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Transmitted drug resistance, selection of resistance mutations and moderate antiretroviral efficacy in HIV-2: Analysis of the HIV-2 Belgium and Luxembourg database

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Abstract
Background: Guidelines established for the treatment of HIV-1 infection and genotype interpretation do not apply for HIV-2. Data about antiretroviral ( ARV) drug efficacy and resistance mutations is scarce. Methods: Clinical data about HIV-2 infected patients in Belgium and Luxembourg were collected and the effect of ARV therapy on plasma viral load and CD4 counts were analysed. Viral RNA encoding for protease ( PR) and reverse transcriptase ( RT) from ARV-naive and treated patients were sequenced. Results: Sixty-five HIV-2 infected patients were included in this cohort. Twenty patients were treated with 25 different ARV combinations in a total of 34 regimens and six months after the start of ARV therapy, only one third achieved viral load suppression. All of these successful regimens bar one contained protease inhibitors (PIs). Mean CD4 gains in the group of viral load suppressors and the group of patients treated with PI-containing regimens were respectively significantly higher than in the group of non-suppressors and the group of PI-sparing regimens. The most frequent mutations selected under therapy ( compared to HIV-2 ROD) were V7II, L90M and I89V within PR. Within RT, they were M184V, Q151M, VI111 and K65R. All of these mutations, except K65R and M184V, were also found in variable proportions in ARV-naive patients. Conclusion: Despite a high rate of ARV treatment failure, better virological and immunological results were achieved with PI-containing regimens. The analysis of polymorphic positions and HIV-2 specific mutations selected during therapy showed for the first time that transmission of drug resistant viruses has occurred in Belgium and Luxembourg. The high heterogeneity in ARV combinations reflects a lack of guidelines for the treatment of HIV-2 infection.
Keywords
INFECTED-PATIENTS, NATURAL POLYMORPHISMS, PROTEASE INHIBITORS, HIV-2-INFECTED PATIENTS, REVERSE-TRANSCRIPTASE, HUMAN-IMMUNODEFICIENCY-VIRUS, PLASMA VIRAL LOAD, TYPE-2 INFECTION, CELL DECLINE, COTE-DIVOIRE

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MLA
Ruelle, Jean et al. “Transmitted Drug Resistance, Selection of Resistance Mutations and Moderate Antiretroviral Efficacy in HIV-2: Analysis of the HIV-2 Belgium and Luxembourg Database.” BMC INFECTIOUS DISEASES 8.21 (2008): n. pag. Print.
APA
Ruelle, J., Roman, F., Vandenbroucke, A.-T., Lambert, C., Fransen, K., Echahidi, F., Pierard, D., et al. (2008). Transmitted drug resistance, selection of resistance mutations and moderate antiretroviral efficacy in HIV-2: Analysis of the HIV-2 Belgium and Luxembourg database. BMC INFECTIOUS DISEASES, 8(21).
Chicago author-date
Ruelle, Jean, Francois Roman, Anne-Therese Vandenbroucke, Christine Lambert, Katrien Fransen, Fedoua Echahidi, Denis Pierard, et al. 2008. “Transmitted Drug Resistance, Selection of Resistance Mutations and Moderate Antiretroviral Efficacy in HIV-2: Analysis of the HIV-2 Belgium and Luxembourg Database.” Bmc Infectious Diseases 8 (21).
Chicago author-date (all authors)
Ruelle, Jean, Francois Roman, Anne-Therese Vandenbroucke, Christine Lambert, Katrien Fransen, Fedoua Echahidi, Denis Pierard, Chris Verhofstede, Kristel Van Laethem, Marie-Luce Delforge, Dolores Vaira, Jean-Claude Schmit, and Patrick Goubau. 2008. “Transmitted Drug Resistance, Selection of Resistance Mutations and Moderate Antiretroviral Efficacy in HIV-2: Analysis of the HIV-2 Belgium and Luxembourg Database.” Bmc Infectious Diseases 8 (21).
Vancouver
1.
Ruelle J, Roman F, Vandenbroucke A-T, Lambert C, Fransen K, Echahidi F, et al. Transmitted drug resistance, selection of resistance mutations and moderate antiretroviral efficacy in HIV-2: Analysis of the HIV-2 Belgium and Luxembourg database. BMC INFECTIOUS DISEASES. MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND: BIOMED CENTRAL LTD, CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND; 2008;8(21).
IEEE
[1]
J. Ruelle et al., “Transmitted drug resistance, selection of resistance mutations and moderate antiretroviral efficacy in HIV-2: Analysis of the HIV-2 Belgium and Luxembourg database,” BMC INFECTIOUS DISEASES, vol. 8, no. 21, 2008.
@article{603347,
  abstract     = {Background: Guidelines established for the treatment of HIV-1 infection and genotype interpretation do not apply for HIV-2. Data about antiretroviral ( ARV) drug efficacy and resistance mutations is scarce.

Methods: Clinical data about HIV-2 infected patients in Belgium and Luxembourg were collected and the effect of ARV therapy on plasma viral load and CD4 counts were analysed. Viral RNA encoding for protease ( PR) and reverse transcriptase ( RT) from ARV-naive and treated patients were sequenced.

Results: Sixty-five HIV-2 infected patients were included in this cohort. Twenty patients were treated with 25 different ARV combinations in a total of 34 regimens and six months after the start of ARV therapy, only one third achieved viral load suppression. All of these successful regimens bar one contained protease inhibitors (PIs). Mean CD4 gains in the group of viral load suppressors and the group of patients treated with PI-containing regimens were respectively significantly higher than in the group of non-suppressors and the group of PI-sparing regimens. The most frequent mutations selected under therapy ( compared to HIV-2 ROD) were V7II, L90M and I89V within PR. Within RT, they were M184V, Q151M, VI111 and K65R. All of these mutations, except K65R and M184V, were also found in variable proportions in ARV-naive patients.

Conclusion: Despite a high rate of ARV treatment failure, better virological and immunological results were achieved with PI-containing regimens. The analysis of polymorphic positions and HIV-2 specific mutations selected during therapy showed for the first time that transmission of drug resistant viruses has occurred in Belgium and Luxembourg. The high heterogeneity in ARV combinations reflects a lack of guidelines for the treatment of HIV-2 infection.},
  author       = {Ruelle, Jean and Roman, Francois and Vandenbroucke, Anne-Therese and Lambert, Christine and Fransen, Katrien and Echahidi, Fedoua and Pierard, Denis and Verhofstede, Chris and Van Laethem, Kristel and Delforge, Marie-Luce and Vaira, Dolores and Schmit, Jean-Claude and Goubau, Patrick},
  issn         = {1471-2334},
  journal      = {BMC INFECTIOUS DISEASES},
  keywords     = {INFECTED-PATIENTS,NATURAL POLYMORPHISMS,PROTEASE INHIBITORS,HIV-2-INFECTED PATIENTS,REVERSE-TRANSCRIPTASE,HUMAN-IMMUNODEFICIENCY-VIRUS,PLASMA VIRAL LOAD,TYPE-2 INFECTION,CELL DECLINE,COTE-DIVOIRE},
  language     = {eng},
  number       = {21},
  publisher    = {BIOMED CENTRAL LTD, CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND},
  title        = {Transmitted drug resistance, selection of resistance mutations and moderate antiretroviral efficacy in HIV-2: Analysis of the HIV-2 Belgium and Luxembourg database},
  url          = {http://dx.doi.org/10.1186/1471-2334-8-21},
  volume       = {8},
  year         = {2008},
}

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