Browsing by Author "Fraser, Christophe"

Now showing 1 - 8 of 8
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    Bimodal distribution and set point HBV DNA viral loads in chronic infection : retrospective analysis of cohorts from the UK and South Africa
    (Wellcome Open Research, 2020-10-14) Downs, Louise O.; Vawda, Sabeehah; Bester, Phillip Armand; Lythgoe, Katrina A.; Wang, Tingyan; McNaughton, Anna L.; Smith, David A.; Maponga, Tongai; Freeman, Oliver; Várnai, Kinga A.; Davies, Jim; Woods, Kerrie; Fraser, Christophe; Barnes, Eleanor; Goedhals, Dominique; Matthews, Philippa C.
    ENGLISH ABSTRACT: Hepatitis B virus (HBV) viral load (VL) is used as a biomarker to assess risk of disease progression, and to determine eligibility for treatment. While there is a well recognised association between VL and the expression of the viral e-antigen protein, the distributions of VL at a population level are not well described. We here present cross-sectional, observational HBV VL data from two large population cohorts in the UK and in South Africa, demonstrating a consistent bimodal distribution. The right skewed distribution and low median viral loads are different from the left-skew and higher viraemia in seen in HIV and hepatitis C virus (HCV) cohorts in the same settings. Using longitudinal data, we present evidence for a stable 'set-point' VL in peripheral blood during chronic HBV infection. These results are important to underpin improved understanding of HBV biology, to inform approaches to viral sequencing, and to plan public health interventions.
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    Effect of Universal Testing and Treatment on HIV Incidence — HPTN 071 (PopART)
    (Massachusetts Medical Society, 2019-07) Hayes, Richard J.; Donnell, Deborah; Floyd, Sian; Mandla, Nomtha; Bwalya, Justin; Sabapathy, Kalpana; Yang, Blia; Phiri, Mwelwa; Schaap, Ab; Eshleman, Susan H.; Piwowar-Manning, Estelle; Kosloff, Barry; James, Anelet; Skalland, Timothy; Wilson, Ethan; Emel, Lynda; Macleod, David; Dunbar, Rory; Simwinga, Musonda; Makola, Nozizwe; Bond, Virginia; Moore, Ayana; Griffith, Sam; Sista, Nirupama Deshmane; Vermund, Sten H.; El-Sadr, Wafaa; Burns, David N.; Hargreaves, James R.; Hauck, Katharina; Fraser, Christophe; Shanaube, Kwame; Bock, Peter; Beyers, Nulda; Ayles, Helen; Fidler, Sarah
    BACKGROUND: A universal testing and treatment strategy is a potential approach to reduce the incidence of human immunodeficiency virus (HIV) infection, yet previous trial results are inconsistent. METHODS: In the HPTN 071 (PopART) community-randomized trial conducted from 2013 through 2018, we randomly assigned 21 communities in Zambia and South Africa (total population, approximately 1 million) to group A (combination prevention intervention with universal antiretroviral therapy [ART]), group B (the prevention intervention with ART provided according to local guidelines [universal since 2016]), or group C (standard care). The prevention intervention included home-based HIV testing delivered by community workers, who also supported linkage to HIV care and ART adherence. The primary outcome, HIV incidence between months 12 and 36, was measured in a population cohort of approximately 2000 randomly sampled adults (18 to 44 years of age) per community. Viral suppression (<400 copies of HIV RNA per milliliter) was assessed in all HIV-positive participants at 24 months. RESULTS: The population cohort included 48,301 participants. Baseline HIV prevalence was 21% or 22% in each group. Between months 12 and 36, a total of 553 new HIV infections were observed during 39,702 person-years (1.4 per 100 person-years; women, 1.7; men, 0.8). The adjusted rate ratio for group A as compared with group C was 0.93 (95% confidence interval [CI], 0.74 to 1.18; P=0.51) and for group B as compared with group C was 0.70 (95% CI, 0.55 to 0.88; P=0.006). The percentage of HIV-positive participants with viral suppression at 24 months was 71.9% in group A, 67.5% in group B, and 60.2% in group C. The estimated percentage of HIV-positive adults in the community who were receiving ART at 36 months was 81% in group A and 80% in group B. CONCLUSIONS: A combination prevention intervention with ART provided according to local guidelines resulted in a 30% lower incidence of HIV infection than standard care. The lack of effect with universal ART was unanticipated and not consistent with the data on viral suppression. In this trial setting, universal testing and treatment reduced the population-level incidence of HIV infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; HPTN 071 [PopArt] ClinicalTrials.gov number, NCT01900977. opens in new tab.)
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    HIV treatment as prevention : debate and commentary : will early infection compromise treatment-as-prevention strategies?
