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At least 595 records · Page 33Linked to original sources
PubMed2006

[Clinical use of HIV-1 resistance genotyping. Predictive factors of poor virological evolution in salvage treatments].

OBJECTIVES: To describe the use of genotype resistance testing (GRT) for virological failure in clinical practice, and the long-term clinical and virological evolution in patients for whom it is requested. To identify the predictive factors of virological failure in patients with antiretroviral (ARV) salvage therapy. METHODS: Observational study in HIV-infected patients for whom GRT was requested for virological failure (VF) in the period of 1 October 1999 to 31 December 2001. Logistic regression analysis was used to determine the predictive factors of virological progression. RESULTS: Over the period studied, 196 patients required GRT for VF (15%) among those monitored in specific units. GRT was mainly requested for patients who had been extensively pretreated for a mean of 5 years and with a median of 5 ARV combinations. Half the patients presented 3 or more mutations associated with thymidine analogs (TAMs), mutations associated with non-nucleoside analogs (NNRTIs), and 5 or more mutations associated with protease inhibitors (PIs). In 143 (74%) patients, the RTV regimen was changed on the basis of GRT results. In the intent-to-treat analysis, the percentage of patients with plasma VL < 400 cop/mL at 6, 12 and 18 months was 41%, 29% and 17%, respectively. In the on-treatment analysis, the results were 50%, 48% and 46%, respectively. Mean CD4 lymphocyte increase was 59.74 and 94 cells/mm 3. The variables predicting virological failure (plasma VL > 400 cop/mL) at 12 months were plasma VL > 30,000 cop/mL (OR 6, 1.8-19.5) and accumulation of 3 or more TAMs (OR 4.4, 1.3-15) at the start of ARV salvage therapy. CONCLUSION: Even though in clinical practice GRT is requested for patients with various treatment failures, when ART salvage treatment was started, plasma VL was undetectable and immunological response persisted in 40% of patients followed-up for 18 months. The factors best predicting virological evolution were VL and the number of baseline TAMs.

Adult↗
PubMed2003

Clinical and therapeutical follow-up of HIV-associated pulmonary hypertension: prospective study of 10 patients.

OBJECTIVE: To determine the clinical course and prognosis of pulmonary hypertension (PH) in HIV-infected patients in comparison with a group of PH patients without HIV infection. The secondary objective was to ascertain whether more powerful antiretroviral treatments (highly active antiretroviral therapy) could modify the course of PH in HIV-infected patients. DESIGN: Patients with PH and HIV (HIV-PH, group 1) and patients without HIV (PPH, group 2) were prospectively followed. SETTING: A tertiary care institution. PATIENTS: Group 1 included 10 patients, and group 2 included 25 patients. INTERVENTIONS: In group 1, HIV infection was staged according to Centers for Disease Control and Prevention (CDC) classification when patients entered the study, and was re-staged every fourth month. In both groups, PH functional classes and right heart catheterization (RHC) were determined at baseline. RESULTS: In group 1, one of 10 patients was assigned to New York Heart Association (NYHA) class II, seven patients to NYHA class III, and two patients to NYHA class IV. CDC stages ranged from A1 (three patients) to C3 (one patient). No patient showed progression of HIV disease during follow-up. By May 2001, six patients had died. The median survival by the time of RHC was 15.1 months. Causes of death were heart failure in three cases, sepsis in two, and suicide in one case. In seven patients, epoprostenol was started; three patients survived and four died. The cause of death was heart failure in one patient, suicide in one, non-catheter-related sepsis in one patient and catheter-related sepsis in the last patient. In group 2, 11 patients out of 25 were assigned to NYHA class II, 11 patients to NYHA class III, and three patients to NYHA class IV. RHC was not statistically different in the two groups. By May 2001, nine of 25 patients died and one underwent a double-lung transplant. The median survival from the time of RHC was 6.86 months. Cumulative survival rates by RHC were not statistically different (hazard ratio close to 1). CONCLUSIONS: In HIV-infected patients, the onset of PH adversely affects the prognosis at any stage of infection. Clinically adverse progression of PH is not correlated with HIV initial stage and evolution. Moreover, prognosis in patients with sporadic or familial PPH and in patients with HIV-PH with similar RHC is so similar as to strengthen the concept that pulmonary vascular disease overshadows the overall clinical problem in HIV-infected patients.

