Antiretroviral genotypic resistance in plasma RNA and whole blood DNA in HIV-1 infected patients failing HAART

Salvatrice Mancuso, Nicola Gianotti, Annalisa Saracino, Laura Monno, Gioacchino Angarano, Donatella C. Cibelli, Grazia Punzi, Marianna Marangi, Adriano Lazzarin, Andrea Galli

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Abstract

The extent to which HIV-1 proviral DNA mutations cause clinically relevant antiretroviral resistance is still controversial. Paired plasma HIV-1 RNA and whole blood DNA were compared in patients failing HAART to investigate if the additional knowledge of archived mutations could improve the selection of potentially active drugs. Seventy-three HIV-1-infected patients with first/second HAART failure were studied before starting a new regimen based on RNA genotyping. Follow-up data after a 12-week therapy were available. DNA genotyping was retrospectively performed on stored whole blood samples and mutational profiles were compared to those from RNA. The mean number of IAS pol mutations was significantly higher in RNA (4.45 ± 2.76) than in DNA (2.88 ± 2.47) (P < 0.001). DNA genotyping provided a 6% increase in detection of resistance-associated mutations. Among 64/73 patients showing discordant DNA/RNA profiles, 54 (84%) also differed for predicted active drugs. 16/73 (22%) patients had ≥1 mutation revealed by DNA genotyping alone, probably affecting therapy success in 2/16. However, neither RNA/DNA discordance nor detection of isolated DNA mutations were statistically associated with outcome. In conclusion, plasma RNA remains the elective choice for HIV genotyping in patients with therapy failure, even if the detection of proviral resistance-associated mutations, not simultaneously found in RNA, is a frequent event. Therefore, in some cases DNA plus RNA genotyping might assist in choosing more accurately subsequent antiretroviral regimens. © 2008 Wiley-Liss, Inc.
Original languageEnglish
Pages (from-to)1695-1706
Number of pages12
JournalJournal of Medical Virology
Volume80
Publication statusPublished - 2008

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Highly Active Antiretroviral Therapy
HIV-1
RNA
DNA
Mutation
Pharmaceutical Preparations
Therapeutics
HIV

All Science Journal Classification (ASJC) codes

  • Virology
  • Infectious Diseases

Cite this

Mancuso, S., Gianotti, N., Saracino, A., Monno, L., Angarano, G., Cibelli, D. C., ... Galli, A. (2008). Antiretroviral genotypic resistance in plasma RNA and whole blood DNA in HIV-1 infected patients failing HAART. Journal of Medical Virology, 80, 1695-1706.

Antiretroviral genotypic resistance in plasma RNA and whole blood DNA in HIV-1 infected patients failing HAART. / Mancuso, Salvatrice; Gianotti, Nicola; Saracino, Annalisa; Monno, Laura; Angarano, Gioacchino; Cibelli, Donatella C.; Punzi, Grazia; Marangi, Marianna; Lazzarin, Adriano; Galli, Andrea.

In: Journal of Medical Virology, Vol. 80, 2008, p. 1695-1706.

Research output: Contribution to journalArticle

Mancuso, S, Gianotti, N, Saracino, A, Monno, L, Angarano, G, Cibelli, DC, Punzi, G, Marangi, M, Lazzarin, A & Galli, A 2008, 'Antiretroviral genotypic resistance in plasma RNA and whole blood DNA in HIV-1 infected patients failing HAART', Journal of Medical Virology, vol. 80, pp. 1695-1706.
Mancuso, Salvatrice ; Gianotti, Nicola ; Saracino, Annalisa ; Monno, Laura ; Angarano, Gioacchino ; Cibelli, Donatella C. ; Punzi, Grazia ; Marangi, Marianna ; Lazzarin, Adriano ; Galli, Andrea. / Antiretroviral genotypic resistance in plasma RNA and whole blood DNA in HIV-1 infected patients failing HAART. In: Journal of Medical Virology. 2008 ; Vol. 80. pp. 1695-1706.
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AU - Mancuso, Salvatrice

AU - Gianotti, Nicola

AU - Saracino, Annalisa

AU - Monno, Laura

AU - Angarano, Gioacchino

AU - Cibelli, Donatella C.

AU - Punzi, Grazia

AU - Marangi, Marianna

AU - Lazzarin, Adriano

AU - Galli, Andrea

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N2 - The extent to which HIV-1 proviral DNA mutations cause clinically relevant antiretroviral resistance is still controversial. Paired plasma HIV-1 RNA and whole blood DNA were compared in patients failing HAART to investigate if the additional knowledge of archived mutations could improve the selection of potentially active drugs. Seventy-three HIV-1-infected patients with first/second HAART failure were studied before starting a new regimen based on RNA genotyping. Follow-up data after a 12-week therapy were available. DNA genotyping was retrospectively performed on stored whole blood samples and mutational profiles were compared to those from RNA. The mean number of IAS pol mutations was significantly higher in RNA (4.45 ± 2.76) than in DNA (2.88 ± 2.47) (P < 0.001). DNA genotyping provided a 6% increase in detection of resistance-associated mutations. Among 64/73 patients showing discordant DNA/RNA profiles, 54 (84%) also differed for predicted active drugs. 16/73 (22%) patients had ≥1 mutation revealed by DNA genotyping alone, probably affecting therapy success in 2/16. However, neither RNA/DNA discordance nor detection of isolated DNA mutations were statistically associated with outcome. In conclusion, plasma RNA remains the elective choice for HIV genotyping in patients with therapy failure, even if the detection of proviral resistance-associated mutations, not simultaneously found in RNA, is a frequent event. Therefore, in some cases DNA plus RNA genotyping might assist in choosing more accurately subsequent antiretroviral regimens. © 2008 Wiley-Liss, Inc.

AB - The extent to which HIV-1 proviral DNA mutations cause clinically relevant antiretroviral resistance is still controversial. Paired plasma HIV-1 RNA and whole blood DNA were compared in patients failing HAART to investigate if the additional knowledge of archived mutations could improve the selection of potentially active drugs. Seventy-three HIV-1-infected patients with first/second HAART failure were studied before starting a new regimen based on RNA genotyping. Follow-up data after a 12-week therapy were available. DNA genotyping was retrospectively performed on stored whole blood samples and mutational profiles were compared to those from RNA. The mean number of IAS pol mutations was significantly higher in RNA (4.45 ± 2.76) than in DNA (2.88 ± 2.47) (P < 0.001). DNA genotyping provided a 6% increase in detection of resistance-associated mutations. Among 64/73 patients showing discordant DNA/RNA profiles, 54 (84%) also differed for predicted active drugs. 16/73 (22%) patients had ≥1 mutation revealed by DNA genotyping alone, probably affecting therapy success in 2/16. However, neither RNA/DNA discordance nor detection of isolated DNA mutations were statistically associated with outcome. In conclusion, plasma RNA remains the elective choice for HIV genotyping in patients with therapy failure, even if the detection of proviral resistance-associated mutations, not simultaneously found in RNA, is a frequent event. Therefore, in some cases DNA plus RNA genotyping might assist in choosing more accurately subsequent antiretroviral regimens. © 2008 Wiley-Liss, Inc.

KW - Antiretroviral genotypic resistance; HAART failure; HIV-1; Plasma RNA; Proviral DNA; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; DNA Mutational Analysis; DNA, Viral; Drug Resistance, Viral; HIV Infections; HIV Protease; HIV Reverse Transcripta

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