific for HIV-1 subtype B env by estimating nucleotide substitution rates and the site-to-site heterogeneity in 100 individuals from the United States. The method of estimating the model should provide users of large data sets with a way to quickly compute a model of sequence evolution, while the nucleotide substitution model we identified should prove useful in the phylogenetic analysis of HIV-1 subtype B env sequences.

Evolution, Molecular↗
PubMed1990

[Prediction of the clinical course of AIDS in a cohort of 77 seropositive persons. Importance of p24 antigen in the blood and the level of serum IgA].

Among the HIV-1 seropositive subjects detected through blood donation in Paris area who every six months voluntarily went through a thorough clinical and biological follow-up in the Institut National de Transfusion Sanguine, a cohort of 77 subjects had completed at least four biannual controls by september 1988. Upon inclusion in the study, all subjects were CDC stage II or III, none had received any treatment. Biological parameters in entrance in the study were assessed in a attempt to forecast the CD4 lymphocyte count decrease during the 18 months follow-up time. Multivariate forward stepwise analysis indicated that only p24 ag level, IgA level, and partially neopterin or Beta-2-Microglobulin levels were independently predictive of CD4 count at the end of the follow-up and of the CD4 loss at the same time. The prediction by these biological parameters is a rather poor one, 39% of the variation of CD4 lymphocyte count or 30% of the variation of CD4 loss after 18 months of the cohort follow-up being explained. In conclusion, HIV-infection seems to possess an intrinsic evolution which escapes our surveillance by biological parameters.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

HIV-specific cytotoxic T lymphocytes against alveolar macrophages: specificities and downregulation.

To analyse the evolution of alveolar-lymphocyte-mediated cytotoxic activity directed against autologous alveolar macrophages (AM), cytotoxic assays against various HIV+ target cells were performed in a cohort of 75 patients with HIV-associated lymphoid interstitial pneumonitis (LIP) studied at distinct stages of HIV infection. Our data confirm that alveolar HIV-specific cytotoxic T lymphocytes (CTL) against AM were detectable before AIDS in patients with CD8+ LIP. Mild CD8+ lymphocytic alveolitis occurs silently in 62% of stage II and III patients with no respiratory symptoms. In these cases, the lack of spontaneous alveolar-lymphocyte-mediated cytotoxic activity against autologous AM may contrast with the detection of primary alveolar CTL specific for HIV proteins such as nef. In AIDS patients, the alveolar CTL lytic efficiency against both AM- and HIV-antigen-expressing cells can be inhibited by a suppressor factor produced by alveolar CD8+ CD57+ cells. Therefore, spontaneous CTL lysis of AM may be (1) limited to a subgroup of patients with active LIP and (2) controlled by distinct mechanisms, including suppressor phenomenons, and HIV replication levels in AM.

Cohort Studies↗
PubMed1998

Visceral leishmaniosis in HIV-positive patients: primary infection, reactivation and latent infection. Impact of the CD4+ T-lymphocyte counts.

OBJECTIVE: To discriminate cases of visceral leishmaniosis (VL) following a primary infection from cases originating in a reactivation of a latent Leishmania infection and to assess the impact of CD4+ T-cell counts on the occurrence of VL in patients with HIV disease. METHODS: We searched by Western blotting for the presence of Leishmania infantum-specific antibodies in the sera of 236 HIV-positive patients. We performed a follow-up of antileishmanial serology and analysed the evolution of the CD4+ T-cell counts for 14 HIV-positive VL patients and for 18 HIV-positive Leishmania-seropositive patients without VL. RESULTS: This study (1) showed that the VL disease/Leishmania infection ratio in HIV-positive individuals is high (1 : 10); (2) discriminated between a primary Leishmania infection (five patients who converted from Leishmania-seronegative to Leishmania-seropositive) and a reactivation of a latent infection (seven patients); (3) showed that HIV-positive individuals with dramatically low CD4+ T-cell counts maintained or generated a specific antileishmanial antibody production; (4) demonstrated that the primary-VL appeared at significantly higher (P = 0.028) CD4+ T-cell levels than the reactivation-VL; (5) documented the existence of HIV-positive Leishmania-seropositive individuals who despite a severe and prolonged immunosuppression did not develop VL (eight of 18). CONCLUSION: Our data stress the utility of the follow-up by Western blotting for an early diagnosis of VL, and therefore an early treatment, for HIV-positive patients living in endemic areas. They suggest that in a latent Leishmania infection supplementary control mechanism(s) might operate in addition to the T-cell-mediated response, and provide a further example of non-appearance of an opportunistic infection despite a severe reduction in CD4+ T cells.

AIDS-Related Opportunistic Infections↗
PubMed2005

BioAfrica's HIV-1 proteomics resource: combining protein data with bioinformatics tools.

