Browsing by Author "Ndembi, Nicaise"

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    Profile of T Cell Recognition of HIV Type 1 Consensus Group M Gag and Nef Peptides in a Clade A1- and D-Infected Ugandan Population
    (AIDS research and human retroviruses, 2012) Serwanga, Jennifer; Mugaba, Susan; Pimego, Edward; Nanteza, Bridget; Lyagoba, Fred; Nakubulwa, Susan; Heath, Laura; Nsubuga, Rebecca N.; Ndembi, Nicaise; Gotch, Frances; Kaleebu, Pontiano
    Reagents for evaluating non-clade B HIV-specific T cell responses are uncommon. Peptides based on highly conserved HIV-1 consensus group M sequences that are phylogenetically closer to most circulating strains may provide potential alternative reagents in populations with diverse infections, and may be relevant for vaccine design. Recognition of such reagents in clade A1-and D-infected populations has not been previously evaluated. Interferon (IFN)-c ELISpot assay was used to evaluate T cell recognition of Gag and Nef peptides based on consensus group M sequences in 50 treatment-naive adults predominantly infected with HIV-1 clades A1 and D. Gag-induced T cell responses were correlated with gag sequence diversity. Infecting clades were determined from gag sequences for 45 of the 50 subjects as 40% clade A1 (18/45), 45% clade D (20/45), 2% clade C (1/45), 2% A1/C recombinant (1/45), 2% A1/D (1/45), 7% CRF10_CD (3/45), and 2% U (unclassifiable) (1/45). The mean genetic divergence and diversity of clade A and D gag region compared to group M consensus sequences at synonymous and nonsynonymous nucleotide and amino acid levels were not always significant. Gag peptides were targeted at significantly higher frequency [88% (44/50)] than Nef [64% (32/50)]; p = 0.014, although their mean IFN-c magnitudes were comparable ([3703 (95% CI 2567–4839)] vs. [2120 (95% CI 478–3762)]), respectively. Measurable virus-induced IFN-c responses were detected in 96% (48/50) individuals, primarily targeting the more conserved Gag p24 and Nef central core regions. Use of these reagents to screen for HIV-specific IFN-c responses may mitigate the challenge of viral diversity; although this targeting is apparently biased toward a few highly conserved epitopes.
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    The rates of HIV-1 superinfection and primary HIV-1 infection are similar in female sex workers in Uganda
    (Theoretical Medicine and Bioethics, 2008) Redd, Andrew D.; Ssemwanga, Deogratius; Vandepitte, Judith; Wendel, Sarah K.; Ndembi, Nicaise; Bukenya, Justine; Nakubulwa, Susan; Grosskurth, Heiner; Parry, Chris M.; Martens, Craig; Bruno, Daniel; Porcella, Stephen F.; Quinn, Thomas C.; Kaleebu, Pontiano
    To determine and compare the rates of HIV superinfection and primary HIV infection in high-risk female sex workers in Kampala, Uganda. Design—A retrospective analysis of individuals who participated in a clinical cohort study among high-risk female sex workers in Kampala, Uganda. Methods—Plasma samples from HIV-infected female sex workers (FSW) in Kampala, Uganda were examined with next-generation sequencing of the p24 and gp41HIV genomic regions for the occurrence of superinfection. Primary HIV incidence was determined from initially HIV-uninfected FSW from the same cohort, and incidence rate ratios were compared. Results—The rate of superinfection in these women (7/85; 3.4/100py) was not significantly different from the rate of primary infection in the same population (3.7/100py; IRR=0.91, p=0.42). Seven women also entered the study dual infected (16.5% either dual or superinfected). The women with any presence of dual infection were more likely to report sex work as their only source of income (p=0.05), and trended to be older and more likely to be widowed (p=0.07). Conclusions—In this cohort of female sex workers, HIV superinfection occurred at a high rate and was similar to that of primary HIV infection. These results differ from a similar study of high-risk female bar-workers in Kenya that found the rate of superinfection to be significantly lower than the rate of primary HIV infection.
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    Transmitted antiretroviral drug resistance among newly HIV-1 diagnosed young individuals in Kampala
    (Aids, 2011) Ndembi, Nicaise; Hamers, Raph; Lyagoba, Frederick; Magambo, Brian; Nanteza, Bridget; Watera, Christine; Kaleebu, Pontiano; Rinke, de Wit
    To assess the emergence of transmitted HIV-1 drug resistance (TDR) in Kampala, Uganda, 10 years after the scale-up of antiretroviral treatment (ART) and to compare with a previous survey among antenatal clinic attendees in 2007 (reporting 0% TDR). A cross-sectional survey was conducted among newly HIV-1 diagnosed, antiretroviral-naive young adults attending two large voluntary counseling and testing centers within the geographic area of Kampala. Proxy criteria for recent HIV-1 infection were used as defined by the WHO. Population sequencing of the pol gene was performed on plasma samples with HIV-1 RNA at least 1000 copies/ml. Surveillance drug resistance mutations (SDRMs) were identified according to the 2009 WHO list for surveillance of TDR. HIV-1 subtypes were designated using maximum likelihood phylogenetic reconstruction. Genotypic test results were obtained for 70 of 77 (90.9%) participants. SDRMs were identified in six samples yielding a prevalence of TDR of 8.6% (95% confidence interval 3.2–17.7%). Two had SDRMs to nucleoside reverse-transcriptase inhibitors (D67G and L210W), three had SDRMs to nonnucleoside reverse transcriptase inhibitors (G190A, G190S, and K101E), and one had SDRMs to protease inhibitors (N88D). Frequencies of HIV-1 subtypes were A (36/70, 51.4%), C ( two of 70; 2.9%), D (23/70, 32.9%), and unique recombinant forms (nine of 70, 12.9%). This repeated survey suggests an increase in TDR in Kampala, compared with a previous survey. This finding justifies increased vigilance with respect to surveillance of TDR in areas in Africa where ART programs are rolled-out.