Rebecca Nsubuga - Profile on Academia.edu (original) (raw)

Papers by Rebecca Nsubuga

PLOS ONE, Jan 3, 2014

The basic reproduction number, R 0 , is one of the many measures of the epidemic potential of an ... more The basic reproduction number, R 0 , is one of the many measures of the epidemic potential of an infection in a population. We estimate HIV R 0 over 18 years in a rural population in Uganda, examine method-specific differences in estimated R 0 , and estimate behavioural changes that would reduce R 0 below one. Methods: Data on HIV natural history and infectiousness were collated from literature. Data on new sexual partner count were available from a rural clinical cohort in Uganda over 1991-2008. R 0 was estimated using six methods. Behavioural changes required to reduce R 0 below one were calculated. Results: Reported number of new partners per year was 0 to 16 (women) and 0 to 80 (men). When proportionate sexual mixing was assumed, the different methods yielded comparable R 0 estimates. Assuming totally assortative mixing led to increased R 0 estimates in the high sexual activity class while all estimates in the low-activity class were below one. Using the ''effective'' partner change rate introduced by Anderson and colleagues resulted in R 0 estimates all above one except in the lowest sexual activity class. R 0 could be reduced below one if: (a) medium risk individuals reduce their partner acquisition rate by 70% and higher risk individuals reduce their partner acquisition rate by 93%, or (b) higher risk individuals reduce the partner acquisition rate by 95%. The estimated R 0 depended strongly on the method used. Ignoring variation in sexual activity leads to an underestimation of R 0 . Relying on behaviour change alone to eradicate HIV may require unrealistically large reductions in risk behaviour, even though for a small proportion of the population. To control HIV, complementary prevention strategies such as male circumcision and HIV treatment services need rapid scale up.

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...

BMC Infectious Diseases, Aug 9, 2017

Background: UNAIDS calls for fewer than 500,000 new HIV infections/year by 2020, with treatment-a... more Background: UNAIDS calls for fewer than 500,000 new HIV infections/year by 2020, with treatment-as-prevention being a key part of their strategy for achieving the target. A better understanding of the contribution to transmission of people at different stages of the care pathway can help focus intervention services at populations where they may have the greatest effect. We investigate this using Uganda as a case study. Methods: An individual-based HIV/ART model was fitted using history matching. 100 model fits were generated to account for uncertainties in sexual behaviour, HIV epidemiology, and ART coverage up to 2015 in Uganda. A number of different ART scale-up intervention scenarios were simulated between 2016 and 2030. The incidence and proportion of transmission over time from people with primary infection, post-primary ART-naïve infection, and people currently or previously on ART was calculated. Results: In all scenarios, the proportion of transmission by ART-naïve people decreases, from 70% (61%-79%) in 2015 to between 23% (15%-40%) and 47% (35%-61%) in 2030. The proportion of transmission by people on ART increases from 7.8% (3.5%-13%) to between 14% (7.0%-24%) and 38% (21%-55%). The proportion of transmission by ART dropouts increases from 22% (15%-33%) to between 31% (23%-43%) and 56% (43%-70%). Conclusions: People who are currently or previously on ART are likely to play an increasingly large role in transmission as ART coverage increases in Uganda. Improving retention on ART, and ensuring that people on ART remain virally suppressed, will be key in reducing HIV incidence in Uganda.

Costs and effects of changes to ART eligibility criteria in Uganda

Sexually Transmitted Infections, Jul 18, 2011

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

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

F1000Research, Feb 15, 2017

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

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 (...

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...

