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3. SAT-404 The Lipidome in phenotyping hepatitis B infection (‘LiPHe-B’): preliminary results from our pilot study

Author

Delphin, Marion, primary, Palma-Duran, Susana, additional, Santos, Mariana Silva dos, additional, Martyn, Emily, additional, Waddilove, Elizabeth, additional, Wall, Emma, additional, Maponga, Tongai Gibson, additional, Martin, Jacqueline, additional, De Lara, Catherine, additional, Klenerman, Paul, additional, Barnes, Eleanor, additional, Macrae, James, additional, and Matthews, Philippa C, additional

Published
2024
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4. Cytomegalovirus viremia as a risk factor for mortality in HIV-associated cryptococcal and tuberculous meningitis

Author

Skipper, Caleb P., Hullsiek, Katherine Huppler, Cresswell, Fiona V., Tadeo, Kiiza K., Okirwoth, Michael, Blackstad, Mark, Hernandez-Alvarado, Nelmary, Fernández-Alarcón, Claudia, Walukaga, Stewart, Martyn, Emily, Ellis, Jayne, Ssebambulidde, Kenneth, Tugume, Lillian, Nuwagira, Edwin, Rhein, Joshua, Meya, David B., Boulware, David R., and Schleiss, Mark R.

Published
2022
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5. Peer support for people living with hepatitis B virus—A foundation for treatment expansion

Author

Downs, Louise O., primary, Kabagambe, Kenneth, additional, Williams, Sarah, additional, Waddilove, Elizabeth, additional, Delphin, Marion, additional, Lumley, Sheila F., additional, Ndungutse, Richard, additional, Kimono, Beatrice, additional, Newton, Robert, additional, Ko, Joy, additional, Martyn, Emily, additional, Carter, Jessica, additional, Kemper, Agnieszka, additional, Monteiro, Fernando, additional, O'Regan, Sive, additional, Surey, Julian, additional, Sultan, Binta, additional, Story, Alistair, additional, MacDonald, Douglas, additional, Tu, Thomas, additional, Seeley, Janet, additional, Dusheiko, Geoffrey, additional, Maponga, Tongai, additional, Andersson, Monique I., additional, Spearman, C. Wendy, additional, Tucker, Joseph D., additional, Cohen, Chari, additional, Wang, Su, additional, Adda, Danjuma, additional, Freeland, Catherine, additional, Halford, Rachel, additional, Jack, Kathryn, additional, Ghosh, Indrajit, additional, Elsharkawy, Ahmed M., additional, Matthews, Philippa C., additional, and Flanagan, Stuart, additional

Published
2024
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7. Corrigendum to A systematic review and meta-analysis of the risk of hepatitis B virus (HBV) resistance in people treated with entecavir or tenofovir.: Journal of Clinical Virology 174 (2024) 105711

Author

Lumley, Sheila F., Delphin, Marion, Mokaya, Jolynne, Tan, Cedric C.S., Martyn, Emily, Anderson, Motswedi, Li, Ka Chun, Waddilove, Elizabeth, Sukali, Gloria, Downs, Louise O., Said, Khadija, Okanda, Dorcas, Campbell, Cori, Harriss, Eli, Shimakawa, Yusuke, and Matthews, Philippa C.

Published
2024
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8. A systematic review and meta-analysis of the risk of hepatitis B virus (HBV) genotypic resistance in people treated with entecavir or tenofovir

Author

Lumley, Sheila F, primary, Delphin, Marion, additional, Mokaya, Jolynne F, additional, Tan, Cedric CS, additional, Martyn, Emily, additional, Anderson, Motswedi, additional, Li, Ka Chun, additional, Waddilove, Elizabeth, additional, Sukali, Gloria, additional, Downs, Louise O, additional, Said, Kadija, additional, Okanda, Dorcas, additional, Campbell, Cori, additional, Harriss, Eli, additional, Shimakawa, Yusuke, additional, and Matthews, Philippa C, additional

Published
2023
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10. Contrasting immune fingerprints of chronic hepatitis B Virus infection in adults from South Africa and the United Kingdom

