Caroline A Sabin

UK Department of Health, Londinium, England, United Kingdom

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Publications (492)3736.31 Total impact

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    ABSTRACT: The objective of this study is to assess whether pregnancy is associated with an increased risk of liver enzyme elevation (LEE) and severe LEE in HIV-positive women on antiretroviral therapy (ART). Two observational studies: the UK Collaborative HIV Cohort (UK CHIC) study and the UK and Ireland National Study of HIV in Pregnancy and Childhood (NSHPC). Combined data from UK CHIC and NSHPC were used to identify factors associated with LEE (grade 1-4) and severe LEE (grade 3-4). Women starting ART in 2000-2012 were included irrespective of pregnancy status. Cox proportional hazards were used to assess fixed and time-dependent covariates including pregnancy status, CD4 cell count, drug regimen and hepatitis B virus/hepatitis C virus (HBV/HCV) coinfection. One-quarter (25.7%, 982/3815) of women were pregnant during follow-up, 14.2% (n = 541) when starting ART. The rate of LEE was 14.5/100 person-years in and 6.0/100 person-years outside of pregnancy. The rate of severe LEE was 3.9/100 person-years in and 0.6/100 person-years outside of pregnancy. The risk of LEE and severe LEE was increased during pregnancy [LEE: aHR 1.66 (1.31-2.09); severe LEE: aHR 3.57 (2.30-5.54)], including in secondary analyses excluding 541 women pregnant when starting ART. Other factors associated with LEE and severe LEE included lower CD4 cell count (<250 cells/μl), HBV/HCV coinfection and calendar year. Although few women developed severe LEE, this study provides further evidence that pregnancy is associated with an increased risk of LEE and severe LEE, reinforcing the need for regular monitoring of liver biomarkers during pregnancy.This is an open access article distributed under the Creative Commons Attribution-Non Commercial License 4.0, where it is permissible to download, share and reproduce the work in any medium, provided it is properly cited. The work cannot be used commercially.
    AIDS (London, England) 02/2015; · 6.56 Impact Factor
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    ABSTRACT: OBJECTIVE: The prevalence of overweight and obesity is increasing among HIV-infected patients. Whether standard antiretroviral drug dosage is adequate in heavy individuals remains unresolved. We assessed the virological and immunological responses to initial efavirenz (EFV)-containing regimens in heavy compared to normal-weight HIV-infected patients. DESIGN: Observational European cohort collaboration study. METHODS: Eligible patients were antiretroviral-naïve with documented weight prior to EFV start and follow-up viral loads after treatment initiation. Cox regression analyses evaluated the association between weight and time to first undetectable viral load (<50 copies/ml) after treatment initiation, and time to viral load rebound (two consecutive viral load >50 copies/ml) after initial suppression over 5 years of follow-up. Recovery of CD4 cell count was evaluated 6 and 12 months after EFV initiation. Analyses were stratified by weight (kg) group (I - <55; II - >55, <80 (reference); III - >80, <85; IV - >85, <90; V - >90, <95; VI - >95). RESULTS: The study included 19 968 patients, of whom 9.1, 68.3, 9.1, 5.8, 3.5, and 4.3% were in weight groups I-VI, respectively. Overall, 81.1% patients attained virological suppression, of whom 34.1% subsequently experienced viral load rebound. After multiple adjustments, no statistical difference was observed in time to undetectable viral load and virological rebound for heavier individuals compared to their normal-weight counterparts. Although heaviest individuals had significantly higher CD4 cell count at baseline, CD4 cell recovery at 6 and 12 months after EFV initiation was comparable to normal-weight individuals. CONCLUSION: Virological and immunological responses to initial EFV-containing regimens were not impaired in heavy individuals, suggesting that the standard 600 mg EFV dosage is appropriate across a wide weight range.
    AIDS 11/2014; 29(2). · 6.56 Impact Factor
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    ABSTRACT: Combination antiretroviral therapy (cART) may affect vitamin D [25(OH)D], parathyroid hormone (PTH), bone mineral density (BMD) and bone turnover (BT). Reduced BMD and secondary hyperparathyroidism have been reported with tenofovir (TDF). We investigated the associations between TDF and bone markers, especially in 25(OH)D-deficient patients.
    Journal of the International AIDS Society 11/2014; 17(4 Suppl 3):19568. · 4.21 Impact Factor
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    ABSTRACT: Most people achieve and maintain viral load (VL) suppression on first-line antiretroviral therapy (ART) but for a minority this does not happen. It is unclear whether those who have maintained VL suppression for several years will be able to continue to do so, or if rates of VL failure - due to poor adherence, ART interruption and/or resistance - remain at appreciable levels.
