32 results on '"Churchill, Duncan"'
Search Results
2. BHIVA guidelines on antiretroviral treatment for adults living with HIV-1 2022.
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Waters L, Winston A, Reeves I, Boffito M, Churchill D, Cromarty B, Dunn D, Fink D, Fidler S, Foster C, Fox J, Gupta R, Hilton A, Khoo S, Leen C, Mackie N, Naous N, Ogbonmwan D, Orkin C, Panton L, Post F, Pozniak A, Sabin C, and Walsh J
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- Adult, Humans, Anti-Retroviral Agents therapeutic use, HIV-1, HIV Infections drug therapy, HIV Seropositivity
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- 2022
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3. Chemsex and antiretroviral prescribing in an HIV cohort in Brighton, UK.
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Adler Z, Fitzpatrick C, Broadwell N, Churchill D, and Richardson D
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- Anti-Retroviral Agents therapeutic use, Cobicistat, Cross-Sectional Studies, Homosexuality, Male, Humans, Male, Ritonavir therapeutic use, Sexual Behavior, United Kingdom epidemiology, Unsafe Sex, HIV Infections drug therapy, HIV Infections epidemiology, Illicit Drugs, Sexual and Gender Minorities, Substance-Related Disorders epidemiology
- Abstract
Objectives: Chemsex has been reported among men who have sex with men (MSM) living with HIV. There have been concerns about potentially harmful drug-drug interactions between chemsex drugs and antiretroviral therapy (ritonavir and cobicistat). We aimed to describe the prevalence and patterns of chemsex users in our HIV clinic population and to evaluate antiretroviral prescribing among chemsex users., Methods: We undertook a cross-sectional study of patients attending our HIV clinic between January 2019 and December 2020. We collected data on patients who disclosed recent recreational drug use including chemsex in the previous 3 months., Results: In all, 2202/2501 (88%) patients were asked about recreational drug use and 514 (23%) disclosed recreational drug use. Eighty-two (4%) of these disclosed recent chemsex; 73 (89%) used crystal methamphetamine, 51 (62%) used gamma-hydroxybutyrate (GHB)/gamma-butyrolactone (GBL), 55 (67%) reported poly-drug use and 63 (76%) reported injecting drug use. The chemsex users were all cis-male MSM and were significantly older (53 vs. 46 years, p < 0.0001), and more likely to have had previous syphilis (73% vs. 28%, p < 0.0001) than patients reporting non-chemsex drug use. All chemsex users were prescribed antiretrovirals and 74 (90%) had an undetectable HIV viral load; 31 (38%) patients were taking either ritonavir (N = 12) or cobicistat (N = 19) as part of their antiretroviral regimen and this was similar to other patients attending for HIV care [31/82 (38%) vs. 768/2419 (31%), p = 0.25]., Conclusions: The prevalence of chemsex users among our HIV clinic attendants is 4%, and 38% of these were prescribed either ritonavir or cobicistat. Chemsex use should be a factor in antiretroviral therapy decision-making to avoid potential harm., (© 2022 British HIV Association.)
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- 2022
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4. The impact of COVID-19 on HIV testing in the UK's first Fast-Track HIV city.
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Wenlock RD, Shillingford C, Mear J, Churchill D, Vera JH, and Dean G
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- Aged, Female, HIV Testing, Humans, Pandemics, United Kingdom epidemiology, COVID-19 diagnosis, COVID-19 epidemiology, HIV Infections diagnosis, HIV Infections epidemiology
- Abstract
Objectives: To describe the impact that the COVID-19 pandemic has had on HIV testing in Brighton and Hove, United Kingdom., Methods: All HIV tests performed in Brighton and Hove from January 2016 to June 2021 were extracted, de-duplicated and anonymized. Analysis was performed to compare the monthly numbers of tests and diagnoses before and during the pandemic across different services., Results: The number of patients having tests for HIV in sexual health services (SHS) decreased by 64% in April 2020, followed by a recovery to baseline levels by the start of 2021. Similarly, the monthly number of diagnoses decreased drastically after April 2020, with almost half of diagnoses made by SHS in 2020 occurring in the three pre-pandemic months of the year. 'Self-sampling', used more by women and younger patients, has contributed significantly to the recovery. The number of patients tested in secondary care was seemingly unaffected by the pandemic. However, testing numbers were reduced in specialist services, whereas in the emergency department (ED) testing increased four-fold (most notably in the elderly) without finding any cases. General practice saw decreases in both the number of HIV tests performed and the number of new diagnoses made, which had not returned to baseline by June 2021., Discussion: The COVID-19 pandemic has had a large impact on the number of HIV tests performed in Brighton and Hove with sizeable decreases in the number of patients tested likely leading to 'missed' diagnoses. By June 2021 testing had still not returned to normal across the city., (© 2022 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)
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- 2022
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5. A phase IV randomised, open-label pilot study to evaluate switching from protease-inhibitor based regimen to Bictegravir/Emtricitabine/Tenofovir Alafenamide single tablet regimen in Integrase inhibitor-naïve, virologically suppressed HIV-1 infected adults harbouring drug resistance mutations (PIBIK study): study protocol for a randomised trial.
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Iwuji CC, Churchill D, Bremner S, Perry N, To Y, Lambert D, Bruce C, Waters L, Orkin C, and Geretti AM
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- Adenine therapeutic use, Adult, Alanine, Amides, Drug Combinations, Emtricitabine adverse effects, Female, HIV Infections genetics, HIV Infections virology, HIV Integrase Inhibitors adverse effects, Heterocyclic Compounds, 3-Ring, Heterocyclic Compounds, 4 or More Rings adverse effects, Humans, Male, Mutation, Pilot Projects, Piperazines, Prospective Studies, Protease Inhibitors adverse effects, Pyridones, Reverse Transcriptase Inhibitors adverse effects, Tenofovir analogs & derivatives, Treatment Outcome, Adenine analogs & derivatives, Drug Resistance, Viral genetics, Emtricitabine therapeutic use, HIV Infections drug therapy, HIV Integrase Inhibitors therapeutic use, HIV-1 drug effects, Heterocyclic Compounds, 4 or More Rings therapeutic use, Protease Inhibitors therapeutic use, Reverse Transcriptase Inhibitors therapeutic use
- Abstract
Background: Currently recommended boosted protease-inhibitor (bPI) regimens may be associated with increased risk of cardiovascular or chronic kidney diseases; in addition, boosted regimens are particularly associated with drug-drug interactions. Since both cardiovascular and renal disease, and polypharmacy, are common in ageing people with HIV, there is a need for alternative efficacious regimens. bPI-based regimens are often the treatment of choice for individuals with pre-treatment or treatment-acquired resistance but it is plausible that carefully selected HIV-positive individuals with drug resistance, who are virologically suppressed on their current bPI regimen, could maintain virological efficacy when switched to bictegravir, emtricitabine and tenofovir alafenamide (B/F/TAF) fixed dose combination (FDC)., Methods/design: A phase IV, investigator-initiated, multicentre, open label pilot, randomised two-arm study to assess the safety and efficacy of switching from bPI regimen to B/F/TAF single tablet regimen in integrase inhibitor-naïve, virologically suppressed adults with HIV-1 infection harbouring drug resistance mutations. Eligible individuals will either continue on their bPI regimen or switch to B/F/TAF FDC. After 24 weeks, all participants in the bPI arm will be switched to B/F/TAF and followed for a further 24 weeks and all participants will be followed for 48 weeks. The primary efficacy endpoint is the proportion of participants with HIV-1 RNA < 50 copies/mL at week 24 using pure virologic response whilst the secondary efficacy endpoint is the proportion of participants with HIV-1 RNA < 50 copies/mL at Week 48. Other secondary outcome measures include between arm comparisons of drug resistance at virological failure, safety and tolerability and patient-reported outcome measures., Discussion: We aim to provide preliminary evidence of the efficacy of switching to B/F/TAF in patients with virological suppression on a bPI-based regimen who harbour select drug resistance mutations., Trial Registration: ISRCTN 44453201 , registered 19 June 2019 and EudraCT 2018-004732-30.
