Diagnostic tests for HIV resistance are created as quickly as the new drugs. Research is leading individualized medicine evolution.
Explore the source record for details and available documents.
Anti-HIV Agents↗
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.
Differential coreceptor expression allows for independent evolution of non-syncytium-inducing and syncytium-inducing HIV-1.
We demonstrated previously that CD45RA(+) CD4(+) T cells are infected primarily by syncytium-inducing (SI) HIV-1 variants, whereas CD45RO(+) CD4(+) T cells harbor both non-SI (NSI) and SI HIV-1 variants. Here, we studied evolution of tropism for CD45RA(+) and CD45RO(+) CD4(+) cells, coreceptor usage, and molecular phylogeny of coexisting NSI and SI HIV-1 clones that were isolated from four patients in the period spanning SI conversion. NSI variants were CCR5-restricted and could be isolated throughout infection from CD45RO(+) CD4(+) cells. SI variants seemed to evolve in CD45RO(+) CD4(+) cells, but, in time, SI HIV-1 infection of CD45RA(+) CD4(+) cells equaled infection of CD45RO(+) CD4(+) cells. In parallel with this shift, SI HIV-1 variants first used both coreceptors CCR5 and CXCR4, but eventually lost the ability to use CCR5. Phylogenetically, NSI and SI HIV-1 populations diverged over time. We observed a differential expression of HIV-1 coreceptors within CD45RA(+) and CD45RO(+) cells, which allowed us to isolate virus from purified CCR5(+) CXCR4(-) and CCR5(-) CXCR4(+) CD4(+) cells. The CCR5(+) subset was exclusively infected by CCR5-dependent HIV-1 clones, whereas SI clones were preferentially isolated from the CXCR4(+) subset. The differential expression of HIV-1 coreceptors provides distinct cellular niches for NSI and SI HIV-1, contributing to their coexistence and independent evolutionary pathways.
Amino Acid Sequence↗
V3 seroreactivity and sequence variation: tracking the emergence of V3 genotypic variation in HIV-1-infected patients.
OBJECTIVE: To investigate the relationship between V3-specific immune responses and viral quasispecies evolution in 10 HIV-1-seropositive patients enrolled in a phase I trial of recombinant gp160. METHODS: Serologic responses to the HIVLAI V3 loop and autologous V3 loop DNA sequences were sequentially determined over a 3-4-year interval. RESULTS: Six patients either seroconverted or had a > or = 42-fold boost in titer to the V3 reagent associated with an average of 3.2 amino-acid changes in their autologous V3 loops. Four patients with < or = 11-fold change in titer to the V3 loop showed an average of 0.75 amino-acid changes. Attempts to measure autologous V3 loop responses in four patients using a peptide enzyme-linked immunosorbent assay technique did not show a distinct binding preference for autologous versus heterologous V3 loop peptides. Thus, we interpret seroreactivity to the heterologous HIVLAI V3 loop to reflect the broadness of the V3 immune response rather than a direct measure of epitope-specific immune pressure. CONCLUSIONS: These data suggest that the broadness of serologic responses to viral epitopes are reflected in the rate of evolution of their cognate coding sequences and support the view that the immune response to HIV-1 results in the continuous selection of new viral variants during the course of disease.
AIDS Vaccines↗
Active generation and selection for HIV intersubtype A/D recombinant forms in a coinfected patient in Kenya.
To investigate the in vivo evolution of recombinant HIV, we followed up on a mother who was initially coinfected with subtypes A and D in Kenya. Blood samples were obtained in 1996 and 2002, and HIV pol and env genes were amplified by PCR, cloned, sequenced, and phylogenetically analyzed. As for the 1996 sample most of the clones generated from the pol and env genes clustered either with subtypes A and D reference strains. However, two clones from the pol gene were found to be independent recombinants between subtypes A and D by RIP analysis, suggesting active generation of recombinant forms. As for the 2002 sample, all the clones from the pol gene clustered only with the subtype A reference strain, while all the env clones clustered only with subtype D, denoting a dominance of an A/D recombinant form. These results indicate that in patients dually infected with subtypes A and D there is an ongoing generation and selection for A/D recombinant forms.
Adult↗
Evolution of lamivudine-resistant hepatitis B virus and HIV-1 in co-infected individuals: an analysis of the CAESAR study. CAESAR co-ordinating committee.
