Abstract
Raltegravir, an integrase inhibitor, is not a component of the current South African antiretroviral treatment guidelines, but it could be introduced in the near future as cases of virological failures from current treatment regimens begin to occur. The aim of this study was to analyze the complete HIV integrase gene obtained from individuals at two treatment sites in northeastern South Africa for the presence of Raltegravir associated drug resistant mutations and viral subtypes based on the integrase gene. Examination for mutations against other integrase inhibitors, such as Elvitegravir and Dolutegravir, was also done. Viruses from 127 treatment naive individuals were analyzed. Genetic drug resistance mutations were determined using the Stanford HIV Drug Resistance Interpretation program and the International AIDS society-USA guidelines. Viral subtyping was done by phylogenetic analysis, and recombinants were determined using the REGA, jpHMM and RIP tools. No major resistance mutations were detected. However, 7% of the sequences had minor mutations and polymorphisms. The majority (99%) of the viruses were HIV-1 C. Recombination analysis showed that the polymerase gene of one virus was likely composed of HIV-1 subtype A1 and C sequences. The present study indicates that Raltegravir, Elvitegravir and Dolutegravir resistant mutations may be absent in the study communities and further indicates the presence of recombinant viruses in northeastern South Africa.
Highlights
The use of antiretrovirals (ARV) inevitably leads to the emergence of resistant viruses and subsequent treatment failure
Integrase catalyzes the chromosomal integration of newly synthesized double-stranded DNA into the host genomic DNA. It plays a role in stabilizing a pre-integration complex (PIC), which consists of the 3'-end processed genome, and one or more cellular co-factors involved in nuclear transfer of the PIC [2]
No major Raltegravir, Elvitegravir and Dolutegravir resistance mutations were observed in the study population
Summary
The use of antiretrovirals (ARV) inevitably leads to the emergence of resistant viruses and subsequent treatment failure. Integrase catalyzes the chromosomal integration of newly synthesized double-stranded DNA into the host genomic DNA It plays a role in stabilizing a pre-integration complex (PIC), which consists of the 3'-end processed genome, and one or more cellular co-factors involved in nuclear transfer of the PIC [2]. The integrase inhibitor Raltegravir was approved by the US Food and Drug Administration for use in patients failing treatment due to drug resistance. No data is available from northeastern South Africa, where HIV prevalence is relatively high, and with the possibility that viruses may differ in their sensitivity to integrase inhibitors [11], it is important to provide sequence data on drug targets in the evolving HIV genetic landscape
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