Adult↗
PubMed2001

Fragment-Based flexible ligand docking by evolutionary optimization.

A new computational approach for the efficient docking of flexible ligands in a rigid protein is presented. It exploits the binding modes of functional groups determined by an exhaustive search with solvation. The search in ligand conformational space is performed by a genetic algorithm whose scoring function approximates steric effects and intermolecular hydrogen bonds. Ligand conformations generated by the genetic algorithm are docked in the protein binding site by optimizing the fit of their fragments to optimal positions of chemically related functional groups. We show that the use of optimal binding modes of molecular fragments allows to dock known inhibitors with about ten rotatable bonds in the active site of the uncomplexed and complexed conformations of thrombin and HIV-1 protease.

Algorithms↗
PubMed2005

Library versus library recognition and inhibition of the HIV-1 Nef allelome.

Rapid evolution of drug-resistant viruses renders essentially all small-molecule antiviral treatments ineffective. We demonstrate an in vitro library versus library approach to identify small molecules targeting a broad spectrum of HIV-1 Nef protein variants. The technique could provide more effective antiviral therapies. First, a library of clinically derived Nef allelic variants, termed an allelome, was selected for function by binding to Nef ligands p53, actin, or p56lck. Next, a library of small-molecule inhibitors challenged the Nef allelome in competition assays. In contrast to single-variant inhibition, structurally simpler molecules could better inhibit the Nef allelome. Additionally, Nef sequences selected for binding to p53 resembled sequences from patients with a rapid progression to AIDS phenotype. Thus, the allelome versus small-molecule library approach offers a route for improving antiviral drug discovery and elucidating fundamental mechanisms of viral pathogenesis and resistance.

Binding Sites↗
PubMed2005

Molecular footprint of drug-selective pressure in a human immunodeficiency virus transmission chain.

Known human immunodeficiency virus (HIV) transmission histories are invaluable models for investigating the evolutionary and transmission dynamics of the virus and to assess the accuracy of phylogenetic reconstructions. Here we have characterized an HIV-1 transmission chain consisting of nine infected patients, almost all of whom were treated with antiviral drugs at later stages of infection. Partial pol and env gp41 regions of the HIV genome were directly sequenced from plasma viral RNA for at least one sample from each patient. Phylogenetic analyses in pol using likelihood methods inferred an evolutionary history not fully compatible with the known transmission history. This could be attributed to parallel evolution of drug resistance mutations resulting in the incorrect clustering of multidrug-resistant virus. On the other hand, a fully compatible phylogenetic tree was reconstructed from the env sequences. We were able to identify and quantify the molecular footprint of drug-selective pressure in pol using maximum likelihood inference under different codon substitution models. An increased fixation rate of mutations in the HIV population of the multidrug-resistant patient was demonstrated using molecular clock modeling. We show that molecular evolutionary analyses, guided by a known transmission history, can reveal the presence of confounding factors like natural selection and caution should be taken when accurate descriptions of HIV evolution are required.

Anti-HIV Agents↗
PubMed2000

[Evolution of the new number of diagnoses of HIV infection in Asturias, Navarra and La Rioja].

BACKGROUND: To describe the time-trend of people diagnosed with HIV infection in Asturias, Navarra and La Rioja up to 1998. METHODS: HIV case reports since the beginning of the epidemic have been analysed. Only the first positive confirmed result for each patient was taken into account. RESULTS: In the three regions a total of 7,870 HIV infections had been diagnosed by 1998 (4 cases per 1,000 inhabitants). New diagnoses decreased 60% since 1991 to 1998, with the greatest fall among intravenous drug users, and the lowest fall in sexually transmitted infections. CONCLUSIONS: This time-trend supports a reduction in HIV transmission in these three regions; however, the number of new diagnosed infections remains high.