OBJECTIVES: Lamivudine has potent activity against HIV-1 and hepatitis B virus (HBV). Co-infection with these two viruses is common, and this may therefore influence the choice of antiretroviral therapies. A cohort of co-infected patients treated with lamivudine were studied in order to evaluate the differential effects of lamivudine on the two viral populations within the same individual after 44-52 weeks of therapy. DESIGN AND METHODS: Retrospective virological analysis of an HIV-1/HBV co-infected lamivudine cohort derived from a randomized, placebo-controlled study of lamivudine in HIV infection, the CAESAR study. RESULTS: Five of thirteen patients with HBV viral load > 10,000 copies/ml after 44-52 weeks of lamivudine therapy had genotypic drug resistance. Four of these five had a rebound of viral replication over the period of study and in one case this was associated with an alanine transaminase serum elevation. Ten of the thirteen patients had a 44-52 week HIV viral load > 1000 copies/ml, all of whom also had HIV reverse transcriptase M184V or M184I mutations. CONCLUSIONS: Extrapolating these results to the population yields an estimated 1-year incidence of drug-resistant HBV of at least 14% in lamivudine-treated HIV-1/HBV co-infected patients. The clinical and virological benefit of HBV lamivudine monotherapy in co-infected patients should be balanced against the potential for emergence of drug resistance. Further, these data suggest that the determinants of HIV and HBV drug resistance are different and that parallel evolution, rather than co-evolution of HBV and HIV-1 in co-infected individuals occurs.
CD4 Lymphocyte Count↗
[Evolution of hematological parameters in a group of children with human immunodeficiency virus infection - HIV 1]
OBJECTIVE: To analyze the evolution of clinical and hematological aspects of the children infected with HIV 1. METHODS: Using the CDC criteria, 1994, 37 children with HIV infection were selected, followed up at the Immunodeficiency Clinic at UNICAMP. The study is longitudinal descriptive. Complete blood count, ferritin, serum iron, TIBC and direct Coombs were carried out. RESULTS: The clinical category that predominated wasB(45.94%) and categories A and C were equal (27.03%). All of them were having antiretroviral therapy. Hypochromic and microcytic anemia were seen in 100% of patients up to 12 months of age. There was association between anemia and the progression of the disease, both clinical (p=0.031) and immunological (p=0.0027) and with lymphopenia too (p=0.033). Thrombocytopenia occurred in 10 to 25% of the patients. Low serical ferritin was seen in 2.7% of the cases and low serum iron in 11.1%. All the 15 patients analyzed had negative Coombs test. There was weight and height reduction in 23.5 to 45% of the children and 70.3% had clinical manifestations up to 9 months of age. During the follow up 13.2% of the patients died. CONCLUSIONS: There was association between anemia and lymphopenia with the progression of the disease. In relation to the aetiology of the anemia, about 10% can be considered anemia of chronic disease. Probably the hematological abnormalities seen in peripheral blood are the consequences of loss of control of cellular death mechanism and hematopoiesis in individuals infected by HIV 1.
Journal Article↗
Evolution of neutralizing antibody response against HIV type 1 virions and pseudovirions in multicenter AIDS cohort study participants.
Changes in neutralizing antibody (NA) titers in stored sera collected over 5 years from 10 participants in the Multicenter AIDS Cohort Study (MACS) were evaluated. The participants were HIV-1 infected on enrollment in the MACS, and remained AIDS free during the 5-year study interval. Seven viruses derived from molecular clones were used in NA assays; five of the viruses were T tropic (NL4-3, ALA1, NY5, SF2, and Z2Z6) and two were M tropic [AD8 and NL(SF162)]. In addition, pseudoviruses (PVs) were constructed that expressed envelope genes from NL4-3, ALA1, AD8, and SF162 and from primary viruses from two MACS participants (PV-9 and PV-10). There was significant correlation between NA titers obtained in four of five virus/PV comparisons, while the SF162 PV was more sensitive to NA than the corresponding virus. Comparable changes in NA titers were detected using viruses and PVs. Fourfold or greater increases in NA titers were noted in each of the participants, involving recognition of one to five of the nine strains tested. In some patients these NA titer changes appeared as discrete episodes of immune responses, while in others there may have been either multiple episodes or continuous evolution of the NA responses. The data indicate that changes in NA specificity occur during HIV-1 infection, which may result from the occurrence of neutralization escape mutation. The use of PVs for the study of phenotypic characteristics of envelope glycoproteins should facilitate the study of neutralization escape mutation in HIV-1 infection.
