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During a recent study on the sequencing data of our database between 2012 and 2016 in Southwestern France, we observed that eight patients harbored what seemed to be the same virus. Indeed, routine genotyping at the time of HIV diagnosis showed that protease and reverse transcriptase were related to CRF06_cpx and subtype B, respectively. The integrase sequences (available for three patients) were clustering with CRF06_cpx and envelope (Env) gp120 sequences (available for two patients) with subtype B. Since such a recombinant has not been recorded in the Los Alamos database, we decided to characterize the full-length genome of this virus. The data suggest the identification of a new circulating recombinant form (CRF) between CRF06_cpx and subtype B, the structure of which is very complex with multiple breakpoints. We will refer this CRF as CRF98_cpx.

We have estimated the prevalence of the different viral subtypes between January 2012 and December 2016 in HIV-1-infected patients of the Aquitaine region (southwest part of France) who had a routine HIV-1 genotype resistance testing (GRT) centralized at the Bordeaux University Hospital. GRT was performed on viral RNA (1,784 samples) before treatment initiation or at failure, whereas proviral DNA was used as template (1,420 samples) in the event of a treatment switch in patients with viral load below 50 copies/mL. Pol and integrase sequences were obtained; subtypes, circulating recombinant forms (CRFs), and unique recombinant forms (URFs) were assigned by combining the results of SCUEAL, REGA, COMET, and HIV BLAST. Globally, subtype B was predominant with 71.7%, whereas non-B subtypes accounted for 28.3%. Within the non-B viruses, CRF02_AG was the most prominent (11.6%) followed by non-B non-URF (13.5%), A, CRF01_AE, G, CRF06_cpx, F, C, D, H, J, and finally URF (3.2%). The analysis of the two compartments separately showed that RNA exhibits higher percentages of non-B viruses than DNA. This study reveals a high degree of diversity of HIV-1 non-B subtype strains in Aquitaine, with an increasing prevalence of CRF02_AG and URF in the population investigated for viral RNA, that is, including more recently detected HIV-1-infected patients. Future studies should attempt to identify the transmission clusters while paying special attention to URF, since they seem to be increasing in the population and could potentially host CRF.

The scientific and medical community is seeking to cure HIV. Several pathways have been or are being explored including therapeutic vaccination. Viroimmunological studies on primary infection as well as on elite controllers have demonstrated the importance of the cytotoxic CD8 response and have mainly oriented research on vaccine constructs toward this type of response. The results of these trials are clearly not commensurate with the hope placed in them. Might there be one or more uncontrolled variables? The genetics of patients need to be taken into consideration, especially their human lymphocyte antigen (HLA) alleles. There is a need to find a balance between the conservation of cytotoxic T lymphocyte (CTL) epitopes and presentation by HLA alleles. The pathway is a narrow one between adaptation of the virus to HLA I restriction and the definition of conserved proviral CTL epitopes presentable by HLA I alleles. It is likely that the genetics of patients will need to be considered for HIV-1 vaccine studies and that multidisciplinary collaboration will be essential in this field of infectious diseases.