Female↗
PubMed2000

Dynamics of dominance of a dipeptide insertion in reverse transcriptase of HIV-1 from patients subjected to prolonged therapy.

A small proportion (0.8%) of individuals of a cohort of HIV-1 infected patients subjected to prolonged therapy with nucleoside analogues included a recently recognised dipeptide insertion in their RT (Ser-Ser or Ser-Gly between RT codons 69 and 70). To study the dynamics of dominance of genomes with this genetic change, sequential HIV-1 isolates from two patients were analyzed with regard to consensus sequences and complexity of mutant spectra. The two patients displayed completely different, complex evolutionary patterns leading to temporary dominance of dipeptide insertions. In one patient, a virus very closely related to an ancestor virus from the same patient overtook the population at late times, displacing genomes encoding a Ser-Ser insertion. In another patient the sequential dominance of genomes with Ser-Ser insertion-->no insertion-->Ser-Gly insertion was observed. These three types of genomes coexisted in the mutant spectrum of one HIV-1 isolate. Complexity was also reflected in the shape of phylogenetic trees derived with genomes from the mutant spectrum at each time point. The results suggest that HIV-1 genomes encoding a dipeptide insertion between RT codons 69 and 70 do not show a clear selective advantage over other genomes lacking the insertion. Such an absence of a clear selective advantage will favor that such genomes encoding this RT insertion become dominant only in a transient fashion, and following disparate kinetics in different patients.

Adult↗
PubMed2000

Health-related quality-of-life measurements in HIV/AIDS care.

The measurement of health-related quality of life (HRQL) for patients infected with the human immunodeficiency virus (HIV) is still in evolution. With the development of antiretroviral therapies and prophylaxis treatments for opportunistic infections, for many individuals HIV infection has become a chronic illness. Very few studies have been undertaken toward understanding the patient's experience of integrating HIV infection as a chronic illness into one's life and the impact of therapy on the quality of the patient's life. To stimulate research into this area, a review of existing studies, with an emphasis on different types of HRQL measurements was undertaken to identify a comprehensive set of measures that allow one to examine the more diffuse impact of the illness on activities of daily living within the social, physical, mental, and existential domains.

Activities of Daily Living↗
PubMed2006

Serial evolution of TCR beta chain transcript mobilization in HIV type-1-infected patients following vaccine immune stimulation and HAART interruption.

In this article, we studied the T cell receptor (TCR)beta chain transcript mobilization in peripheral blood lymphocytes harvested from HIV-1-infected patients before and after vaccination with a mixture of six lipopeptides and at the moment and serially after highly active antiretroviral therapy (HAART) interruption. This study was performed by using a combined qualitative and quantitative assessment of Vbeta mRNA alterations at the level of complementary determining region 3 length distribution (CDR3-LD) of the TCR. Whereas healthy individuals displayed both stable CDR3-LD profiles and Vbeta transcript accumulations over time, the four HIV-1-infected patients in a quiescent disease phase under HAART have a highly significantly biased CDR3-LD. In addition, they displayed a significant further increase of alterations of their beta CDR3-LD profile after vaccination and both a more altered CDR3-LD (p < 0.05) and an increased transcript accumulation of some Vbeta families after HAART interruption. These modifications mostly concerned the CD8(+ve) T cells. Such a global approach of TCR alterations may help to follow the immune response of these patients and allow targeting of more complex in vivo studies by identifying the T cells with a selected repertoire.

AIDS Vaccines↗
PubMed1995

[Fever evolution after treatment in patients with tuberculosis and HIV infection].