Base Sequence↗
Parallel evolution in the V3 region of HIV type 1 after infection of hemophiliacs from a homogeneous source.
To determine the genetic diversification in the highly functional V3 loop, we followed up five hemophiliacs who were infected by a homogeneous HIV-1 population from a contaminated clotting factor lot. Initially, all patients displayed identical DNA sequences in this part of the proviral env gene. Therefore, this unique outbreak allows us to investigate the biological and genetic development of a common ancestor virus in different patients. A high degree of homology is maintained in the predominant sequences from 5 until 35 months after seroconversion. Only one patient showed a remarkable diversification 3 years postinfection. However, these genetic changes in the V3 region were not associated with disease progression. Discontinuous sequence changes were observed mainly in a region downstream of the V3 loop. Two positions in particular are involved in a sequence evolution within the V3 loop leading to the same amino acids in different patients. These directed changes occurred at sites that are reported to be critical for the specificity of antibodies (position 308) and viral cytopathicity (position 324). However, the parallel evolution was associated neither with differentiation of the viral phenotype nor with progression of the disease.
Amino Acid Sequence↗
Concomitant syphilitic and HIV infection. A case report.
Evolution of syphilis has been studied in HIV-seropositive patients with regard to progression mode and clinical pictures. Reciprocal interactions between syphilis and HIV have been suggested based on the observation of unusually aggressive forms of treponemic infection, particularly at the CNS level. We describe a case of a 52-year-old homosexual male AIDS presenting with clinically manifest tabe dorsalis. The evolution to neurosyphilis seems, at least in this stage, to be accelerated by superimposed HIV infection.
Acquired Immunodeficiency Syndrome↗
Demographics of HIV-1 infection in Denmark: results from the Danish HIV Cohort Study.
We used a population-based cohort study design to describe the demographic characteristics of the HIV-infected population in Denmark and their variation over time. HIV treatment in Denmark is restricted to 9 centres, and all 3941 HIV-1 infected patients more than 15 y old seen at these centres in 1995-2003 were included. We found an estimated HIV prevalence of 70 per 100,000, and a mean annual incidence rate of 5.1 per 100,000 persons. The number of newly infected individuals was stable with a median of 231 per y (period 1995-2002), whereas the number of deaths decreased from 166 in 1995 to 50 in 2000 (p=0.000) and remained stable thereafter. Of the enrolled patients, 75% were males, 80% were Caucasian, 13% were black African, and the primary risk behaviour was male-to-male sexual contact (44%), heterosexual contact (36%), and injection drug use (11%). During the y 1995-2003 we found an increase in age at diagnosis (p=0.000), and no major changes in gender, race, mode of infection, or baseline CD4+ cell count and viral load, neither overall not within subgroups of patients. In this period 14.5% had AIDS at the time of HIV diagnosis. Our data do not confirm concerns about unmonitored evolution in the HIV epidemic in Denmark.
Adult↗
Early multitherapy including a protease inhibitor for human immunodeficiency virus type 1-infected infants.
BACKGROUND: To assess tolerance and efficacy of early multitherapy including a protease inhibitor for infants perinatally infected with HIV. METHODS: Observational study of tolerance and clinical and immunovirologic evolution in HIV-infected infants treated before the age of 1 year in the French Perinatal Study. RESULTS: Thirty-one infants were included. The median age was 3.7 months at initiation of multitherapy. Clinical stage was C (n = 8), B (n = 5) or A/N (n = 18). The median HIV RNA viral load was 5.8 log copies/ml, and the median CD4 cell percentage was 29%. Median follow-up of treatment was 27 months. Of 31 infants 15 experienced mild to moderate adverse events. No infant had clinical or immunologic progression. The median change in viral load was -2.7 log copies/ml after 3 months, -2.0 log after 12 months and -1.7 log after 24 months of treatment. The proportion of infants with a viral load below 500 copies/ml decreased from 53% at 6 months to 18% at 24 months of treatment. The virologic response was not correlated with viral load at baseline. However, the slope of the viral load decrease during the first month of treatment was predictive of the virologic response at 3 and 6 months. Fourteen infants with a viral load of >500 copies/ml after 6 months of treatment displayed viruses with antiretroviral resistance mutations in reverse transcriptase and/or protease genes. CONCLUSIONS: Despite the absence of clinical or immunologic progression, the high frequency of virologic failure associated with genotypic resistance reveals the difficulties associated with implementing antiretroviral multitherapy in infants. Suboptimal doses of protease inhibitor could be a factor contributing to treatment failure.
