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Journal of the International AIDS Society 04/2012; 11:1-1. · 3.26 Impact Factor
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C Kober,
M Johnson,
M Fisher,
T Hill,
J Anderson,
L Bansi,
M Gompels,
A Palfreeman,
D Dunn,
B Gazzard,
R Gilson,
F Post,
A N Phillips,
J Walsh,
C Orkin,
V Delpech,
J Ainsworth, C Leen,
C A Sabin
[show abstract]
[hide abstract]
ABSTRACT: Current British HIV Association (BHIVA) guidelines recommend that all patients with a CD4 count <350 cells/μL are offered highly active antiretroviral therapy (HAART). We identified risk factors for delayed initiation of HAART following a CD4 count <350 cells/μL.
All adults under follow-up in 2008 who had a first confirmed CD4 count <350 cells/μL from 2004 to 2008, who had not initiated treatment and who had >6 months of follow-up were included in the study. Characteristics at the time of the low CD4 cell count and over follow-up were compared to identify factors associated with delayed HAART uptake. Analyses used proportional hazards regression with fixed (sex/risk group, age, ethnicity, AIDS, baseline CD4 cell count and calendar year) and time-updated (frequency of CD4 cell count measurement, proportion of CD4 counts <350 cells/μL, latest CD4 cell count, CD4 percentage and viral load) covariates.
Of 4871 patients with a confirmed low CD4 cell count, 436 (8.9%) remained untreated. In multivariable analyses, those starting HAART were older [adjusted relative hazard (aRH)/10 years 1.15], were more likely to be female heterosexual (aRH 1.13), were more likely to have had AIDS (aRH 1.14), had a greater number of CD4 measurements < 350 cells/μL (aRH/additional count 1.18), had a lower CD4 count over follow-up (aRH/50 cells/μL higher 0.57), had a lower CD4 percentage (aRH/5% higher 0.90) and had a higher viral load (aRH/log(10) HIV-1 RNA copies/ml higher 1.06). Injecting drug users (aRH 0.53), women infected with HIV via nonsexual or injecting drug use routes (aRH 0.75) and those of unknown ethnicity (aRH 0.69) were less likely to commence HAART.
A substantial minority of patients with a CD4 count < 350 cells/μL remain untreated despite its indication.
HIV Medicine 11/2011; 13(1):73-8. · 3.01 Impact Factor
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HIV Medicine 09/2011; 12 Suppl 2:61-9. · 3.01 Impact Factor
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R A Hughes,
J A C Sterne,
J Walsh,
L Bansi,
R Gilson,
C Orkin,
T Hill,
J Ainsworth,
J Anderson,
M Gompels,
D Dunn,
M A Johnson,
A N Phillips,
D Pillay, C Leen,
P Easterbrook,
B Gazzard,
M Fisher,
C A Sabin
[show abstract]
[hide abstract]
ABSTRACT: The aim of the study was to describe trends in CD4 cell counts in HIV-infected patients after initiation of combination antiretroviral therapy (cART), according to CD4 cell count at initiation (baseline), and to quantify the implications of virological failure for these trends.
Eligible participants from the UK Collaborative HIV Cohort (CHIC) were antiretroviralnaïve and started cART after 1997. Random effects were used to model CD4 cell count trends, accounting for multiple measurements within participants. We assessed whether CD4 cell count trends varied according to baseline CD4 cell count and separately in participants with and without post-cART virological failure. Effects of post-cART virological failure (>1000 HIV-1 RNA copies/mL) on subsequent CD4 cell counts were evaluated.
A total of 7069 participants were included in the analysis (median follow-up in all baseline CD4 cell count groups was ≥ 35 months). Among participants without virological failure ≥ 6 months after the start of cART, CD4 cell counts continued to increase up to 8 years, with little evidence that differences between baseline CD4 cell count groups diminished over time. Virological failure ≥ 6 months after the start of cART was associated with lower subsequent CD4 cell counts, with greater CD4 cell count reduction for more recent virological failure and higher viral load.
Post-cART CD4 cell counts are strongly related to pre-cART CD4 cell counts. CD4 cell count recovery is greatest in individuals who can avoid viral loads >1000 copies/mL while on cART.
