AEGiS-14IAC: Biological phenotype of recombinants and non-B HIV primary isolates from Spanish patients.

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

Biological phenotype of recombinants and non-B HIV primary isolates from Spanish patients.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no.. ThOrA1434)

Perez-Alvarez L, Delgado E, Villahermosa ML, Cuevas MT, Carmona R, Vazquez de Parga E, Medrano L, Thomson MM, Cuevas L, Sierra M, Prieto A, Rodriguez R, Lopez-Alvarez MJ, Ojea de Castro R, Najera R
Area de Patogenia Viral. CNBF. Instituto de Salud Carlos III., Majadahonda. Madrid, Spain

BACKGROUND: To study the biological phenotype and amino acid changes in V3 of recombinants and non-B HIV isolates from Galicia. PATIENTS: 40 patients, diagnosed between 1999-2001, infected with different recombinants and non-B HIV subtypes. 72.5% were Spanish. Transmission route: IDU(60.6%), HT(36.8%), HO(2.6%).

METHODS: pol and V3 regions were amplified and sequenced. Phylogenetic analysis were performed using Clustal W, Treeview, Chromas, Seqman and Simplot. Primary isolates were obtained by coculture of PBMCs from patients and from healthy donors. SI phenotype was studied in MT2. Coreceptor use (CCR1,CCR2b,CCR3, CCR5, CXCR4, BOB, BONZO) and tropism was evaluated in GHOST-CD4 and U87-CD4 cells. Replication capacity was determined in primary coculture. Positively charged amino acid substitutions were evaluated in V3, and viral phenotype was based on total net charge (NSI:+2 to +4 or SI:>+4).

RESULTS: The genetic forms(pol/V3) were: A(2); C(3); F(1); G( 4); H/A(1); BG/B(3); BG/G(1); DF/F(1); FBF/F(1); G/B(10); GH/K(1); AGA/A(1); GU/A(5); KU/A(1); AJU/G(3); dual infection G+B(1)(U=unknown fragment). The phenotype based on V3 resulted NSI/CCR5 in 29 of 36(80.5%) and SI/CXCR4 in the other 7(19.5%), corresponding in the 7 cases to G/B recombinants. A correlation between phenotype based on V3 and biological phenotype in primary isolates was observed. G/B recombinants resulted SI/CXCR4,CCR5,CCR3 and with several mutations in positions 13, 14, 20, 25 and 32 as characteristics of these G/B recombinants. G clone from dual G+B HIV infection resulted NSI/CCR5 and B clone SI/CXCR4.

CONCLUSIONS: The most frequent viral phenotype detected in these recombinant strains circulating in Galicia was NSI/CCR5. However, in the majority of the G/B recombinants the phenotype was SI/CXCR4/MULTITROPIC, underlining the importance of performing a follow-up of these cases, in order to establish whether these findings are associated with a faster progression of the disease.

Keywords: AEGIS, HIV Infections, Phenotype, HIV Seropositivity, Virus Replication, CD4-Positive T-Lymphocytes, Human, genetics, virology

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ThOrA1434