AEGiS-14IAC: Coordinated vaccine trials in Kenya, Uganda, and Tanzania will be required to define cross protective immunity among HIV-1 subtypes A, C, and D.

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

Coordinated vaccine trials in Kenya, Uganda, and Tanzania will be required to define cross protective immunity among HIV-1 subtypes A, C, and D.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. TuOrC1193)

McCutchan FE, Carr JK, Harris M, Dowling W, Hoelscher M, Robb M, Birx DL
Henry M. Jackson Foundation, Rockville, MD, United States

BACKGROUND: Phase III HIV-1 vaccine trials in populations with multiple subtypes can potentially define the breadth of cross protective immunity. HIV-1 subtypes A, C, and D, which circulate in East Africa, constitute, alongside subtype B, CRF01_AE, and CRF02_AG, the most prevalent strains in the pandemic and are the most important for vaccine development. The distribution of these subtypes and proportion of recombinant strains in potential vaccine cohorts, although incompletely documented, will be a critical parameter for estimating cross protective immunity.

METHODS: DNA extracted from the primary PBMC of individuals in Kenya (n = 41), Uganda (n = 47), and Tanzania (n = 64) was evaluated for HIV-1 subtype either by near full-genome sequencing (n=97) or by a multi-region hybridization assay (MHA) (n = 55). Sequences were aligned with reference sequences and phylogenetically analyzed. Recombinants were detected and mapped with Bootscanning and Distance Scanning. The MHA used subtype-specific probes in gag, pol, vpu, env, and gp41.

RESULTS: HIV-1 subtype A constituted 57% of strains in Kenya, 15% in Uganda, and 9% in Tanzania. Subtype C comprised 30% of Tanzanian strains, 2% in Kenya and was not found in Uganda. Subtype D was 55% in Uganda, 6% in Tanzania, and 2% in Kenya. Recombinants were all unique and were similarly disproportionate: AC ranged from 34% to 4%, AD from 25% to 9%, and CD from 6% to 2% in different countries.

CONCLUSIONS: Due to significant recombination, complete genetic analysis of all inter-current infections should accompany vaccine trails in East Africa. A trial in any one country cannot provide complete information about cross protective immunity and the breadth of vaccines. Coordinated trials in multiple countries should be strongly advocated.

Keywords: AEGIS, Tanzania, HIV-1, Uganda, Kenya, Recombination, Genetic, AIDS Vaccines, Vaccines, Africa, genetics

020707
TuOrC1193