HIV Medicine 05/2011; 12(10):583-93. · 3.01 Impact Factor
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L Garvey,
A Winston,
J Walsh,
F Post,
K Porter,
B Gazzard,
M Fisher, C Leen,
D Pillay,
T Hill, [......],
R Gilson,
J Anderson,
P Easterbrook,
L Bansi,
C Orkin,
J Ainsworth,
A Palfreeman,
M Gompels,
A N Phillips,
C A Sabin
[show abstract]
[hide abstract]
ABSTRACT: The impact of different antiretroviral agents on the risk of developing or surviving CNS disease remains unknown. The aim of this study was to investigate whether using antiretroviral regimens with higher CNS penetration effectiveness (CPE) scores was associated with reduced incidence of CNS disease and improved survival in the UK Collaborative HIV Cohort (CHIC) Study.
Adults without previous CNS disease, who commenced combination antiretroviral therapy (cART) between 1996 and 2008, were included (n = 22,356). Initial and most recent cART CPE scores were calculated. CNS diseases were HIV encephalopathy (HIVe), progressive multifocal leukoencephalopathy (PML), cerebral toxoplasmosis (TOXO), and cryptococcal meningitis (CRYPTO). Incidence rates and overall survival were stratified by CPE score. A multivariable Poisson regression model was used to identify independent associations.
The median (interquartile range) CPE score for initial cART regimen increased from 7 (5-8) in 1996-1997 to 9 (8-10) in 2000-2001 and subsequently declined to 6 (7-8) in 2006-2008. Differences in gender, HIV acquisition risk group, and ethnicity existed between CPE score strata. A total of 251 subjects were diagnosed with a CNS disease (HIVe 80; TOXO 59; CRYPTO 56; PML 54). CNS diseases occurred more frequently in subjects prescribed regimens with CPE scores ≤ 4, and less frequently in those with scores ≥ 10; however, these differences were nonsignificant. Initial and most recent cART CPE scores ≤ 4 were independently associated with increased risk of death.
Clinical status at time of commencing cART influences antiretroviral selection and CPE score. This information should be considered when utilizing CPE scores for retrospective analyses.
Neurology 02/2011; 76(8):693-700. · 8.31 Impact Factor
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L Waters,
M Fisher,
J Anderson,
C Wood,
V Delpech,
T Hill,
J Walsh,
C Orkin,
L Bansi,
M Gompels,
A Phillips,
M Johnson,
R Gilson,
P Easterbrook, C Leen,
K Porter,
B Gazzard,
C Sabin
[show abstract]
[hide abstract]
ABSTRACT: We investigated whether adverse responses to highly active antiretroviral therapy (HAART) associated with late HIV presentation are secondary to low CD4 cell count per se or other confounding factors.
A longitudinal analysis of the UK Collaborative HIV Cohort (CHIC) Study of individuals starting HAART in 1998-2007 was carried out, comparing late presenters (presenting/starting HAART at a CD4 count <200 cells/μL) with late starters (presenting at a CD4 count>350 cells/μL; starting HAART at a CD4 count<200 cells/μL), using 'ideal starters' (presenting at a CD4 count>350 cells/μL; starting HAART at a CD4 count of 200-350 cells/μL) as a comparator. Virological, immunological and clinical (new AIDS event/death) outcomes at 48 and 96 weeks were analysed, with the analysis being limited to those remaining on HAART for>3 months.
A total of 4978 of 9095 individuals starting first-line HAART with HIV RNA>500 HIV-1 RNA copies/mL were included in the analysis: 2741 late presenters, 947 late starters and 1290 ideal starters. Late presenters were more commonly female, heterosexual and Black African. Most started nonnucleoside reverse transcriptase inhibitors (NNRTIs); 48-week virological suppression was similar in late presenters and starters (and marginally lower than in ideal starters); by week 96 differences were reduced and nonsignificant. The median CD4 cell count increase in late presenters was significantly lower than that in late starters (weeks 48 and 96). During year 1, new clinical events were more frequent for late presenters [odds ratio (OR) 2.04; 95% confidence interval (CI) 1.19-3.51; P=0.01]; by year 2, event rates were similar in all groups.
