Rebecca Nsubuga | Makerere University (original) (raw)

Papers by Rebecca Nsubuga

Research paper thumbnail of Sustainable Statistical Capacity-Building for Africa: The Biostatistics Case

Annual Review of Statistics and Its Application

Several major global challenges, including climate change and water scarcity, warrant a scientifi... more Several major global challenges, including climate change and water scarcity, warrant a scientific approach to generating solutions. Developing high quality and robust capacity in (bio)statistics is key to ensuring sound scientific solutions to these challenges, so collaboration between academic and research institutes should be high on university agendas. To strengthen capacity in the developing world, South–North partnerships should be a priority. The ideas and examples of statistical capacity-building presented in this article are the result of several monthly online discussions between a mixedgroup of authors having international experience and formal links with Hasselt University in Belgium. The discussion focuses on statistical capacity-building through education (teaching), research, and societal impact. We have adopted an example-based approach, and in view of the background of the authors, the examples refer mainly to biostatistical capacity-building. Although many universi...

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Research paper thumbnail of Improving ART programme retention and viral suppression are key to maximising impact of treatment as prevention – a modelling study

BMC Infectious Diseases, Aug 9, 2017

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Research paper thumbnail of Costs and effects of changes to ART eligibility criteria in Uganda

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Research paper thumbnail of Attaining realistic and substantial reductions in HIV incidence: model projections of combining microbicide and male circumcision interventions in rural Uganda

Sexually Transmitted Infections, Jul 18, 2011

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Research paper thumbnail of Combination prevention to achieve significant reductions in HIV incidence: Projections of the impact of microbicide and male circumcision interventions in rural Uganda

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Research paper thumbnail of Analysis of nearly full-genome HIV-1 sequences from Uganda: results from PANGEA_HIV

F1000Research, Feb 15, 2017

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Research paper thumbnail of Abstracts of the Eighth EDCTP Forum, 6–9 November 2016

BMJ Global Health, 2017

S OF PLENARY PRESENTATIONS A3 ABSTRACTS OF ORAL PRESENTATIONS A5S OF ORAL PRESENTATIONS A5 ABSTRA... more S OF PLENARY PRESENTATIONS A3 ABSTRACTS OF ORAL PRESENTATIONS A5S OF ORAL PRESENTATIONS A5 ABSTRACTS OF POSTER PRESENTATIONS A16S OF POSTER PRESENTATIONS A16

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Research paper thumbnail of Pervasive and non-random recombination in near full-length HIV genomes from Uganda

Virus Evolution, 2020

Recombination is an important feature of HIV evolution, occurring both within and between the maj... more Recombination is an important feature of HIV evolution, occurring both within and between the major branches of diversity (subtypes). The Ugandan epidemic is primarily composed of two subtypes, A1 and D, that have been co-circulating for 50 years, frequently recombining in dually infected patients. Here, we investigate the frequency of recombinants in this population and the location of breakpoints along the genome. As part of the PANGEA-HIV consortium, 1,472 consensus genome sequences over 5 kb have been obtained from 1,857 samples collected by the MRC/UVRI & LSHTM Research unit in Uganda, 465 (31.6 per cent) of which were near full-length sequences (>8 kb). Using the subtyping tool SCUEAL, we find that of the near full-length dataset, 233 (50.1 per cent) genomes contained only one subtype, 30.8 per cent A1 (n = 143), 17.6 per cent D (n = 82), and 1.7 per cent C (n = 8), while 49.9 per cent (n = 232) contained more than one subtype (including A1/D (n = 164), A1/C (n = 13), C/D (...

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Research paper thumbnail of Rates of HIV-1 virological suppression and patterns of acquired drug resistance among fisherfolk on first-line antiretroviral therapy in Uganda