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- 2020
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6. Prevalence of and risk factors for gout in HIV-positive adults: A case-control study.
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Nicholson P, Saunsbury E, D'Angelo S, Churchill D, and Walker-Bone K
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- Adult, Case-Control Studies, Comorbidity, England epidemiology, Female, Gout diagnosis, HIV Infections diagnosis, Humans, Hypertension epidemiology, Male, Middle Aged, Prevalence, Risk Factors, Antiretroviral Therapy, Highly Active, Gout epidemiology, HIV Infections drug therapy
- Abstract
Gout is the most common inflammatory arthritis worldwide. Its principal risk factor is hyperuricaemia. While gout has been described in HIV patients and numerous more outdated anti-retroviral therapies (ARTs) have been implicated, there have been few recent studies. Our case-control study investigated the prevalence of and risk factors for gout in an established HIV cohort. Cases were identified from database searches using key search terms, with two age- and gender-matched controls. These were compared for demographic factors, co-morbidities, HIV factors and ART exposure. Forty-five cases with gout were identified (point prevalence 2.2%). All were male and were more likely than controls to be of black African origin. Hypertension was associated with an almost five-fold increased gout risk (OR 4.8, 95% CI 1.8-12.4). No individual drug or ART class was associated with gout in this study but exposure to non-nucleoside reverse transcriptase inhibitors had a significantly protective effect against the risk of gout (OR 0.3, 95% CI 0.1-0.9). Our data suggest that gout is common in HIV patients and that the traditional risk factors, especially hypertension, play a key role. Gout and hyperuricaemia should be regarded as a biomarker of cardiovascular disease in HIV patients as they are in the general population.
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- 2019
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7. UK diploma examinations in genitourinary and HIV medicine.
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Williams D, Churchill D, Richardson D, and Rodgers M
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- Humans, Societies, Medical, United Kingdom, Certification, HIV Infections, Sexual Health, Venereology education
- Abstract
Competing Interests: Competing interests: None declared.
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- 2019
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8. Assessment and management of musculoskeletal disorders among patients living with HIV.
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Walker-Bone K, Doherty E, Sanyal K, and Churchill D
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- Disease Management, Drug Interactions, HIV Infections drug therapy, Humans, Musculoskeletal Diseases diagnosis, Musculoskeletal Diseases drug therapy, Rheumatic Diseases diagnosis, Rheumatic Diseases drug therapy, Symptom Assessment, Anti-Retroviral Agents adverse effects, Antirheumatic Agents adverse effects, HIV Infections complications, Musculoskeletal Diseases virology, Rheumatic Diseases virology
- Abstract
HIV is a global pandemic. However, anti-retroviral therapy has transformed the prognosis and, providing compliance is good, a normal life expectancy can be anticipated. This has led to increasing numbers of people with chronic prevalent, treated infection living to older ages. Musculoskeletal pain is commonly reported by HIV patients and, with resumption of near-normal immune function, HIV-infected patients develop inflammatory rheumatic diseases that require assessment and management in rheumatology clinics. Moreover, it is becoming apparent that avascular necrosis and osteoporosis are common comorbidities of HIV. This review will contextualize the prevalence of musculoskeletal symptoms in HIV, informed by data from a UK-based clinic, and will discuss the management of active inflammatory rheumatic diseases among HIV-infected patients taking anti-retroviral therapy, highlighting known drug interactions., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Published
- 2017
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9. An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs.
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Smit E, White E, Clark D, Churchill D, Zhang H, Collins S, Pillay D, Sabin C, Nelson M, Winston A, Jose S, Tostevin A, and Dunn DT
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- Adult, Antiretroviral Therapy, Highly Active, Didanosine administration & dosage, Didanosine therapeutic use, Dideoxynucleosides administration & dosage, Dideoxynucleosides therapeutic use, Drug Resistance, Viral genetics, Female, Genetic Association Studies, Genotype, HIV Infections virology, HIV-1 classification, Humans, Male, Multivariate Analysis, Sequence Analysis, DNA, Stavudine administration & dosage, Stavudine therapeutic use, Tenofovir administration & dosage, Tenofovir therapeutic use, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, HIV-1 drug effects, HIV-1 genetics, Mutation, Reverse Transcriptase Inhibitors therapeutic use
- Abstract
Objectives: HIV-1 subtype C might have a greater propensity to develop K65R mutations in patients with virological failure compared with other subtypes. However, the strong association between viral subtype and confounding factors such as exposure groups and ethnicity affects the calculation of this propensity. We exploited the diversity of viral subtypes within the UK to undertake a direct comparative analysis., Patients and Methods: We analysed only sequences with major IAS-defined mutations from patients with virological failure. Prevalence of K65R was related to subtype and exposure to the NRTIs that primarily select for this mutation (tenofovir, abacavir, didanosine and stavudine). A multivariate logistic regression model quantified the effect of subtype on the prevalence of K65R, adjusting for previous and current exposure to all four specified drugs., Results: Subtype B patients ( n = 3410) were mostly MSM (78%) and those with subtype C ( n = 810) were mostly heterosexual (82%). K65R was detected in 7.8% of subtype B patients compared with 14.2% of subtype C patients. The subtype difference in K65R prevalence was observed irrespective of NRTI exposure and K65R was frequently selected by abacavir, didanosine and stavudine in patients with no previous exposure to tenofovir. Multivariate logistic regression confirmed that K65R was significantly more common in subtype C viruses (adjusted OR = 2.02, 95% CI = 1.55-2.62, P < 0.001)., Conclusions: Patients with subtype C HIV-1 have approximately double the frequency of K65R in our database compared with other subtypes. The exact clinical implications of this finding need to be further elucidated., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.)
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- 2017
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10. No Evidence That HIV-1 Subtype C Infection Compromises the Efficacy of Tenofovir-Containing Regimens: Cohort Study in the United Kingdom.
- Author
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White E, Smit E, Churchill D, Collins S, Booth C, Tostevin A, Sabin C, Pillay D, and Dunn DT
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- Adult, Cohort Studies, Drug Resistance, Viral drug effects, Drug Resistance, Viral genetics, Female, HIV-1 genetics, Humans, Male, Middle Aged, Mutation genetics, Treatment Failure, United Kingdom, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, HIV-1 drug effects, Reverse Transcriptase Inhibitors therapeutic use, Tenofovir therapeutic use
- Abstract
Concern has been expressed that tenofovir-containing regimens may have reduced effectiveness in the treatment of human immunodeficiency virus type 1 (HIV-1) subtype C infections because of a propensity for these viruses to develop a key tenofovir-associated resistance mutation. We evaluated whether subtype influenced rates of virological failure in a cohort of 8746 patients from the United Kingdom who received a standard tenofovir-containing first-line regimen and were followed for a median of 3.3 years. In unadjusted analyses, the rate of failure was approximately 2-fold higher among patients infected with subtype C virus as compared to those with subtype B virus (hazard ratio [HR], 1.86; 95% confidence interval [CI], 1.50-2.31; P < .001). However, the increased risk was greatly attenuated in analyses adjusting for demographic and clinical factors (adjusted HR, 1.14; 95% CI, .83-1.58; P = .41). There were no differences between subtypes C and subtypes non-B and non-C in either univariate or multivariate analysis. These observations imply there is no intrinsic effect of viral subtype on the efficacy of tenofovir-containing regimens., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.)
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- 2016
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11. British HIV Association guidelines for the treatment of HIV-1-positive adults with antiretroviral therapy 2015.