Amongst patients who initiate, and remain on, HAART, late presentation is associated with lower rates of virological suppression, blunted CD4 cell count increases and more clinical events compared with late starters in year 1, but similar clinical and immunological outcomes by year 2 to those of both late and ideal starters. Differences between late presenters and late starters suggest that factors other than CD4 cell count alone may be driving adverse treatment outcomes in late-presenting individuals.
HIV Medicine 11/2010; 12(5):289-98. · 3.01 Impact Factor
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L Bansi,
C Sabin,
V Delpech,
T Hill,
M Fisher,
J Walsh,
T Chadborn,
P Easterbrook,
R Gilson,
M Johnson,
K Porter,
J Anderson,
M Gompels, C Leen,
J Ainsworth,
C Orkin,
M Nelson,
B Rice,
A Phillips
[show abstract]
[hide abstract]
ABSTRACT: Effective antiretroviral therapy (ART) has transformed the care of people with HIV, but it is important to monitor time trends in indicators of treatment success and antic future changes.
We assessed time trends from 2000 to 2007 in several indicators of treatment success in the UK Collaborative HIV Cohort (CHIC) Study, and using national HIV data from the Health Protection Agency (HPA) we developed a model to project future trends.
The proportion of patients on ART with a viral load <50 HIV-1 RNA copies/mL increased from 62% in 2000 to 84% in 2007, and the proportion of all patients with a CD4 count <200 cells/microL decreased from 21% to 10%. During this period, the number of patients who experienced extensive triple class failure (ETCF) rose from 147 (0.9%) to 1771 (3.9%). The number who experienced such ETCF and had a current viral load >50 copies/mL rose fromz 118 (0.7%) to 857 (1.9%). Projections to 2012 suggest sustained high levels of success, with a continued increase in the number of patients who have failed multiple drugs but a relatively stable number of such patients experiencing viral loads >50 copies/mL. Numbers of deaths are projected to remain low.
There have been continued improvements in key indicators of success in patients with HIV from 2000 to 2007. Although the number of patients who have ETCF is projected to rise in the future, the number of such patients with viral loads >50 copies/mL is not projected to increase up to 2012. New drugs may be needed in future to sustain these positive trends.
HIV Medicine 02/2010; 11(7):432-8. · 3.01 Impact Factor
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G Brook,
J Main,
M Nelson,
S Bhagani,
E Wilkins, C Leen,
M Fisher,
Y Gilleece,
R Gilson,
A Freedman,
R Kulasegaram,
K Agarwal,
C Sabin,
C Deacon-Adams
HIV Medicine 01/2010; 11(1):1-30. · 3.01 Impact Factor
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J Turner,
L Bansi,
R Gilson,
B Gazzard,
J Walsh,
D Pillay,
C Orkin,
A Phillips,
P Easterbrook,
M Johnson,
K Porter,
A Schwenk,
T Hill, C Leen,
J Anderson,
M Fisher,
C Sabin
[show abstract]
[hide abstract]
ABSTRACT: We examined the prevalence of hepatitis C virus (HCV) infection among HIV-positive individuals in the UK, trends in HCV testing and the impact of HCV on HIV treatment outcomes. Trends over time in HCV prevalence were calculated using each patient's most recent HCV status at the end of each calendar year. Logistic regression was used to identify factors associated with having a HCV antibody test, and Cox regression was used to determine whether HCV status was associated with the time to experiencing an immunological response to highly active antiretroviral treatment (HAART), time to virological response and viral rebound. Of the 31,765 HIV-positive individuals seen for care between January 1996 and September 2007, 20,365 (64.1%) individuals were tested for HCV, and 1807 (8.9%) had detectable HCV antibody. The proportion of patients in follow-up ever tested for HCV increased over time, from 782/8505 (9.2%) in 1996 to 14,280/17,872 (79.9%) in 2007. Nine thousand six hundred and sixty-nine individuals started HAART for the first time in or after January 2000, of whom, 396 (4.1%) were HCV positive. Presence of HCV infection did not affect initial virological response, virological rebound or immunological response. The cumulative prevalence of HCV in the UK CHIC Study is 8.9%. Despite UK guidelines, over 20% of HIV-positive individuals have not had their HCV status determined by 2007. HCV infection had no impact on HIV virological outcomes or immunological response to HIV treatment. The long-term impact on morbidity and mortality remain to be determined.
