Publications (14)76.26 Total impact
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Article: Effects of age on antiretroviral plasma drug concentration in HIV-infected subjects undergoing routine therapeutic drug monitoring.
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ABSTRACT: OBJECTIVES: The pharmacokinetic and pharmacodynamic effects of antiretroviral therapy may differ in older compared with younger subjects with HIV infection. We aimed to assess factors associated with plasma antiretroviral drug exposure, including age, within a large HIV-infected cohort undergoing therapeutic drug monitoring (TDM). METHODS: Data from the Liverpool TDM Registry were linked with the UK Collaborative HIV Cohort (CHIC) Study. All TDM of protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) was included and in order to account for different antiretroviral drugs the plasma concentrations were standardized by group measurements according to drug, dosing and timing of TDM. Regression modelling was used to evaluate associations of drug exposure with age and clinical parameters, including hepatic transaminase results and time to antiretroviral treatment modification. RESULTS: Data from 3589 TDM samples were available from 2447 subjects. The greatest numbers of plasma concentrations were assessed for lopinavir (22.4%), efavirenz (18.5%), atazanavir (17.0%) and saquinavir (11.6%). As age increased, median standardized NNRTI concentrations remained constant, whereas PI concentrations increased (correlation coefficient 0.04, P = 0.033). In a regression analysis stratified by antiretroviral drug class, standardized plasma concentrations were significantly associated with age for PIs (0.05 increase in standard deviation of drug concentration with each 10 year increase in age, P = 0.044), but not for NNRTIs or other clinical parameters, including hepatic transaminase results or time to antiretroviral treatment modification. CONCLUSIONS: With increasing age, statistically significant rises in plasma PI exposure, but not NNRTI exposure, were observed. The clinical relevance of this observation merits further investigation.Journal of Antimicrobial Chemotherapy 02/2013; · 5.07 Impact Factor -
Article: Platelet count kinetics following Interruption of antiretroviral treatment: Results from the SMART study.
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ABSTRACT: OBJECTIVES:: To investigate the mechanisms of platelet kinetics in the SMART study that demonstrated excess mortality with CD4 guided episodic antiretroviral therapy (ART) (drug conservation [DC]) compared to continuous treatment (viral suppression [VS]). Follow up analyses of stored plasma samples demonstrated increased activation of both inflammatory and coagulation pathways after stopping ART. DESIGN:: SMART patients from sites that determined platelets routinely. METHODS:: Platelet counts were retrospectively collected from 2206 patients from visits at study entry, and during follow-up. D-dimer levels were measured at study entry, month 1, and 2. RESULTS:: Platelet levels decreased in the DC group following randomization, but remained stable in the VS group [median (IQR) decline from study entry to month 4: -24,000/μL(-54,000-4,000) vs. 3000 (-22,000-24,000), respectively, p < 0.0001)] and the rate of developing thrombocytopenia (<100,000/μL) was significantly higher in the DC versus the VS arm (unadjusted DC/VS HR (95%CI) = 1.8 (1.2-2.7)). The decline in platelet count among DC participants on fully suppressive ART correlated with the rise in D-dimer from baseline to either month 1 or 2 (r = -0.41; p = 0.02). Among DC participants who resumed ART 74% recovered to their study entry platelet levels. CONCLUSION:: Interrupting ART increases the risk of thrombocytopenia, but re-initiation of ART typically reverses it. Factors contributing to declines in platelets after interrupting ART may include activation of coagulation pathways or HIV-1 replication itself. The contribution of platelets in HIV-related pro-coagulant activity requires further study.AIDS (London, England) 09/2012; · 4.91 Impact Factor -
Article: Increasing uptake of HIV tests in men who have sex with men.
