Long-term immunovirogical effect and tolerability of a Maraviroc-containing regimen in routine clinical practice
Biochemistry Department, Virgen del Rocío University Hospital, Biomedicine Institute of Seville, Spain. Current HIV research
(Impact Factor: 1.76).
to analyze the long-term immunovirological effect and tolerability of a maraviroc-containing antiretroviral therapy in viraemic and pretreated HIV-infected patients with a high prevalence of hepatitis C virus (HCV) coinfection.
forty-six R5 HIV-infected patients (48% HCV-coinfected) started a maraviroc-containing antiretroviral regimen, including patients with multidrug resistant virus and patients after first virologic failure. A retrospective study was performed, analysing percentage of patients with undetectable viral load, mean CD4+ gain, liver enzymes, clinical events and treatment modification up to week 48.
Raltegravir plus a boosted protease inhibitor was combined with maraviroc in 65.2% of the patients (mainly patients with multidrug resistant virus), while the coformulation lamivudine/abacavir was combined with maraviroc in 26.1% (all of them patients after first virologic failure). After 48 weeks on maraviroc-containing regimen, 96.3% of the patients had achieved undetectability and a mean CD4+ count increase of 151 cells/mm3 was observed. Liver enzymes did not increase along the follow up. One patient died after 24 weeks follow up due to heroin overdose. One patient developed a non-Hodgkin lymphoma after 36 weeks follow up, despite undetectable viral load and significant CD4+ increase was achieved (the only AIDS-defining event observed). Treatment modification was performed in 19.6% of the patients: 77.7% of them experienced a treatment simplification and only 1/46 suspended maraviroc.
maraviroc-containing regimen is long-term effective and well tolerated in HIV-infected patients in routine clinical practice and in different clinical scenarios.
Available from: Sara Ferrando-Martinez
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ABSTRACT: The only clinically validated assay available to determine HIV tropism is Trofile, an assay that possesses some limitations. Our first aim was to develop a new phenotypic tropism test (TROCAI [tropism coreceptor assay information]) and to categorize results generated by this test according to the virological response to a short-term exposure to the CCR5 receptor antagonist maraviroc (maraviroc clinical test). Our second aim was to compare TROCAI results to those obtained by Trofile enhanced sensitivity (ES) and to different genotypic algorithms. TROCAI assayed HIV tropism in 33 HIV-infected patient viral isolates obtained from a modified coculture, followed by multiple infection cycles of indicator cells. TROCAI obtained a reportable result in all patients with viral loads of >500 HIV RNA copies/ml and in 3/6 patients with <500 HIV RNA copies/ml (30/33 patients, 91.9%). Patients who responded to maraviroc had an X4-using virus proportion in indicator cell supernatant of 0 to 0.41%. Hence, we used the threshold of 0.5% to categorize TROCAI results as R5 (<0.5%) or dual/mixed (>0.5%). The concordance between TROCAI and Trofile (ES) was 22/24 (91.6%), and with genotypic approaches it was 22/26 (84.6%). TROCAI results, which were categorized in this study by the maraviroc clinical test, could be used as a test in addition to those currently used to select patients for treatment with CCR5 antagonists.
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ABSTRACT: Enhanced sensitivity Trofile (ES-Trofile) is the most frequently used technique to assay HIV tropism. A clinical approach to predict CCR5-antagonists efficacy, based on the virological response to a short-term maraviroc exposure (Maraviroc Clinical Test, MCT), has been recently reported. We compared the results of ES-Trofile with MCT in 47 HIV-infected patients, and a global discordance around 15% was observed between the phenotypic method and the clinical approach. Discordance results were mainly found in patients with an ES-Trofile reported as dual/mixed. These provocative results might have important clinical implications and should be considered in order to accurately prescribe treatment with CCR5 antagonists.
Available from: Francesc Vidal
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ABSTRACT: The virological response after an 8-day maraviroc monotherapy has been proposed to be an alternative method to determine whether
an CCR5 antagonist should be prescribed to HIV-infected patients. The frequency of patients eligible for a combined antiretroviral
therapy which includes maraviroc on the basis of the result of this clinical test is not well-known at the moment. In the
same way, clinical and immunovirological factors associated with the virological response after antagonist exposure need to
be determined. Ninety consecutive HIV-infected patients were exposed to an 8-day maraviroc monotherapy. The virological response
was considered positive if either a reduction of ≥1-log10 HIV RNA copies/ml or an undetectable viral load (<40 HIV RNA copies/ml) was achieved. CXCR4- and CCR5-tropic virus levels
were determined by using patients' viral isolates and multiple rounds of infection of indicator cell lines (U87-CXCR4 and
U87-CCR5). The frequency of patients with a positive virological response was 72.2% (94.7% and 66.2% for treatment-naïve and
pretreated patients, respectively). The positive response rates dramatically decreased in patients with lower CD4+ T-cell counts. The CXCR4-tropic virus level was the only variable independently associated with the virological response
after short-term maraviroc exposure. Lower CD4+ T-cell strata were associated with higher CXCR4-tropic virus levels. These results support the suggestion that CCR5 antagonists
should be an early treatment option before the expansion of CXCR4-tropic strains.
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