Journal of Antimicrobial Chemotherapy, 2019

ObjectivesWe examined virological outcomes, patterns of acquired HIV drug resistance (ADR), corre... more ObjectivesWe examined virological outcomes, patterns of acquired HIV drug resistance (ADR), correlates of virological failure (VF) and acquired drug resistance among fisherfolk on first-line ART.MethodsWe enrolled 1169 adults on ART for a median duration of 6, 12, 24, 36 and ≥48 months and used a pooled VL testing approach to identify VF (VL ≥1000 copies/mL). We performed genotyping among VF cases and determined correlates of VF and ADR by logistic regression.ResultsThe overall virological suppression rate was 91.7% and ADR was detected in 71/97 (73.2%) VF cases. The most prevalent mutations were M184V/I (53.6%) for NRTIs and K103N (39.2%) for NNRTIs. Thymidine analogue mutations were detected in 21.6% of VF cases while PI mutations were absent. A zidovudine-based ART regimen, duration on ART (≥24 months) and secondary/higher education level were significantly associated with VF. A nevirapine-based regimen [adjusted OR (aOR): 1.87; 95% CI: 0.03–0.54)] and VL ≥10000 copies/mL (aOR: 3...

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Research paper thumbnail of P2-207 Epidemiology of non-communicable diseases and their risk factors in rural Uganda

Journal of Epidemiology and Community Health, Aug 1, 2011

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Research paper thumbnail of Discovery and fine-mapping of kidney function loci in first genome-wide association study in Africans

Genome-wide association studies (GWAS) for kidney function have uncovered hundreds of risk loci, ... more Genome-wide association studies (GWAS) for kidney function have uncovered hundreds of risk loci, primarily in populations of European ancestry. We conducted the first GWAS of estimated glomerular filtration rate (eGFR) in Africa in 3288 Ugandans and replicated the findings in 8224 African Americans. We identified two loci associated with eGFR at genome-wide significance (p<5×10−8). The most significantly associated variant (rs2433603, p=2.4×10−9) in GATM was distinct from previously reported signals. A second association signal mapping near HBB (rs141845179, p=3.0×10−8) was not significant after conditioning on a previously reported SNP (rs334) for eGFR. However, fine-mapping analyses highlighted rs141845179 to be the most likely causal variant at the HBB locus (posterior probability of 0.61). A trans-ethnic GRS of eGFR constructed from previously reported lead SNPs was not predictive into the Ugandan population, indicating that additional large-scale efforts in Africa are necess...

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Research paper thumbnail of Uganda Genome Resource Enables Insights into Population History and Genomic Discovery in Africa

Cell, 2019

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Research paper thumbnail of The 5-HTTLPR-rs25531 S-A-S-A Haplotype and Chronic Stress Moderate the Association Between Acute Stress and Internalizing Mental Disorders Among HIV+ Children and Adolescents in Uganda

Frontiers in Genetics, 2021

Background: Internalizing mental disorders (IMDs) among HIV-positive (HIV+) children and adolesce... more Background: Internalizing mental disorders (IMDs) among HIV-positive (HIV+) children and adolescents are associated with poor disease outcomes, such as faster HIV disease progression. Although it has been suggested that the development of IMDs is moderated by interaction of stressful life events and vulnerability factors, the underlying etiology is largely unknown. Serotonin transporter gene [solute carrier family 6 member A4 (SLC6A4)] and human tryptophan hydroxylase 2 gene (TPH2) polymorphisms have been implicated in the development of IMDs. This study investigated the association between acute stress and IMDs, and moderation by chronic stress and genetic variants in SLC6A4 and TPH2.Hypothesis: Acute stress acts through genetic and environmental vulnerability factors to increase the risk of developing IMDs.Methods: Polymorphisms in SLC6A4 (5-HTTLPR, rs25531, 5-HTTLPR-rs25531, and STin2 VNTR) and TPH2 (rs1843809, rs1386494, rs4570625, and rs34517220) were genotyped in 368 HIV+ chil...

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Research paper thumbnail of Mathematical Modelling of HIV-HCV Co-infection Dynamics in Presence of HIV Therapy

BIOMATH

In this work, we formulated and analysed a deterministic model to study the HIV-HCV co-infection ... more In this work, we formulated and analysed a deterministic model to study the HIV-HCV co-infection dynamics in presence of HIV therapy. The HCV chronic stage was split into two periods: the period before and the period after onset of cirrhosis. This was done because the HCV chronic stage of infection is long, asymptomatic and infectious. The effective reproduction numbers, one of our outcome measures, were computed using the next generation matrix method. Numerical simulations were performed to support the analytical results from the model. The different parameters in the model were subjected to a sensitivity analysis to determine their relative importance on the HIV-HCV co-infection dynamics. The results indicated that both HIV and HCV infections enhance each other; and in the long run, increasing the rates at which people are put on HIV treatment reduces the prevalence of HCV in the community; however, it increases the prevalence of HIV. Therefore, there should be increased safer se...

