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At least 649 records · Page 36Linked to original sources
PubMed2006

Immunological and virological effects of structured treatment interruptions following exposure to hydroxyurea plus didanosine.

Both hydroxyurea (HU) and structured treatment interruptions (STI) have been investigated as therapeutic approaches to enhance immune responses in chronically HIV-infected individuals. HIV-specific T cell responses as well as T cell activation were analyzed longitudinally in 31 HIV-infected individuals who had been treated for the prior 12 months with didanosine (ddI) plus HU and thereafter completed three STI cycles consisting of 2 months off and 2 months on ddI-HU. Similar increases in plasma HIV-RNA were seen in each of the three cycles off therapy, whereas CD4 counts remained fairly stable along the study period. T cell activation paralleled the evolution of plasma HIV-RNA during the first STI cycle and waned afterward. At baseline most patients presented a high level of CD8+ responses to different HIV peptide pools and 23% of them had CD4+ responses to Gag and/or Env. The level of CD8+ responses against each pool was stable and did not increase during STI cycles, while CD4 responses tended to decline. However, the contribution of Nef-specific response to the total CD8 response tended to increase. In a multivariate model, both a higher baseline plasma HIV-RNA and a higher level of Nef-specific response contribution to the total CD8+ response were independently associated with lower plasma HIV-RNA increases during each of the three STI cycles. Nef-specific CD8+ responses might contribute to a better virological control of HIV replication following treatment interruptions in HIV-infected individuals and might be boosted by the immunomodulatory effect of HU.

ADP-ribosyl Cyclase 1↗
PubMed1996

Replication rate and evolution in the human immunodeficiency virus.

Population genetic and virological methods yield estimates for the mean replication rate of the Human Immunodeficiency Virus type 1 (HIV-1) that differ by six fold. I present a simple model that can reconcile the estimates obtained from each method by considering the role of intra-host population structure on viral dynamics. The model shows how latently infected cells, which may produce only a small fraction of infective viruses, can nonetheless have an important influence on estimates of mean replication rate. This contribution of latently infected cells is most important when considering the evolution of HIV and the clinical consequences of viral evolution.

Biological Evolution↗
PubMed1997

Slower evolution of human immunodeficiency virus type 1 quasispecies during progression to AIDS.

The evolution of human immunodeficiency virus type 1 (HIV-1) quasispecies at the envelope gene was studied from the time of infection in 11 men who experienced different rates of CD4+ cell count decline and 6 men with unknown dates of infection by using DNA heteroduplex mobility assays. Quasispecies were genetically homogeneous near the time of seroconversion. Subsequently, slower proviral genetic diversification and higher plasma viremia correlated with rapid CD4+ cell count decline. Except for the fastest progressors to AIDS, highly diverse quasispecies developed in all subjects within 3 to 4 years. High quasispecies diversity was then maintained for years until again becoming more homogeneous in a subset of late-stage AIDS patients. Individuals who maintained high CD4+ cell counts showed continuous genetic turnover of their complex proviral quasispecies, while more closely related sets of variants were found in longitudinal samples of severely immunocompromised patients. The limited number of variants that grew out in short-term PBMC cocultures were rare in the uncultured proviral quasispecies of healthy, long-term infected individuals but more common in vivo in patients with low CD4+ cell counts. The slower evolution of HIV-1 observed during rapid progression to AIDS and in advanced patients may reflect ineffective host-mediated selection pressures on replicating quasispecies.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Selection by AZT and rapid replacement in the absence of drugs of HIV type 1 resistant to multiple nucleoside analogs.

We studied the intrahost evolution and dynamics of a multidrug-resistant HIV-1, which contains an insertion of two amino acids (aa) and several aa changes within the reverse transcriptase (RT) gene. From an individual receiving intermittent therapy, sequences of 231 full-length molecular clones of HIV-1 RT were obtained from serum-derived viruses at 12 consecutive time points over a period of 6 years, 17 to 20 clones per time point. In the 3.5-year period prior to the first course of therapy, only wild-type (wt) viruses were found. As soon as 6 months after the start of zidovudine (AZT) monotherapy, all viruses contained an insertion of two aa between positions 68 and 69 of the RT and aa changes at positions 67 and 215, a combination conferring resistance to multiple nucleoside analogs. After termination of therapy, the insertion mutants were rapidly and completely replaced by the wt viruses. In turn, the insertion mutants replaced the wt viruses after initiation of therapy with 3TC, d4T, and saquinavir. After termination of triple therapy, the wt viruses completely replaced the mutants within 1 month, which is markedly faster than has been observed earlier for the replacement of AZT-resistant viruses. Fast replacements of the mutant virus populations after termination of therapy indicate gross competitive disadvantage of the insertion mutant in the absence of therapy, which we estimated by using several models. The insertion mutants attained high virus loads, demonstrating that virus load cannot be used as a direct measure of virus fitness.

