Browsing by Author "Lyagoba, Fred"

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    Effect of Human Immunodeficiency Virus (HIV) Type 1 Envelope Subtypes A and D on Disease Progression in a Large Cohort of HIV-1–Positive Persons in Uganda
    (The Journal of Infectious Diseases, 2002) Kaleebu, Pontiano; French, Neil; Mahe, Cedric; Yirrell, David; Watera, Christine; Lyagoba, Fred; Nakiyingi, Jessica; Rutebemberwa, Alleluiah; Morgan, Dilys; Weber, Jonathan; Gilks, Charles; Whitworth, Jimmy
    The effect of human immunodeficiency virus (HIV) type 1 envelope subtypes A and D on disease progression was investigated in 1045 adults in Uganda. At enrollment and every 6 months, a clinical history, examination, and laboratory investigations that included CD4 cell counts were done. HIV-1 envelope subtype was assessed mainly by peptide serology supplemented by heteroduplex mobility assay and DNA sequencing. A multivariate analysis of survival was performed to assess the prognostic value of HIV-1 subtype on death. A marginal general linear model also determined the effect of subtype on CD4 cell count during follow-up. Subtype D was associated with faster progression to death (relative risk, 1.29; 95% confidence interval, 1.07–1.56; P ¼ .009) and with a lower CD4 cell count during follow-up (P ¼ .001), compared with subtype A, after adjusting for CD4 cell count at enrollment. In Africa, envelope subtype D is associated with faster disease progression, compared with subtype A
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    High Rate of HIV Resuppression After Viral Failure on First-line Antiretroviral Therapy in the Absence of Switch to Second-line Therapy
    (Clinical infectious diseases, 2014) Gupta, Ravindra K.; Goodall, Ruth L.; Kityo, Cissy; Munderi, Paula; Lyagoba, Fred; Mugarura, Lincoln; Kaleebu, Pontiano; Pillay, Deenan
    In a randomized comparison of nevirapine or abacavir with zidovudine plus lamivudine, routine viral load monitoring was not performed, yet 27% of individuals with viral failure at week 48 experienced resuppression by week 96 without switching. This supports World Health Organization recommendations that suspected viral failure should trigger adherence counseling and repeat measurement before a treatment switch is considered.
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    High Rate of HIV Resuppression After Viral Failure on First-line Antiretroviral Therapy in the Absence of Switch to Second-line Therapy
    (Clinical infectious diseases, 2013-12-18) Gupta, Ravindra K.; Ranopa, Michael; Kityo, Cissy; Lyagoba, Fred; Mugarura,Lincoln; Kaleebu, Pontiano
    In a randomized comparison of nevirapine or abacavir with zidovudine plus lamivudine, routine viral load monitoring was not performed, yet 27% of individuals with viral failure at week 48 experienced resuppression by week 96 without switching. This supports World Health Organization recommendations that suspected viral failure should trigger adherence counseling and repeat measurement before a treatment switch is considered.
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    Molecular Epidemiology of HIV Type 1 in a Rural Community in Southwest Uganda
    (AIDS Research and Human Retroviruses, 2000) Kaleebu, Pontiano; Whitworth, James; Hamilton, Laura; Rutebemberwa, Alleluiah; Lyagoba, Fred; Morgan, Dilys; Duffield, Melanie; Biryahwaho, Benon; Magambo, Brian; Oram, Jon
    The molecular epidemiology of a population-based cohort in a cluster of 15 villages in southwestern Uganda was investigated by sequencing part of the p24 gag gene and performing heteroduplex mobility assays (HMAs) of the V3 region of the env gene. Sequence and HM A data, obtained for 69 and 88 proviruses, respectively, showed that the clade A and D viruses were present at a ratio of about 0.67:1. No other clades were detected. Thirteen (22%) of 59 proviruses for which both gag and env data were obtained appeared to be recombinants. Although both clade A and D viruses were present in 13 of the villages, their distribution was unequal: for example, from env data 59% of clade A viruses were found in the eastern villages, compared with only 27% of clade D viruses. Phylogenetic (maximum likelihood) analysis of the p24 gag sequences showed a total of five clusters supported by bootstrap resampling values above or close to 75%. Four clusters were sexual partners, but there was no known sexual contact between the persons in the other cluster. The DNA sequences showed between 0.5 and 8.3% divergence from the cohort clade A or D consensus sequences. The sequences were not closely related to those published for other clade A or D proviruses.
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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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    Relationship between HIV-1 Env subtypes A and D and disease progression in a rural Ugandan cohort
    (AIDS, 2001) Kaleebu, Pontiano; Ross, Amanda; Morgan, Dilys; Yirrell, Davida; Oram, Jonb; Rutebemberwa, Alleluiah; Lyagoba, Fred; Hamilton, Laura; Biryahwaho, Benon; Whitworth, James
    To investigate the role of HIV-1 envelope subtypes on disease progression in a rural cohort of Ugandan adults where two major HIV-1 subtypes (A and D) exist. Participants of a clinical cohort seen between December 1995 and December 1998 had blood collected for HIV-1 subtyping. These included prevalent cases (people already infected with HIV at the start of the study in 1990) and incident cases (those who seroconverted between 1990 and December 1998). HIV-1 subtyping was carried out by heteroduplex mobility assay and DNA sequencing in the V3 env region. Disease progression was measured by the rate of CD4 lymphocyte count decline, clinical progression for the incident cases as time from seroconversion to AIDS or death, to ®rst CD4 lymphocyte count , 200 3 106/l and to the World Health Organization clinical stage 3. All analyses were adjusted for age and sex. One hundred and sixty-four individuals, including 47 prevalent and 117 incident cases, had V3 env subtype data of which 65 (40%) were subtyped as A and 99 as D. In the incident cases, 44 (38%) were subtyped as A and 73 as D. There was a suggestion that for most end-points A had a slower progression than D. The cumulative probability of remaining free from AIDS or death at 6 years post-seroconversion was 0.72 [95% con®dence interval (CI), 0.50 to 0.85] for A and 0.58 (95% CI, 0.42 to 0.71) for D, and the adjusted hazard ratio of subtype D compared to A was estimated to be 1.39 (95% CI, 0.66 to 2.94; P 0.39). The estimated difference in rates of decline in square root CD4 lymphocyte counts was ÿ0.41 per year (95% CI, ÿ0.98 to 0.15; P 0.15). This study suggests that although subtype A may have a slower progression than D, HIV-1 envelope subtype is not a major factor in determining the progression of HIV-1 disease in a rural population in Uganda.