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Churchill D, Waters L, Ahmed N, Angus B, Boffito M, Bower M, Dunn D, Edwards S, Emerson C, Fidler S, Fisher M, Horne R, Khoo S, Leen C, Mackie N, Marshall N, Monteiro F, Nelson M, Orkin C, Palfreeman A, Pett S, Phillips A, Post F, Pozniak A, Reeves I, Sabin C, Trevelion R, Walsh J, Wilkins E, Williams I, and Winston A
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- Adult, HIV-1, Humans, United Kingdom, Anti-Retroviral Agents therapeutic use, Antiretroviral Therapy, Highly Active, HIV Infections drug therapy, Practice Guidelines as Topic
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- 2016
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12. Improved darunavir genotypic mutation score predicting treatment response for patients infected with HIV-1 subtype B and non-subtype B receiving a salvage regimen.
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De Luca A, Flandre P, Dunn D, Zazzi M, Wensing A, Santoro MM, Günthard HF, Wittkop L, Kordossis T, Garcia F, Castagna A, Cozzi-Lepri A, Churchill D, De Wit S, Brockmeyer NH, Imaz A, Mussini C, Obel N, Perno CF, Roca B, Reiss P, Schülter E, Torti C, van Sighem A, Zangerle R, and Descamps D
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- Adolescent, Adult, Aged, Aged, 80 and over, Anti-HIV Agents therapeutic use, Darunavir therapeutic use, Europe, Female, HIV Infections drug therapy, HIV Protease genetics, HIV-1 genetics, HIV-1 isolation & purification, Humans, Male, Microbial Sensitivity Tests methods, Middle Aged, Prognosis, Treatment Outcome, Young Adult, Anti-HIV Agents pharmacology, Darunavir pharmacology, Drug Resistance, Viral, Genotyping Techniques methods, HIV Infections virology, HIV-1 drug effects, Mutation
- Abstract
Objectives: The objective of this study was to improve the prediction of the impact of HIV-1 protease mutations in different viral subtypes on virological response to darunavir., Methods: Darunavir-containing treatment change episodes (TCEs) in patients previously failing PIs were selected from large European databases. HIV-1 subtype B-infected patients were used as the derivation dataset and HIV-1 non-B-infected patients were used as the validation dataset. The adjusted association of each mutation with week 8 HIV RNA change from baseline was analysed by linear regression. A prediction model was derived based on best subset least squares estimation with mutational weights corresponding to regression coefficients. Virological outcome prediction accuracy was compared with that from existing genotypic resistance interpretation systems (GISs) (ANRS 2013, Rega 9.1.0 and HIVdb 7.0)., Results: TCEs were selected from 681 subtype B-infected and 199 non-B-infected adults. Accompanying drugs were NRTIs in 87%, NNRTIs in 27% and raltegravir or maraviroc or enfuvirtide in 53%. The prediction model included weighted protease mutations, HIV RNA, CD4 and activity of accompanying drugs. The model's association with week 8 HIV RNA change in the subtype B (derivation) set was R(2) = 0.47 [average squared error (ASE) = 0.67, P < 10(-6)]; in the non-B (validation) set, ASE was 0.91. Accuracy investigated by means of area under the receiver operating characteristic curves with a binary response (above the threshold value of HIV RNA reduction) showed that our final model outperformed models with existing interpretation systems in both training and validation sets., Conclusions: A model with a new darunavir-weighted mutation score outperformed existing GISs in both B and non-B subtypes in predicting virological response to darunavir., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)
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- 2016
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13. British HIV Association guidelines for HIV-associated malignancies 2014.
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Bower M, Palfreeman A, Alfa-Wali M, Bunker C, Burns F, Churchill D, Collins S, Cwynarski K, Edwards S, Fields P, Fife K, Gallop-Evans E, Kassam S, Kulasegaram R, Lacey C, Marcus R, Montoto S, Nelson M, Newsom-Davis T, Orkin C, Shaw K, Tenant-Flowers M, Webb A, Westwell S, and Williams M
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- Female, HIV Infections complications, Humans, Immunotherapy, Lymphoma, AIDS-Related diagnosis, Lymphoma, AIDS-Related virology, Male, Neoplasm Staging, Prognosis, Referral and Consultation, Sarcoma, Kaposi diagnosis, Sarcoma, Kaposi virology, Uterine Cervical Neoplasms diagnosis, Uterine Cervical Neoplasms virology, Antiretroviral Therapy, Highly Active, HIV Infections therapy, Lymphoma, AIDS-Related therapy, Sarcoma, Kaposi therapy, Uterine Cervical Neoplasms therapy
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- 2014
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14. The emergence of drug resistant HIV variants at virological failure of HAART combinations containing efavirenz, tenofovir and lamivudine or emtricitabine within the UK Collaborative HIV Cohort.
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Bulteel N, Bansi-Matharu L, Churchill D, Dunn D, Bibby D, Hill T, Sabin C, and Nelson M
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- Adenine analogs & derivatives, Adenine pharmacology, Adenine therapeutic use, Adult, Alkynes, Anti-HIV Agents pharmacology, Antiretroviral Therapy, Highly Active, Benzoxazines pharmacology, Benzoxazines therapeutic use, Cohort Studies, Cyclopropanes, Deoxycytidine analogs & derivatives, Deoxycytidine pharmacology, Deoxycytidine therapeutic use, Drug Resistance, Viral drug effects, Drug Resistance, Viral genetics, Emtricitabine, Female, Humans, Lamivudine pharmacology, Lamivudine therapeutic use, Male, Middle Aged, Organophosphonates pharmacology, Organophosphonates therapeutic use, Tenofovir, Treatment Failure, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, HIV Infections virology, HIV-1 genetics
- Abstract
Background: Lamivudine (3TC) and emtricitabine (FTC) are guideline choices for combination highly active antiretroviral therapy (HAART). 3TC has a shorter intracellular half life than FTC and may be more likely to lead to the development of drug resistant HIV variants., Methods: In this study we analysed linked data from the observational UK Collaborative HIV Cohort (CHIC) Study and UK HIV Drug Resistance Database (HDRD) to investigate the rate of development of K65R or M184V resistance mutations in patients failing on combinations containing tenofovir (TDF) and efavirenz (EFV) with either 3TC or FTC. Virological failure was defined as 1 viral load >400 copies/ml. Rates were stratified by demographic variables, baseline viral load, current CD4 count, current viral load and year of starting regimen. Significant associations were identified using Poisson regression models and multivariable analyses were performed adjusting for the variables above. Logistic regression was used to determine whether there were any significant associations between type of regimen and detection of resistance mutation., Results: 5455 patients received either (or both) 3TC, TDF and EFV or FTC, TDF and EFV contributing 6465 treatment episodes over 9962 person-years follow up. 47 of these episodes were preceded by resistance tests showing development of K65R or M184V mutation and were hence excluded. The majority of treatment episodes consisted of FTC- (n = 5190) rather than 3TC- (n = 1228) based regimens. 21 cases of K65R were detected over the course of follow up, giving an overall event rate of 0.21 (95% CI: 0.12-0.31)/100 person years follow up (PYFU). The overall event rate for detection of M184V was 0.38 (95% CI: 0.26-0.5)/100 PYFU. 201 patients receiving either regimen for the first time experienced virological failure. Of those receiving 3TC (n = 53), 7 (13.2%), 12 (22.6%) and 15 (28.3%) developed K65R, M184V and either K65R or M184V respectively. Of those receiving FTC (n = 148), 13 (8.8%), 20 (13.5%) and 26 (17.6%) developed K65R, M184V and either K65R or M184V respectively. Although patients on 3TC were more likely to develop resistance, this was not statistically significant in univariable (OR 1.85 (95% CI: 0.89-3.85, p = 0.09)) or multivariable analyses (OR 1.89 (95% CI: 0.89-4.01, p = 0.1))., Conclusions: We have not found evidence of an increased risk of development of M184V and K65R in patients exposed to 3TC., (Copyright © 2013 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)
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- 2014
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15. British HIV Association guidelines for the treatment of HIV-1-positive adults with antiretroviral therapy 2012 (Updated November 2013. All changed text is cast in yellow highlight.).