Most Internet online resources for investigating HIV biology contain either bioinformatics tools, protein information or sequence data. The objective of this study was to develop a comprehensive online proteomics resource that integrates bioinformatics with the latest information on HIV-1 protein structure, gene expression, post-transcriptional/post-translational modification, functional activity, and protein-macromolecule interactions. The BioAfrica HIV-1 Proteomics Resource http://bioafrica.mrc.ac.za/proteomics/index.html is a website that contains detailed information about the HIV-1 proteome and protease cleavage sites, as well as data-mining tools that can be used to manipulate and query protein sequence data, a BLAST tool for initiating structural analyses of HIV-1 proteins, and a proteomics tools directory. The Proteome section contains extensive data on each of 19 HIV-1 proteins, including their functional properties, a sample analysis of HIV-1HXB2, structural models and links to other online resources. The HIV-1 Protease Cleavage Sites section provides information on the position, subtype variation and genetic evolution of Gag, Gag-Pol and Nef cleavage sites. The HIV-1 Protein Data-mining Tool includes a set of 27 group M (subtypes A through K) reference sequences that can be used to assess the influence of genetic variation on immunological and functional domains of the protein. The BLAST Structure Tool identifies proteins with similar, experimentally determined topologies, and the Tools Directory provides a categorized list of websites and relevant software programs. This combined database and software repository is designed to facilitate the capture, retrieval and analysis of HIV-1 protein data, and to convert it into clinically useful information relating to the pathogenesis, transmission and therapeutic response of different HIV-1 variants. The HIV-1 Proteomics Resource is readily accessible through the BioAfrica website at: http://bioafrica.mrc.ac.za/proteomics/index.html.

Africa↗
PubMedDate not supplied

Molecular evolution of human immunodeficiency virus type 1 subtype A in Senegal: 1988-1997.

OBJECTIVE: Few studies have been able to track the genetic diversity of HIV-1 viruses in human populations over time. We analyzed the molecular evolution of subtype A over a 10-year period, in a cohort of female sex workers with a known time of infection. STUDY DESIGN/METHODS: We amplified and sequenced the C2-V3 region of the surface envelope glycoprotein from 73 HIV-1-infected women, infected between 1987-1997. RESULTS: Fifty-one patients were infected by subtype A viruses. The viruses demonstrated significant diversification (p < 0.001) with mean genetic distance increasing from 8.6% in 1989 to 15.9% in 1997. The slope of the fitted curve suggested a rate of diversification of 0.7% per year. The majority of subtype A viruses clustered with HIV-1 subtype A/G recombinant form (IbNG). CONCLUSION: The genetic diversity of HIV-1 subtype A infections doubled over the first 10 years of this high risk population's epidemic, suggesting that implementation of vaccines early in the epidemic may have a higher likelihood of success based on levels of genetic diversity. The A/G recombinant form (IbNG) has taken epidemic proportions in West Africa. This is of particular importance in understanding the epidemiology of HIV-1 subtypes in Africa and to further dissect the potential phenotypic and biological characteristics of these viruses.

Cohort Studies↗
PubMed1998

[Tuberculosis trends in Barcelona (1987-1995). Impact of the human immunodeficiency virus and control measures].

BACKGROUND: To study the epidemiology to tuberculosis (TB) in Barcelona, Spain from 1987 to 1995, analyzing the influence of HIV infection and the impact of control measures. PATIENTS, MATERIAL AND METHODS: All cases detected by the Barcelona Tuberculosis Prevention and Control Program were included in the study of the evolution of TB incidence according to different variables. The impact of HIV infection was analyzed through the attributable risk per cent (AR), and control measures through the evolution of the rate of treatment compliance, contact studies, and diagnostic delay. RESULTS: We detected 8,942 patients, 23.2% of whom were found through the active epidemiological surveillance system, representing an average annual incidence of 60.4/100,000. The incidence peaked in 1991 (68.7/100,000) and slowly declined to 55.7/100,000 in 1995. Men showed higher incidence (RR: 2.74; CI 95%: 2.62-2.87), particularly among the young (25-34 years olds), 53.3% of whom were HIV (+). The AR for HIV was 92.7%. In this period there was an increase in TB HIV (+), IVDU, and prisoners. Treatment compliance (80.8% in 1987 to 93.8% in 1995) and contact studies (3.2 studies/case in 1995) evolved favorably, unlike but diagnostic delay (35 days in 1995) did not. CONCLUSIONS: The Active Epidemiological Surveillance System has affored us a clear view of the actual situation regarding TB in Barcelona, Spain. Despite the HIV epidemics and the high number of IVDU, the evolution of TB has shown a steady decline due to improvement in control measures.

Adolescent↗
PubMed1991

[Simultaneous acute infection with human immunodeficiency virus and cytomegalovirus].

2 cases of simultaneous acute infection caused by HIV and CV that showed clinical features of infectious mononucleosis with spontaneous resolution and good evolution is presented. After 12 months following them up, both are symptom free carriers of HIV and without clinical features of CV infection. These cases had a good evolution, which is contrary to what is described in other medical literature.

AIDS Serodiagnosis↗
PubMed2023

Autologous neutralizing antibodies increase with early antiretroviral therapy and shape HIV rebound after treatment interruption.

