Biomedical subjects

Charles A Boucher

Publications and source records attributed to Charles A Boucher.

5 recordsLinked to original sources

PubMed2005

Prevalence of drug-resistant HIV-1 variants in untreated individuals in Europe: implications for clinical management.

BACKGROUND: Infection with drug-resistant human immunodeficiency virus type 1 (HIV-1) can impair the response to combination therapy. Widespread transmission of drug-resistant variants has the disturbing potential of limiting future therapy options and affecting the efficacy of postexposure prophylaxis. METHODS: We determined the baseline rate of drug resistance in 2208 therapy-naive patients recently and chronically infected with HIV-1 from 19 European countries during 1996-2002. RESULTS: In Europe, 1 of 10 antiretroviral-naive patients carried viruses with > or = 1 drug-resistance mutation. Recently infected patients harbored resistant variants more often than did chronically infected patients (13.5% vs. 8.7%; P=.006). Non-B viruses (30%) less frequently carried resistance mutations than did subtype B viruses (4.8% vs. 12.9%; P<.01). Baseline resistance increased over time in newly diagnosed cases of non-B infection: from 2.0% (1/49) in 1996-1998 to 8.2% (16/194) in 2000-2001. CONCLUSIONS: Drug-resistant variants are frequently present in both recently and chronically infected therapy-naive patients. Drug-resistant variants are most commonly seen in patients infected with subtype B virus, probably because of longer exposure of these viruses to drugs. However, an increase in baseline resistance in non-B viruses is observed. These data argue for testing all drug-naive patients and are of relevance when guidelines for management of postexposure prophylaxis and first-line therapy are updated.

Adult↗

PubMed2005

An automated genotyping system for analysis of HIV-1 and other microbial sequences.

MOTIVATION: Genetic analysis of HIV-1 is important not only for vaccine development, but also to guide treatment strategies, track the emergence of new viral variants and ensure that diagnostic assays are contemporary and fully optimized. However, most genotyping methods are laborious and complex, and involve the use of multiple software applications. Here, we describe the development of an automated genotyping system that can be easily applied to HIV-1 and other rapidly evolving viral pathogens. RESULTS: The new REGA subtyping tool, developed using Java programming and PERL scripts, combines phylogenetic analyses with boot-scanning methods for the genetic subtyping of full-length and subgenomic fragments of HIV-1. When used to investigate the subtype of previously published reference datasets that were analysed using manual phylogenetic methods, the automated method correctly identified 97.5-100% of non-recombinant and circulating recombinant forms of HIV-1, including 108 full-length, 108 gag and 221 env sequences downloaded from the Los Alamos database.

Algorithms↗

PubMed2005

A Grid-based HIV expert system.

OBJECTIVES: This paper addresses Grid-based integration and access of distributed data from infectious disease patient databases, literature on in-vitro and in-vivo pharmaceutical data, mutation databases, clinical trials, simulations and medical expert knowledge. METHODS: Multivariate analyses combined with rule-based fuzzy logic are applied to the integrated data to provide ranking of patient-specific drugs. In addition, cellular automata-based simulations are used to predict the drug behaviour over time. Access to and integration of data is done through existing Internet servers and emerging Grid-based frameworks like Globus. Data presentation is done by standalone PC based software, Web-access and PDA roaming WAP access. The experiments were carried out on the DAS2, a Dutch Grid testbed. RESULTS: The output of the problem-solving environment (PSE) consists of a prediction of the drug sensitivity of the virus, generated by comparing the viral genotype to a relational database which contains a large number of phenotype-genotype pairs. CONCLUSIONS: Artificial Intelligence and Grid technology are effectively used to abstract knowledge from the data and provide the physicians with adaptive interactive advice on treatment applied to drug resistant HIV. An important aspect of our research is to use a variety of statistical and numerical methods to identify relationships between HIV genetic sequences and antiviral resistance to investigate consistency of results.

Biometry↗

PubMed2003

The effect of lamivudine on the replication of hepatitis B virus in HIV-infected patients depends on the host immune status (CD4 cell count).

We retrospectively analysed the effect of lamivudine on hepatitis B virus (HBV) in HIV-co-infected patients. In this small study we document a CD4 cell-dependent response on HBV replication with lamivudine therapy. In this respect, hepatitis B may be considered an opportunistic infection. Our finding may have important clinical consequences, and large prospective studies are necessary to investigate this further.

Adult↗

PubMedDate not supplied

Worldwide transmission of drug-resistant HIV.

The availability of highly active antiretroviral therapy (HAART), that suppresses replication of the human immunodeficiency virus type 1 (HIV-1), has dramatically improved the prognosis of HIV-infected patients. In populations with access to HAART, the course of the infection has changed from an inevitably fatal disease, characterized by a high incidence of opportunistic infections, into a potentially-treatable chronic condition. Unfortunately, HAART does not durably suppress HIV replication in 20-50% of treatment-naive patients and in up to 50-70% of treatment-experienced patients. In the majority of patients with viral rebound, drug-resistance-related mutations are detected. New infections through transmission of drug-resistant strains to individuals who have never been exposed to therapy are now being increasingly reported, despite all HIV prevention efforts. Moreover, recent reports correlate new infections by drug-resistant virus with suboptimal therapy response, which raises major public health concerns. Despite a large number of publications on the rate of primary resistance, it is very difficult to draw general conclusions. The large variation in methodology and interpretation illustrates the need for systematic approaches. Global surveillance is urgently warranted to monitor the circulating HIV-strains. In addition, follow-up research has to be performed to reveal the impact of drug resistance on future therapy options. This paper reviews current literature to elucidate the mechanisms, implications and magnitude of transmission of drug-resistant HIV-1.

Anti-HIV Agents↗