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Williams I, Churchill D, Anderson J, Boffito M, Bower M, Cairns G, Cwynarski K, Edwards S, Fidler S, Fisher M, Freedman A, Geretti AM, Gilleece Y, Horne R, Johnson M, Khoo S, Leen C, Marshall N, Nelson M, Orkin C, Paton N, Phillips A, Post F, Pozniak A, Sabin C, Trevelion R, Ustianowski A, Walsh J, Waters L, Wilkins E, Winston A, and Youle M
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- Adult, Antiretroviral Therapy, Highly Active, Humans, United Kingdom, Anti-Retroviral Agents therapeutic use, HIV Infections drug therapy, HIV-1
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- 2014
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16. Older HIV-infected individuals present late and have a higher mortality: Brighton, UK cohort study.
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Iwuji CC, Churchill D, Gilleece Y, Weiss HA, and Fisher M
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- Aged, CD4 Lymphocyte Count, Cohort Studies, Delayed Diagnosis statistics & numerical data, Female, HIV Infections blood, HIV Infections diagnosis, Health Knowledge, Attitudes, Practice, Humans, Male, Middle Aged, United Kingdom epidemiology, HIV Infections mortality
- Abstract
Background: Initiating therapy with a low CD4 cell count is associated with a substantially greater risk of disease progression and death than earlier initiation. We examined factors associated with late presentation of HIV using the new European consensus definition (CD4 cell count <350 cells/mm3) and mortality., Methods: Patients newly diagnosed with HIV infection at a UK clinic were recruited from January 1996 to May 2010. Factors associated with late presentation were assessed using logistic regression. Factors associated with mortality rates were analysed using Poisson regression., Results: Of the 1536 included in the analysis, 86% were male and 10% were aged 50 years and older. Half the cohort (49%) had a CD4 cell count below 350 cells/mm3 at presentation ("late presentation"). The frequency of late presentation was highest in those aged 50 years or older and remained unchanged over time (64.3% in 1996-1998 and 65.4% in 2008-2010). In contrast, among those aged less than 50 years, the proportion with late presentation decreased over time (57.1% in 1996-1998 and 38.5% in 2008-2010). Other factors associated with late presentation were African ethnicity and being a male heterosexual.The mortality rate was 15.47/1000 person-years (pyrs) (95%-CI: 13.00-18.41). When compared with younger adults, older individuals had a higher mortality, after adjusting for confounders (rate ratio (RR) = 2.87; 95%-CI: 1.88-4.40)., Conclusions: Older adults were more likely to present late and had a higher mortality. Initiatives to expand HIV testing in clinical and community setting should not neglect individuals aged over 50.
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- 2013
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17. British HIV Association guidelines for the treatment of HIV-1-positive adults with antiretroviral therapy 2012.
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Williams I, Churchill D, Anderson J, Boffito M, Bower M, Cairns G, Cwynarski K, Edwards S, Fidler S, Fisher M, Freedman A, Geretti AM, Gilleece Y, Horne R, Johnson M, Khoo S, Leen C, Marshall N, Nelson M, Orkin C, Paton N, Phillips A, Post F, Pozniak A, Sabin C, Trevelion R, Ustianowski A, Walsh J, Waters L, Wilkins E, Winston A, and Youle M
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- Adult, Anti-Retroviral Agents therapeutic use, Humans, Societies, Medical, United Kingdom, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, HIV-1 drug effects
- Abstract
The overall purpose of these guidelines is to provide guidance on best clinical practice in the treatment and management of adults with HIV infection with antiretroviral therapy (ART). The scope includes: (i) guidance on the initiation of ART in those previously naïve to therapy; (ii)support of patients on treatment; (iii) management of patients experiencing virological failure; and (iv) recommendations in specific patient populations where other factors need to be taken into consideration. The guidelines are aimed at clinical professionals directly involved with and responsible for the care of adults with HIV infection and at community advocates responsible for promoting the best interests and care of HIV-positive adults. They should be read in conjunction with other published BHIVA guidelines.
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- 2012
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18. Time trends in drug resistant HIV-1 infections in the United Kingdom up to 2009: multicentre observational study.
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Dolling D, Sabin C, Delpech V, Smit E, Pozniak A, Asboe D, Brown AL, Churchill D, Williams I, Geretti AM, Phillips A, Mackie N, Murphy G, Castro H, Pillay D, Cane P, Dunn D, and Dolling D
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- Adolescent, Adult, Aged, Aged, 80 and over, Cohort Studies, Female, HIV Infections drug therapy, HIV Infections epidemiology, HIV-1 drug effects, Humans, Linear Models, Logistic Models, Male, Microbial Sensitivity Tests, Middle Aged, Mutation Rate, Prevalence, United Kingdom epidemiology, Young Adult, Anti-Retroviral Agents pharmacology, Anti-Retroviral Agents therapeutic use, Drug Resistance, Viral genetics, HIV Infections virology, HIV-1 genetics
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Objective: To evaluate whether the prevalence of HIV-1 transmitted drug resistance has continued to decline in infections probably acquired within the United Kingdom., Design: Multicentre observational study., Setting: All UK public laboratories conducting tests for genotypic HIV resistance as a part of routine care., Participants: 14,584 patients infected with HIV-1 subtype B virus, who were first tested for resistance before receiving antiretroviral therapy between January 2002 and December 2009., Main Outcome Measure: Prevalence of transmitted drug resistance, defined as one or more resistance mutations from the surveillance list recommended by the World Health Organization., Results: 1654 (11.3%, 95% confidence interval 10.8% to 11.9%) patients had one or more mutations associated with transmitted HIV-1 drug resistance; prevalence was found to decline from 15.5% in 2002 to 9.6% in 2007, followed by a slight increase to 10.9% in 2009 (P=0.21). This later rise was mainly a result of increases in resistance to nucleos(t)ide reverse transcriptase inhibitors (from 5.4% in 2007 to 6.6% in 2009, P=0.24) and protease inhibitors (1.5% to 2.1%, P=0.12). Thymidine analogue mutations, including T215 revertants, remained the most frequent mutations associated with nucleos(t)ide reverse transcriptase inhibitors, despite a considerable fall in stavudine and zidovudine use between 2002 and 2009 (from 29.4% of drug regimens in 2002 to 0.8% in 2009, from 47.9% to 8.8%, respectively)., Conclusions: The previously observed decline in the prevalence of transmitted drug resistance in HIV-1 infections probably acquired in the UK seems to have stabilised. The continued high prevalence of thymidine analogue mutations suggests that the source of this resistance may be increasingly from patients who have not undergone antiretroviral therapy and who harbour resistant viruses. Testing of all newly diagnosed HIV-1 positive people should be continued.
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- 2012
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19. A case of immune reconstitution syndrome: adult-onset Still's disease in a patient with HIV infection.
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Lawson E, Bond K, Churchill D, and Walker-Bone K
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- Adult, Anti-HIV Agents therapeutic use, Antiretroviral Therapy, Highly Active, Humans, Male, HIV Infections immunology, Immune Reconstitution Inflammatory Syndrome immunology, Still's Disease, Adult-Onset immunology
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- 2009
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20. British HIV Association Guidelines for the treatment of HIV-1-infected adults with antiretroviral therapy 2008.