    Journal of the International AIDS Society 11/2014; 17(4 Suppl 3):19527. · 4.21 Impact Factor
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    ABSTRACT: A recent meta-analysis of 4 RCTs showed an increased rate of suicidality events (suicidal ideation or attempted/completed suicide) associated with efavirenz (EFV) compared to other regimens, but only a trend towards a higher rate of completed/attempted suicides, as only 17 events occurred. We investigated the association between EFV use and completed suicide.
    Journal of the International AIDS Society 11/2014; 17(4 Suppl 3):19512. · 4.21 Impact Factor
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    ABSTRACT: High rates of hepatotoxicity have been observed among HIV-positive pregnant women using antiretroviral therapy (ART). However, the extent to which pregnancy affects the risk of ART-induced hepatotoxicity is unclear since studies in this area have generated conflicting results.
    Journal of the International AIDS Society 11/2014; 17(4 Suppl 3):19486. · 4.21 Impact Factor
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    ABSTRACT: There is a lack of data on potential gender differences in the use of interventions to prevent and treat cardiovascular disease (CVD) in HIV-positive individuals. We investigated whether such differences exist in the D:A:D study.
    Journal of the International AIDS Society 11/2014; 17(4 Suppl 3):19516. · 4.21 Impact Factor
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    ABSTRACT: Introduction: Several resistance mutations have been shown to affect viral fitness, and the presence of certain mutations might result in clinical benefit for patients kept on a virologically failing regimen due to an exhaustion of drug options. We sought to quantify the effect of resistance mutations on CD4 slopes in patients undergoing episodes of viral failure. Materials and Methods: Patients from the EuroSIDA and UK CHIC cohorts undergoing at least one episode of virological failure (>3 consecutive RNA measurements >500 on ART) with at least three CD4 measurements and a resistance test during the episode were included. Mutations were identified using the IAS-US (2013) list, and were presumed to be present from detection until the end of an episode. Multivariable linear mixed models with a random intercept and slope adjusted for age, baseline CD4 count, hepatitis C, drug type, RNA (log-scale), risk group and subtype were used to estimate CD4 slopes. Individual mutations with a population prevalence of >10% were tested for their effect on the CD4 slope. Results: A total of 2731 patients experiencing a median of 1 (range 1-4) episodes were included in this analysis. The prevalence of any resistance per episode was 88.4%; NNRTI resistance was most common (78.5%). Overall, CD4 counts declined by 17.1 (-19.7; -14.5) cells per year; this decline was less marked with partial viral suppression (current HIV RNA more than 1.5 log below the setpoint; p=0.01). In multivariable models adjusting for viral load, CD4 decline was slower during episodes with detected resistance compared to episodes without detected resistance (21.0 cells/year less, 95% CI 11.75-30.31, p<0.001). Among those with more than one resistance mutation, there was only weak evidence that class-specific mutations had any effect on the CD4 slope (Table 1). The effects of individual mutations (incl. M184V) were explored, but none were significantly associated with the CD4 slope; for these comparisons, a Bonferroni-corrected p-value level was 0.003. Conclusions: In our study population, detected resistance was associated with slightly less steep CD4 declines. This may be due to a biological effect of resistance on CD4 slopes, or other unmeasured factors such as poor adherence among individuals without resistance. Among individuals with detected drug resistance, we found no evidence suggesting that the presence of individual mutations was associated with beneficial CD4 slope changes.
    Journal of the International AIDS Society 11/2014; 17(4(Suppl 3)):19737. · 4.21 Impact Factor
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    ABSTRACT: To evaluate the prevalence, impact and risk factors for pain among a cohort of HIV-infected adults treated with combination anti-retroviral therapy (cART) if indicated according to current guidelines.