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ABSTRACT: In 2010, just under half of new HIV diagnoses in the UK were in men who have sex with men (MSM). This group are most at risk of acquiring and transmitting HIV in the UK. In March 2011, NICE published guidance specifically aimed at increasing uptake of HIV testing in MSM, because of the high levels of infection, high levels of recent acquisition of HIV infection and continued high-risk behaviour in this group. Delayed diagnosis of HIV confers a poor prognosis: 73% of the 516 patients with HIV who died in 2009 had been diagnosed late. An estimated 39% of MSM in 2009 were diagnosed when their immune system was below the threshold at which antiretroviral treatment should be commenced. Many of these men had seen their own GP with signs and symptoms of HIV and the opportunity to make the diagnosis had been missed. One of the most important indicators is primary HIV infection. This seroconversion illness presents with a flu-like illness often lasting more than two weeks with a rash, sore throat and lymphadenopathy. An HIV test should be performed straightaway on all MSM presenting with these features. The benefits of increased testing and early diagnosis include reduced mortality and morbidity related to HIV and the potential to reduce onward transmission. NICE recommends that MSM have HIV tests at least annually as part of routine care, and additionally if the patient: has a new sexual partner has high-risk sexual intercourse; is diagnosed with another STI; requests a sexual health screen; or presents with an HIV indicator disease.The Practitioner 04/2011; 255(1739):25-8, 3. -
Article: Diagnosis and management of HIV infection.
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ABSTRACT: Infection with human immunodeficiency virus (HIV) is now increasingly common in the UK, but the diagnosis is often missed or overlooked. This article summarizes who to test and how best to offer testing to patients in whom HIV testing is clinically indicated.British journal of hospital medicine (London, England: 2005) 03/2011; 72(3):146-50. · 0.19 Impact Factor -
Article: Outcomes in the first year after initiation of first-line HAART among heterosexual men and women in the UK CHIC Study.
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ABSTRACT: We analysed the influence of gender on use and outcomes of first-line HAART in a UK cohort. Analyses included heterosexuals starting HAART from 1998-2007 with pre-treatment CD4(+) T-cell count<350 cells/mm(3) and viral load (VL)>500 copies/ml. Virological suppression (<50 copies/ml), virological rebound (>500 copies/ml), CD4(+) T-cell counts at 6 and 12 months, clinical events and treatment discontinuation/switch in the first year of HAART were compared using linear, logistic and Cox regression. Compared with women (n=2,179), men (n=1,487) were older and had lower CD4(+) T-cell count and higher VL at start of HAART. Median follow-up was 3.8 years (IQR 2.0-6.2). At 6 and 12 months, 72.7% and 75.3% had VL≤50 copies/ml, with no large differences between genders at either time after adjustment for confounders (6 months, OR 0.92 [95% CI 0.76-1.13]; 12 months, OR 1.06 [95% CI 0.85-1.31]). Overall, 79.4% patients achieved virological suppression and 19.2% experienced virological rebound, without gender differences, although men had an increased risk of rebound after excluding pregnant women (adjusted relative hazard [RH] 1.33 [95% CI 1.04-1.71]). Mean CD4(+) T-cell count increases at 6 and 12 months were, respectively, 112 and 156 cells/mm(3) overall, with mean differences between men and women of -14.6 cells/mm(3) (95% CI -24.6--4.5) and -12.1 cells/mm(3) (95% CI -24.4-0.2) at 6 and 12 months, respectively. Clinical progression was similar in men and women, but men were less likely to experience treatment discontinuation/switch (adjusted RH 0.72 [95% CI 0.63-0.83]). Despite higher discontinuation rates among women, men had an increased risk of virological rebound and slightly poorer CD4(+) T-cell count responses. Identifying the reasons underlying treatment discontinuation/switch may help optimize treatment strategies for both genders.Antiviral therapy 01/2011; 16(6):805-14. · 3.16 Impact Factor -
Article: Impact of late diagnosis and treatment on life expectancy in people with HIV-1: UK Collaborative HIV Cohort (UK CHIC) Study.
