Identification of new, emerging HIV-1 unique recombinant forms and drug resistant viruses circulating in Cameroon

Viswanath Ragupathy,Owen Wood,Phillipe Nyambi,Indira Hewlett,Sherwin Lee,Shixing Tang,Jiangqin Zhao

doi:10.1186/1743-422x-8-185

Viswanath Ragupathy, Owen Wood + Show 5 more

Open Access

https://doi.org/10.1186/1743-422x-8-185

Copy DOI

Abstract

BackgroundThe HIV epidemic in Cameroon is characterized by a high degree of viral genetic diversity with circulating recombinant forms (CRFs) being predominant. The goal of our study was to determine recent trends in virus evolution and emergence of drug resistance in blood donors and HIV positive patients.MethodologyBlood specimens of 73 individuals were collected from three cities and a few villages in Cameroon and viruses were isolated by co-cultivation with PBMCs. Nested PCR was performed for gag p17 (670 bp) pol (840 bp) and Env gp41 (461 bp) genes. Sequences were phylogenetically analyzed using a reference set of sequences from the Los Alamos database.ResultsPhylogenetic analysis based on partial sequences revealed that 65% (n = 48) of strains were CRF02_AG, 4% (n = 3) subtype F2, 1% each belonged to CRF06 (n = 1), CRF11 (n = 1), subtype G (n = 1), subtype D (n = 1), CRF22_01A1 (n = 1), and 26% (n = 18) were Unique Recombinant Forms (URFs). Most URFs contained CRF02_AG in one or two HIV gene fragments analyzed. Furthermore, pol sequences of 61 viruses revealed drug resistance in 55.5% of patients on therapy and 44% of drug naïve individuals in the RT and protease regions. Overall URFs that had a primary HIV subtype designation in the pol region showed higher HIV-1 p24 levels than other recombinant forms in cell culture based replication kinetics studies.ConclusionsOur results indicate that although CRF02_AG continues to be the predominant strain in Cameroon, phylogenetically the HIV epidemic is continuing to evolve as multiple recombinants of CRF02_AG and URFs were identified in the individuals studied. CRF02_AG recombinants that contained the pol region of a primary subtype showed higher replicative advantage than other variants. Identification of drug resistant strains in drug-naïve patients suggests that these viruses are being transmitted in the population studied. Our findings support the need for continued molecular surveillance in this region of West Central Africa and investigating impact of variants on diagnostics, viral load and drug resistance assays on an ongoing basis.

Highlights

Phylogenetic analysis based on partial sequences revealed that 65% (n = 48) of strains were CRF02_AG, 4% (n = 3) subtype F2, 1% each belonged to CRF06 (n = 1), CRF11 (n = 1), subtype G (n = 1), subtype D (n = 1), CRF22_01A1 (n = 1), and 26% (n = 18) were Unique Recombinant Forms (URFs)
HIV/AIDS was first identified in Cameroon during 1985 [1] and the epidemic has continued to increase with the identification of multiple, divergent HIV subtypes and circulating recombinant forms (CRFs) [2]
About 80% of drug resistance was detected for Nucleoside Reverse Transcriptase Inhibitors (NRTI) class, followed by the non-nucleoside reverse transcriptase Inhibitors (NNRTI) (76%) and Protease Inhibitor (PI) class (19%) drugs

Summary

Introduction

HIV/AIDS was first identified in Cameroon during 1985 [1] and the epidemic has continued to increase with the identification of multiple, divergent HIV subtypes and circulating recombinant forms (CRFs) [2]. New strains have been shown to emerge in Cameroon, studies that analyzed three immunodominant regions gag/pol/env have documented that 60-70% of infections continue to be CRF02_AG [12,13]. In the first study it was reported that CRF02_AG accounted for 60%, followed by URFs(26%), 12 pure subtypes and CRFs [16] and in another study CRF02_AG accounted for 58.2% of infections followed by 14.8% of URFs, 0.2 - 6.1% of subtypes, A, B, C, D, F2, G and CRFs 01, 06, 09, 11, 13, 22, and 37 [12] Both studies confirmed CRF02_AG is a dominant strain in urban Cameroon. In recent studies from rural Cameroon, CRF02_AG was shown to be a dominant strain 66.5% whether analyzed from a single pol fragment [14] or individual fragments of gag (65%), pol (75%) and env (55%) [13] followed by a second dominant strain CRF22_01_A1 in 5-10% of infections [14,18]. The goal of our study was to determine recent trends in virus evolution and emergence of drug resistance in blood donors and HIV positive patients

Objectives

Methods

Results

Discussion

Conclusion