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The frequencies of naturally occurring protease inhibitor resistance mutations in HIV proviral sequences of drug naïve sex workers in Nairobi, Kenya and their correlation with host immune response driven positively selected mutations in HIV-1

  • Raghavan Sampathkumar1, 3,
  • Elnaz Shadabi1, 3,
  • David La3,
  • John Ho3,
  • Binhua Liang1, 3,
  • Joshua Kimani1, 2,
  • Francis A Plummer1, 3 and
  • Ma Luo1, 3Email author
BMC Infectious Diseases201414(Suppl 3):O2

https://doi.org/10.1186/1471-2334-14-S3-O2

Published: 27 May 2014

Keywords

NelfinavirDrug Resistance MutationProviral SequenceMinor MutationSeropositive Woman

Background

Sub Saharan Africa accounts for 69% of the people living with HIV globally. Antiretroviral therapy (ART) has saved 9 million life years in Sub Saharan Africa. However, drug resistance mutations reduce the effectiveness of ART, and need to be monitored for effective ART. Naturally occurring primary antiretroviral drug resistance mutations have not been well analyzed in ART naïve HIV+ patients from Kenya.

Methods

We examined protease inhibitor (PI) resistance mutations in ART naïve HIV-1 seropositive women from Pumwani sex worker cohort, established in Nairobi, Kenya, wherein HIV-1 infection is predominantly caused by subtypes A and D viruses. We have analyzed consensus sequences of HIV protease from 234 drug naïve patients, as a part of HIV-1 whole genome sequencing using 454 sequencing methodology.

Results

Analysis using HIVdb program revealed a prevalence of 0.56% of PI resistance major mutations (1/178; D30N) and 19.1% PI resistance minor mutations (34/178) among the study subjects. D30N mutation, which occurred along with minor mutations G48K and G73S, is known to confer high level resistance to nelfinavir. Several minor mutations were found at five different drug resistance sites. Positive selection analysis and correlation with disease progression revealed L10I, a PI resistance minor mutation and a positively selected mutation driven by host immune response, to be detrimental to host.

Conclusion

This study provides valuable data on primary drug resistance in Kenyan HIV-1 infected patients before ART became available as well as HLA mediated immune pressure over HIV-1 protease.

Authors’ Affiliations

(1)
Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada
(2)
Department of Medical Microbiology, University of Nairobi, Nairobi, Kenya
(3)
National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Canada

Copyright

© Sampathkumar et al; licensee BioMed Central Ltd. 2014

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/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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