Amino Acid Sequence↗
PubMedDate not supplied

Coronary artery bypass grafting in patients with human immunodeficiency virus.

The role of surgery in the natural history of HIV disease is in evolution. A review was conducted of 2980 CABG operations taking place between January 1992 and January 1996 at St. Vincents Hospital; four of these patients were known to be HIV-positive prior to the operation. Preoperative work-up, operative course, and postoperative events were largely unremarkable. Only 1 of the 4 patients required rehospitalization within 30 days. Follow-up averaged 28 months (range 7-49 months). Three of four patients were in NYHA Class II or better at follow-up. Other reviews of CABG performed on HIV+ patients also indicate that, although CPB can be linked with immune suppression, there is no conclusive evidence of the acceleration of HIV into AIDS associated with CPB. In conclusion, due to the lack of controlled trials and large patient reviews, no firm recommendations about the effect of CPB on immunocompromized patients can be generated.

Adult↗
PubMed2006

Molecular Mechanisms for Altered Glucose Homeostasis in HIV Infection.

A complete understanding of the molecular mechanisms leading to HIV-associated insulin resistance remains elusive. Complex interrelationships between genetic predisposition, disease-related body changes and multidrug therapy all contribute to alterations in glucose homeostasis. These abnormalities can be differentiated between acute and reversible changes directly induced by HAART medications and more chronic and less reversible changes due to the development of lipodystrophy and hyperlipidemia. Implicated pathways include changes in adipokine secretion, insulin signaling, lipid homeostasis and disease-related increases in inflammatory mediators. The insulin responsive facilitative glucose transporter GLUT4 is the first molecule to have been identified as a direct target of HIV protease inhibitors. Efforts to elucidate the mechanisms directly responsible for the evolution of insulin resistance during HIV infection and therapy will be greatly assisted by the further identification and characterization of direct molecular targets amenable to pharmacologic therapy and/or the development of newer antiretroviral agents that do not adversely affect these target proteins.

Journal Article↗
PubMed1994

[Intestinal tuberculosis in patients with and without HIV infection].

GOAL: To Study the main characteristics of intestinal tuberculosis (ITB), comparing patients with and without infection by HIV (HIV and non-HIV, respectively). PATIENTS AND METHODS: The clinical records of patients diagnosed of this disease in the past five years in our center, were retrospectively reviewed. We used as inclusion criteria the histological and/or microbiological corroboration of the intestinal anatomical piece or the bacteriological and/or histological corroboration of tuberculosis at any other location with clinical and radiological signs compatible with intestinal affection. Two groups were established according to the serological results for HIV: HIV and non-HIV. RESULTS: We studied seven cases, three of them infected by the HIV. The mean age of HIV patients was 23 years, whereas the mean age of non-HIV patients was 49 years. Three non-HIV patients referred pulmonary tuberculosis when they were young. The interval between the onset of symptoms and the diagnosis in HIV patients was 45 days, ranging in the non-HIV patients between one month and four years. All the patients had abdominal pain. Six patients, including three HIV, had fever and constitutional syndrome. Thoracal radiography showed tuberculosis activity, bacteriologically demonstrated, in a HIV patient and in a non-HIV patient. Except one HIV-patient, the remainder were laparotomized. In all the HIV patients, intestinal tuberculosis was suspected upon admission, but this was not the case in the four non-HIV patients. CAT was the most useful of all the supplementary explorations conducted. Retrospectively, only four laparotomies were justified, although before this procedure, four patients were incorrectly oriented, one of them infected by the HIV. All the patients showed a good response to an specific treatment. CONCLUSIONS: Laparotomy is still a frequent diagnostic method. The characteristics of the HIV patients are similar to the ones of the non-HIV patients. The main differences are: younger ages and shorter time of evolution until diagnosis in the HIV group, and evidence of former or current pulmonary tuberculosis in the non-HIV group.