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Research paper thumbnail of Mathematical Modelling of HIV-HCV Coinfection Dynamics in Absence of Therapy

Computational and Mathematical Methods in Medicine, 2020

Globally, it is estimated that of the 36.7 million people infected with human immunodeficiency vi... more Globally, it is estimated that of the 36.7 million people infected with human immunodeficiency virus (HIV), 6.3% are coinfected with hepatitis C virus (HCV). Coinfection with HIV reduces the chance of HCV spontaneous clearance. In this work, we formulated and analysed a deterministic model to study the HIV and HCV coinfection dynamics in absence of therapy. Due to chronic stage of HCV infection being long, asymptomatic, and infectious, our model formulation was based on the splitting of the chronic stage into the following: before onset of cirrhosis and its complications and after onset of cirrhosis. We computed the basic reproduction numbers using the next generation matrix method. We performed numerical simulations to support the analytical results. We carried out sensitivity analysis to determine the relative importance of the different parameters influencing the HIV-HCV coinfection dynamics. The findings reveal that, in the long run, there is a substantial number of individuals ...

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Research paper thumbnail of Heterogeneity of HIV incidence: a comparative analysis between fishing communities and in a neighbouring rural general population, Uganda, and implications for HIV control

Sexually Transmitted Infections, 2016

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Research paper thumbnail of Rare variant in scavenger receptor BI raises HDL cholesterol and increases risk of coronary heart disease

Science (New York, N.Y.), Jan 11, 2016

Scavenger receptor BI (SR-BI) is the major receptor for high-density lipoprotein (HDL) cholestero... more Scavenger receptor BI (SR-BI) is the major receptor for high-density lipoprotein (HDL) cholesterol (HDL-C). In humans, high amounts of HDL-C in plasma are associated with a lower risk of coronary heart disease (CHD). Mice that have depleted Scarb1 (SR-BI knockout mice) have markedly elevated HDL-C levels but, paradoxically, increased atherosclerosis. The impact of SR-BI on HDL metabolism and CHD risk in humans remains unclear. Through targeted sequencing of coding regions of lipid-modifying genes in 328 individuals with extremely high plasma HDL-C levels, we identified a homozygote for a loss-of-function variant, in which leucine replaces proline 376 (P376L), in SCARB1, the gene encoding SR-BI. The P376L variant impairs posttranslational processing of SR-BI and abrogates selective HDL cholesterol uptake in transfected cells, in hepatocyte-like cells derived from induced pluripotent stem cells from the homozygous subject, and in mice. Large population-based studies revealed that subj...

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Research paper thumbnail of Discovery and Refinement Supplementary

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Research paper thumbnail of Antiretroviral therapy and sexual behavior in Uganda: a cohort study

AIDS, 2011

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Research paper thumbnail of Phylogeography of HIV-1 suggests that Ugandan fishing communities are a sink for, not a source of, virus from general populations

Scientific Reports, 2019

Although fishing communities (FCs) in Uganda are disproportionately affected by HIV-1 relative to... more Although fishing communities (FCs) in Uganda are disproportionately affected by HIV-1 relative to the general population (GP), the transmission dynamics are not completely understood. We earlier found most HIV-1 transmissions to occur within FCs of Lake Victoria. Here, we test the hypothesis that HIV-1 transmission in FCs is isolated from networks in the GP. We used phylogeography to reconstruct the geospatial viral migration patterns in 8 FCs and 2 GP cohorts and a Bayesian phylogenetic inference in BEAST v1.8.4 to analyse the temporal dynamics of HIV-1 transmission. Subtype A1 (pol region) was most prevalent in the FCs (115, 45.1%) and GP (177, 50.4%). More recent HIV transmission pairs from FCs were found at a genetic distance (GD) <1.5% than in the GP (Fisher’s exact test, p = 0.001). The mean time depth for pairs was shorter in FCs (5 months) than in the GP (4 years). Phylogeographic analysis showed strong support for viral migration from the GP to FCs without evidence of su...

