Oral Abstract Session 01 - Global HIV Vaccine Enterprise

POSTERS
Posters
Topic 5: HIV Transmission and Viral Diversity
P05.09
Analysis of HIV-1 gp120 Quasispecies Suggests High
Prevalence of Intra-subtype Recombination
I.E. Kiwelu 1 , V. Novitsky 1 , L. Margolin 1 , J. Baca 1 , R. Manongi 2 ,
N. Sam 2 , J. Shao 3 , M.F. MacLane 1 , S.H. Kapiga 4 , M. Essex 1
1 Harvard School of Public Health, Boston, MA, USA;
2 Kilimanjaro Christian Medical College, Moshi, United Republic
of Tanzania; 3 Kilimanjaro Medical Christian College, Moshi,
United Republic of Tanzania; 4 London School of Hygiene and
Tropical Medicine, London, United Kingdom (Great Britain)
Background: Recombination between viruses of the same HIV-
1 subtype has been understudied primarily due to the lack of
reference sequences, as well as appropriate bio-informatics tools.
The introduction of recombination detection program (RDP3)
made the detection of HIV-1 intra-subtype recombination feasible
Methods: This study determined the prevalence and patterns
of HIV-1 intra-subtype recombinants among female bar and
hotel workers in Moshi, Tanzania. The HIV-1 env gp120 V1-C5
quasispecies from 45 subjects classified as pure HIV-1 subtypes
A1, C, or D were analyzed for recombination events by RDP3.
Results: HIV-1 quasispecies with evidence for recombination
were found in 89% of subjects infected with pure HIV-1 subtypes
A, C, and D. Recombinant viruses were observed at both the
baseline and the 12 month visits in 88% of the subjects; in 12%
of subjects recombination was identified only at the later time
point. Two major patterns were observed: 70% of subjects had
unique recombination breakpoints without dominance of any
particular variant, while in 30% of subjects a specific recombinant
variant dominated in the pool of viral quasispecies.
Conclusion: A large proportion of female bar and hotel workers
were infected with intra-subtype recombinant viruses. These
results suggest that HIV-1 co- and super-infections are common
in this population, and occur more frequently than previously
thought. Intra-subtype recombination contributes to the increased
viral diversity which poses a challenge to HIV-1 vaccine design.
168
AIDS Vaccine 2012
P05.10
HIV-1 Diversity in Cameroon: New Insights on the
Evolution of the Virus
T. Aime Marcel Simon 1 , Z. Lycias 2 , M. Eitel 3 , W. Carolyn 2 ,
B.A. Wendy 2 , M.P. Darren 2
1 Institute of Infectious Disease and Molecula, University of
Cape Town, Cape Town, South Africa; 2 IIDMM, University of
Cape Town, Cape Town, South Africa; 3 Institute of Medical
Research and Study of Medicinal Plants, Yaounde, Cameroon
Background: Given the central role of HIV-1 diversity in the HIV
pandemic and its impact on vaccine development, it is imperative
that global molecular epidemiology surveillance continues.
Constantly improving phylogenetics-based analytical techniques
and rapidly expanding HIV sequence datasets promise to yield
important insights into the origin, evolution and spread of HIV-1.
Methods: In an effort to study the phylogeography and
phylodynamics of the HIV-1 M epidemic in the early 20th century,
we analysed 50 plasma samples from HIV-infected blood donors
from Cameroon. Full length gag sequences were generated and
aligned using MUSCLE along with a representative selection of
HIV sequences from the rest of the world and all published gag
sequences from Cameroon and other West African countries.
A maximum likelihood phylogenetic tree was constructed from
these sequences following removal of recombinant sequence
fragments by a blinded fully exploratory screen for recombination
using RDP3.
Results: All the Cameroonian sequences were derived from HIV-1
M viruses. The phylogenetic tree indicated that at least one of the
newly-sequenced CRF02_AG viruses is an outlier of the CRF02_
AG clade and may help resolve the controversy surrounding
the origins of this clade. Furthermore, isolates from Cameroon
were spread throughout the phylogenetic tree clustering with
different subtypes and circulating recombinant forms, a finding
consistent with West Africa being the geographic origin of the
global HIV epidemic. Importunately, our blind recombination
screen suggested that many divergent Cameroonian viruses
previously identified as being unique recombinant forms, may
be divergent, relatively non-recombinant, but under-sampled
subtype-level lineages.
Conclusion: Lineages diverging early after the origin of HIV-1
M are likely still circulating in Cameroon and could be suitable
for retracing the movement and evolutionary dynamics of HIV-1
during the earliest stages of the pandemic. These lineages will be
useful for reconstructing ancestral HIV-1M sequences for use as
vaccine immunogens.