Browsing by Author "Kaleebu, P."

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    Group M consensus Gag and Nef peptides are as efficient at detecting clade A1 and D cross-subtype T-cell functions as subtype-specific consensus peptides
    (Vaccine, 2014) Mugaba, S.; Nakiboneka, R.; Nanyonjo, M.; Bugembe-Lule, D.; Kaddu, I.; Nanteza, B.; Tweyongyere, R.; Kaleebu, P.; Serwanga, J.
    Evaluating HIV-1 specific T-cell response in African populations is sometimes compromised by extensive virus diversity and paucity of non-clade B reagents. We evaluated whether consensus group M (ConM) peptides could serve as comparable substitutes for detecting immune responses in clade A and clade D HIV-1 infection. Frequencies, breadths and polyfunctionality (≥3 functions: IFN-γ, IL-2, TNF-α and Perforin) of HIV-specific responses utilizing ConM, ConA and ConD Gag and Nef peptides was compared. Median genetic distances of infecting gag sequences from consensus group M were (8.9%, IQR 8.2–9.7 and 9%, IQR 3.3–10) for consensus A and D, respectively. Of 24 subjects infected with A and D clade virus, Gag responses were detected in comparable proportions of subjects when using ConM peptides 22/24, ConA peptides 17/24, and ConD peptides 21/24; p=0.12. Nef responses were also detected at similar proportions of subjects when using ConM peptides 15/23, ConA peptides 19/23, and ConD peptides 16/23, p=0.39. Virus-specific CD4+ and CD8+ T-cell polyfunctionality were also detected in similar proportions of infected individuals when using different peptide sets. These data support the use of consensus group M overlapping peptide sets as reagents for detecting HIV-specific responses in a clade A and D infected population, but underscore the limitations of utilizing these reagents when evaluating the breadth of virus-specific responses.
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    P20-10. Differences in patterns of Gag-induced immunogenetic pressure occur between clades A and D chronic HIV-1 infection in a Ugandan population
    (Retrovirology, 2009) Serwanga, J.; Ndembi, N.; Nanteza, B.; Mugaba, S.; Pimego, E.; Pala, P.; Auma, B.; Lyagoba, F.; Kaleebu, P.
    We previously reported slow HIV-1 disease progression in this population to be associated with the inherent host HLA B allele-mediated ability to induce broader Gag T-cell responses and faster disease progression to be more associated with clade D than A. Since Gag escape mutations often reduce viral fitness leading to significant reduction in virus replication, in this study, we evaluated the immunogenetic characteristics of clades A and D-associated escape mutations that could be harnessed for vaccine design.
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    Transmitted Antiretroviral Drug Resistance Surveillance among Newly HIV Type 1-Diagnosed Women Attending an Antenatal Clinic in Entebbe, Uganda
    (AIDS research and human retroviruses, 2008) Ndembi, N.; Lyagoba, F.; Nanteza, B.; Kushemererwa, G.; Serwanga, J.; Mbidde, E. Katongole; Grosskurth, H.; Kaleebu, P.; on behalf of the Uganda HIV Drug Resistance Working Group
    To evaluate transmitted HIV-1 drug resistance and study the natural polymorphism in pol of HIV-1 strains of newly diagnosed women attending an antenatal clinic in Uganda we sequenced the protease and reverse transcriptase genes for 46 HIV-1 strains from the threshold surveillance. Of the 46 sequences analyzed, 48.0% were subtype A1 (n = 22), 39.0% subtype D (n = 18), 2.0% subtype A2 (n = 1), 2.0% subtype C (n = 1), and 9.0% intersubtype recombinant A1/D (n = 4). Overall, many minor mutations were identified in the protease sequences. None of the strains had major associated mutations to any RTI drug or drug class interest after genotyping 37 samples of our cohort. The HIV drug resistance prevalence estimate in Entebbe following the HIVDR-TS methodology is less than 5% as set out by WHO guidelines.