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Research paper thumbnail of Sustainable Statistical Capacity-Building for Africa: The Biostatistics Case

Annual Review of Statistics and Its Application

Several major global challenges, including climate change and water scarcity, warrant a scientifi... more Several major global challenges, including climate change and water scarcity, warrant a scientific approach to generating solutions. Developing high quality and robust capacity in (bio)statistics is key to ensuring sound scientific solutions to these challenges, so collaboration between academic and research institutes should be high on university agendas. To strengthen capacity in the developing world, South–North partnerships should be a priority. The ideas and examples of statistical capacity-building presented in this article are the result of several monthly online discussions between a mixedgroup of authors having international experience and formal links with Hasselt University in Belgium. The discussion focuses on statistical capacity-building through education (teaching), research, and societal impact. We have adopted an example-based approach, and in view of the background of the authors, the examples refer mainly to biostatistical capacity-building. Although many universi...

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Research paper thumbnail of Improving ART programme retention and viral suppression are key to maximising impact of treatment as prevention – a modelling study

BMC Infectious Diseases, Aug 9, 2017

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Research paper thumbnail of Costs and effects of changes to ART eligibility criteria in Uganda

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Attaining realistic and substantial reductions in HIV incidence: model projections of combining microbicide and male circumcision interventions in rural Uganda

Sexually Transmitted Infections, Jul 18, 2011

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Research paper thumbnail of Combination prevention to achieve significant reductions in HIV incidence: Projections of the impact of microbicide and male circumcision interventions in rural Uganda

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Analysis of nearly full-genome HIV-1 sequences from Uganda: results from PANGEA_HIV

F1000Research, Feb 15, 2017

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Research paper thumbnail of Abstracts of the Eighth EDCTP Forum, 6–9 November 2016

BMJ Global Health, 2017

S OF PLENARY PRESENTATIONS A3 ABSTRACTS OF ORAL PRESENTATIONS A5S OF ORAL PRESENTATIONS A5 ABSTRA... more S OF PLENARY PRESENTATIONS A3 ABSTRACTS OF ORAL PRESENTATIONS A5S OF ORAL PRESENTATIONS A5 ABSTRACTS OF POSTER PRESENTATIONS A16S OF POSTER PRESENTATIONS A16

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Research paper thumbnail of Pervasive and non-random recombination in near full-length HIV genomes from Uganda

Virus Evolution, 2020

Recombination is an important feature of HIV evolution, occurring both within and between the maj... more Recombination is an important feature of HIV evolution, occurring both within and between the major branches of diversity (subtypes). The Ugandan epidemic is primarily composed of two subtypes, A1 and D, that have been co-circulating for 50 years, frequently recombining in dually infected patients. Here, we investigate the frequency of recombinants in this population and the location of breakpoints along the genome. As part of the PANGEA-HIV consortium, 1,472 consensus genome sequences over 5 kb have been obtained from 1,857 samples collected by the MRC/UVRI & LSHTM Research unit in Uganda, 465 (31.6 per cent) of which were near full-length sequences (>8 kb). Using the subtyping tool SCUEAL, we find that of the near full-length dataset, 233 (50.1 per cent) genomes contained only one subtype, 30.8 per cent A1 (n = 143), 17.6 per cent D (n = 82), and 1.7 per cent C (n = 8), while 49.9 per cent (n = 232) contained more than one subtype (including A1/D (n = 164), A1/C (n = 13), C/D (...

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Research paper thumbnail of Rates of HIV-1 virological suppression and patterns of acquired drug resistance among fisherfolk on first-line antiretroviral therapy in Uganda