Author

Delphin, Marion, primary, Downs, Louise, additional, Martyn, Emily, additional, Kelly, Gavin, additional, Van Schalkwyk, Marije, additional, Hugo, Susan, additional, Waddilove, Elizabeth, additional, Campbell, Cori, additional, Wang, Tingyan, additional, Lumley, Sheila, additional, De Lara, Catherine, additional, Goedhals, Dominique, additional, van Rensburg, Christo, additional, Wareing, Sue, additional, Fengou, Polly, additional, Martin, Jacqueline, additional, Andersson, Monique, additional, Carey, Ivana, additional, Ansari, Azim, additional, Preiser, Wolfgang, additional, Gabriel, Shiraaz, additional, Taljaard, Jantjie, additional, Barnes, Eleanor, additional, Maponga, Tongai Gibson, additional, and Matthews, Philippa, additional

Published
2023
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11. Social, clinical and biological barriers to hepatitis B virus suppression with nucleos/tide analogue therapy: who is at risk and what should we do about it?

Author

Im, Yu Ri, Mohammed, Khadija Said, Martyn, Emily, Lumley, Sheila, Ko, Joy, Mokaya, Jolynne, Flanagan, Stuart, and Matthews, Philippa Clare

Abstract

Optimising treatment outcomes for people living with hepatitis B virus (HBV) is key to advancing progress towards international targets for the elimination of viral hepatitis as a public health threat. Nucleos/tide analogue agents (most commonly tenofovir or entecavir) are well-tolerated and suppress viraemia effectively in the majority of those who are offered therapy. However, outcomes are not consistent, and we explore the factors that may contribute to incomplete therapeutic responses. We discuss situations in which therapy is not accessible, affordable or acceptable, reflecting the impact of social, cultural and economic barriers, stigma and discrimination, low awareness, poor access to health systems and comorbidity. These challenges are amplified in certain vulnerable populations, increasing the risk of adverse outcomes—which include liver cirrhosis and hepatocellular carcinoma—among people who already experience marginalisation and health inequities. We also tackle the physiological and biological mechanisms for incomplete virological suppression in individuals receiving HBV treatment, considering the possible impact of inadequate tissue drug levels, poor drug–target avidity and genomic resistance. These factors are interdependent, leading to a complex landscape in which socioeconomic challenges increase the challenge of consistent daily therapy and set the scene for selection of drug resistance. By putting a spotlight on this neglected topic, we aim to raise awareness, prompt dialogue, inform research and advocate for enhanced interventions. As criteria for HBV treatment eligibility relax, the population receiving therapy will expand, and there is a pressing need to optimise outcomes and close the equity gap.

Published
2024
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12. The forgotten people: Hepatitis B virus (HBV) infection as a priority for the inclusion health agenda

Author

Martyn, Emily, primary, Eisen, Sarah, additional, Longley, Nicky, additional, Harris, Philippa, additional, Surey, Julian, additional, Norman, James, additional, Brown, Michael, additional, Sultan, Binta, additional, Maponga, Tongai G, additional, Iwuji, Collins, additional, Flanagan, Stuart, additional, Ghosh, Indrajit, additional, Story, Alistair, additional, and Matthews, Philippa C, additional

Published
2023
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13. COLDA poster_print.pdf

Author

Martyn, Emily, Van Schalkwyk, Marije, Hugo, Susan, Goedhals, Dominique, Preiser, Wolfgang, Taljaard, Jantjie, van Rensburg, Christoffel, Matthews, Philippa, and Maponga, Tongai

Abstract

Poster presented at the Conference on Liver Disease Africa 2022, Cape Town, South Africa (29 September - 1 October) Background Globally, an estimated 300 million people are living with chronic hepatitis B (CHB), with 1 million deaths each year due to hepatitis B virus (HBV)-related cirrhosis and hepatocellular carcinoma (HCC). Males living with HBV often fare worse; compared to females they have increased exposure among certain risk groups, increased risk of HBV flares, cirrhosis and progression to HCC. Comorbidities may play a role in modulating progression to liver disease in CHB, for example diabetes is a risk factor for developing HBV-associated HCC. There are few studies addressing these questions in Africa, where their significance is critical due to high HBV prevalence. We investigate the impact of sex, comorbidity and treatment on liver disease in a cohort of adults with CHB in South Africa. Methods Adults (>18 years) with CHB were recruited from routine outpatient appointments at Tygerberg Hospital, Cape Town, South Africa. Basic demographic data, laboratory tests, elastography, treatment status and comorbidities were collected. Mann-Whitney tests were used for continuous and Fisher’s exact test for categorical variables using GraphPad Prism. Ethics approval was granted by University of Oxford Tropical Research Ethics Committee (ref. OXTREC 01-18) and Stellenbosch University Human Research Ethics Committee (HREC ref. N17/01/013). Results Between July 2018 and February 2020, 271 adults with CHB were recruited. Median age was 41 years (IQR 34, 50) and 43% (117/271) were female. Most participants were Black African (63%, 171/271) or mixed-race (31%, 84/271). 59% (159/271) were on HBV treatment, of which 74% (117/159) were on anti-retroviral therapy. A significantly higher proportion of males than females had platelets 17 mmol/L (22% vs 5%, p2 (indicating cirrhosis), but this difference was not significant (14% vs 4%, p=0.07). There was no significant difference in the proportion of F2/3/4 (>7kPa) fibrosis scores derived from fibroscan measurements (34% vs 29%, p=0.62) or median HBV viral load (210 vs 373 copies/mL, p= 0.92) between sexes. There was no significant difference in sex distribution of those treated for HBV mono-infection or HBV/HIV co-infection. Hypertension was the most common comorbidity (23%, 62/271), followed by chronic kidney disease (6%, 17/271) and diabetes (4%, 12/271). HIV was the most common co-infection (140/271, 52%), followed by TB (7%, 18/271) and hepatitis C (0% 1/271). There were no significant differences in prevalence of comorbidities between sexes. Conclusions In this South African CHB cohort, males have evidence of more severe liver disease than females based on several parameters (though not fibrosis scores). There was no evidence of difference in proportion on anti-HBV treatment, nor differences in prevalence of comorbidities between sexes, based on univariate analysis. Due to high prevalence of HIV in this setting, disaggregating the confounding effects of HIV co-infection and therapy is difficult. Multivariate analysis of larger cohorts is required to further investigate this observation, and deepen our understanding of the complex interplay between sex, co-morbidity and HBV.

Published
2022
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15. Evaluation of the Diagnostic Performance of a Semiquantitative Cryptococcal Antigen Point-of-Care Assay among HIV-Infected Persons with Cryptococcal Meningitis

Author

Tadeo, Kiiza Kandole, primary, Nimwesiga, Audrey, additional, Kwizera, Richard, additional, Apeduno, Lucy, additional, Martyn, Emily, additional, Okirwoth, Michael, additional, Nalintya, Elizabeth, additional, Rajasingham, Radha, additional, Williams, Darlisha A., additional, Rhein, Joshua, additional, Meya, David B., additional, Kafufu, Bosco, additional, Boulware, David R., additional, and Skipper, Caleb P., additional

Published
2021
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17. High-Dose Oral and Intravenous Rifampicin for the Treatment of Tuberculous Meningitis in Predominantly Human Immunodeficiency Virus (HIV)-Positive Ugandan Adults : A Phase II Open-Label Randomized Controlled Trial

Author

Cresswell, Fiona, V, Meya, David B., Kagimu, Enock, Grint, Daniel, Te Brake, Lindsey, Kasibante, John, Martyn, Emily, Rutakingirwa, Morris, Quinn, Carson M., Okirwoth, Micheal, Tugume, Lillian, Ssembambulidde, Kenneth, Musubire, Abdu K., Bangdiwala, Ananta S., Buzibye, Allan, Muzoora, Conrad, Svensson, Elin, Aarnoutse, Rob, Boulware, David R., Elliott, Alison M., Cresswell, Fiona, V, Meya, David B., Kagimu, Enock, Grint, Daniel, Te Brake, Lindsey, Kasibante, John, Martyn, Emily, Rutakingirwa, Morris, Quinn, Carson M., Okirwoth, Micheal, Tugume, Lillian, Ssembambulidde, Kenneth, Musubire, Abdu K., Bangdiwala, Ananta S., Buzibye, Allan, Muzoora, Conrad, Svensson, Elin, Aarnoutse, Rob, Boulware, David R., and Elliott, Alison M.

Abstract

Background: High-dose rifampicin may improve outcomes of tuberculous meningitis (TBM). Little safety or pharmacokinetic (PK) data exist on high-dose rifampicin in human immunodeficiency virus (HIV) coinfection, and no cerebrospinal fluid (CSF) PK data exist from Africa. We hypothesized that high-dose rifampicin would increase serum and CSF concentrations without excess toxicity. Methods: In this phase II open-label trial, Ugandan adults with suspected TBM were randomized to standard-of-care control (PO-10, rifampicin 10 mg/kg/day), intravenous rifampicin (IV-20, 20 mg/kg/day), or high-dose oral rifampicin (PO-35, 35 mg/kg/day). We performed PK sampling on days 2 and 14. The primary outcomes were total exposure (AUC(0-24)), maximum concentration (C-max), CSF concentration, and grade 3-5 adverse events. Results: We enrolled 61 adults, 92% were living with HIV, median CD4 count was 50 cells/mu L (interquartile range [IQR] 46-56). On day 2, geometric mean plasma AUC(0-24hr) was 42.9.h mg/L with standard-of-care 10 mg/kg dosing, 249.h mg/L for IV-20 and 327.h mg/L for PO-35 (P<.001). In CSF, standard of care achieved undetectable rifampicin concentration in 56% of participants and geometric mean AUC(0-24hr) 0.27 mg/L, compared with 1.74 mg/L (95% confidence interval [CI] 1.2-2.5) for IV-20 and 2.17 mg/L (1.6-2.9) for PO-35 regimens (P<.001). Achieving CSF concentrations above rifampicin minimal inhibitory concentration (MIC) occurred in 11% (2/18) of standard-of-care, 93% (14/15) of IV-20, and 95% (18/19) of PO-35 participants. Higher serum and CSF levels were sustained at day 14. Adverse events did not differ by dose (P=.34). Conclusions: Current international guidelines result in sub-therapeutic CSF rifampicin concentration for 89% of Ugandan TBM patients. High-dose intravenous and oral rifampicin were safe and respectively resulted in exposures similar to 6- and similar to 8-fold higher than standard of care, and CSF levels above the MIC.

Published
2021
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18. COVID-19 and the HIV care continuum in Uganda: minimising collateral damage

Author

Kagimu, Enock, primary, Martyn, Emily M., additional, Gakuru, Jane, additional, Kasibante, John, additional, Rutakingirwa, Morris K, additional, Kwizera, Richard, additional, Ssebambulidde, Kenneth, additional, Williams, Darlisha, additional, Ellis, Jayne, additional, Cresswell, Fiona V, additional, and Meya, David B., additional

Published
2021
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19. High-Dose Oral and Intravenous Rifampicin for the Treatment of Tuberculous Meningitis in Predominantly Human Immunodeficiency Virus (HIV)-Positive Ugandan Adults: A Phase II Open-Label Randomized Controlled Trial

Author

Cresswell, Fiona V, primary, Meya, David B, additional, Kagimu, Enock, additional, Grint, Daniel, additional, te Brake, Lindsey, additional, Kasibante, John, additional, Martyn, Emily, additional, Rutakingirwa, Morris, additional, Quinn, Carson M, additional, Okirwoth, Micheal, additional, Tugume, Lillian, additional, Ssembambulidde, Kenneth, additional, Musubire, Abdu K, additional, Bangdiwala, Ananta S, additional, Buzibye, Allan, additional, Muzoora, Conrad, additional, Svensson, Elin M, additional, Aarnoutse, Rob, additional, Boulware, David R, additional, and Elliott, Alison M, additional

Published
2021
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21. WED-181 - Contrasting immune fingerprints of chronic hepatitis B Virus infection in adults from South Africa and the United Kingdom

Author

Delphin, Marion, Downs, Louise, Martyn, Emily, Kelly, Gavin, Van Schalkwyk, Marije, Hugo, Susan, Waddilove, Elizabeth, Campbell, Cori, Wang, Tingyan, Lumley, Sheila, De Lara, Catherine, Goedhals, Dominique, van Rensburg, Christo, Wareing, Sue, Fengou, Polly, Martin, Jacqueline, Andersson, Monique, Carey, Ivana, Ansari, Azim, Preiser, Wolfgang, Gabriel, Shiraaz, Taljaard, Jantjie, Barnes, Eleanor, Maponga, Tongai Gibson, and Matthews, Philippa

Published
2023
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22. A Journey of Hope: giving research participants a voice to share their experiences and improve community engagement around advanced HIV disease in Uganda

Author

Cresswell, Fiona V., primary, Kasibante, John, additional, Martyn, Emily M., additional, Tugume, Lillian, additional, Stead, Gavin, additional, Ssembambulidde, Kenneth, additional, Rutakingirwa, Morris K., additional, Kagimu, Enock, additional, Nsangi, Laura, additional, Namuju, Carol, additional, Ndyetukira, Jane F., additional, Ahimbisibwe, Cynthia, additional, Kugonza, Florence, additional, Sadiq, Alisat, additional, Namudde, Alice, additional, Dobbin, Joanna, additional, Srishyla, Diksha, additional, Quinn, Carson, additional, Kabahubya, Mable, additional, Muzoora, Conrad, additional, Watiti, Stephen, additional, Meya, David B., additional, and Elliott, Alison M., additional

Published
2020
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23. Cerebrospinal Fluid Bacillary Load by Xpert MTB/RIF Ultra Polymerase Chain Reaction Cycle Threshold Value Predicts 2-Week Mortality in Human Immunodeficiency Virus–Associated Tuberculous Meningitis

Author

Martyn, Emily M, primary, Bangdiwala, Ananta S, additional, Kagimu, Enock, additional, Rutakingirwa, Morris K, additional, Kasibante, John, additional, Okirwoth, Michael, additional, Stead, Gavin, additional, Wadda, Vincent, additional, Pullen, Matthew F, additional, Bold, Tyler D, additional, Meya, David B, additional, Boulware, David R, additional, Bahr, Nathan C, additional, and Cresswell, Fiona V, additional

Published
2020
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24. High dose oral rifampicin to improve survival from adult tuberculous meningitis: A randomised placebo-controlled double-blinded phase III trial (the HARVEST study)

Author

Marais, Suzaan, primary, Cresswell, Fiona V, additional, Hamers, Raph L., additional, te Brake, Lindsey H.M., additional, Ganiem, Ahmad R., additional, Imran, Darma, additional, Bangdiwala, Ananta, additional, Martyn, Emily, additional, Kasibante, John, additional, Kagimu, Enock, additional, Musubire, Abdu, additional, Maharani, Kartika, additional, Estiasari, Riwanti, additional, Kusumaningrum, Ardiana, additional, Kusumadjayanti, Nadytia, additional, Yunivita, Vycke, additional, Naidoo, Kogieleum, additional, Lessells, Richard, additional, Moosa, Yunus, additional, Svensson, Elin M., additional, Huppler Hullsiek, Katherine, additional, Aarnoutse, Rob E., additional, Boulware, David R., additional, van Crevel, Reinout, additional, Ruslami, Rovina, additional, and Meya, David B., additional

Published
2020
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26. COVID-19 and the HIV care continuum in Uganda: minimising collateral damage

Author

Kagimu, Enock, primary, Martyn, Emily M., additional, Gakuru, Jane, additional, Kasibante, John, additional, Rutakingirwa, Morris K, additional, Kwizera, Richard, additional, Ssebambulidde, Kenneth, additional, Williams, Darlisha, additional, Ellis, Jayne, additional, Cresswell, Fiona V, additional, and Meya, David B., additional

Published
2020
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28. Standardized Urine-Based Tuberculosis (TB) Screening With TB-Lipoarabinomannan and Xpert MTB/RIF Ultra in Ugandan Adults With Advanced Human Immunodeficiency Virus Disease and Suspected Meningitis

Author

Cresswell, Fiona V, primary, Ellis, Jayne, primary, Kagimu, Enock, primary, Bangdiwala, Ananta S, primary, Okirwoth, Michael, primary, Mugumya, Gerald, primary, Rutakingirwa, Morris, primary, Kasibante, John, primary, Quinn, Carson M, primary, Ssebambulidde, Kenneth, primary, Rhein, Joshua, primary, Nuwagira, Edwin, primary, Tugume, Lillian, primary, Martyn, Emily, primary, Skipper, Caleb P, primary, Muzoora, Conrad, primary, Grint, Daniel, primary, Meya, David B, primary, Bahr, Nathan C, primary, Elliott, Alison M, primary, and Boulware, David R, primary