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Gazzard BG, Anderson J, Babiker A, Boffito M, Brook G, Brough G, Churchill D, Cromarty B, Das S, Fisher M, Freedman A, Geretti AM, Johnson M, Khoo S, Leen C, Nair D, Peters B, Phillips A, Pillay D, Pozniak A, Walsh J, Wilkins E, Williams I, Williams M, and Youle M
- Subjects
- Anti-Retroviral Agents therapeutic use, Antiretroviral Therapy, Highly Active, Humans, Anti-Retroviral Agents administration & dosage, HIV Infections drug therapy, HIV-1
- Published
- 2008
- Full Text
- View/download PDF
21. Nucleoside analogues in 2008.
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Warwick Z and Churchill D
- Subjects
- Clinical Trials as Topic, Drug Therapy, Combination, HIV Infections virology, HIV-1 drug effects, Humans, Nucleosides adverse effects, Nucleosides therapeutic use, Treatment Outcome, Anti-HIV Agents adverse effects, Anti-HIV Agents chemistry, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, Nucleosides chemistry, Reverse Transcriptase Inhibitors adverse effects, Reverse Transcriptase Inhibitors chemistry, Reverse Transcriptase Inhibitors therapeutic use
- Published
- 2008
22. Population trends in the prevalence and patterns of protease resistance related to exposure to unboosted and boosted protease inhibitors.
- Author
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Dunn D, Geretti AM, Green H, Fearnhill E, Pozniak A, Churchill D, Pillay D, Sabin C, and Phillips A
- Subjects
- Cohort Studies, Cross-Sectional Studies, Databases, Factual, Genetic Testing, HIV enzymology, HIV genetics, HIV Infections virology, HIV Protease drug effects, Humans, Mutation, Prevalence, Treatment Outcome, United Kingdom epidemiology, Drug Resistance, Viral genetics, HIV drug effects, HIV Infections drug therapy, HIV Protease genetics, HIV Protease Inhibitors administration & dosage, Ritonavir administration & dosage
- Abstract
Background: In recent years, several new drugs from the protease inhibitor (PI) class designed to treat HIV infection have become available and the use of ritonavir-boosting has increased in popularity. These changes might be expected to affect the prevalence and patterns of protease resistance in the population of patients who experience treatment failure., Methods: The UK HIV Drug Resistance Database aims to capture the results of all genotypic resistance tests conducted nationally. Tests on antiretroviral therapy-experienced patients were identified through linkage with the UK Collaborative HIV Cohort Study, from which detailed clinical information on these patients, including a full antiretroviral therapy history, was obtained., Results: Analyses were on the basis of 8,553 genotypic resistance tests carried out between 1998 and 2005, during which time the overall prevalence of protease resistance halved from 35% to 16%. Substantial declines were observed regardless of whether the patient had been exposed to unboosted PIs and/or boosted PIs. The frequency of protease resistance among patients who had received boosted PIs fell sharply until 2002 with a weaker trend thereafter, falling to 12% in 2005. Individual mutations L33F, M461/L, V82A/F/T/S/L and 184V became relatively more frequent over the period of study., Conclusions: The decline in protease resistance was partly due to increasing use of ritonavir-boosting. Nonetheless, the prevalence of resistance was higher than suggested by clinical trials, indicating that prolonged exposure to a boosted PI could ultimately select for major protease mutations.
- Published
- 2008
23. Primary pneumococcal peritonitis as a presenting feature of HIV infection.
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Alifrangis C, Thompson P, Thwaites G, and Churchill D
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- Adult, Female, Humans, Pneumococcal Infections pathology, HIV, HIV Infections microbiology, Peritonitis microbiology, Peritonitis virology, Pneumococcal Infections virology, Streptococcus pneumoniae isolation & purification
- Abstract
We report a case of primary pneumococcal peritonitis in a 28-year old previously healthy woman. There are no previously reported associations between this rare form of spontaneous peritonitis and HIV infection, and it is usually associated with underlying cirrhosis, ascites or other immune compromise. In this case this was the presenting illness of HIV infection. When atypical infections such as this arise in previously healthy adults the clinician must have a high index of suspicion of HIV or other underlying immunodeficiency.
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- 2006
- Full Text
- View/download PDF
24. Long term probability of detection of HIV-1 drug resistance after starting antiretroviral therapy in routine clinical practice.
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Phillips AN, Dunn D, Sabin C, Pozniak A, Matthias R, Geretti AM, Clarke J, Churchill D, Williams I, Hill T, Green H, Porter K, Scullard G, Johnson M, Easterbrook P, Gilson R, Fisher M, Loveday C, Gazzard B, and Pillay D
- Subjects
- Adult, Cohort Studies, Dideoxynucleosides therapeutic use, Drug Resistance, Viral, Drug Therapy, Combination, Female, HIV Protease Inhibitors therapeutic use, HIV-1 genetics, Humans, Male, Mutation genetics, Reverse Transcriptase Inhibitors therapeutic use, Risk Factors, Ritonavir therapeutic use, Time Factors, Viral Load, Anti-Retroviral Agents therapeutic use, HIV Infections drug therapy, HIV-1 drug effects
- Abstract
Background: Little is known about the long term risk of development of HIV-1 drug resistance for patients starting antiretroviral therapy (ART) with three or four drug regimens in routine clinical practice., Methods: We analysed a large cohort study of patients seen in one of six large HIV clinics in and around London, UK. The focus of this analysis was on patients who started ART with two nucleosides plus either a single protease inhibitor (PI), a PI with ritonavir, abacavir or a non-nucleoside reverse transcriptase inhibitor (NNRTI)., Results: 4306 patients were followed; 1436 (33%) started with a single PI, 279 (6%) with a PI plus ritonavir, 156 (4%) with triple nucleosides and 2435 (57%) with an NNRTI. The overall cumulative risk of viral load failure was 38% by 6 years. Risk of > or =1 major IAS-USA mutation was 27% by 6 years; risk of mutations from at least two of the three main drug classes was 20% over the same period. These are lower limit estimates as test results were not available for many with viral load failure. Risk of PI mutations being detected in people who started ART with regimens containing a PI with ritonavir was significantly lower than the risk of NNRTI mutations being detected in those starting with NNRTI-containing regimens (relative hazard 0.3195% CI 0.15-0.61; p = 0.0008)., Conclusion: In routine practice, rates of viral load failure and of resistance detection in patients who started ART with three or four drugs are appreciable.
- Published
- 2005
- Full Text
- View/download PDF
25. Characteristics of autoimmune thyroid disease occurring as a late complication of immune reconstitution in patients with advanced human immunodeficiency virus (HIV) disease.
- Author
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Chen F, Day SL, Metcalfe RA, Sethi G, Kapembwa MS, Brook MG, Churchill D, de Ruiter A, Robinson S, Lacey CJ, and Weetman AP
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- Adult, Autoantibodies blood, CD4 Lymphocyte Count, Cohort Studies, Female, Graves Disease diagnosis, Humans, Leukocyte Common Antigens analysis, Male, Middle Aged, Receptors, Thyrotropin immunology, Antiretroviral Therapy, Highly Active adverse effects, Graves Disease etiology, HIV Infections drug therapy
- Abstract
Experimental evidence from animal models has provided a framework for our current understanding of autoimmune disease pathogenesis and supports the importance of genetic predisposition, molecular mimicry, and immune dysregulation. However, only recently has evidence emerged to support the role of immune dysregulation in human organ-specific autoimmune disease. In the current study of the "late" manifestation of autoimmune thyroid disease (AITD) in a cohort of human immunodeficiency virus (HIV)-positive patients following highly active antiretroviral therapy (HAART), we discuss how immune dysregulation and factors associated with the immunopathology of HIV infection fit the current understanding of autoimmunity and provide a plausible basis for our clinical observations. De novo diagnoses of thyroid disease were identified between 1996 and 2002 in 7 HIV treatment centers (5/7 centers completed the study). Patients were diagnosed as clinical case entities and not discovered through thyroid function test screening. Paired plasma specimens were used to demonstrate sequential rise in thyroid antibodies. Seventeen patients were diagnosed with AITD (median age, 38 yr; 65% were of black African or black Caribbean ethnicity; and 82% were female). The median duration of immune reconstitution was 17 months. Graves disease (GD) was diagnosed in 15 of 17 patients. One patient developed hashithyrotoxicosis with atypically raised C-reactive protein, and another developed hypothyroidism. One GD patient had associated secondary hypoadrenalism. The estimated combined prevalence of GD for 4 treatment centers for female patients was 7/234 and for males was 2/1289. The denominator numbers were matched controls, from 4 centers able to provide data, who commenced HAART during the same time (January 1996 to July 2002) and who did not develop clinical AITD. The mean baseline pre-HAART CD4 count was 67 cells/mL, and the mean increase from nadir to AITD presentation was 355 cells/mL. AITD patients were more likely than controls (95% confidence interval, chi-square test) to be severely compromised at baseline (as defined by a CD4 count < 200 cells/mL or the presence of an acquired immunodeficiency syndrome [AIDS]-defining diagnosis), and to experience greater CD4 increments following HAART. AITD may be a late manifestation of immune reconstitution in HIV-positive patients taking HAART, and immune dysregulation may be an important factor.
- Published
- 2005
- Full Text
- View/download PDF
26. Low frequency of genotypic resistance in HIV-1-infected patients failing an atazanavir-containing regimen: a clinical cohort study
- Author
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Dolling, David I, Dunn, David T, Sutherland, Katherine A, Pillay, Deenan, Mbisa, Jean L, Parry, Chris M, Post, Frank A, Sabin, Caroline A, Cane, Patricia A, Aitken, Celia, Asboe, David, Webster, Daniel, Cane, Patricia, Castro, Hannah, Dunn, David, Dolling, David, Chadwick, David, Churchill, Duncan, Clark, Duncan, Collins, Simon, Delpech, Valerie, Geretti, Anna Maria, Goldberg, David, Hale, Antony, Hué, Stéphane, Kaye, Steve, Kellam, Paul, Lazarus, Linda, Leigh-Brown, Andrew, Mackie, Nicola, Orkin, Chloe, Rice, Philip, Phillips, Andrew, Sabin, Caroline, Smit, Erasmus, Templeton, Kate, Tilston, Peter, Tong, William, Williams, Ian, Zhang, Hongyi, Zuckerman, Mark, Greatorex, Jane, Wildfire, Adrian, O'Shea, Siobhan, Mullen, Jane, Mbisa, Tamyo, Cox, Alison, Tandy, Richard, Hale, Tony, Fawcett, Tracy, Hopkins, Mark, Ashton, Lynn, Booth, Claire, Garcia-Diaz, Ana, Shepherd, Jill, Schmid, Matthias L, Payne, Brendan, Hay, Phillip, Rice, Phillip, Paynter, Mary, Bibby, David, Kirk, Stuart, MacLean, Alasdair, Gunson, Rory, Coughlin, Kate, Fearnhill, Esther, Fradette, Lorraine, Porter, Kholoud, Ainsworth, Jonathan, Anderson, Jane, Babiker, Abdel, Fisher, Martin, Gazzard, Brian, Gilson, Richard, Gompels, Mark, Hill, Teresa, Johnson, Margaret, Kegg, Stephen, Leen, Clifford, Nelson, Mark, Palfreeman, Adrian, Post, Frank, Sachikonye, Memory, Schwenk, Achim, Walsh, John, Huntington, Susie, Jose, Sophie, Thornton, Alicia, Glabay, Adam, Orkin, C, Garrett, N, Lynch, J, Hand, J, de Souza, C, Fisher, M, Perry, N, Tilbury, S, Gazzard, B, and Nelson, M
- Subjects
Medical Microbiology ,Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Trials and Supportive Activities ,Infectious Diseases ,Antimicrobial Resistance ,Clinical Research ,Infection ,Adult ,Anti-HIV Agents ,Atazanavir Sulfate ,Cohort Studies ,Drug Resistance ,Viral ,Female ,HIV Infections ,HIV Protease ,HIV-1 ,Humans ,Male ,Medication Adherence ,Middle Aged ,Mutation Rate ,Mutation ,Missense ,Oligopeptides ,Pyridines ,Treatment Failure ,United States ,UK HIV Drug Resistance Database ,UK Collaborative HIV Cohort Study ,HIV ,drug resistance mutations ,naive patients ,protease inhibitors ,virological failure ,Microbiology ,Pharmacology and Pharmaceutical Sciences ,Clinical sciences ,Pharmacology and pharmaceutical sciences - Abstract
ObjectivesTo determine protease mutations that develop at viral failure for protease inhibitor (PI)-naive patients on a regimen containing the PI atazanavir.MethodsResistance tests on patients failing atazanavir, conducted as part of routine clinical care in a multicentre observational study, were randomly matched by subtype to resistance tests from PI-naive controls to account for natural polymorphisms. Mutations from the consensus B sequence across the protease region were analysed for association and defined using the IAS-USA 2011 classification list.ResultsFour hundred and five of 2528 (16%) patients failed therapy containing atazanavir as a first PI over a median (IQR) follow-up of 1.76 (0.84-3.15) years and 322 resistance tests were available for analysis. Recognized major atazanavir mutations were found in six atazanavir-experienced patients (P < 0.001), including I50L and N88S. The minor mutations most strongly associated with atazanavir experience were M36I, M46I, F53L, A71V, V82T and I85V (P < 0.05). Multiple novel mutations, I15S, L19T, K43T, L63P/V, K70Q, V77I and L89I/T/V, were also associated with atazanavir experience.ConclusionsViral failure on atazanavir-containing regimens was not common and major resistance mutations were rare, suggesting that adherence may be a major contributor to viral failure. Novel mutations were described that have not been previously documented.
