TY - JOUR
T1 - The number and complexity of pure and recombinant HIV-1 strains observed within incident infections during the HIV and malaria cohort study conducted in Kericho, Kenya, from 2003 to 2006
AU - Billings, Erik
AU - Sanders-Buell, Eric
AU - Bose, Meera
AU - Bradfield, Andrea
AU - Lei, Esther
AU - Kijak, Gustavo H.
AU - Arroyo, Miguel A.
AU - Kibaya, Rukia M.
AU - Scott, Paul T.
AU - Wasunna, Monique K.
AU - Sawe, Frederick K.
AU - Shaffer, Douglas N.
AU - Birx, Deborah L.
AU - McCutchan, Francine E.
AU - Michael, Nelson L.
AU - Robb, Merlin L.
AU - Kim, Jerome H.
AU - Tovanabutra, Sodsai
N1 - Funding Information:
This study was supported and approved by the U.S. Military HIV Research Program at the Walter Reed Army Institute of Research (WRAIR protocol #855, RV142) and by the Kenya Medical Research Institute, Nairobi, Kenya. The authors would like to acknowledge the technical contributions of William Murtaugh during collection of the sequencing data. We also thank the management and employees of James K. Finlay LLC (formerly African Highlands Produce) for their invaluable assistance and cooperation during the conduct of this research among plantation employees and their dependents; and we are grateful to the dedicated and committed 2801 participants of the Kericho HIV Cohort Study. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
Funding Information:
Disclosure Statements: The material has been reviewed by the Walter Reed Army Institute of Research and there is no objection to its presentation and/or publication. This work is published with the permission of the Director, Kenya Medical Research Institute, Nairobi, Kenya. The Walter Reed Army Institute of Research Institutional Research Board human use protocol #855 (RV142), "HIV and Malaria Cohort Study Among Plantation Workers and Adult Dependents in Kericho, Kenya" is funded through the United States Military HIV Research Program (the Walter Reed Army Institute of Research and the Henry M. Jackson Foundation for the Advancement of Military Medicine). No competing financial interests exist.
PY - 2015/8/19
Y1 - 2015/8/19
N2 - Characterization of HIV-1 subtype diversity in regions where vaccine trials are conducted is critical for vaccine development and testing. This study describes the molecular epidemiology of HIV-1 within a tea-plantation community cohort in Kericho, Kenya. Sixty-three incident infections were ascertained in the HIV and Malaria Cohort Study conducted in Kericho from 2003 to 2006. HIV-1 strains from 58 of those individuals were full genome characterized and compared to two previous Kenyan studies describing 41 prevalent infections from a blood bank survey (1999-2000) and 21 infections from a higher-risk cohort containing a mix of incident and prevalent infections (2006). Among the 58 strains from the community cohort, 43.1% were pure subtypes (36.2% A1, 5.2% C, and 1.7% G) and 56.9% were intersubtype recombinants (29.3% A1D, 8.6% A1CD, 6.9% A1A2D, 5.2% A1C, 3.4% A1A2CD, and 3.4% A2D). This diversity and the resulting genetic distance between the observed strains will need to be addressed when vaccine immunogens are chosen. In consideration of current vaccine development efforts, the strains from these three studies were compared to five candidate vaccines (each of which are viral vectored, carrying inserts corresponding to parts of gag, pol, and envelope), which have been developed for possible use in sub-Saharan Africa. The sequence comparison between the observed strains and the candidate vaccines indicates that in the presence of diverse recombinants, a bivalent vaccine is more likely to provide T-cell epitope coverage than monovalent vaccines even when the inserts of the bivalent vaccine are not subtype-matched to the local epidemic.
AB - Characterization of HIV-1 subtype diversity in regions where vaccine trials are conducted is critical for vaccine development and testing. This study describes the molecular epidemiology of HIV-1 within a tea-plantation community cohort in Kericho, Kenya. Sixty-three incident infections were ascertained in the HIV and Malaria Cohort Study conducted in Kericho from 2003 to 2006. HIV-1 strains from 58 of those individuals were full genome characterized and compared to two previous Kenyan studies describing 41 prevalent infections from a blood bank survey (1999-2000) and 21 infections from a higher-risk cohort containing a mix of incident and prevalent infections (2006). Among the 58 strains from the community cohort, 43.1% were pure subtypes (36.2% A1, 5.2% C, and 1.7% G) and 56.9% were intersubtype recombinants (29.3% A1D, 8.6% A1CD, 6.9% A1A2D, 5.2% A1C, 3.4% A1A2CD, and 3.4% A2D). This diversity and the resulting genetic distance between the observed strains will need to be addressed when vaccine immunogens are chosen. In consideration of current vaccine development efforts, the strains from these three studies were compared to five candidate vaccines (each of which are viral vectored, carrying inserts corresponding to parts of gag, pol, and envelope), which have been developed for possible use in sub-Saharan Africa. The sequence comparison between the observed strains and the candidate vaccines indicates that in the presence of diverse recombinants, a bivalent vaccine is more likely to provide T-cell epitope coverage than monovalent vaccines even when the inserts of the bivalent vaccine are not subtype-matched to the local epidemic.
UR - http://www.scopus.com/inward/record.url?scp=84942636523&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0135124
DO - 10.1371/journal.pone.0135124
M3 - Article
C2 - 26287814
AN - SCOPUS:84942636523
SN - 1932-6203
VL - 10
JO - PLoS ONE
JF - PLoS ONE
IS - 8
M1 - e0135124
ER -