Journal of Antimicrobial Chemotherapy, 2019

ObjectivesWe examined virological outcomes, patterns of acquired HIV drug resistance (ADR), corre... more ObjectivesWe examined virological outcomes, patterns of acquired HIV drug resistance (ADR), correlates of virological failure (VF) and acquired drug resistance among fisherfolk on first-line ART.MethodsWe enrolled 1169 adults on ART for a median duration of 6, 12, 24, 36 and ≥48 months and used a pooled VL testing approach to identify VF (VL ≥1000 copies/mL). We performed genotyping among VF cases and determined correlates of VF and ADR by logistic regression.ResultsThe overall virological suppression rate was 91.7% and ADR was detected in 71/97 (73.2%) VF cases. The most prevalent mutations were M184V/I (53.6%) for NRTIs and K103N (39.2%) for NNRTIs. Thymidine analogue mutations were detected in 21.6% of VF cases while PI mutations were absent. A zidovudine-based ART regimen, duration on ART (≥24 months) and secondary/higher education level were significantly associated with VF. A nevirapine-based regimen [adjusted OR (aOR): 1.87; 95% CI: 0.03–0.54)] and VL ≥10000 copies/mL (aOR: 3...

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Research paper thumbnail of P2-207 Epidemiology of non-communicable diseases and their risk factors in rural Uganda

Journal of Epidemiology and Community Health, Aug 1, 2011

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Research paper thumbnail of Discovery and fine-mapping of kidney function loci in first genome-wide association study in Africans

Genome-wide association studies (GWAS) for kidney function have uncovered hundreds of risk loci, ... more Genome-wide association studies (GWAS) for kidney function have uncovered hundreds of risk loci, primarily in populations of European ancestry. We conducted the first GWAS of estimated glomerular filtration rate (eGFR) in Africa in 3288 Ugandans and replicated the findings in 8224 African Americans. We identified two loci associated with eGFR at genome-wide significance (p<5×10−8). The most significantly associated variant (rs2433603, p=2.4×10−9) in GATM was distinct from previously reported signals. A second association signal mapping near HBB (rs141845179, p=3.0×10−8) was not significant after conditioning on a previously reported SNP (rs334) for eGFR. However, fine-mapping analyses highlighted rs141845179 to be the most likely causal variant at the HBB locus (posterior probability of 0.61). A trans-ethnic GRS of eGFR constructed from previously reported lead SNPs was not predictive into the Ugandan population, indicating that additional large-scale efforts in Africa are necess...

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Research paper thumbnail of Uganda Genome Resource Enables Insights into Population History and Genomic Discovery in Africa

Cell, 2019

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Research paper thumbnail of The 5-HTTLPR-rs25531 S-A-S-A Haplotype and Chronic Stress Moderate the Association Between Acute Stress and Internalizing Mental Disorders Among HIV+ Children and Adolescents in Uganda

Frontiers in Genetics, 2021

Background: Internalizing mental disorders (IMDs) among HIV-positive (HIV+) children and adolesce... more Background: Internalizing mental disorders (IMDs) among HIV-positive (HIV+) children and adolescents are associated with poor disease outcomes, such as faster HIV disease progression. Although it has been suggested that the development of IMDs is moderated by interaction of stressful life events and vulnerability factors, the underlying etiology is largely unknown. Serotonin transporter gene [solute carrier family 6 member A4 (SLC6A4)] and human tryptophan hydroxylase 2 gene (TPH2) polymorphisms have been implicated in the development of IMDs. This study investigated the association between acute stress and IMDs, and moderation by chronic stress and genetic variants in SLC6A4 and TPH2.Hypothesis: Acute stress acts through genetic and environmental vulnerability factors to increase the risk of developing IMDs.Methods: Polymorphisms in SLC6A4 (5-HTTLPR, rs25531, 5-HTTLPR-rs25531, and STin2 VNTR) and TPH2 (rs1843809, rs1386494, rs4570625, and rs34517220) were genotyped in 368 HIV+ chil...

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Research paper thumbnail of Mathematical Modelling of HIV-HCV Co-infection Dynamics in Presence of HIV Therapy

BIOMATH

In this work, we formulated and analysed a deterministic model to study the HIV-HCV co-infection ... more In this work, we formulated and analysed a deterministic model to study the HIV-HCV co-infection dynamics in presence of HIV therapy. The HCV chronic stage was split into two periods: the period before and the period after onset of cirrhosis. This was done because the HCV chronic stage of infection is long, asymptomatic and infectious. The effective reproduction numbers, one of our outcome measures, were computed using the next generation matrix method. Numerical simulations were performed to support the analytical results from the model. The different parameters in the model were subjected to a sensitivity analysis to determine their relative importance on the HIV-HCV co-infection dynamics. The results indicated that both HIV and HCV infections enhance each other; and in the long run, increasing the rates at which people are put on HIV treatment reduces the prevalence of HCV in the community; however, it increases the prevalence of HIV. Therefore, there should be increased safer se...