Journal of Viral Hepatitis 10/2009; 17(8):569-77. · 4.09 Impact Factor
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R J C Gilson,
S-L Man,
A Copas,
A Rider,
S Forsyth,
T Hill,
L Bansi,
K Porter,
B Gazzard,
C Orkin,
D Pillay,
A Schwenk,
M Johnson,
P Easterbook,
J Walsh,
M Fisher, C Leen,
J Anderson,
C A Sabin
[show abstract]
[hide abstract]
ABSTRACT: Patients starting highly active antiretroviral therapy (HAART) may have a suboptimal CD4 increase despite rapid virological suppression. The frequency and the significance for patient care of this discordant response are uncertain. This study was designed to determine the incidence of a discordant response at two time-points, soon after 6 months and at 12 months, and to determine the relationship with clinical outcomes.
Data obtained in the UK Collaborative HIV Cohort Study were analysed. A total of 2584 treatment-naïve patients starting HAART with HIV viral load (VL) > 1000 HIV-1 RNA copies/mL at baseline and < 50 copies/mL within 6 months were included in the analysis. Patients were classified at either 6-10 (midpoint 8) months or 10-14 (midpoint 12) months as having a discordant (CD4 count increase < 100 cells/microL from baseline) or concordant response (CD4 count increase >or= 100 cells/microL).
Discordant responses occurred in 32.1% of patients at 8 months and in 24.2% at 12 months; 35% of those discordant at 8 months were concordant at 12 months. A discordant response was associated with older age, lower baseline VL, and (at 12 months) higher baseline CD4 cell count. In a multivariate analysis it was associated with an increased risk of death, more strongly at 12 months [incidence rate ratio (IRR) 3.35, 95% confidence interval (CI) 1.73-6.47, P < 0.001] than at 8 months (IRR 2.08, 95% CI 1.19-3.64, P = 0.010), but not with new AIDS events.
Discordant responders have a worse outcome, but assessment at 12 months may be preferred, given the number of 'slow' responders. Management strategies to improve outcomes for discordant responders need to be investigated.
HIV Medicine 10/2009; 11(2):152-60. · 3.01 Impact Factor
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CA Sabin,
CJ Smith,
V Delpech,
J Anderson,
L Bansi,
R Gilson,
A Schwenk, C Leen,
B Gazzard,
K Porter,
N Mackie,
M Fisher,
C Orkin,
M Johnson,
P Easterbrook,
T Hill,
AN Phillips,
on behalf of the UK Collaborative HIV Cohort (CHIC) Study
[show abstract]
[hide abstract]
ABSTRACT: Objective
The aim of this study was to describe the relationship between age and the time to treatment discontinuation in the absence of virological failure as well as the development of specific laboratory abnormalities, in patients starting highly active antiretroviral therapy (HAART) for the first time.Methods
Analyses included 8708 antiretroviral-naïve patients from the UK Collaborative HIV Cohort (CHIC) study who started HAART from 1998 onwards. We considered time to the first discontinuation of any drug in the initial HAART regimen for reasons other than virological failure; the association between this and age at the start of HAART was determined using proportional hazards regression after adjustment for potential confounders. The incidence of specific laboratory abnormalities in the first year after starting HAART was compared in those of different ages using multiple logistic regression.ResultsA total of 2650 patients discontinued at least one drug in their HAART regimen in the first year for reasons other than virological failure; after controlling for confounders, those aged < 30 years at the time of starting HAART were more likely to discontinue than those aged 30–39 years [relative hazard (RH) 1.12; 95% confidence interval (CI) 1.01, 1.24] as were those aged 50 years (RH 1.14; 95% CI 1.00, 1.31). There were strong associations between greater age and raised total cholesterol, decreased haemoglobin and raised triglycerides over the first year, although the latter disappeared after adjustment for pre-HAART levels, suggesting that this finding reflected higher pre-HAART triglyceride levels in older individuals.Conclusions
Continued attempts to improve the tolerability of HAART regimens may help to sustain the good outcomes in all age groups over the longer term.
