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271 46 Near Full-Length HIV Genome Sequences from Rakai District, Uganda Show Subtype A and D Plus 30% Unique Recombinants
M. Harris*1, D. Serwada3, N. Sewankambo3, F. Wabwire3, J. Philips2, M. Meehen6, B. Kim2, T. Lutalo4, N. Kiwanuka3, R. Gray5, M. Wawer6, D. Birx1, M. Robb1, and F. McCutchan2
1Walter Reed Army Inst. of Res., Washington, DC, USA; 2The Henry M. Jackson Fndn., Rockville, MD, USA; 3Makerere Univ., Kampala, Uganda; 4Uganda Virus Res. Inst., Entebbe; 5Johns Hopkins Univ., Baltimore, MD, USA; and 6Columbia Univ., New York, NY, USA
Background: The US Military HIV Research Program plans to conduct a phase III efficacy trial of an HIV vaccine in the Rakai district of Uganda. Preparations for this trial are being conducted through 2 studies: the Community HIV Epidemiological Research (CHER) and the Molecular Epidemiological Research (MER) projects. This work will address 2 goals of MER: (1) the distribution of HIV-1 genetic subtypes in the region, and (2) the presence and character of recombinant forms of HIV. This research contributes to our overall vaccine strategy of matching a candidate vaccine as closely as possible to the genetic subtype circulating in the population in which the vaccine is tested.
Methods: Genomic DNA was extracted from PBMCs from volunteers, or when available from cocultures of volunteers' PBMCs and fresh, stimulated PBMCs. Near full-length proviral DNA was amplified with a nested PCR strategy. Proviral amplicons were sequenced and then analyzed by bootscanning and neighbor-joining trees.
Results: A total of 46 near full-length sequences were analyzed. The predominant subtype found was D, which comprises 54.3% of the sequences analyzed. Subtype A represented 15.2%, whereas the remaining 30.4% of sequences were unique recombinants. AD recombinants are the most common representing 23.9% of the total sequences, but AC and CD recombinants were also found.
Conclusions: Subtype D and A vaccine products under development are matched to the 2 pure subtypes in the Rakai district. However, one-third of the sequences were recombinants. The role of recombinants in limiting vaccine protection is unknown. Clearly, a genetic screening assay used to analyze breakthrough infections after vaccination must have the capability of detecting recombinants.
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