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Research paper thumbnail of Mathematical Modelling of HIV-HCV Coinfection Dynamics in Absence of Therapy

Computational and Mathematical Methods in Medicine, 2020

Globally, it is estimated that of the 36.7 million people infected with human immunodeficiency vi... more Globally, it is estimated that of the 36.7 million people infected with human immunodeficiency virus (HIV), 6.3% are coinfected with hepatitis C virus (HCV). Coinfection with HIV reduces the chance of HCV spontaneous clearance. In this work, we formulated and analysed a deterministic model to study the HIV and HCV coinfection dynamics in absence of therapy. Due to chronic stage of HCV infection being long, asymptomatic, and infectious, our model formulation was based on the splitting of the chronic stage into the following: before onset of cirrhosis and its complications and after onset of cirrhosis. We computed the basic reproduction numbers using the next generation matrix method. We performed numerical simulations to support the analytical results. We carried out sensitivity analysis to determine the relative importance of the different parameters influencing the HIV-HCV coinfection dynamics. The findings reveal that, in the long run, there is a substantial number of individuals ...

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Research paper thumbnail of Heterogeneity of HIV incidence: a comparative analysis between fishing communities and in a neighbouring rural general population, Uganda, and implications for HIV control

Sexually Transmitted Infections, 2016

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Research paper thumbnail of Rare variant in scavenger receptor BI raises HDL cholesterol and increases risk of coronary heart disease

Science (New York, N.Y.), Jan 11, 2016

Scavenger receptor BI (SR-BI) is the major receptor for high-density lipoprotein (HDL) cholestero... more Scavenger receptor BI (SR-BI) is the major receptor for high-density lipoprotein (HDL) cholesterol (HDL-C). In humans, high amounts of HDL-C in plasma are associated with a lower risk of coronary heart disease (CHD). Mice that have depleted Scarb1 (SR-BI knockout mice) have markedly elevated HDL-C levels but, paradoxically, increased atherosclerosis. The impact of SR-BI on HDL metabolism and CHD risk in humans remains unclear. Through targeted sequencing of coding regions of lipid-modifying genes in 328 individuals with extremely high plasma HDL-C levels, we identified a homozygote for a loss-of-function variant, in which leucine replaces proline 376 (P376L), in SCARB1, the gene encoding SR-BI. The P376L variant impairs posttranslational processing of SR-BI and abrogates selective HDL cholesterol uptake in transfected cells, in hepatocyte-like cells derived from induced pluripotent stem cells from the homozygous subject, and in mice. Large population-based studies revealed that subj...

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Research paper thumbnail of Discovery and Refinement Supplementary

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Antiretroviral therapy and sexual behavior in Uganda: a cohort study

AIDS, 2011

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Research paper thumbnail of Phylogeography of HIV-1 suggests that Ugandan fishing communities are a sink for, not a source of, virus from general populations

Scientific Reports, 2019

Although fishing communities (FCs) in Uganda are disproportionately affected by HIV-1 relative to... more Although fishing communities (FCs) in Uganda are disproportionately affected by HIV-1 relative to the general population (GP), the transmission dynamics are not completely understood. We earlier found most HIV-1 transmissions to occur within FCs of Lake Victoria. Here, we test the hypothesis that HIV-1 transmission in FCs is isolated from networks in the GP. We used phylogeography to reconstruct the geospatial viral migration patterns in 8 FCs and 2 GP cohorts and a Bayesian phylogenetic inference in BEAST v1.8.4 to analyse the temporal dynamics of HIV-1 transmission. Subtype A1 (pol region) was most prevalent in the FCs (115, 45.1%) and GP (177, 50.4%). More recent HIV transmission pairs from FCs were found at a genetic distance (GD) <1.5% than in the GP (Fisher’s exact test, p = 0.001). The mean time depth for pairs was shorter in FCs (5 months) than in the GP (4 years). Phylogeographic analysis showed strong support for viral migration from the GP to FCs without evidence of su...

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