title: X4 tropic multi-drug resistant quasi-species detected at the time of primary HIV-1 infection remain exclusive or at least dominant far from PHI.
abstract: Our objective was to analyze the evolution of resistance mutations (RM) and viral tropism of multi-drug-resistant (MDR) strains detected at primary HIV-1 infection (PHI). MDR HIV strain was defined as the presence of genotypic resistance to at least 1 antiretroviral of the 3 classes. Tropism determinations (CCR5 or CXCR4) were performed on baseline plasma HIV-RNA and/or PBMC-HIV-DNA samples, then during follow-up using population-based sequencing of V3 loop and phenotypic tests. Clonal analysis was performed at baseline for env, RT and protease genes, and for HIV-DNA env gene during follow-up. Five patients were eligible. At baseline, RT, protease and env clones from HIV-RNA and HIV-DNA were highly homogenous for each patient; genotypic tropism was R5 in 3 (A,B,C) and X4 in 2 patients (D,E). MDR strains persisted in HIV-DNA throughout follow-up in all patients. For patient A, tropism remained R5 with concordance between phenotypic and genotypic tests. Clonal analysis on Month (M) 78 HIV-DNA evidenced exclusively R5 (21/21) variants. In patient B, clonal analysis at M36 showed exclusively R5 variants (19/19) using both genotypic and phenotypic tests. In patient C, baseline tropism was R5 by genotypic test and R5/X4 by phenotypic test. An expansion of these X4 clones was evidenced by clonal analysis on M72 HIV-DNA (12/14 X4 and 2/14 R5 variants). In patient D, baseline tropism was X4 with concordance between both techniques and HIV-RNA and HIV-DNA remained X4-tropic up to M72, confirmed by the clonal analysis. Patient E harboured highly homogenous X4-using population at baseline; tropism was unchanged at M1 and M18. In all patients, the initial MDR population was highly homogenous initially, supporting the early expansion of a monoclonal population and its long-term persistence. X4-tropic variants present at baseline were still exclusive (patients D and E) or dominant (at least one time point, patient C) far from PHI.
authors: Université Paris Descartes, EA 3620, CHU Necker-Enfants Malades, Paris, France. jade.ghosn@bct.aphp.fr
authors: Jade
authors: J
authors: Ghosn
authors: Julie
authors: J
authors: Galimand
authors: Stéphanie
authors: S
authors: Raymond
authors: Laurence
authors: L
authors: Meyer
authors: Christiane
authors: C
authors: Deveau
authors: Cécile
authors: C
authors: Goujard
authors: Jacques
authors: J
authors: Izopet
authors: Christine
authors: C
authors: Rouzioux
authors: Marie-Laure
authors: ML
authors: Chaix
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D004279:DNA, Viral / Q000097:blood; D024921:Drug Resistance, Multiple, Viral; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000821:virology*; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000201:enzymology / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010802:Phylogeny; D012367:RNA, Viral / Q000097:blood; D018523:Tropism; D055815:Young Adult
chemical_list: D004279:DNA, Viral; D012367:RNA, Viral; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase