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Philippa Matthews


Honorary Consultant in Infectious Diseases & Microbiology

I am a research fellow in Clinical Infection funded by the Wellcome Trust to work on a study of chronic hepatitis B virus (HBV) infection, with a particular focus on populations in southern Africa.

Together with a group of collaborators at the Wellcome Trust Centre for Human Genetics, I am pioneering a new pipeline to generate full length deep HBV sequences, alongside collecting human demographic, clinical and genetic data. The aim of the study is to identify factors that impact on the outcomes of chronic HBV infection, and specifically to characterise the adaptive immune response.

In the long-term, advancing this knowledge will feed into optimising therapy and developing strategies for cure.

I have a background in HIV immunology, and also have research interests in other chronic viral infections including CMV, herpes viruses and human parvovirus-4 (PARV4), and virus discovery.

I am interested in data visualisation, which includes promoting Open Access publication, and also designing my own resources for use in primary and secondary school workshops to inspire school students in topics around science and medicine.

I continue to contribute to clinical work, and teaching graduate and undergraduate medical students in Microbiology and Infectious Diseases at Oxford University Hospitals. My particular clinical interests include the management of bone and joint infection, and antimicrobial prescribing and stewardship.

 

Publications

Leitman EM, Willberg CB, De Burgh-Thomas A, Streeck H, Goulder PJ, Matthews PC. 2016. Subdominant Gag-specific anti-HIV efficacy in an HLA-B*57-positive elite controller. AIDS, 30 (6), pp. 972-974. | Read more

 

Article has an altmetric score of 3
Leitman EM, Hurst J, Mori M, Kublin J, Ndung'u T, Walker BD, Carlson J, Gray GE, Matthews PC, Frahm N, Goulder PJ. 2016. Lower Viral Loads and Slower CD4+ T-Cell Count Decline in MRKAd5 HIV-1 Vaccinees Expressing Disease-Susceptible HLA-B*58:02. J Infect Dis, 214 (3), pp. 379-389. | Show Abstract | Read more

 

BACKGROUND: HLA strongly influences human immunodeficiency virus type 1 (HIV-1) disease progression. A major contributory mechanism is via the particular HLA-presented HIV-1 epitopes that are recognized by CD8(+) T-cells. Different populations vary considerably in the HLA alleles expressed. We investigated the HLA-specific impact of the MRKAd5 HIV-1 Gag/Pol/Nef vaccine in a subset of the infected Phambili cohort in whom the disease-susceptible HLA-B*58:02 is highly prevalent. METHODS: Viral loads, CD4(+) T-cell counts, and enzyme-linked immunospot assay-determined anti-HIV-1 CD8(+) T-cell responses for a subset of infected antiretroviral-naive Phambili participants, selected according to sample availability, were analyzed. RESULTS: Among those expressing disease-susceptible HLA-B*58:02, vaccinees had a lower chronic viral set point than placebo recipients (median, 7240 vs 122 500 copies/mL; P = .01), a 0.76 log10 lower longitudinal viremia level (P = .01), and slower progression to a CD4(+) T-cell count of

Article has an altmetric score of 2
Matthews PC, Carlson JM, Beloukas A, Malik A, Jooste P, Ogwu A, Shapiro R, Riddell L, Chen F, Luzzi G, Jesuthasan G, Jeffery K, Jojic N, Ndung'u T, Carrington M, Goulder PJ, Geretti AM, Klenerman P et al. 2016. HLA-A is a Predictor of Hepatitis B e Antigen Status in HIV-Positive African Adults. J Infect Dis, 213 (8), pp. 1248-1252. | Show Abstract | Read more

 

Outcomes of chronic infection with hepatitis B virus (HBV) are varied, with increased morbidity reported in the context of human immunodeficiency virus (HIV) coinfection. The factors driving different outcomes are not well understood, but there is increasing interest in an HLA class I effect. We therefore studied the influence of HLA class I on HBV in an African HIV-positive cohort. We demonstrated that virologic markers of HBV disease activity (hepatitis B e antigen status or HBV DNA level) are associated with HLA-A genotype. This finding supports the role of the CD8(+) T-cell response in HBV control, and potentially informs future therapeutic T-cell vaccine strategies.

Matthews P, Beloukas A, Malik A, Carlson J, Jooste P, Ogwu A, Shapiro R, Riddell L, Chen F, Luzzi G, Jaggernath M, Jesuthasan G, Jeffery K, Ndung'u T, Goulder P, Geretti AM, Klenerman P et al. 2015. HLA CONTRIBUTES TO IMMUNE CONTROL OF HEPATITIS B IN HIV-POSITIVE AFRICAN ADULTS JOURNAL OF INFECTION, 71 (6), pp. 685-686. | Read more

 

Article has an altmetric score of 2
Adland E, Klenerman P, Goulder P, Matthews PC. 2015. Ongoing burden of disease and mortality from HIV/CMV coinfection in Africa in the antiretroviral therapy era. Front Microbiol, 6 (SEP), pp. 1016. | Show Abstract | Read more

 

Human Cytomegalovirus (CMV) is a well-recognized pathogen in the context of HIV infection, but since the roll out of ART, clinical and scientific interest in the problem of HIV/CMV coinfection has diminished. However, CMV remains a significant cofactor in HIV disease, with an influence on HIV acquisition, disease progression, morbidity, and mortality. Disease manifestations may be a result of direct interplay between the two viruses, or may arise as a secondary consequence of immune dysregulation and systemic inflammation. The problem is most relevant when the rates of coinfection are high, most notably in sub-Saharan Africa, and in children at risk of acquiring both infections early in life. Understanding the interplay between these viruses and developing strategies to diagnose, treat and prevent CMV should be a priority.

Leitman EM, Hurst J, Mori M, Matthews PC, Frahm N, Kublin J, Gray GE, Goulder PJR. 2015. HLA-B*58:02-specific benefit of MRKAd5 Gag/Pol/Nef vaccine in an African population JOURNAL OF THE INTERNATIONAL AIDS SOCIETY, 18 | Read more

 

Article has an altmetric score of 5
Brener J, Gall A, Batorsky R, Riddell L, Buus S, Leitman E, Kellam P, Allen T, Goulder P, Matthews PC. 2015. Disease progression despite protective HLA expression in an HIV-infected transmission pair Retrovirology, | Show Abstract | Read more

 

© 2015 Brener et al.Background: The precise immune responses mediated by HLA class I molecules such as HLA-B*27:05 and HLA-B*57:01 that protect against HIV disease progression remain unclear. We studied a CRF01_AE clade HIV infected donor-recipient transmission pair in which the recipient expressed both HLA-B*27:05 and HLA-B*57:01. Results: Within 4.5 years of diagnosis, the recipient had progressed to meet criteria for antiretroviral therapy initiation. We employed ultra-deep sequencing of the full-length virus genome in both donor and recipient as an unbiased approach by which to identify specific viral mutations selected in association with progression. Using a heat map method to highlight differences in the viral sequences between donor and recipient, we demonstrated that the majority of the recipient's mutations outside of Env were within epitopes restricted by HLA-B*27:05 and HLA-B*57:01, including the well-studied Gag epitopes. The donor, who also expressed HLA alleles associated with disease protection, HLA-A*32:01/B*13:02/B*14:01, showed selection of mutations in parallel with disease progression within epitopes restricted by these protective alleles. Conclusions: These studies of full-length viral sequences in a transmission pair, both of whom expressed protective HLA alleles but nevertheless failed to control viremia, are consistent with previous reports pointing to the critical role of Gag-specific CD8+ T cell responses restricted by protective HLA molecules in maintaining immune control of HIV infection. The transmission of subtype CRF01_AE clade infection may have contributed to accelerated disease progression in this pair as a result of clade-specific sequence differences in immunodominant epitopes.

Article has an altmetric score of 5
Matthews PC. 2015. Rolling back malaria ELIFE, 4 | Read more

 

Matthews PC, Sharp CP, Malik A, Gregory WF, Adland E, Jooste P, Goulder PJ, Simmonds P, Klenerman P. 2015. Human parvovirus 4 infection among mothers and children in South Africa. Emerg Infect Dis, 21 (4), pp. 713-715. | Read more

 

Article has an altmetric score of 9
Matthews PC, Beloukas A, Malik A, Carlson JM, Jooste P, Ogwu A, Shapiro R, Riddell L, Chen F, Luzzi G, Jaggernath M, Jesuthasan G, Jeffery K, Ndung'u T, Goulder PJ, Geretti AM, Klenerman P et al. 2015. Prevalence and Characteristics of Hepatitis B Virus (HBV) Coinfection among HIV-Positive Women in South Africa and Botswana. PLoS One, 10 (7), pp. e0134037. | Show Abstract | Read more

 

There is progressive concern about the evolving burden of morbidity and mortality caused by coinfection with HIV-1 and hepatitis B virus (HBV) in sub-Saharan Africa, but the epidemiology and impact of this problem are not well defined. We therefore set out to assimilate more information about the nature of HBV/HIV coinfection in this region by undertaking a retrospective observational study of southern African adult women. We used samples from previously recruited HIV-1 positive women attending antenatal clinics in three settings in South Africa and Botswana (n = 950) and added a small cohort of HIV-negative antenatal South African women for comparison (n = 72). We tested for HBsAg and followed up HBsAg-positive samples by testing for HBeAg, HBV DNA, HBV genotype, presence of drug-resistance associated mutations (RAMs) and HDV. We identified HBsAg in 72 individuals (7% of the whole cohort), of whom 27% were HBeAg-positive, and the majority HBV genotypes A1 and A2. We did not detect any HDV coinfection. HBV prevalence was significantly different between geographically distinct cohorts, but did not differ according to HIV status. Among adults from South Africa, HBV/HIV coinfected patients had lower CD4+ T cell counts compared to those with HIV-monoinfection (p = 0.02), but this finding was not replicated in the cohort from Botswana. Overall, these data provide a snapshot of the coinfection problem at the heart of the HIV/HBV co-epidemic, and are important to inform public health policy, resource allocation, education, surveillance and clinical care.

Article has an altmetric score of 6
Matthews PC, Geretti AM, Goulder PJ, Klenerman P. 2014. Epidemiology and impact of HIV coinfection with hepatitis B and hepatitis C viruses in Sub-Saharan Africa. J Clin Virol, 61 (1), pp. 20-33. | Show Abstract | Read more