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HIV-1 DNA dynamics and variations in HIV-1 DNA protease and reverse transcriptase sequences in multidrug-resistant patients during successful raltegravir-based therapy.

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Michelini Z, Galluzzo CM, Pirillo MF, Francisci D, Degli Antoni A, Vivarelli A, Ladisa N, Cirioni O, Weimer LE, Fragola V, Cara A, Floridia M, Baroncelli S,


Michelini Z, Galluzzo CM, Pirillo MF, Francisci D, Degli Antoni A, Vivarelli A, Ladisa N, Cirioni O, Weimer LE, Fragola V, Cara A, Floridia M, Baroncelli S, (click to view)

Michelini Z, Galluzzo CM, Pirillo MF, Francisci D, Degli Antoni A, Vivarelli A, Ladisa N, Cirioni O, Weimer LE, Fragola V, Cara A, Floridia M, Baroncelli S,

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Journal of medical virology 2016 5 19() doi 10.1002/jmv.24581

Abstract
BACKGROUND
There is limited information on the variations of HIV-1 DNA mutation profile in reverse transcriptase (RT) and protease (PR) genes during suppressive antiretroviral treatment (plasma HIV-1 RNA continuously <50 copies/ml) with raltegravir (RAL)-based regimens in patients with baseline RT/PR resistant HIV. METHODS
Twelve multidrug resistant (RT: 12/12, PR: 8/12) HIV-infected patients were followed during effectively suppressive RAL-based therapy. Total and integrated HIV-1 DNA were assessed by Real Time PCR at baseline and every six months. Ultrasensitive (threshold: 2.5 copies/ml) plasma HIV-1 RNA and genotypic analysis of RT and PR in proviral DNA were performed at baseline and at 24 months.

RESULTS
Half of the patients had full viral suppression (plasma HIV-RNA < 2.5 copies/ml) at month 12. Total HIV-1 DNA declined significantly after 12 month of therapy (from 249.2 to 145.7 copies/10(6) cells, p = 0.023), and remained stable until 24 months, when total HIV-1 DNA levels raised, concomitantly with a less stringent suppression of HIV-1 RNA (81.8% of patients with >2.5 copies/ml). Integrated HIV-1 DNA did not show fluctuations during the study period. Sequencing of the PR and RT regions from HIV-1 DNA revealed changes in the resistance mutation profile in 5 patients.

CONCLUSION
Total HIV-1 DNA declined after the introduction of RAL-based therapy, with a rebound after two years. No changes were observed in levels of integrated DNA, suggesting limited effect on archived HIV. The RT and PR sequence changes in archived HIV-1 DNA suggest that variation of the mutation profile can occur even in absence of detectable HIV-1 RNA. This article is protected by copyright. All rights reserved.

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