Journal of Epidemiology and Community Health, Aug 1, 2011

At baseline, BMI was inversely associated with physical and mental SF-12 summary scores (b [95% C... more At baseline, BMI was inversely associated with physical and mental SF-12 summary scores (b [95% CI]¼À0.3 [À0.4 to À0.2], and À0.1 [À0.1 to 0.0]). An increase in BMI of 1 kg/m 2 within 12 months was associated with a significant decrease in physical but not mental SF-12 scores (0.3 [À0.4 to À0.1]). Due to an interaction with gender, the association between change in BMI and physical SF-12 scores was only prevalent in women (b¼À0.5 [À0.7 to-0.2], p<0.001) but not in men (p¼0.32). Conclusion BMI is inversely associated with quality of life in highrisk cardiovascular patients. Increases in BMI may lead to a decrease in physical quality of life in women but not in men.

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...

Cell, 2019

Highlights d The Uganda Genome Resource comprises genetic and phenotypic data on 6,400 individual... more Highlights d The Uganda Genome Resource comprises genetic and phenotypic data on 6,400 individuals d Ugandans show geographically correlated genetic substructure and complex admixture d The Uganda sequence panel substantially improves imputation in African populations d The Uganda Genome Resource enables novel discovery of loci associated with traits

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...

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...

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 ...

Sexually Transmitted Infections, 2016

Objectives To describe HIV heterogeneity in rural Uganda using incidence data collected between J... more Objectives To describe HIV heterogeneity in rural Uganda using incidence data collected between January 2012 and December 2014 among fishing cohort (FC) and in an adjacent rural general population cohort (GPC). Methods In the FC, eligible HIV high-risk adults aged 18+ years were enrolled, followed and HIV tested every 3 months. Demographic and sexual behaviour data were also collected. The GPC, approximately 47 km away from the FC, was followed through annual surveys, and sociodemographic and behavioural data collected. A subset of GPC with comparable risk profiles to the FC was selected. We presented sociodemographic and risk profiles and also computed stratified HIV incidence. Cox regression was used to assess factors associated with HIV incidence. Results Overall HIV incidence was higher in the FC than in the 'high-risk' GPC, 6.04 and 0.56 per 100 person years at risk, respectively, with a rate ratio (RR) of 10.83 (95% CI 6.11 to 19.76). This was higher among those aged 18-24 years, unmarried and those with more than two sex partners in the past year, RR of 15.44, 22.99 and 19.29, respectively. In the FC, factors associated with high incidence in multivariate analysis were duration in the community and unprotected sex. The factors in the GPC were ethnicity, marital status and duration in the community. Conclusions We have observed a substantial heterogeneity in HIV incidence. The high incidence in fishing communities is contributing greatly to the overall HIV burden in Uganda, and thus urgent combination prevention efforts are needed towards national goal to reduce HIV epidemic.

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...

Discovery and Refinement Supplementary

AIDS, 2011

Objective: To assess evidence for sexual behavior change in response to antiretroviral therapy (A... more Objective: To assess evidence for sexual behavior change in response to antiretroviral therapy (ART) among members of a Ugandan clinical cohort. Secondarily, to examine factors associated with both sexual behavior and ART independently, that may help to assess the impact that ART is likely to have on the HIV epidemic. Design: Retrospective analysis of data from an open cohort. Methods: ART roll-out began in the cohort in 2004. Using 3-monthly data from 2002 to 2009, we conducted regression and descriptive analyses to examine associations between timing of ART initiation and sexual behavior among HIV-infected, and timing of ART availability and sexual behavior among HIV-uninfected. We also examined partner turnover rates, and the proportion of HIV-infected on ART-two important factors for modeling the potential impact of ART on the HIV epidemic. Results: Risky sexual behavior among HIV-infected people rose on several indicators after ART initiation, but not to levels higher than two or more years before initiation. Some evidence suggests that the availability of ART may impact risky behavior among HIV-uninfected people, although this was inconsistent across different reported behavior variables. Conclusion: The HIV-uninfected is larger than the HIV-infected population. If risky behavior among this population increases due to the feeling of safety that ART provides, this will affect the impact of ART on the HIV epidemic. Policy makers are urged to intensify messages associating sexual behavior and HIV and to target both HIV-infected and uninfected people.