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ABSTRACT: To estimate life expectancy for people with HIV undergoing treatment compared with life expectancy in the general population and to assess the impact on life expectancy of late treatment, defined as CD4 count <200 cells/mm(3) at start of antiretroviral therapy. Cohort study. Outpatient HIV clinics throughout the United Kingdom. Population Adult patients from the UK Collaborative HIV Cohort (UK CHIC) Study with CD4 count ≤ 350 cells/mm(3) at start of antiretroviral therapy in 1996-2008. Life expectancy at the exact age of 20 (the average additional years that will be lived by a person after age 20), according to the cross sectional age specific mortality rates during the study period. 1248 of 17,661 eligible patients died during 91,203 person years' follow-up. Life expectancy (standard error) at exact age 20 increased from 30.0 (1.2) to 45.8 (1.7) years from 1996-9 to 2006-8. Life expectancy was 39.5 (0.45) for male patients and 50.2 (0.45) years for female patients compared with 57.8 and 61.6 years for men and women in the general population (1996-2006). Starting antiretroviral therapy later than guidelines suggest resulted in up to 15 years' loss of life: at age 20, life expectancy was 37.9 (1.3), 41.0 (2.2), and 53.4 (1.2) years in those starting antiretroviral therapy with CD4 count <100, 100-199, and 200-350 cells/mm(3), respectively. Life expectancy in people treated for HIV infection has increased by over 15 years during 1996-2008, but is still about 13 years less than that of the UK population. The higher life expectancy in women is magnified in those with HIV. Earlier diagnosis and subsequent timely treatment with antiretroviral therapy might increase life expectancy.BMJ (Clinical research ed.). 01/2011; 343:d6016. -
Article: Haemoglobin and anaemia in the SMART study.
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ABSTRACT: Data from randomized trials on the development of anaemia after interruption of therapy are not well-described. A total of 2,248 patients from the SMART study were included. We used Cox proportional hazards models to investigate development of new (≤12 mg/dl for females and ≤14 mg/dl for males) or worsening (≤8 mg/dl if anaemic at randomization) anaemia and Poisson regression analyses to explore the relationship between anaemia and the development of AIDS, death or non-AIDS events. Overall, 759 patients developed new or worsening anaemia: 420/1,106 (38.0%) in the drug conservation (DC) arm and 339/1127 (30.1%) in the viral suppression (VS) arm (P<0.0001). At 4 months after randomization, patients in the DC arm had a significantly increased risk of developing new or worsening anaemia (adjusted relative hazard 1.56, 95% CI 1.28-1.89). Currently anaemic patients had an increased incidence of AIDS (adjusted incidence rate ratio [IRR] 2.31, 95% CI 1.34-3.98), death (adjusted IRR 2.19, 95% CI 1.23-3.87) and non-AIDS events (adjusted IRR 2.98, 95% CI 2.01-4.40) compared to non-anaemic patients. Patients who interrupted combination antiretroviral therapy had a higher risk of new or worsening anaemia. Anaemic patients had a higher incidence of AIDS, non-AIDS defining events or deaths, possibly due to deteriorating health and subclinical disease.Antiviral therapy 01/2011; 16(3):329-37. · 3.16 Impact Factor -
Article: HIV testing in primary care will help improve early diagnosis.
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ABSTRACT: HIV is now a treatable medical condition and the majority of those diagnosed with the virus remain fit and well on treatment. Patients living with HIV may well now have a near-normal life expectancy with antiretroviral treatment. In all, 77,000 people are known to be infected with HIV in the UK. However, 28% are unaware of their infection and are therefore unable to access treatment. Late diagnosis is the most important factor associated with HIV-related morbidity and mortality in the UK. The RCP guidelines recommend that GPs should offer an HIV test to patients: from communities or geographical locations where HIV is common; who present with a medical condition in which HIV might be implicated; with a medical condition compatible with AIDS or with any HIV indicator disease. GPs should also consider offering an HIV test to new patients who register with the practice in areas where diagnosed HIV prevalence in the local population (PCT/LA) exceeds 2 in 1,000. The pre-test discussion should cover: an explanation of why the test is recommended; the benefits of testing to the individual; details of how the result will be given; confidentiality and informed consent. The need for a repeat HIV test, if the patient is still within the window after a specific exposure, should be discussed.The Practitioner 11/2009; 253(1723):27-30, 3. -
Article: Testing for HIV: concise guidance.
