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  • Open Access

HIV drug resistance profile of HIV-1 CRF 01_AE protease and integrase coding regions in HIV infected Cambodian patients failing LPV-based 2nd line antiretroviral regimen

  • 1Email author,
  • 1,
  • 1,
  • 2,
  • 2, 3,
  • 1,
  • 1,
  • 4 and
  • 1
BMC Proceedings20115 (Suppl 1) :P89

https://doi.org/10.1186/1753-6561-5-S1-P89

  • Published:

Keywords

  • Raltegravir
  • Etravirine
  • Integrase Inhibitor
  • Detectable Viral Load
  • Elvitegravir

Background

By the end of 2009, the number of HIV-1 infected patients on RTI-based 1st line and PI-based 2nd line ARV regimen in Cambodia reached 34,000 and 1,500, respectively. We already reported good virological and immunological responses after 1 to 4 years in cohorts of patients on 1st line and more recently, among an Esther cohort of 70 patients after 2 years on LPVr-based 2nd line regimen. However, emergence of LPV resistant associated mutations is becoming a major concern in low and middle income countries.

Objective

This study aimed to describe the resistance pattern of both the protease (PR) and integrase (IN) coding regions in HIV-1 CRF01-AE infected patients failing LPV-based 2nd line regimen in Cambodia.

Methods

Analysis of the Protease and Integrase drug resistance genotyping of 95 HIV-1 strains infected patients presenting detectable viral load on LPV/r-based 2nd line regimen in Cambodia.

Results

Lack of amplification in PR gene was observed for 18/95 presenting low viral load (median VL: 2.9Log10 copies/ml [IQR: 2.8-3.4]). The 77 other CRF01_AE strains, harbored polymorphism mutation in position M36, H69 and L89 conferring possibly resistance to TPV/r. Forty-nine (median VL: 5Log10 copies/ml [IQR: 4 - 5.5]) did not present any other PI associated resistance mutation. In contrast, 28 patients showed multiple resistances to PI. The median duration on LPV/r regimen was 34.5 months [IQR: 23.5 – 53.3] and the median VL was 5Log10 copies/ml [IQR: 4.3-5.6]. Twenty-five patients were resistant to LPV/r (7 possibly resistant). Twenty-seven were resistant to IDV, 21 and 19 to ATV/r and FPV/r, respectively. Twenty-five were resistant to NFV (10 possibly), 22 resistant to SQV/r (9 possibly). Seven showed resistance to DRV/r (5 possibly). Finally, excluding possible resistance, 21/28 (75%) was resistant for at least 3 PIs. Clinical investigation revealed that most of these 28 patients starting several RTIs and PIs early around 2000. All of them were sensitive to raltegravir, elvitegravir (integrase inhibitors), and etravirine (Non-Nucleoside reverse transcriptase inhibitorse).

Conclusion

This study indicates that 28/95 (29.5%) of Cambodian patients presenting detectable viral load on LPV/r–based 2nd line regimen developed resistance mutation for a large number of PIs. Most of them were not naïve for PI before LPV/r initiation. These results highlight an urgent need to evaluate the efficacy of LPV/r-based 2nd line regimen at the national levels, allowing to design of a next 3rd line ARV regiment in low and middle income countries.

Authors’ Affiliations

(1)
HIV/Hepatitis Laboratory, Institut Pasteur du Cambodge, Phnom Penh, Cambodia
(2)
Esther Program, Calmette Hospital, Phnom Penh, Cambodia
(3)
Clinical Immunology Department, Bicêtre Hospital, Kremlin Bicêtre, France
(4)
ANRS, Paris, France

Copyright

© Nouhin et al; licensee BioMed Central Ltd. 2011

This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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