Oral Abstract Session 01 - Global HIV Vaccine Enterprise

POSTERS
Posters
Topic 5: HIV Transmission and Viral Diversity
P05.21
Genetic Variability and Drug Resistance Mutations in
HIV-1 Infected Individuals on HAART or Drug Naïve in
Limbe, Cameroon
L. Agyingi 1 , D. Barengolts 1 , L. Mayr 1 , T. Kinge 2 , M. MBida 3 ,
P. Nyambi 1
1 New York University School of Medicine, New York, NY,
USA; 2 Limbe Regional Hospital, South West Region, Limbe,
Cameroon; 3 Faculty of Biomedical Sciences, University of
Dschang, Dschang, Cameroon
Background: Cameroon is a country in West Central Africa with a
population of about 20 million inhabitants, with an estimated HIV
prevalence of 5.1% in the general population. The HIV epidemic
in this region is marked by a broad genetic diversity dominated
by Circulating Recombinant Forms (CRFs).
Methods: To characterize HIV-1 genotypes circulating in HIV
positive individuals in Limbe, Cameroon, we phylogenetically
analyzed blood samples from 116 HIV positive patients. Of 116
samples tested, 110 were amplified by nested PCR at the Gag,
Pol and Env genes. Sequences obtained were phylogenetically
analyzed with reference sequences from the Los Alamos
database. The RT region of samples was also amplified to
identify mutations that conferred resistance to Reverse
Transcriptase inhibitors (RTIs) using the Stanford University
Drug resistance database.
Results: Our results revealed a broad genetic diversity, dominated
by circulating recombinant forms as follows: CRF02_AG 50.4%
(n=54), CRF22_01A1 7.4% (n=8) F2 3.7% (n=4), D 2% (n=2),
CRF43_02G 2.8% (n=3), CRF18_CPX 2.8% (n=3) and recombinant
forms (RFs) 31.7 %( n=34). Most RFs contained CRF02_AG in
one or two HIV loci analyzed. RT sequences of 3 patients on
HAART and 15 drug naïve individuals harbored mutations which
conferred resistance to RTIs.
Conclusion: CRF02_AG continues to be the most predominant
strain in Cameroon, CRF22_01A1 on the increase. Identification
of drug resistance strains in drug naïve patients suggest these
viruses are being transmitted in the study population and
highlights the need of drug resistance testing before start of ART
for HIV patients.
174
AIDS Vaccine 2012
P05.22
Intrasubtype C Superinfected Individuals Mount
Delayed and Low-Titer Autologous Neutralizing
Antibody Responses Prior to Superinfection
D. Basu 1 , C. Kraft 1 , P. Campbell 1 , M. Murphy 1 , T. Yu 1 , P. Hraber 2 ,
E. Chomba 3 , J. Mulenga 3 , W. Kilembe 3 , S. Allen 4 , C. Derdeyn 1 ,
E. Hunter 1
1 Emory University, Atlanta, GA, USA; 2 Los Alamos National
Laboratory, Los Alamos, NM, USA; 3 Zambia Emory HIV
Research Project, Lusaka, Zambia; 4 Department of Global
Health, Emory University, Atlanta, GA, USA
Background: The potential role of neutralizing antibody in
protecting against intra-subtype HIV-1 superinfection remains
to be understood. We compared the early neutralizing antibody
responses in three individuals, who were superinfected within
one year of primary infection, to ten case-matched nonsuperinfected
controls from a Zambian cohort of subtype
C transmission cases. Sequence analysis of single genome
amplified full-length env showed minimal diversification in the
individuals who became superinfected with the same subtype
of HIV-1 within year one post-seroconversion. We hypothesized
that these superinfected individuals had a muted neutralizing
antibody response that elicited little pressure on the founder
virus to escape.
Methods: We molecularly cloned envs from virus at the
time of seroconversion and from virus at the time point that
superinfection was detected. Using a TZM-BL pseudovirus
reporter assay, we tested plasma neutralization of these
autologous variants over the first year of infection.
Results: Neutralization assays showed that autologous plasma
NAb titers to founder virus were low to undetectable in all three
superinfected individuals prior to superinfection. In contrast,
neutralizing antibodies with a median IC50 of 1:1896 were
detected as early as three months post-seroconversion in nonsuperinfected
matched controls. There was no evidence, prior to
superinfection, of cross-neutralization of superinfecting variants
in any of the three cases, although cross-neutralization breadth
and potency to the subtype C pseudovirus reference panel was
also limited in the plasma from non-superinfected individuals.
Although there was a trend towards superinfected individuals
having reduced levels of gp120 binding antibodies prior to
superinfection compared to non-superinfected controls, this
difference was not statistically significant between the groups.
Conclusion: These data suggest that development of antibodies,
as reflected in autologous neutralizing antibodies to the primary
infection variants, may provide protection and decrease
susceptibility to superinfection.