Adult↗
PubMed2003

Legionnaires disease and HIV infection.

STUDY OBJECTIVES: To compare the outcome of Legionnaires disease (LD) in patients with and without HIV infection. DESIGN: Retrospective review of clinical charts. SETTING: Six hundred-bed university hospital. PATIENTS: We studied the clinical findings of 64 patients without HIV and 15 patients with HIV. Patients with a serologic diagnosis only were not included. Patients with previous immunosuppressive therapy or transplant recipients were excluded from the former group. In the HIV group, the mean CD4 cell count was 347.5/ microL, plasma viral load was undetectable in 50% of the patients, and only one patient (7%) was receiving cotrimoxazole as prophylaxis against Pneumocystis carinii at the time of pneumonia. No differences were observed in the two groups with respect to community or nosocomial acquisition, delay in the initiation of appropriate treatment, the use of macrolides or fluoroquinolones, and Fine score in cases of community-acquired LD. RESULTS: Univariate analysis showed that time to apyrexia was longer, and respiratory symptoms, bilateral infiltrates in chest radiograph, hyponatremia, increase in aspartate aminotransferase and creatine phosphokinase (CK), and respiratory failure were more frequent in the HIV group. Mortality was greater in patients with HIV, achieving a statistically significant value of 20%; however, multivariate analysis only confirmed these differences with respect to the increase in CK. CONCLUSIONS: LD has a more severe clinical presentation and worse evolution in patients with HIV.

AIDS-Related Opportunistic Infections↗
PubMed1994

Evolution of chest radiographs in treated patients with pulmonary tuberculosis and HIV infection.

A large number of patients with coexisting tuberculosis and HIV infection has been reported. The chest radiographic findings are well described and primarily consist of bilateral, medium-to-coarse reticulonodular opacities often associated with hilar and mediastinal adenopathy. The evolution of chest radiographic abnormalities following treatment for tuberculosis in patients with HIV infection has not been previously studied. Initial and follow-up chest films of 33 patients with tuberculosis and HIV infection were evaluated. All 25 patients whose only pulmonary infection was tuberculosis exhibited radiographic improvement after appropriate treatment. In 8 patients, the chest radiograph worsened while on tuberculosis therapy. In each of these individuals, a newly acquired nontuberculous pulmonary disease was diagnosed as the cause of radiographic deterioration. We conclude that chest radiographs in patients with tuberculosis and HIV-infection will improve with appropriate tuberculosis therapy. Worsening of the chest radiograph does not suggest a poor therapeutic response, but instead indicates the presence of another pulmonary disease.

AIDS-Related Opportunistic Infections↗
PubMed1999

[Infective endocarditis].

Two different series of patients with Infectious Endocarditis (IE), hospitalized in the same ward of Curry Cabral Hospital in Lisbon, are presented and compared. The two series were separated by a ten-year period--the first included patients observed from 1970 to 1976 and the second from 1988 to 1998. In the first series (20 patients), IE occurred mainly in patients with previous cardiac valvular lesion, the course was subacute and Streptococcus viridans was the predominant agent. In the last series (65 patients), most of the patients were young and had no previous valvular lesions. Right side endocarditis predominated and the course was acute. Most of patients were drug addicts and had HIV infection. Staphylococcus aureus was the predominant agent. The ages of the two series were significantly different (p < 0.005). The diagnostic value of transthoracic and transesophageal echocardiography is stressed. The details of the evolution of patients with HIV infection are presented according to the values of CD4+ lymphocyte counts. The relatively good prognosis of IE in drug addicts with antibiotic treatment, even with HIV infection, is emphasized.

Adult↗
PubMed2006

Proviral progeny of heterodimeric virions reveal a high crossover rate for human immunodeficiency virus type 2.