    (Public Library of Science (PLOS), 2012-07) Cohen, Myron S.; Dye, Christopher; Fraser, Christophe; Miller, William C.; Powers, Kimberly A.; Williams, Brian G.
    Universal HIV testing and immediate antiretroviral therapy for infected individuals has been proposed as a way of reducing the transmission of HIV and thereby bringing the HIV epidemic under control. It is unclear whether transmission during early HIV infection—before individuals are likely to have been diagnosed with HIV and started on antiretroviral therapy—will compromise the effectiveness of treatment as prevention
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    HIV treatment as prevention : optimising the impact of expanded HIV treatment programmes
    (Public Library of Science (PLOS), 2012-07) Delva, Wim; Eaton, Jeffrey W.; Meng, Fei; Fraser, Christophe; White, Richard G.; Vickerman, Peter; Boily, Marie-Claude; Hallett, Timothy B.
    Until now, decisions about how to allocate ART have largely been based on maximising the therapeutic benefit of ART for patients. Since the results of the HPTN 052 study showed efficacy of antiretroviral therapy (ART) in preventing HIV transmission, there has been increased interest in the benefits of ART not only as treatment, but also in prevention. Resources for expanding ART in the short term may be limited, so the question is how to generate the most prevention benefit from realistic potential increases in the availability of ART. Although not a formal systematic review, here we review different ways in which access to ART could be expanded by prioritising access to particular groups based on clinical or behavioural factors. For each group we consider (i) the clinical and epidemiological benefits, (ii) the potential feasibility, acceptability, and equity, and (iii) the affordability and cost-effectiveness of prioritising ART access for that group. In re-evaluating the allocation of ART in light of the new data about ART preventing transmission, the goal should be to create policies that maximise epidemiological and clinical benefit while still being feasible, affordable, acceptable, and equitable.
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    HIV treatment as prevention : systematic comparison of mathematical models of the potential impact of antiretroviral therapy on HIV incidence in South Africa
    (Public Library of Science -- PLOS, 2012-07) Eaton, Jeffrey W.; Johnson, Leigh F.; Salomon, Joshua A.; Barnighausen, Till; Bendavid, Eran; Bershteyn, Anna; Bloom, David E.; Cambiano, Valentina; Fraser, Christophe; Hontelez, Jan A. C.; Humair, Salal; Klein, Daniel J.; Long, Elisa F.; Phillips, Andrew N.; Pretorius, Carel; Stover, John; Wenger, Edward A.; Williams, Brian G.; Hallett, Timothy B.
    Background: Many mathematical models have investigated the impact of expanding access to antiretroviral therapy (ART) on new HIV infections. Comparing results and conclusions across models is challenging because models have addressed slightly different questions and have reported different outcome metrics. This study compares the predictions of several mathematical models simulating the same ART intervention programmes to determine the extent to which models agree about the epidemiological impact of expanded ART. Methods and Findings: Twelve independent mathematical models evaluated a set of standardised ART intervention scenarios in South Africa and reported a common set of outputs. Intervention scenarios systematically varied the CD4 count threshold for treatment eligibility, access to treatment, and programme retention. For a scenario in which 80% of HIV-infected individuals start treatment on average 1 y after their CD4 count drops below 350 cells/ml and 85% remain on treatment after 3 y, the models projected that HIV incidence would be 35% to 54% lower 8 y after the introduction of ART, compared to a counterfactual scenario in which there is no ART. More variation existed in the estimated long-term (38 y) reductions in incidence. The impact of optimistic interventions including immediate ART initiation varied widely across models, maintaining substantial uncertainty about the theoretical prospect for elimination of HIV from the population using ART alone over the next four decades. The number of person-years of ART per infection averted over 8 y ranged between 5.8 and 18.7. Considering the actual scale-up of ART in South Africa, seven models estimated that current HIV incidence is 17% to 32% lower than it would have been in the absence of ART. Differences between model assumptions about CD4 decline and HIV transmissibility over the course of infection explained only a modest amount of the variation in model results. Conclusions: Mathematical models evaluating the impact of ART vary substantially in structure, complexity, and parameter choices, but all suggest that ART, at high levels of access and with high adherence, has the potential to substantially reduce new HIV infections. There was broad agreement regarding the short-term epidemiologic impact of ambitious treatment scale-up, but more variation in longer term projections and in the efficiency with which treatment can reduce new infections. Differences between model predictions could not be explained by differences in model structure or parameterization that were hypothesized to affect intervention impact.
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    HIV treatment-as-prevention research : taking the right road at the crossroads
    (Public Library of Science, 2015) Hayes, Richard; Fidler, Sarah; Cori, Anne; Fraser, Christophe; Floyd, Sian; Ayles, Helen; Beyers, Nulda; El-Sadr, Wafaa; HPTN 071 (PopART) Study Team
    No abstract available
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    HPTN 071 (PopART) : a cluster-randomized trial of the population impact of an HIV combination prevention intervention including universal testing and treatment : mathematical model
    (PLoS, 2014-01-15) Cori, Anne; Ayles, Helen; Beyers, Nulda; Schaap, Ab; Floyd, Sian; Sabapathy, Kalpana; Eaton, Jeffrey W.; Hauck, Katharina; Smith, Peter; Griffith, Sam; Moore, Ayana; Donnell, Deborah; Vermund, Sten H.; Fidler, Sarah; Hayes, Richard; Fraser, Christophe
    Background: The HPTN 052 trial confirmed that antiretroviral therapy (ART) can nearly eliminate HIV transmission from successfully treated HIV-infected individuals within couples. Here, we present the mathematical modeling used to inform the design and monitoring of a new trial aiming to test whether widespread provision of ART is feasible and can substantially reduce population-level HIV incidence. Methods and Findings: The HPTN 071 (PopART) trial is a three-arm cluster-randomized trial of 21 large population clusters in Zambia and South Africa, starting in 2013. A combination prevention package including home-based voluntary testing and counseling, and ART for HIV positive individuals, will be delivered in arms A and B, with ART offered universally in arm A and according to national guidelines in arm B. Arm C will be the control arm. The primary endpoint is the cumulative three-year HIV incidence. We developed a mathematical model of heterosexual HIV transmission, informed by recent data on HIV-1 natural history. We focused on realistically modeling the intervention package. Parameters were calibrated to data previously collected in these communities and national surveillance data. We predict that, if targets are reached, HIV incidence over three years will drop by >60% in arm A and >25% in arm B, relative to arm C. The considerable uncertainty in the predicted reduction in incidence justifies the need for a trial. The main drivers of this uncertainty are possible community-level behavioral changes associated with the intervention, uptake of testing and treatment, as well as ART retention and adherence. Conclusions: The HPTN 071 (PopART) trial intervention could reduce HIV population-level incidence by >60% over three years. This intervention could serve as a paradigm for national or supra-national implementation. Our analysis highlights the role mathematical modeling can play in trial development and monitoring, and more widely in evaluating the impact of treatment as prevention.
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    HPTN 071 (PopART) : rationale and design of a cluster-randomised trial of the population impact of an HIV combination prevention intervention including universal testing and treatment - a study protocol for a cluster randomised trial
    (BioMed Central, 2014-02) Hayes, Richard; Ayles, Helen; Beyers, Nulda; Sabapathy, Kalpana; Floyd, Sian; Shanaube, Kwame; Bock, Peter; Griffith, Sam; Moore, Ayana; Watson-Jones, Deborah; Fraser, Christophe; Vermund, Sten H.; Fidler, Sarah; The HPTN 071 (PopART) Study Team
    Abstract Background Effective interventions to reduce HIV incidence in sub-Saharan Africa are urgently needed. Mathematical modelling and the HIV Prevention Trials Network (HPTN) 052 trial results suggest that universal HIV testing combined with immediate antiretroviral treatment (ART) should substantially reduce incidence and may eliminate HIV as a public health problem. We describe the rationale and design of a trial to evaluate this hypothesis. Methods/Design A rigorously-designed trial of universal testing and treatment (UTT) interventions is needed because: i) it is unknown whether these interventions can be delivered to scale with adequate uptake; ii) there are many uncertainties in the models such that the population-level impact of these interventions is unknown; and ii) there are potential adverse effects including sexual risk disinhibition, HIV-related stigma, over-burdening of health systems, poor adherence, toxicity, and drug resistance.In the HPTN 071 (PopART) trial, 21 communities in Zambia and South Africa (total population 1.2 m) will be randomly allocated to three arms. Arm A will receive the full PopART combination HIV prevention package including annual home-based HIV testing, promotion of medical male circumcision for HIV-negative men, and offer of immediate ART for those testing HIV-positive; Arm B will receive the full package except that ART initiation will follow current national guidelines; Arm C will receive standard of care. A Population Cohort of 2,500 adults will be randomly selected in each community and followed for 3 years to measure the primary outcome of HIV incidence. Based on model projections, the trial will be well-powered to detect predicted effects on HIV incidence and secondary outcomes. Discussion Trial results, combined with modelling and cost data, will provide short-term and long-term estimates of cost-effectiveness of UTT interventions. Importantly, the three-arm design will enable assessment of how much could be achieved by optimal delivery of current policies and the costs and benefits of extending this to UTT. Trial registration ClinicalTrials.gov NCT01900977.