HIV Medicine 11/2008; 10(1):35 - 43. · 3.01 Impact Factor
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C A Sabin,
C J Smith,
V Delpech,
J Anderson,
L Bansi,
R Gilson,
A Schwenk, C Leen,
B Gazzard,
K Porter,
N Mackie,
M Fisher,
C Orkin,
M Johnson,
P Easterbrook,
T Hill,
A N Phillips
[show abstract]
[hide abstract]
ABSTRACT: The aim of this study was to describe the relationship between age and the time to treatment discontinuation in the absence of virological failure as well as the development of specific laboratory abnormalities, in patients starting highly active antiretroviral therapy (HAART) for the first time.
Analyses included 8708 antiretroviral-naïve patients from the UK Collaborative HIV Cohort (CHIC) study who started HAART from 1998 onwards. We considered time to the first discontinuation of any drug in the initial HAART regimen for reasons other than virological failure; the association between this and age at the start of HAART was determined using proportional hazards regression after adjustment for potential confounders. The incidence of specific laboratory abnormalities in the first year after starting HAART was compared in those of different ages using multiple logistic regression.
A total of 2650 patients discontinued at least one drug in their HAART regimen in the first year for reasons other than virological failure; after controlling for confounders, those aged < 30 years at the time of starting HAART were more likely to discontinue than those aged 30-39 years [relative hazard (RH) 1.12; 95% confidence interval (CI) 1.01, 1.24] as were those aged > or = 50 years (RH 1.14; 95% CI 1.00, 1.31). There were strong associations between greater age and raised total cholesterol, decreased haemoglobin and raised triglycerides over the first year, although the latter disappeared after adjustment for pre-HAART levels, suggesting that this finding reflected higher pre-HAART triglyceride levels in older individuals.
Continued attempts to improve the tolerability of HAART regimens may help to sustain the good outcomes in all age groups over the longer term.
HIV Medicine 11/2008; 10(1):35-43. · 3.01 Impact Factor
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PJ Easterbrook,
AN Phillips,
T Hill,
R Matthias,
M Fisher,
B Gazzard,
R Gilson,
G Scullard,
M Johnson,
DT Dunn,
C Orkin,
J Anderson,
A Schwenk, C Leen,
CA Sabin,
on behalf of the UK Collaborative HIV Cohort (CHIC) Study Steering Committee
[show abstract]
[hide abstract]
ABSTRACT: Background
We describe the patterns of antiretroviral drug use at treatment initiation from 1996 to 2005 in a large UK multicentre cohort.Methods
We examined trends over time and across 10 clinical sites in stage of disease and type of antiretroviral therapy (ART). Multivariable regression was used to identify factors associated with the CD4 cell count at ART initiation, and with the choice of a protease inhibitor (PI) over a nonnucleoside reverse transcriptase inhibitor (NNRTI), and use of nevirapine over efavirenz.ResultsA total of 14 252 patients initiated ART, of whom 54% had a CD4 count <200 cells/μL. The most important predictors of starting ART at a lower CD4 cell count were being male, nonwhite, and heterosexual or an injecting drug user (P<0.0001). Among those starting ART, the use of highly active ART increased from 23% in 1996 to >96% from 2000 onwards. There were differences over time and across the clinics in the use of PIs vs. NNRTIs, in the choice of specific PIs, NNRTIs and nucleoside reverse transcriptase inhibitor (NRTI) backbone, and in the rate at which prescribing practices changed.Conclusions
Clinic site and calendar year were important determinants of choice of drug at ART initiation, whereas clinical and demographic characteristics were more important in influencing the CD4 cell count at initiation of ART.
HIV Medicine 01/2008; 9(1):47 - 56. · 3.01 Impact Factor
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P J Easterbrook,
A N Phillips,
T Hill,
R Matthias,
M Fisher,
B Gazzard,
R Gilson,
G Scullard,
M Johnson,
D T Dunn,
C Orkin,
J Anderson,
A Schwenk, C Leen,
C A Sabin
[show abstract]
[hide abstract]
ABSTRACT: We describe the patterns of antiretroviral drug use at treatment initiation from 1996 to 2005 in a large UK multicentre cohort.