Early initiation of antiretroviral therapy (ART) alters viral rebound kinetics after analytic treatment interruption (ATI) and may play a role in promoting HIV-1 remission. Autologous neutralizing antibodies (aNAbs) represent a key adaptive immune response in people living with HIV-1. We aimed to investigate the role of aNAbs in shaping post-ATI HIV-1 rebound variants. We performed single-genome amplification of HIV-1 env from pre-ART and post-ATI plasma samples of 12 individuals who initiated ART early after infection. aNAb activity was quantified using pseudoviruses derived from the most common plasma variant, and the serum dilution that inhibited 50% of viral infections was determined. aNAb responses matured while participants were on suppressive ART, because on-ART plasma and purified immunoglobulin G (IgG) demonstrated improved neutralizing activity against pre-ART HIV-1 strains when compared with pre-ART plasma or purified IgG. Post-ATI aNAb responses exerted selective pressure on the rebounding viruses, because the post-ATI HIV-1 strains were more resistant to post-ATI plasma neutralization compared with the pre-ART virus. Several pre-ATI features distinguished post-treatment controllers from noncontrollers, including an infecting HIV-1 sequence that was more similar to consensus HIV-1 subtype B, more restricted proviral diversity, and a stronger aNAb response. Post-treatment control was also associated with the evolution of distinct N-glycosylation profiles in the HIV-1 envelope. In summary, aNAb responses appeared to mature after early initiation of ART and applied selective pressure on rebounding viruses. The combination of aNAb activity with select HIV-1 sequence and reservoir features identified individuals with a greater chance of post-treatment control.

Humans↗
PubMed2006

Bayesian network analysis of resistance pathways against HIV-1 protease inhibitors.

Interpretation of Human Immunodeficiency Virus 1 (HIV-1) genotypic drug resistance is still a major challenge in the follow-up of antiviral therapy in infected patients. Because of the high degree of HIV-1 natural variation, complex interactions and stochastic behaviour of evolution, the role of resistance mutations is in many cases not well understood. Using Bayesian network learning of HIV-1 sequence data from diverse subtypes (A, B, C, F and G), we could determine the specific role of many resistance mutations against the protease inhibitors (PIs) nelfinavir (NFV), indinavir (IDV), and saquinavir (SQV). Such networks visualize relationships between treatment, selection of resistance mutations and presence of polymorphisms in a graphical way. The analysis identified 30N, 88S, and 90M for nelfinavir, 90M for saquinavir, and 82A/T and 46I/L for indinavir as most probable major resistance mutations. Moreover we found striking similarities for the role of many mutations against all of these drugs. For example, for all three inhibitors, we found that the novel mutation 89I was minor and associated with mutations at positions 90 and 71. Bayesian network learning provides an autonomous method to gain insight in the role of resistance mutations and the influence of HIV-1 natural variation. We successfully applied the method to three protease inhibitors. The analysis shows differences with current knowledge especially concerning resistance development in several non-B subtypes.

Bayes Theorem↗
PubMed2005

Seminal reservoirs during an HIV type 1 eradication trial.

Despite dramatic reduction of the levels of human immunodeficiency virus type I (HIV-1) virions in blood and seminal plasma of infected patients, highly active antiretroviral therapy (HAART) does not eradicate HIV-1. Three patients, with less than 50 copies/ml of plasma viral RNA, were enrolled in this eradication protocol. Didanosine (DDI) and hydroxyurea (HU) were added to their baseline HAART and after a month of therapy, low dose OKT3, followed by a 2-week course of interleukin 2 (IL-2), was administrated. All antiretroviral therapy was then interrupted and the three patients developed viral rebound in the peripheral blood. The V3 loop region of the HIV-1 gp120 from cell-free viral RNA and proviral DNA in blood and seminal compartments was sequenced in one patient. The two major viral isolates in semen cells were macrophage- tropic (R5) and dual-tropic (R5X4), and these isolates were also present in the PBMCs. Six months after the viral rebound, we demonstrated a shift toward dual tropism in semen cell-associated HIV-1 proviral DNA, with the first appearance of a T-lymphotropic (X4) provirus solely in this compartment. The virus responsible for the blood plasma viral rebound was never found in the semen microenvironment. This study suggests viral compartmentalization of the semen microenvironment after an intensification and stimulatory HIV-1 eradication protocol, with evidence of viral evolution.

Amino Acid Sequence↗
PubMedDate not supplied

Recombination in HIV: an important viral evolutionary strategy.

Human immunodeficiency virus (HIV) is a diploid virus: each virion carries two complete RNA genomic strands. Homologous recombination can occur when a cell is coinfected with two different but related strains. Naturally occurring recombinant HIV strains have been found in infected patients in regions of the world where multiple genotypic variants cocirculate. One recombinant HIV strain has spread rapidly to millions of persons in Southeast Asia. Recombination is a mechanism whereby high level and multidrug-resistant strains may be generated in individual treated patients. Recombination also poses theoretical problems for the development of a safe HIV vaccine. Certain features of HIV replication, such as syncytium formation and transactivation, may be best understood as components of a sexual reproductive cycle. Recombination may be an important HIV evolutionary strategy.

Animals↗