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ABSTRACT: HIV is now a treatable medical condition and the majority of those living with the virus remain fit and well on treatment. Despite this a significant number of people in the UK are unaware of their HIV infection and remain at risk to their own health and of passing their virus unwittingly on to others. Late diagnosis is the most important factor associated with HIV-related morbidity and mortality in the U.K. Testing for HIV infection is often not performed due to misconceptions held by healthcare workers even when it is clinically indicated and this contributes to missed or late diagnosis. This article summarises the recommendations from the U.K. national guidelines for HIV testing 2008. The guidelines provide the information needed to enable any clinician to perform an HIV test within good clinical practice and encourage 'normalisation' of HIV testing. The full version is available at www.bhiva.org/cmsl 222621.asp.Clinical medicine (London, England) 10/2009; 9(5):471-6. · 1.15 Impact Factor -
Article: HIV testing in the UK.
The Lancet 09/2009; 374(9687):376. · 38.28 Impact Factor -
Article: Pneumonia in HIV-infected persons: increased risk with cigarette smoking and treatment interruption.
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ABSTRACT: Bacterial pneumonia is a major cause of morbidity for HIV-infected persons and contributes to excess mortality in this population. To evaluate the frequency and risk factors for occurrence of bacterial pneumonia in the present era of potent antiretroviral therapy. We evaluated data from a randomized trial of episodic antiretroviral therapy. The study, Strategies for Management of Antiretroviral Therapy, enrolled 5,472 participants at 318 sites in 33 countries. Study patients had more than 350 CD4 cells at baseline. Diagnosis of bacterial pneumonia was confirmed by a blinded clinical-events committee. During a mean follow-up of 16 months, 116 participants (2.2%) developed at least one episode of bacterial pneumonia. Patients randomized to receive episodic antiretroviral therapy were significantly more likely to develop pneumonia than patients randomized to receive continuous antiretroviral therapy (hazard ratio, 1.55; 95% confidence interval, 1.07-2.25; P = 0.02). Cigarette smoking was a major risk factor: Current-smokers had more than an 80% higher risk of pneumonia compared with never-smokers (hazard ratio, 1.82; 95% confidence interval, 1.09-3.04; P = 0.02). Participants who were on continuous HIV treatment and were current smokers were three times more likely to develop bacterial pneumonia than nonsmokers. Current smoking status was significant, but a past history of smoking was not. Bacterial pneumonia is a major source of morbidity, even for persons on potent antiretroviral therapy, including those with high CD4 cells. Efforts to reduce this illness should stress the importance of uninterrupted antiretroviral therapy and attainment and/or maintenance of nonsmoking status.American Journal of Respiratory and Critical Care Medicine 07/2008; 178(6):630-6. · 11.08 Impact Factor -
Article: Major clinical outcomes in antiretroviral therapy (ART)-naive participants and in those not receiving ART at baseline in the SMART study.