Drug Therapy, Combination↗
Lack of skin test reactivity to common mycobacterial antigens in human immunodeficiency virus infected individuals with high CD4 counts.
BACKGROUND: T cell response to mycobacterial antigens may be directed against those antigens common to all mycobacteria (group i), those restricted to slow (group ii) or fast growers (group iii), or those which are species- or subspecies-specific (group iv). These responses were assessed by skin testing patients infected with the human immunodeficiency virus (HIV) and healthy controls with reagents derived from different strains of mycobacteria. METHODS: Skin test responses to new tuberculins prepared from Mycobacterium tuberculosis, M avium serotypes 4 and 8, and either M intracellulare or M flavescens antigens were evaluated prospectively in 51 HIV infected patients and 67 healthy controls. RESULTS: Assessment of induration at 72 hours showed absence of skin test response to common mycobacterial antigens in all 27 HIV positive patients with CD4 counts of > or = 400/mm3 (range 400-1594, median 540) compared with 27% reactivity in controls; complete anergy was demonstrated in 24 patients with CD4 counts of < 400/mm3. By contrast, no difference in species or subspecies-specific responses was found between healthy controls and HIV positive patients with CD4 counts of > or = 400/mm3. CONCLUSIONS: Subsets of CD4+ T helper cells are instrumental in determining the balance between cell-mediated and humoral immunity. One T helper subset (TH1) produces cytokines that increase cellular immunity and is stimulated by group i common mycobacterial antigens. Lack of this response, but preservation of responses to species-specific antigens while CD4 counts are near normal, may indicate an early failing of TH1 immunity and explain the increased susceptibility of HIV positive patients to mycobacterial infection early on in the evolution of their HIV infection.
Adolescent↗
[Epidemiology of HIV infection in Italy].
AIDS surveillance systems, which have provided for many years useful information on HIV epidemic dynamics, are no longer useful for estimating the evolution of the HIV epidemic due to the effect of anti-retroviral treatments that have strongly improved survival of HIV-infected persons. To obtain reliable data on the HIV epidemic, some Italian provinces and regions (Lazio, Veneto, Friuli Venezia-Giulia, Trento, Modena) have set up local surveillance systems of the new HIV diagnoses. Aggregated data collected by these systems since 1988, show that the rapid spread of the infection in the eighties has been followed by a progressive decrease in the number of new diagnoses during the nineties; in more recent years this trend has levelled-off. The composition of cases by exposure category has greatly changed over time: in 1988 75.2% of cases were injecting drug users, whereas in 2000 58.5% of cases acquired the infection through sexual contacts. HIV incidence for the considered areas decreased from 19.2 per 100.000 inhabitants in 1992, to 6.7 per 100.000 inhabitants in 2000. Median age at diagnosis increased over time, from 27 years in 1988 to 34 years in 2000. The changed pattern of the HIV epidemic in Italy stresses the need of a nation-wide surveillance system for HIV infections aimed at allocation of adequate economic resources and planning specific prevention programmes.
Adult↗
Unique HIV type 1 V3 region sequences derived from six different regions of brain: region-specific evolution within host-determined quasispecies.
HIV type 1 viral quasispecies were amplified by polymerase chain reaction (PCR) in the hypervariable V3 region of gp120 from six different regions of the brain (right and left frontal; right and left parietal; and right and left occipital) and from the peripheral blood mononuclear cells (PBMCs) of a patient who died of AIDS dementia complex (ADC). Cloning and sequencing of the entire V3 region suggested the presence of genetically unique sequences in different regions of the brain. In contrast, the blood-derived viral quasispecies carried homogeneous sequences that were characterized by a single octapeptide crest motif (HLGPGSAF), a motif important in viral fusion. The brain-derived viral strains showed extensive sequence heterogeneity and the presence of seven different octapeptide and four different tetrapeptide crest motifs (HIGPGRAF, RIGPGRAF, HIGPGSAI, HLGPGSAF, HIGPESAI, HLGPESAI, and YLRPGSAF). In addition, the brain-derived strains were also characterized by variable net V3 loop charge and hydrophilicity, along with distinct amino acid changes specific to different brain regions. Together, the sequence and phylogenetic analyses are unique in identifying the complexity of a viral quasispecies and its independent regional evolution within the brain compartment. Uniquely divergent viral strains were identified in the frontal regions and their presence was further supported by the presence of multinucleated giant cells (characteristic of HIV encephalopathy) predominantly in the left and right frontal regions. In summary, these analyses suggest that genetically different populations of HIV-1 may be present in different brain compartments and confirm that specific neurotropic variants may exist.
