Cartography of Virologic Reservoir Related to Antiretroviral Concentrations in HIV-1 Chronic Patients Treated by a First Line Treatment Containing Dolutegravir and Associated Nucleoside / Nucleotide Reverse Transcriptase Inhibitors Backbone

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The major obstacle to a functional cure of HIV infection is the persistence of the latent HIV reservoir. Several arguments suggest the persistence of a residual viral replication in different compartments, despite an effective antiretroviral treatment. This residual viral replication partially comes...

The major obstacle to a functional cure of HIV infection is the persistence of the latent HIV reservoir. Several arguments suggest the persistence of a residual viral replication in different compartments, despite an effective antiretroviral treatment. This residual viral replication partially comes from pharmacological sanctuaries where the drugs do not largely penetrate. In such sanctuaries a recent report published in Nature has shown that the virus can replicate with less antiviral pressure contributing to continuously replenish the reservoirs. Nevertheless, this study concerned a limited number of patients and only blood and lymph-node samples were collected for viral analysis. Moreover, the drug distribution was estimated based on mathematical hypotheses without drug measure concentration. The International AIDS Society recommend for most patients an optimal initial regimen containing 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus an integrase strand transfer inhibitor (InSTI)2. The new integrase inhibitor dolutegravir is more and more widely used in combination with nucleoside/nucleotide reverse transcriptase. Indeed, this drug shows a good tolerance and demonstrates a particularly fast inhibition of the viral replication. Moreover, dolutegravir is active against HIV strains that are resistant to the first generation of integrase inhibitors, raltegravir and elvitegravir. However the penetration of dolutegravir in deep compartments has not been fully characterized: the studies comprised a small number of patients and were not able to estimate the distribution in several compartments at the same time for each patient. Moreover the levels of residual viral replication in those compartments during treatment are unknown, making it difficult to evaluate the capacity of this drug and associated backbone to efficiently act against viral reservoirs maintenance. The aim of the study is to measure simultaneously dolutegravir and nucleoside/nucleotide reverse transcriptase inhibitors in different compartments to obtain cartography of dolutegravir and associated backbone distribution and the spatial dynamics of virus in each patient. The decision to study dolutegravir and the two associated backbones (abacavir / lamivudine or tenofovir /emtricitabine) was decided as: The International AIDS Society recommend for most patients an optimal initial regimen containing 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus an integrase strand transfer inhibitor (InSTI)2. Dolutegravir viral power is established for high levels of viral load 90 and this drug is widely used. This study is very complementary of studies ANRS SIVART and ANRS 169 OPTIPRIM 2. Dolutegravir is combined with abacavir + lamivudine in a single-tablet and is largely prescribed. Raltegravir and elvitegravir will not be analysed because the number of recruited patients should be more important to obtain sufficient data and the feasibility would not be sure.

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