- Published
- 2013
27. Virological failure and development of new resistance mutations according to CD4 count at combination antiretroviral therapy initiation
- Author
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Jose, S., Quinn, K., Dunn, D., Cox, A., Sabin, C., Fidler, S., Fisher, Martin, Gazzard, Brian, Gilson, Richard, Gompels, Mark, Hay, Phillip, Johnson, Margaret, Kegg, Stephen, Leen, C., Martin, Fabiola, Nelson, Mark, Palfreeman, Adrian, Post, F., Pritchard, Jillian, Sachikonye, Memory, Schwenk, Achim, Tariq, Anjum, Walsh, John, Hill, Teresa, Jose, Sophie, Phillips, Andrew, Sabin, Caroline, Thornton, Alicia, Dunn, David, Glabay, Adam, Fisher, M., Perry, N., Tilbury, S., Youssef, E., Churchill, D., Gazzard, B., Nelson, M., Everett, R., Asboe, D., Mandalia, S., Korat, H., Taylor, C., Gleisner, Z., Ibrahim, F., Campbell, L., Gilson, R., Brima, N., Williams, I., Johnson, M., Youle, M., Lampe, F., Smith, C., Tsintas, R., Chaloner, C., Hutchinson, S., Phillips, A., Hill, T., Thornton, A., Huntington, S., Walsh, J., Mackie, N., Winston, A., Weber, J., Ramzan, F., Carder, M., Orkin, C., Lynch, J., Hand, J., de Souza, C., Anderson, J., Munshi, S., Ainsworth, J., Schwenk, A., Miller, S., Wood, C., Wilson, A., Morris, S., Gompels, M., Allan, S., Palfreeman, A., Memon, K., Lewszuk, A., Chadwick, D., Cope, E., Gibson, J., Kegg, S., Main, P., Mitchell, Hunter, Hay, P., Dhillon, M., Martin, F., Russell-Sharpe, S., Harte, A., Clay, S., Tariq, A., Spencer, H., Jones, R., Pritchard, J., Cumming, S., Atkinson, C., Delpech, Valerie, Sachikony, M., Aitken, Celia, Asboe, David, Pozniak, Anton, Cane, Patricia, Chadwick, David, Churchill, Duncan, Clark, Duncan, Collins, Simon, Douthwaite, Samuel, Fearnhill, Esther, Porter, Kholoud, Tostevin, Anna, White, Ellen, Fraser, Christophe, Geretti, Anna Maria, Hale, Antony, Hué, Stéphane, Kaye, Steve, Kellam, Paul, Lazarus, Linda, Leigh-Brown, Andrew, Mbisa, Tamyo, Mackie, Nicola, Moses, Samuel, Orkin, Chloe, Nastouli, Eleni, Pillay, Deenan, Smit, Erasmus, Templeton, Kate, Tilston, Peter, Webster, Daniel, Williams, Ian, Zhang, Hongyi, Greatorex, Jane, O'Shea, Siobhan, Mullen, Jane, Cox, Alison, Tandy, Richard, Fawcett, Tracy, Hopkins, Mark, Ashton, Lynn, Booth, Claire, Garcia-Diaz, Ana, Shepherd, Jill, Schmid, Matthias L., Payne, Brendan, Pereira, Spiro, Hubb, Jonathan, Kirk, Stuart, Gunson, Rory, Bradley-Stewart, Amanda, and Medical Research Council (MRC)
- Subjects
0301 basic medicine ,Male ,HAART ,HIV Infections ,Treatment failure ,law.invention ,0302 clinical medicine ,Randomized controlled trial ,law ,Antiretroviral Therapy, Highly Active ,Pharmacology (medical) ,030212 general & internal medicine ,Treatment Failure ,virological failure ,Health Policy ,UK CHIC and UK HDRD Steering Committees ,Virological failure ,3. Good health ,Antiretroviral therapy ,Patient benefit ,Infectious Diseases ,Female ,medicine.symptom ,Life Sciences & Biomedicine ,Viral load ,Cart ,medicine.medical_specialty ,Anti-HIV Agents ,Short Communication ,antiretroviral therapy ,CD4 count ,Asymptomatic ,03 medical and health sciences ,HIV-INFECTION ,Virology ,Internal medicine ,Drug Resistance, Viral ,medicine ,Humans ,Science & Technology ,business.industry ,HIV resistance ,1103 Clinical Sciences ,030112 virology ,CD4 Lymphocyte Count ,Immunology ,Mutation ,business - Abstract
Objectives No randomized controlled trials have yet reported an individual patient benefit of initiating combination antiretroviral therapy (cART) at CD4 counts > 350 cells/μL. It is hypothesized that earlier initiation of cART in asymptomatic and otherwise healthy individuals may lead to poorer adherence and subsequently higher rates of resistance development. Methods In a large cohort of HIV-positive individuals, we investigated the emergence of new resistance mutations upon virological treatment failure according to the CD4 count at the initiation of cART. Results Of 7918 included individuals, 6514 (82.3%), 996 (12.6%) and 408 (5.2%) started cART with a CD4 count ≤ 350, 351–499 and ≥ 500 cells/μL, respectively. Virological rebound occurred while on cART in 488 (7.5%), 46 (4.6%) and 30 (7.4%) with a baseline CD4 count ≤ 350, 351–499 and ≥ 500 cells/μL, respectively. Only four (13.0%) individuals with a baseline CD4 count > 350 cells/μL in receipt of a resistance test at viral load rebound were found to have developed new resistance mutations. This compared to 107 (41.2%) of those with virological failure who had initiated cART with a CD4 count
- Published
- 2015
28. Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV‐1 resistance mutation.
- Author
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Stirrup, OT, Asboe, D, Pozniak, A, Sabin, CA, Gilson, R, Mackie, NE, Tostevin, A, Hill, T, Dunn, DT, Chadwick, David, Churchill, Duncan, Clark, Duncan, Collins, Simon, Delpech, Valerie, Douthwaite, Samuel, Fearnhill, Esther, Porter, Kholoud, Fraser, Christophe, Geretti, Anna Maria, and Gunson, Rory
- Subjects
COMBINATION drug therapy ,DRUG resistance ,HIV infections ,HIV-positive persons ,GENETIC mutation ,POISSON distribution ,TREATMENT effectiveness ,PROPORTIONAL hazards models ,LAMIVUDINE ,EMTRICITABINE ,STATISTICAL models ,THERAPEUTICS - Abstract
Objectives: The aim of the study was to investigate whether lamivudine (3TC) or emtricitabine (FTC) use following detection of M184V/I is associated with better virological outcomes. Methods: We identified people with viruses harbouring the M184V/I mutation in UK multicentre data sets who had treatment change/initiation within 1 year. We analysed outcomes of viral suppression (< 200 HIV‐1 RNA copies/mL) and appearance of new major drug resistance mutations (DRMs) using Cox and Poisson models, with stratification by new drug regimen (excluding 3TC/FTC) and Bayesian implementation, and estimated the effect of 3TC/FTC adjusted for individual and viral characteristics. Results: We included 2597 people with the M184V/I resistance mutation, of whom 665 (25.6%) were on 3TC and 458 (17.6%) on FTC. We found a negative adjusted association between 3TC/FTC use and viral suppression [hazard ratio (HR) 0.84; 95% credibility interval (CrI) 0.71–0.98]. On subgroup analysis of individual drugs, there was no evidence of an association with viral suppression for 3TC (n = 184; HR 0.94; 95% CrI 0.73–1.15) or FTC (n = 454; HR 0.99; 95% CrI 0.80–1.19) amongst those on tenofovir‐containing regimens, but we estimated a reduced rate of viral suppression for people on 3TC amongst those without tenofovir use (n = 481; HR 0.71; 95% CrI 0.54–0.90). We found no association between 3TC/FTC and detection of any new DRM (overall HR 0.92; 95% CrI 0.64–1.18), but found inconclusive evidence of a lower incidence rate of new DRMs (overall incidence rate ratio 0.69; 95% CrI 0.34–1.11). Conclusions: We did not find evidence that 3TC or FTC use is associated with an increase in viral suppression, but it may reduce the appearance of additional DRMs in people with M184V/I. 3TC was associated with reduced viral suppression amongst people on regimens without tenofovir. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
29. Reasons For Increased Incidence Of Tuberculosis
- Author
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Pym, Alexander S., Churchill, Duncan R., Coker, Richard J., Gleissberg, Virginia, Hayward, A., Bruce, J., Kumar, D., and Charlett, A.
- Published
- 1995
30. A Case-Control Study of Elective Hip Surgery among HIV-Infected Patients: Exposure to Systemic Glucocorticoids Significantly Increases the Risk
- Author
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Kerr, Elizabeth, Middleton, Annie, Churchill, Duncan, and Walker-Bone, Karen
- Subjects
Adult ,Male ,Arthroplasty, Replacement, Hip ,Osteonecrosis ,HIV Infections ,Comorbidity ,Middle Aged ,Article ,Osteoarthritis, Hip ,Cross-Sectional Studies ,Risk Factors ,Case-Control Studies ,Humans ,Female ,Glucocorticoids - Abstract
This was a cross-sectional study with a nested case-control analysis among a cohort of HIV-infected adults aiming to explore the prevalence of and risk factors for elective hip surgery (total hip arthroplasty and resurfacing).Cases were identified from the out-patient database of HIV-infected adults attending one tertiary hospital service. For each case, five controls from the same database matched by age, gender and ethnicity were identified. From the case notes, information about demographic factors, HIV factors and risk factors for hip surgery attributable to osteoarthritis or avascular necrosis (body mass index, lipids, alcohol, comorbidities and treatment with oral glucocorticoids) was extracted.Among the cohort of 1900 HIV-infected out-patients, 13 cases (12 male) who had undergone hip surgery [0.7%; 95% confidence interval (CI) 0.3-1.1%] were identified, with a median age of 47 years. Eleven of the 13 cases (85%) were Caucasian and seven of the 13 were in stage 3 of HIV infection. Fewer of the cases were in the asymptomatic stage of infection compared with controls [odds ratio (OR) for stage 2 or 3 infection 4.0; 95% CI 0.8-18.5]. Ever having used oral glucocorticoids was highly significantly associated with elective hip surgery (OR 44.6; 95% CI 5.7-347.7).Among this young cohort, the prevalence of elective hip surgery was 0.7%, with the median age at surgery being 47 years. Ever having been exposed to systemic glucocorticoids was highly significantly associated with elective hip surgery, suggesting that the principal mechanism underlying the need for surgery was avascular necrosis. There may be an increased need for elective hip surgery associated with HIV infection.
