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Instituto de Higiene e Medicina Tropical

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Van Laethem K

RegaDB: Community-driven data management and analysis for infectious diseases

RegaDB is a free and open source data management and analysis environment for infectious diseases. RegaDB allows clinicians to store, manage and analyse patient data, including viral genetic sequences. Moreover, RegaDB provides researchers with a mechanism to collect data in a uniform format and offers them a canvas to make newly developed bioinformatics tools available to clinicians and virologists through a user friendly interface.
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Appearance of a single amino acid insertion at position 33 in HIV type 1 protease under a lopinavir-containing regimen, associated with reduced protease inhibitor susceptibility.

HIV drug resistance is a multifactorial phenomenon and constitutes a major concern as it results in therapy failure. The aim of this study was to assess the impact of an amino acid insertion identified at position 33 of the protease gene, derived from samples from three patients under lopinavir therapy, on viral fitness and protease inhibitor (PI) resistance.
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Cellular HIV-1 DNA levels in drug sensitive strains are equivalent to those in drug resistant strains in newly-diagnosed patients in Europe

BACKGROUND:
HIV-1 genotypic drug resistance is an important threat to the success of antiretroviral therapy and transmitted resistance has reached 9% prevalence in Europe. Studies have demonstrated that HIV-1 DNA load in peripheral blood mononuclear cells (PBMC) have a predictive value for disease progression, independently of CD4 counts and plasma viral load.
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Treatment-associated polymorphisms in protease are significantly associated with higher viral load and lower CD4 count in newly diagnosed drug-naive HIV-1 infected patients.

BACKGROUND:
The effect of drug resistance transmission on disease progression in the newly infected patient is not well understood. Major drug resistance mutations severely impair viral fitness in a drug free environment, and therefore are expected to revert quickly. Compensatory mutations, often already polymorphic in wild-type viruses, do not tend to revert after transmission.
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HIV-1 transmitted drug resistance in Latin America and the Caribbean: what do we know?

Latin America and the Caribbean countries have increased the scaling-up of antiretroviral treatment in the last years. The increase of transmitted drug resistance has been feared due to the worrisome indicators associated with the emergence of drug resistance and monitored by the World Health Organization (WHO).
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Superinfection with drug-resistant HIV is rare and does not contribute substantially to therapy failure in a large European cohort

Superinfection with drug resistant HIV strains could potentially contribute to compromised therapy in patients initially infected with drug-sensitive virus and receiving antiretroviral therapy. To investigate the importance of this potential route to drug resistance, we developed a bioinformatics pipeline to detect superinfection from routinely collected genotyping data, and assessed whether superinfection contributed to increased drug resistance in a large European cohort of viremic, drug treated patients.
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Evaluation of the automatic editing tool RECall for HIV-1 pol and V3 loop sequences

Genotypic drug resistance testing is routine practice in HIV-1 clinical care. The visual interpretation of sequencing electropherograms is labour-intensive and subject to intra- and inter-assay variability because decisions are based on operators’ judgments. In this study the performance of the automatic editing tool RECall was compared to the current standard of editing manually and editing using the tool ViroSeq.
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Clinical Evaluation of Rega 8: An Updated Genotypic Interpretation System That Significantly Predicts HIV-Therapy Response

Clinically evaluating genotypic interpretation systems is essential to provide optimal guidance in designing potent individualized HIV-regimens. This study aimed at investigating the ability of the latest Rega algorithm to predict virological response on a short and longer period.
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The rare HIV-1 gp41 mutations 43T and 50V elevate enfuvirtide resistance levels of common enfuvirtide resistance mutations that did not impact susceptibility to sifuvirtide

Mutations that are selected at low frequency and/or reside outside the enfuvirtide target region, amino acid 36-45 of gp41, might still be important determinants for drug resistance.
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