AEGiS-15IAC: HIV-1 group M isolates are significantly more fit than group O or HIV-2 strains: Ex vivo fitness matches prevalence in the epidemic.

15th International AIDS Conference

Bangkok, Thailand - July 11-16, 2004

HIV-1 group M isolates are significantly more fit than group O or HIV-2 strains: Ex vivo fitness matches prevalence in the epidemic.

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. MoOrA1012)

Arts E, Ari[eumln K, Abraha A, Troyer R, Quinones-Mateu M, van der Groen G, Colebunders R, Kestens L, Heyndrickx L, Vanham G
Institute of Tropical Medicine, Antwerpen, Belgium

BACKGROUND: We have shown that HIV-1 group M subtype C viruses are less fit than subtype B and that this differences in fitness may be related to subtype distribution and spread. In this study, we compared the relative fitness of HIV-1 group M, HIV-1 group O and HIV-2. Group M viruses are responsible for the current pandemic while group O and HIV-2 are geographically restricted to West and West Central Africa. It appears that HIV-2 is less pathogenic than HIV-1. We hypothesise that differences in viral fitness may be related to differential spread of HIV groups and subtypes and the low prevelance of HIV-1 group O and HIV-2.

METHODS: We compared fitness of ten HIV-1 M, five HIV-1 O, and six HIV-2 isolates in head-to-head dual infection/competition experiments. All HIV isolates were either CXCR4-tropic and syncytium inducing or dual tropic (CXCR4 and CCR5). Nearly a thousand pair wise dual infections were performed in PHA/IL-2-treated peripheral blood mononuclear cells (PBMC) from different HIV-negative donors. Relative production of each HIV isolate was measured using a standardized heteroduplex tracking assays (HTA).

RESULTS: With the exception of poor subtype C fitness, the isolates of the other group M subtypes (A, B, D and CRF01) had similar relative fitness values. Similar results were observed in the intra group O and HIV-2 competitions. However, all of HIV-1 group M isolates were able to outcompete the group O and HIV-2 strains. The order of replicative capacity was M >M subtype C >2 >O where group M isolates were on average 10- to 100-fold more fit than HIV-2 and HIV-2 100-fold more fit than group O. This order was maintained regardless of the ethnicity of the donor providing the PBMC. Conclusion The relative prevalence of HIV-1 group M, group O, and HIV-2 in the human population matches their relative ex vivo fitness.

Keywords: AEGIS, HIV-2, HIV-1, Prevalence, Receptors, CCR5, Receptors, CXCR4, Disease Outbreaks, Acquired Immunodeficiency Syndrome, HIV Seropositivity, Giant Cells, Africa, Central, Humans, epidemiology

040711
MoOrA1012