We examined trends over time and across 10 clinical sites in stage of disease and type of antiretroviral therapy (ART). Multivariable regression was used to identify factors associated with the CD4 cell count at ART initiation, and with the choice of a protease inhibitor (PI) over a nonnucleoside reverse transcriptase inhibitor (NNRTI), and use of nevirapine over efavirenz.
A total of 14 252 patients initiated ART, of whom 54% had a CD4 count <200 cells/microL. The most important predictors of starting ART at a lower CD4 cell count were being male, nonwhite, and heterosexual or an injecting drug user (P<0.0001). Among those starting ART, the use of highly active ART increased from 23% in 1996 to >96% from 2000 onwards. There were differences over time and across the clinics in the use of PIs vs. NNRTIs, in the choice of specific PIs, NNRTIs and nucleoside reverse transcriptase inhibitor (NRTI) backbone, and in the rate at which prescribing practices changed.
Clinic site and calendar year were important determinants of choice of drug at ART initiation, whereas clinical and demographic characteristics were more important in influencing the CD4 cell count at initiation of ART.
HIV Medicine 01/2008; 9(1):47-56. · 3.01 Impact Factor
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B Gazzard,
A J Bernard,
M Boffito,
D Churchill,
S Edwards,
N Fisher,
A M Geretti,
M Johnson, C Leen,
B Peters,
A Pozniak,
J Ross,
J Walsh,
E Wilkins,
M Youle
HIV Medicine 12/2006; 7(8):487-503. · 3.01 Impact Factor
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A Pozniak,
B Gazzard,
J Anderson,
A Babiker,
D Churchill,
S Collins,
M Fisher,
M Johnson,
S Khoo, C Leen,
C Loveday,
G Moyle,
M Nelson,
B Peter,
A Phillips,
D Pillay,
E Wilkins,
I Williams,
M Youle
HIV Medicine 11/2003; 4 Suppl 1:1-41. · 3.01 Impact Factor
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A N Phillips,
B Gazzard,
R Gilson,
P Easterbrook,
M Johnson,
J Walsh, C Leen,
M Fisher,
C Orkin,
J Anderson,
D Pillay,
V Delpech,
C Sabin,
C. Schwenk,
D Dunn,
M Gompels,
T Hill,
K Porter,
A Babiker
[show abstract]
[hide abstract]
ABSTRACT: Objective: To assess the absolute rate of AIDS and death in antiretroviral therapy (ART)-naive patients with a high CD4 cell count. Such information would be helpful in the design of a trial investigating early initiation of ART.
Design: Analysis of data from an ongoing HIV cohort study.
Methods: The rate of (severe) AIDS or death and death alone was evaluated in ART-naive patients according to the current CD4 cell count, focusing on CD4 cell counts >= 350 cells/µl among patients in the UK CHIC Study.
Results: In a total of 30 313 person-years of follow-up, there were 1557 AIDS or death events. The rate of AIDS or death in persons with most recent CD4 cell count 350–499, 500–649 and > 650 cells/µl was 2.49, 1.54 and 0.96 per 100 person-years, respectively. The rate ratio for those with CD4 cell count 500–649 cells/µl compared with those with CD4 cell count >= 650 cells/µl was 1.55 [95% confidence interval (CI), 1.11–2.17; P = 0.01]. In a Poisson regression model based on person years with CD4 cell count >= 350 cells/µl, there was a strong effect of CD4 cell count on rate of AIDS or death (rate ratio, 0.84; 95% CI, 0.76–0.93; P = 0.001), independent of viral load and age.
Conclusions: The trend of decreasing rate of AIDS and death with higher CD4 cell count is present throughout the CD4 cell count >= 350 cells/µl range in ART-naive people.
Phillips, A.N. and Gazzard, B. and Gilson, R. and Easterbrook, P. and Johnson, M. and Walsh, J. and Leen, C. and Fisher, M. and Orkin, C. and Anderson, J. and Pillay, D. and Delpech, V. and Sabin, C. and Schwenk, C. and Dunn, D. and Gompels, M. and Hill, T. and Porter, K. and Babiker, A. (2007) Rate of AIDS diseases or death in HIV-infected antiretroviral therapy-naive individuals with high CD4 cell count. AIDS, 21 (13). pp. 1717-1721. ISSN 02699370.