Human immunodeficiency virus type 1 (HIV-1), the causative agent of AIDS in humans, exhibits a very high rate of recombination. Bearing in mind the significant epidemiological and clinical contrast between HIV-2 and HIV-1 as well as the critical role that recombination plays in viral evolution, we examined the nature of HIV-2 recombination. Towards this end, a strategy was devised to measure the rate of crossover of HIV-2 by evaluating recombinant progeny produced exclusively by heterodimeric virions. The results showed that HIV-2 exhibits a crossover rate similar to that of HIV-1 and murine leukemia virus, indicating that the extremely high rate of crossover is a common retroviral feature.

Crossing Over, Genetic↗
PubMed2000

Antigenic drift of viruses within a host: a finite site model with demographic stochasticity.

We theoretically study the antigenic drift of viruses within an infected host, as observed in human immunodeficiency virus (HIV) and equine infectious anemia virus (EIAV) infections, assuming that a finite number of antigen-determining sites at the viral envelop gene are responsible for the specific immune response. The pattern of antigen evolution becomes more complex than that predicted from the previous one-dimensional antigen space models. If the viral growth rate is sufficiently large, the demographic stochasticity for the fate of a new antigen mutant can be neglected. The high dimensionality in the way a virus escapes the immune defense in genotype space could then causes a rapid increase in the antigenic diversity and the total viral density, until finally the whole antigen genotypes are used up. The viral population is then driven to extinction in a host by the enhanced immune response to all genotypes. In contrast, if the viral growth rate is moderate or small so that only a small fraction of new antigen mutants can survive during the initial endangered period of random extinction, the viral antigenic diversity and the total density remain bounded, thereby enabling them to persist for a prolonged period by shifting the dominant antigen types. The phylogenetic pattern of antigen divergence is well characterized by the mean number of surviving antigen mutants from an antigen genotype. The substitution rate at antigen-determining sites increases as the efficiency of host immune response increases.

Animals↗
PubMed2005

Weighted least-squares likelihood ratio test for branch testing in phylogenies reconstructed from distance measures.

A variety of analytical methods is available for branch testing in distance-based phylogenies. However, these methods are rarely used, possibly because the estimation of some of their statistics, especially the covariances, is not always feasible. We show that these difficulties can be overcome if some simplifying assumptions are made, namely distance independence. The weighted least-squares likelihood ratio test (WLS-LRT) we propose is easy to perform, using only the distances and some of their associated variances. If no variances are known, the use of the Felsenstein F-test, also based on weighted least squares, is discussed. Using simulated data and a data set of 43 mammalian mitochondrial sequences we demonstrate that the WLS-LRT performs as well as the generalized least-squares test, and indeed better for a large number of taxa data set. We thus show that the assumption of independence does not negatively affect the reliability or the accuracy of the least-squares approach. The results of the WLS-LRT are no worse than the results of the bootstrap methods, such as the Felsenstein bootstrap selection probability test and the Dopazo test. We also show that WLS-LRT can be applied in instances where other analytical methods are inappropriate. This point is illustrated by analyzing the relationships between human immunodeficiency virus type 1 (HIV-1) sequences isolated from various organs of different individuals.

Animals↗
PubMed2001

Clonal evolution of CD8+ T-cell expansions in HIV-infected patients on long-term HAART.

HIV-1 continually replicates in spite of long-term highly active anti-retroviral therapy (HAART) and therefore, it is conceivable that the low level, persistent viral activity could continue to stimulate the hosts immune system despite remaining below the detection limit of the current assays. In this study, we performed a longitudinal analysis of the CD8+ T-cell receptor Vbeta repertoire in HAART-treated and untreated HIV patients. HAART-mediated control of viremia, for up to 18 months, did not prevent similar perturbations within the CD8+ Vbeta repertoire in both study groups as defined by CDR3 spectratyping. Oligoclonal Vbeta expansions, with new dominant CDR3 lengths, were observed throughout the study period. Our findings are compatible with antigen-driven CD8+ immune responses to bursts of replication from a continuously changing viral reservoir, regardless of HAART-mediated suppression of HIV-1 viremia.

Antiretroviral Therapy, Highly Active↗
PubMed2002

QuickTree: building huge Neighbour-Joining trees of protein sequences.

We have written a fast implementation of the popular Neighbor-Joining tree building algorithm. QuickTree allows the reconstruction of phylogenies for very large protein families (including the largest Pfam alignment containing 27000 HIV GP120 glycoprotein sequences) that would be infeasible using other popular methods.

Algorithms↗