High Prevalence of HIV Low Abundance Drug Resistant Variants in a Treatment Naïve Population in North Rift Kenya

The use of antiretroviral treatment (ART) has resulted in dramatic reduction in AIDS related deaths. However the emergence of antiretroviral drug resistance (DR) threatens to negatively impact on treatment regimens. In resource limited settings it is recommended that surveillance for DR occur in conjunction with ART scale-up efforts . However standard DR genotyping methods rely on techniques that miss out on low abundance DR variants (LADRVs) which have been documented to contribute to treatment failure. 

The use of next generation sequencing (NGS) has been shown to be more sensitive for LADRVS. We have carried out a preliminary investigation using NGS to determine the prevalence of LDRVS among a drug naïve population in North Rift Kenya. DNA was extracted, amplified and nested PCR conducted on pol RT region using with primers tagged with multiplex identifiers (MID). Resulting PCR amplicons were purified, quantified and pyrosequenced using a GS FLX Titanium PicoTiterPlate (Roche). Valid pyrosequencing reads were aligned with HXB-2 and the frequency and distribution of nucleotide and amino acid changes determined using an in-house Perl script. DR mutations were identified using the IAS-USA HIV DR mutation database. 

Sixty samples were successfully sequence of which 25 were subtype A, 11 subtypes D, 1 Subtype C and the remaining were recombinants. Forty six (76.6%) had at least one drug resistance mutation; with 25 (41.6%) indicated as major and the rest 21 (35%) minor. The most prevalent mutation was NRTI position K219Q/R (11 of 46, 24%) followed by NRTI M184V (5 of 46, 11%) and NNRTI K103N (4 of 46, 9%). 

Our use of NGS technology revealed a high prevalence of LADRVs among drug naive populations in Kenya . The impact of these mutations on clinical ART outcome can only be ascertained through a long term follow-up.

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By: Cheriro W1, Ji H2, Kiptoo MK3, Liang B4, Kikuvi G5, Mining S6, Emonyi W7, Brooks J8, Songok EM9.

• 1Jomo Kenyatta University of Agriculture and Technology, Institute of Tropical Medicine and Infectious Diseases, Nairobi, Kenya 
• 2Public Health Agency of Canada, HIV Reference Laboratory, Winnipeg, Manitoba, Canada 
• 3Kenya Medical Research Institute, centre For Virus Research, Nairobi, Kenya 
• 4Public Health Agency of Canada, National Microbiology Laboratories, Winnipeg, Manitoba, Canada
• 5Jomo Kenyatta University of Agriculture and Technology, Institute of Tropical Medicine and Infectious Diseases, Nairobi, Kenya
• 6Moi university, Faculty of Medicine, Eldoret, Kenya
• 7Moi university, Faculty of Medicine, Eldoret, Kenya 
• 8Public Health Agency of Canada, HIV Reference laboratory, Winnipeg, Manitoba, Canada 
• 9Kenya medical Research Institute, Centre For Virus Research , p.o.box 54840 , nairobi , nairobi, Nairobi, Kenya

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