Article

In vitro phenotypic susceptibility of human immunodeficiency virus type 2 clinical isolates to protease inhibitors.

Laboratoire de Virologie, Service de Microbiologie, Hôpital Bichat-Claude Bernard, Paris, France.
Antimicrobial Agents and Chemotherapy (Impact Factor: 4.45). 05/2008; 52(4):1545-8. DOI: 10.1128/AAC.01284-07
Source: PubMed

ABSTRACT We determine phenotypic susceptibility of human immunodeficiency virus type 2 (HIV-2) isolates to amprenavir, atazanavir, darunavir, indinavir, lopinavir, nelfinavir, saquinavir, and tipranavir. Saquinavir, lopinavir, and darunavir are potent against wild-type HIV-2 isolates and should be preferred as first-line options for HIV-2-infected patients. Other protease inhibitors are less active against HIV-2 than against HIV-1.

0 Bookmarks
 · 
200 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The human immunodeficiency virus (HIV) protease is a homodimeric aspartyl protease that is crucial for the viral life-cycle, cleaving proviral polyproteins, hence creating mature protein components that are required for the formation of an infectious virus. With diagnostic measures and clinically used protease inhibitors focusing on HIV-1, due to its higher virulence and prevalence, studies of the efficacy of those inhibitors on HIV-2 protease remain widely lacking. Utilizing a wild-type HIV-2 vector backbone and cloning techniques we have developed a cassette system where the efficacy of clinically used protease inhibitors can be studied for various serotypes of HIV-2 protease both in enzymatic and cell culture assays. In our experiments, optimization of the expression protocol led to a relatively stable enzyme, for cell culture assays, the efficiency of transfection and transduction capability of the modified vector was tested and was not found to differ from that of the wild-type, moreover, a 2<sup>nd</sup> generation protease inhibitor was used to demonstrate the usefulness of the system. The combination of assays performed with our cassette system is expected to provide an accurate measure of the efficacy of currently used; as well as experimental protease inhibitors on HIV-2.
    PLoS ONE 11/2014; 9(11):e113221. DOI:10.1371/journal.pone.0113221 · 3.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Although endemic in West Africa, HIV-2 infection dissemination is limited to about 1.2 million people worldwide. However, the prevalence of HIV-2 infection is in Portugal disproportionately high, similarly to other countries with strong socioeconomic ties with West African former colonies. Due to HIV-2 intrinsic resistance to non-nucleoside reverse transcriptase inhibitors (non-NRTIs) and enfuvirtide, along with reduced susceptibility to several of the protease inhibitors (PI), antiretroviral therapy (ART) relies on a regimen containing two NRTIs and a selected boosted PI. The integrase inhibitor raltegravir (RAL) showed, in vitro, activity against HIV-2 infection, and small case series published report RAL efficacy in the treatment of HIV-2 infection. Methods: We report eight HIV-2 ART-experienced patients treated with a RAL-containing regimen. Results: In this small series of eight patients, medium time of known HIV-2 infection before RAL introduction was 9.4 years; all had previous exposition to ART, some with more than 3 past therapeutic regimens. The majority had low CD4+T cell count. Despite these clinical aspects, the majority showed undetectable viral load (75%) and improvement or stability of the CD4+ T cell count (63%). Conclusion: Despite limitations inherent to this small case series, RAL proved to be useful in the treatment of HIV-2 infected patients, with beneficial effect in virus control and CD4+T cell preservation. In the presence of extensive resistance to other antiretrovirals, the benefit of RAL seems to be decreased. Accordingly to other emergent data, RAL may represent a novel therapeutic possibility for HIV-2 infected patients.
    10/2014; 2(2). DOI:10.9734/IJMPCR/2015/13078
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Clinical inhibitors Darunavir (DRV) and Amprenavir (APV) are less effective on HIV-2 protease (PR2) than on HIV-1 protease (PR1). To identify molecular basis associated with the lower inhibition, molecular dynamics (MD) simulations and molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) calculations were performed to investigate the effectiveness of the PR1 inhibitors DRV and APV against PR1/PR2. The rank of predicted binding free energies agrees with the experimental determined one. Moreover, our results show that two inhibitors bind less strongly to PR2 than to PR1, again in agreement with the experimental findings. The decrease in binding free energies for PR2 relative to PR1 is found to arise from the reduction of the van der Waals interactions induced by the structural adjustment of the triple mutant V32I, I47V and V82I. This result is further supported by the difference between the van der Waals interactions of inhibitors with each residue in PR2 and in PR1. The results from the principle component analysis suggest that inhibitor binding tends to make the flaps of PR2 close and the one of PR1 open. We expect that this study can theoretically provide significant guidance and dynamics information for the design of potent dual inhibitors targeting PR1/PR2.
    Scientific Reports 11/2014; 4:6872. DOI:10.1038/srep06872 · 5.08 Impact Factor

Preview

Download
1 Download
Available from