Acquired Immunodeficiency Syndrome↗
Evolution of the human immunodeficiency virus envelope gene is dominated by purifying selection.
The evolution of the human immunodeficiency virus (HIV-1) during chronic infection involves the rapid, continuous turnover of genetic diversity. However, the role of natural selection, relative to random genetic drift, in governing this process is unclear. We tested a stochastic model of genetic drift using partial envelope sequences sampled longitudinally in 28 infected children. In each case the Bayesian posterior (empirical) distribution of coalescent genealogies was estimated using Markov chain Monte Carlo methods. Posterior predictive simulation was then used to generate a null distribution of genealogies assuming neutrality, with the null and empirical distributions compared using four genealogy-based summary statistics sensitive to nonneutral evolution. Because both null and empirical distributions were generated within a coalescent framework, we were able to explicitly account for the confounding influence of demography. From the distribution of corrected P-values across patients, we conclude that empirical genealogies are more asymmetric than expected if evolution is driven by mutation and genetic drift only, with an excess of low-frequency polymorphisms in the population. This indicates that although drift may still play an important role, natural selection has a strong influence on the evolution of HIV-1 envelope. A negative relationship between effective population size and substitution rate indicates that as the efficacy of selection increases, a smaller proportion of mutations approach fixation in the population. This suggests the presence of deleterious mutations. We therefore conclude that intrahost HIV-1 evolution in envelope is dominated by purifying selection against low-frequency deleterious mutations that do not reach fixation.
Base Sequence↗
Evolution and plasticity of CTL responses against HIV.
Exceptionally potent cytotoxic T lymphocyte responses are generated after HIV invasion and probably control the primary infection as well as the asymptomatic phase of HIV infection. The chronic phase appears as a quasi-equilibrium between waves of new HIV variants and variant-specific CTLs, thus sustaining continuous CTL activation which eventually fails to eradicate HIV disease progression and the reascension of viral replication. Meanwhile, both the host and the virus develop various strategies either to stop or to evade this potentially deleterious permanent CTL activity. The transient effectiveness of CTLs opens perspectives for understanding disease progression generally as well as for immune therapeutic strategies.
Carrier State↗
Evolution of the gp41 env region in HIV-infected patients receiving T-20, a fusion inhibitor.
Explore the source record for details and available documents.
Acquired Immunodeficiency Syndrome↗
Impact of immune interventions on proviral HIV-1 DNA decay in patients receiving highly active antiretroviral therapy.
OBJECTIVE: To measure the evolution of proviral HIV-1 DNA levels in patients receiving highly active antiretroviral therapy (HAART) compared to those treated with HAART plus interleukin-2 (IL-2) and hydroxyurea. DESIGN: Prospective randomised trial. METHODS: Twenty-two HIV-1 infected patients were randomly assigned to a five-drug antiretroviral regimen for 72 weeks, with or without IL-2, followed by a three-drug regimen up to week 120 with additional hydroxyurea in patients having received IL-2. HIV-1 DNA levels in peripheral blood mononuclear cells (PBMC) were measured regularly using the Amplicor Monitor kit from Roche Diagnostics (Meylan, France). Potentially infectious HIV-1 was cultured in enhanced conditions from circulating CD4 T cells at week 120. RESULTS: During the study period of 120 weeks, HIV-1 DNA levels in PBMC decreased by -1.1 log in patients treated with HAART only compared with -1.8 log in patients with additional IL-2 and hydroxyurea. A two-phase decay rate was observed, with an inflexion point at 12 weeks. The second decay was slow, with mean half-lives of 130.1 +/- 21.3 weeks and 95.1 +/- 26.3 weeks for patients on HAART and those receiving additional IL-2 and hydroxyurea, respectively. At week 120, one out of 11 patients with HAART alone compared to six out of 11 in the group with IL-2 and hydroxyurea had undetectable proviral DNA levels and three of them had unsuccessful recovery of replication-competent HIV-1 from blood CD4 T cells. CONCLUSION: Therapeutic strategies combining HAART and immune interventions have higher potency to decrease the number of infected cells than HAART alone.
Adult↗