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ABSTRACT: The SMART study randomized 5,472 human immunodeficiency virus (HIV)-infected patients with CD4+ cell counts >350 cells/microL to intermittent antiretroviral therapy (ART; the drug conservation [DC] group) versus continuous ART (the viral suppression [VS] group). In the DC group, participants started ART when the CD4+ cell count was <250 cells/microL. Clinical outcomes in participants not receiving ART at entry inform the early use of ART. Patients who were either ART naive (n=249) or who had not been receiving ART for >or= 6 months (n=228) were analyzed. The following clinical outcomes were assessed: (i) opportunistic disease (OD) or death from any cause (OD/death); (ii) OD (fatal or nonfatal); (iii) serious non-AIDS events (cardiovascular, renal, and hepatic disease plus non-AIDS-defining cancers) and non-OD deaths; and (iv) the composite of outcomes (ii) and (iii). A total of 477 participants (228 in the DC group and 249 in the VS group) were followed (mean, 18 months). For outcome (iv), 21 and 6 events occurred in the DC (7 in ART-naive participants and 14 in those who had not received ART for >or= 6 months) and VS (2 in ART-naive participants and 4 in those who had not received ART for 6 months) groups, respectively. Hazard ratios for DC vs. VS by outcome category were as follows: outcome (i), 3.47 (95% confidence interval [CI], 1.26-9.56; p=.02); outcome (ii), 3.26 (95% CI, 1.04-10.25; p=.04); outcome (iii), 7.02 (95% CI, 1.57-31.38; p=.01); and outcome (iv), 4.19 (95% CI, 1.69-10.39; p=.002 ). Initiation of ART at CD4+ cell counts >350 cells/microL compared with <250 cells/microL may reduce both OD and serious non-AIDS events. These findings require validation in a large, randomized clinical trial.The Journal of Infectious Diseases 04/2008; 197(8):1133-44. · 6.41 Impact Factor -
Article: 8th European Conference on Clinical Aspects and Treatment of HIV Infection, Athens, 28-31 October 2001.
Sexually Transmitted Infections 05/2002; 78(2):149. · 2.85 Impact Factor -
Article: Impact of late diagnosis and treatment on life expectancy in people with HIV-1: UK Collaborative HIV Cohort (UK CHIC) Study
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ABSTRACT: Objectives To estimate life expectancy for people with HIV undergoing treatment compared with life expectancy in the general population and to assess the impact on life expectancy of late treatment, defined as CD4 count <200 cells/mm3 at start of antiretroviral therapy.Design Cohort study.Setting Outpatient HIV clinics throughout the United Kingdom.Population Adult patients from the UK Collaborative HIV Cohort (UK CHIC) Study with CD4 count ≤350 cells/mm3 at start of antiretroviral therapy in 1996-2008.Main outcome measures Life expectancy at the exact age of 20 (the average additional years that will be lived by a person after age 20), according to the cross sectional age specific mortality rates during the study period.Results 1248 of 17 661 eligible patients died during 91 203 person years’ follow-up. Life expectancy (standard error) at exact age 20 increased from 30.0 (1.2) to 45.8 (1.7) years from 1996-9 to 2006-8. Life expectancy was 39.5 (0.45) for male patients and 50.2 (0.45) years for female patients compared with 57.8 and 61.6 years for men and women in the general population (1996-2006). Starting antiretroviral therapy later than guidelines suggest resulted in up to 15 years’ loss of life: at age 20, life expectancy was 37.9 (1.3), 41.0 (2.2), and 53.4 (1.2) years in those starting antiretroviral therapy with CD4 count <100, 100-199, and 200-350 cells/mm3, respectively.Conclusions Life expectancy in people treated for HIV infection has increased by over 15 years during 1996-2008, but is still about 13 years less than that of the UK population. The higher life expectancy in women is magnified in those with HIV. Earlier diagnosis and subsequent timely treatment with antiretroviral therapy might increase life expectancy.BMJ. 343.
Top co-authors
Top Journals
Institutions
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2013
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Imperial College London
- Section of Infectious Diseases
London, ENG, United Kingdom
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2011
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University of Bristol
- School of Social and Community Medicine
Bristol, ENG, United Kingdom
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2009–2011
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University Hospitals of Leicester
Leicester, ENG, United Kingdom
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2002
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Peterborough City Hospital
Peterborough, ENG, United Kingdom
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