- Published
- 2013
31. Vancouver: optimism, but at a cost.
- Author
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Churchill, Duncan, Pym, Alex, Coker, Richard, Churchill, D, Pym, A, and Coker, R
- Subjects
CONFERENCES & conventions ,AIDS ,HIV infections ,THERAPEUTICS - Abstract
The article reports on the outcome of the International Conferences on AIDS in Vancouver, British Columbia. In contrast to the past conferences in Berlin, Germany and Yokohama, Japan, there was a feeling of optimism pervading proceedings in Vancouver. Many felt that in the 2 years since Yokohama, real progress had been made both in the understanding of the pathogenesis of HIV infection and in the development of specific therapies for people infected with HIV.
- Published
- 1996
- Full Text
- View/download PDF
32. Low frequency of genotypic resistance in HIV-1-infected patients failing an atazanavir-containing regimen: a clinical cohort study
- Author
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Dolling, David I., Dunn, David T., Sutherland, Katherine A., Pillay, Deenan, Mbisa, Jean L., Parry, Chris M., Post, Frank A., Sabin, Caroline A., Cane, Patricia A., Aitken, Celia, Asboe, David, Webster, Daniel, Cane, Patricia, Castro, Hannah, Dunn, David, Dolling, David, Chadwick, David, Churchill, Duncan, Clark, Duncan, Collins, Simon, Delpech, Valerie, Geretti, Anna Maria, Goldberg, David, Hale, Antony, Hué, Stéphane, Kaye, Steve, Kellam, Paul, Lazarus, Linda, Leigh-Brown, Andrew, Mackie, Nicola, Orkin, Chloe, Rice, Philip, Phillips, Andrew, Sabin, Caroline, Smit, Erasmus, Templeton, Kate, Tilston, Peter, Tong, William, Williams, Ian, Zhang, Hongyi, Zuckerman, Mark, Greatorex, Jane, Wildfire, Adrian, O'Shea, Siobhan, Mullen, Jane, Mbisa, Tamyo, Cox, Alison, Tandy, Richard, Hale, Tony, Fawcett, Tracy, Hopkins, Mark, Ashton, Lynn, Booth, Claire, Garcia-Diaz, Ana, Shepherd, Jill, Schmid, Matthias L., Payne, Brendan, Hay, Phillip, Rice, Phillip, Paynter, Mary, Bibby, David, Kirk, Stuart, MacLean, Alasdair, Gunson, Rory, Coughlin, Kate, Fearnhill, Esther, Fradette, Lorraine, Porter, Kholoud, Ainsworth, Jonathan, Anderson, Jane, Babiker, Abdel, Fisher, Martin, Gazzard, Brian, Gilson, Richard, Gompels, Mark, Hill, Teresa, Johnson, Margaret, Kegg, Stephen, Leen, Clifford, Nelson, Mark, Palfreeman, Adrian, Post, Frank, Sachikonye, Memory, Schwenk, Achim, Walsh, John, Huntington, Susie, Jose, Sophie, Thornton, Alicia, Glabay, Adam, Orkin, C., Garrett, N., Lynch, J., Hand, J., de Souza, C., Fisher, M., Perry, N., Tilbury, S., Gazzard, B., Nelson, M., Waxman, M., Asboe, D., Mandalia, S., Delpech, V., Anderson, J., Munshi, S., Korat, H., Welch, J., Poulton, M., MacDonald, C., Gleisner, Z., Campbell, L., Gilson, R., Brima, N., Williams, I., Schwenk, A., Ainsworth, J., Wood, C., Miller, S., Johnson, M., Youle, M., Lampe, F., Smith, C., Grabowska, H., Chaloner, C., Puradiredja, D., Walsh, J., Weber, J., Ramzan, F., Mackie, N., Winston, A., Leen, C., Wilson, A., Allan, S., Palfreeman, A., Moore, A., and Wakeman, K.
- Subjects
Male ,Mutation rate ,Pyridines ,Human immunodeficiency virus (HIV) ,HIV Infections ,medicine.disease_cause ,THERAPY ,Cohort Studies ,0302 clinical medicine ,HIV Protease ,Mutation Rate ,1108 Medical Microbiology ,Genotype ,Pharmacology (medical) ,030212 general & internal medicine ,Pharmacology & Pharmacy ,Treatment Failure ,drug resistance mutations ,Original Research ,0303 health sciences ,virological failure ,UK Collaborative HIV Cohort Study (UK CHIC) ,Proteolytic enzymes ,virus diseases ,Middle Aged ,3. Good health ,Infectious Diseases ,Female ,1115 Pharmacology and Pharmaceutical Sciences ,Life Sciences & Biomedicine ,Oligopeptides ,medicine.drug ,Cohort study ,0605 Microbiology ,Microbiology (medical) ,Adult ,medicine.medical_specialty ,Anti-HIV Agents ,Atazanavir Sulfate ,protease inhibitors ,Mutation, Missense ,RITONAVIR ,Biology ,Microbiology ,Medication Adherence ,03 medical and health sciences ,Internal medicine ,SCORE ,Drug Resistance, Viral ,medicine ,Humans ,030304 developmental biology ,Pharmacology ,Science & Technology ,HIV ,Virology ,naive patients ,United States ,Atazanavir ,Regimen ,HIV-1 ,Ritonavir ,UK HIV Drug Resistance Database (UKHDRD) - Abstract
Author(s): Dolling, David I; Dunn, David T; Sutherland, Katherine A; Pillay, Deenan; Mbisa, Jean L; Parry, Chris M; Post, Frank A; Sabin, Caroline A; Cane, Patricia A; UK HIV Drug Resistance Database (UKHDRD); UK Collaborative HIV Cohort Study (UK CHIC) | Abstract: ObjectivesTo determine protease mutations that develop at viral failure for protease inhibitor (PI)-naive patients on a regimen containing the PI atazanavir.MethodsResistance tests on patients failing atazanavir, conducted as part of routine clinical care in a multicentre observational study, were randomly matched by subtype to resistance tests from PI-naive controls to account for natural polymorphisms. Mutations from the consensus B sequence across the protease region were analysed for association and defined using the IAS-USA 2011 classification list.ResultsFour hundred and five of 2528 (16%) patients failed therapy containing atazanavir as a first PI over a median (IQR) follow-up of 1.76 (0.84-3.15) years and 322 resistance tests were available for analysis. Recognized major atazanavir mutations were found in six atazanavir-experienced patients (P l 0.001), including I50L and N88S. The minor mutations most strongly associated with atazanavir experience were M36I, M46I, F53L, A71V, V82T and I85V (P l 0.05). Multiple novel mutations, I15S, L19T, K43T, L63P/V, K70Q, V77I and L89I/T/V, were also associated with atazanavir experience.ConclusionsViral failure on atazanavir-containing regimens was not common and major resistance mutations were rare, suggesting that adherence may be a major contributor to viral failure. Novel mutations were described that have not been previously documented.
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