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1.
Vaccine ; 32(30): 3787-95, 2014 Jun 24.
Article in English | MEDLINE | ID: mdl-24837770

ABSTRACT

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , HIV Infections/immunology , HIV-1/classification , gag Gene Products, Human Immunodeficiency Virus/genetics , nef Gene Products, Human Immunodeficiency Virus/genetics , Adult , Consensus Sequence , Female , HIV-1/genetics , Humans , Interferon-gamma/immunology , Interleukin-2/immunology , Male , Middle Aged , Peptides/immunology , Perforin/immunology , Tumor Necrosis Factor-alpha/immunology
2.
AIDS Res Hum Retroviruses ; 24(6): 889-95, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18544019

ABSTRACT

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.


Subject(s)
Drug Resistance, Viral/genetics , HIV Infections/epidemiology , HIV-1/genetics , Adolescent , Adult , Anti-HIV Agents/therapeutic use , Base Sequence , Female , Genotype , HIV-1/drug effects , Humans , Molecular Sequence Data , Phylogeny , Polymorphism, Genetic , Pregnancy , Prevalence , RNA, Viral/analysis , Uganda/epidemiology , pol Gene Products, Human Immunodeficiency Virus/genetics
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