Published
2020
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30. High dose oral rifampicin to improve survival from adult tuberculous meningitis: A randomised placebo-controlled double-blinded phase III trial (the HARVEST study)

Author

Marais, Suzaan, primary, Cresswell, Fiona V, additional, Hamers, Raph L., additional, te Brake, Lindsey H.M., additional, Ganiem, Ahmad R., additional, Imran, Darma, additional, Bangdiwala, Ananta, additional, Martyn, Emily, additional, Kasibante, John, additional, Kagimu, Enock, additional, Musubire, Abdu, additional, Maharani, Kartika, additional, Estiasari, Riwanti, additional, Kusumaningrum, Ardiana, additional, Kusumadjayanti, Nadytia, additional, Yunivita, Vycke, additional, Naidoo, Kogieleum, additional, Lessells, Richard, additional, Moosa, Yunus, additional, Svensson, Elin M., additional, Huppler Hullsiek, Katherine, additional, Aarnoutse, Rob E., additional, Boulware, David R., additional, van Crevel, Reinout, additional, Ruslami, Rovina, additional, and Meya, David B., additional

Published
2019
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32. Cerebrospinal Fluid Bacillary Load by Xpert MTB/RIF Ultra Polymerase Chain Reaction Cycle Threshold Value Predicts 2-Week Mortality in Human Immunodeficiency Virus–Associated Tuberculous Meningitis.

Author

Martyn, Emily M, Bangdiwala, Ananta S, Kagimu, Enock, Rutakingirwa, Morris K, Kasibante, John, Okirwoth, Michael, Stead, Gavin, Wadda, Vincent, Pullen, Matthew F, Bold, Tyler D, Meya, David B, Boulware, David R, Bahr, Nathan C, and Cresswell, Fiona V

Subjects
*HIV infection complications, *MYCOBACTERIUM, *PREDICTIVE tests, *MOLECULAR diagnosis, *VIRAL load, *LACTATES, *CEREBROSPINAL fluid, *POLYMERASE chain reaction, *LONGITUDINAL method
Abstract

Background The World Health Organization recommends GeneXpert MTB/RIF Ultra (Xpert Ultra), a fully automated polymerase chain reaction (PCR) assay, as the initial tuberculous meningitis (TBM) diagnostic test. The assay's PCR cycle threshold (Ct) values represent the number of PCR cycles required for probe signal to be detected (low Ct value = high bacillary load) and may approximate tuberculosis (TB) bacillary load. We measured the relationship between cerebrospinal fluid (CSF) TB bacillary load with mortality. Methods We prospectively enrolled 102 human immunodeficiency virus (HIV)–positive Ugandans with probable or definite TBM from April 2015 to August 2019. Xpert Ultra Ct tertiles and semi-quantitative categories were separately analyzed as predictors of 2-week mortality. We investigated associations between Ct and baseline clinical and CSF parameters. Results Subjects with Ct values in the low tertile (ie, high bacillary load) had 57% 2-week mortality—worse than the intermediate (17%) and high (25%) Ct tertiles and Xpert Ultra–negative (30%) probable TBM cases (P  = .01). In contrast, the reported semi-quantitative Xpert Ultra categorization was less precise; with the medium to low category trending toward worse 2-week survival (42%) compared with very low (28%), trace (26%), and negative (30%) categories (P  = .48). Ct tertile was significantly associated with baseline CSF lactate (P  = .03). Conclusions High CSF TB bacillary load, as measured by Xpert Ultra Ct tertile, is associated with an almost 2-fold higher 2-week mortality in HIV-associated TBM and is a better predictor than the reported Xpert Ultra semi-quantitative category. Xpert Ultra Ct values could identify TBM patients at increased risk of death who may benefit from enhanced supportive care. [ABSTRACT FROM AUTHOR]

Published
2021
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33. Bacterial Coinfection in COVID-19.

Author

Gil, Eliza, Martyn, Emily, Rokadiya, Sakib, Jain, Sarjana, and Chin, Teh Li

Subjects
*COVID-19, *ANTI-infective agents, *MYCOSES, *MIXED infections, *DRUG prescribing, *BACTERIAL diseases, *PHYSICIAN practice patterns
Published
2021
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