OBJECTIVES: To compare the fever course after starting therapy in patients diagnosed of active tuberculosis with and without HIV infection and evaluate the usefulness of empiric antituberculous therapy in diagnosing the disease. METHODS: Review of clinical records from all patients meeting the following criteria for three years: recovery of Mycobacterium tuberculosis from any clinical sample, knowledge of serological status to HIV, initial therapy of tuberculosis, absence of ther causes of fever identified, and not being treated with drugs which potentially could interfere with the course of fever during their hospital stay. RESULTS: At admission HIV-positive patients with tuberculosis were afebrile in a significantly lower proportion than HIV-negative patients (17% vs. 54%, respectively; p < 0.001). After initiating antituberculous therapy, the median time to fever resolution was similar in both HIV-positive and HIV-negative patients (6 and 4 days, respectively). After two weeks of therapy, 25% of HIV-positive patients and 23% HIV-negative patients still had fever. No factor was identified which could predict the delay in resolution of fever. CONCLUSIONS: The course of fever was similar in both HIV-positive and HIV-negative patients after initiating antituberculous therapy. This empirical therapy may be useful in diagnosing tuberculosis, as fever resolved in the first two weeks of therapy in most patients.

AIDS-Related Opportunistic Infections↗
PubMed1997

[The clinical and evolutional characteristics of visceral leishmaniasis in patients with HIV infection].

OBJECTIVE: To analyze the clinical features, yield of the diagnostic techniques, and therapeutic response of HIV-associated visceral leishmaniasis (VL), and compare the initial episodes to the relapses. METHODS: Forty-one episodes of leishmaniasis visceral, diagnosed in 31 HIV-positive patients between 1st February 1992 and 31st January 1996 were reviewed. RESULTS: The prevalence of VL in HIV-positive patients in our center was 4.2%. Fifty-eight percent of the patients had AIDS prior to the diagnosis of VL. Fever was more frequent in the initial episodes than in the relapses (90.3% versus 60%; p < 0.05; OR: 6.2; IC 95%: 0.8-51.5), splenomegaly was more frequent in the relapses (100% versus 71%; p = 0.05). The diagnostic delay was longer in the initial episodes (27.2 +/- 22.7 versus 5 +/- 4.8 days; p < 0.05). The diagnostic yield of bone marrow biopsy was 82.1%, of liver biopsy 72.7% and of splenic fine-needle aspiration 87.5%. The indirect immunofluorescence test for Leishmania antibodies was positive in 5.9% of cases. Therapeutic failure occurred in 47.6% of patients treated with antimonials and 3.3% of patients treated with amphotericin B. Those patients who received secondary prophylaxis had less relapses than those who did not (17.6% versus 66.7%; p < 0.05; OR: 0.11; IC 95%: 0.01-1.28). Of the 31 patients, twenty-six (83.8%) died, and in none of them was the cause of the death directly related to LV. CONCLUSION: HIV-associated VL manifests clinically in a similar fashion to the immunocompetent's disease. It appears in advanced immunosuppression phases, behaving like other AIDS-defining illnesses. In spite of a good therapeutic response the relapse rate is high.

AIDS-Related Opportunistic Infections↗
PubMed1988

Fidelity of HIV-1 reverse transcriptase.

The human immunodeficiency virus type 1 (HIV-1) shows extensive genetic variation and undergoes rapid evolution. The fidelity of purified HIV-1 reverse transcriptase was measured during DNA polymerization in vitro by means of three different assays. Reverse transcriptase from HIV-1 introduced base-substitution errors in DNA from the bacteriophage phi X174 amber3 at estimated frequencies of 1/2000 to 1/4000. Analyses of misincorporation rates opposite a single template adenine residue showed that HIV-1 reverse transcriptase catalyzed nucleotide mismatches with a specificity of A:C much greater than A:G greater than A:A. The high error rate of HIV-1 reverse transcriptase in vitro translates to approximately five to ten errors per HIV-1 genome per round of replication in vivo. This high error rate suggests that misincorporation by HIV-1 reverse transcriptase is, at least in part, responsible for the hypermutability of the AIDS virus. The specificity of misincorporation may provide a basis for the systematic construction of antiviral nucleosides.

Avian Myeloblastosis Virus↗