    Clinical Journal of Pain 10/2014; · 2.70 Impact Factor
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    ABSTRACT: Background Some individuals remain AIDS-free with a high and stable CD4 cell count without antiretroviral therapy (ART) for many years. We estimated long-term progression-free survival after HIV seroconversion and aimed to identify factors associated with loss of long-term non-progression (LTNP) status. Methods For this cohort study, we used data for individuals with well-estimated dates of HIV-1 seroconversion from the CASCADE Collaboration a network of 28 HIV seroconverter cohort studies in Europe, Australia, Canada, and sub-Saharan Africa. The fi rst cohort began enrolling patients in 1979, and for this analysis we used data pooled in May 1, 2011. We defi ned non-progression as being HIV-positive without AIDS, ART-naive, and with CD4 counts of 500 cells per μL or higher. We defi ned LTNP as non-progression during the fi rst 10 years after seroconversion. We used longitudinal methods to characterise LTNP. Findings Of the 4979 HIV seroconverters in our dataset, 3708 (75%) were men. Median time to progression was 2·07 years (95% CI 1·96–2·17), giving estimated progression-free survivals of 18·4% (17·2–19·6) 5 years, 4·0% (3·6–4·5) 10 years, and 1·4% (0·9–1·5) 15 years after seroconversion. The rate of progression did not change beyond 10 years after seroconversion (0·28 [95%CI 0·26–0·31] per person-year at 10 years after seroconversion, 0·24 [0·19–0·29] per person-year at 15 years, and 0·18 [0·10–0·33] per person-year at 20 years). At 10 years since HIV seroconversion, 283 individuals had LTNP, of whom 202 subsequently lost this status (median time to loss of status 2·49 years [2·05–2·92]). In univariable analyses, loss of LTNP status was associated with CD4 cell count at 10 years after seroconversion (p<0·0001) and HIV RNA load at 10 years after seroconversion (p=0·005), but not age (p=0·544), mode of infection (p=0·621), sex (p=0·676), or calendar year of seroconversion (p=0·397). In the multivariable analyses, loss of LTNP status was associated with lower CD4 counts at 10 years after seroconversion (p<0·0001). After exclusion of CD4 cell counts from the model, higher HIV RNA load at 10 years after seroconversion was independently associated with loss of LTNP status (p=0·009). Interpretation Progression-free survival is rare. Most individuals with LTNP eventually lose immunological and clinical control of HIV infection eventually. Funding European Union Seventh Framework Programme.
    The Lancet HIV 10/2014; 1(1):e41-e48.
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    ABSTRACT: Ethnic differences have the potential to confound associations between HIV-1 subtype and immunologic progression. We compared declines in CD4 cell counts during untreated infection for the most prevalent HIV-1 subtypes, focusing on distinguishing between the effects of viral subtype and ethnicity. We combined data from 4 European and 6 Canadian cohorts, selecting adults in the stable chronic phase of untreated HIV infection. We estimated the change in square root CD4 cell count over time for subtypes and ethnicities using mixed models, adjusting for covariates selected for their potential effect on initial CD4 cell count or its decline. Data from 9772 patients were analyzed, contributing 79 175 measurements of CD4 cell count and 24 157 person-years of follow-up. Overall, there were no appreciable differences in CD4 cell count decline for viral subtypes A, CRF01_AE, CRF02_AG, C and G compared with viral subtype B; whereas the decline in CD4 cell count in patients of African ancestry was considerably slower than in patients of other ethnicity. When ethnic groups were studied separately, there was evidence for slower declines in CD4 cell count in viral subtypes C, and possibly A and G, compared with viral subtype B in patients of African ancestry but not among patients of other ethnicities, suggesting an interaction between subtype and ethnicity. Ethnicity is a major determinant of CD4 cell count decline; viral subtype differences may have existed but were small compared with the effect of ethnicity and were most apparent in patients of African ancestry. In developing countries, slower CD4 cell count declines among individuals of African descent may translate to a longer asymptomatic phase and increase the opportunity for HIV transmission.
    CMAJ open. 10/2014; 2(4):E318-E329.
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    ABSTRACT: Low bone mineral density (BMD) is common in HIV-positive patients, although the role played by HIV infection versus sociodemographic and metabolic factors remains unclear.
    AIDS (London, England) 09/2014; 28(14):2051-60. · 6.56 Impact Factor
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    ABSTRACT: End-stage kidney disease (ESKD) is a major complication of HIV infection. We observed a 3.8 fold increase in ESKD prevalence among black patients in the UK CHIC cohort during the 12 year study period. As of 2005, 107 patients had an ESKD diagnosis, 69 (64%) of whom were considered suitable for kidney transplantation (KT) and 34 (32%) had received a KT. Survival was similar for KT recipients and those awaiting KT (85% and 89% at five years respectively, p=0.53). Our results endorse the use of KT to manage ESKD in HIV positive patients.
    Journal of acquired immune deficiency syndromes (1999). 07/2014;
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    ABSTRACT: Background With the advent of effective antiretroviral treatment, the life expectancy for people with HIV is now approaching that seen in the general population. Consequently, the relative importance of other traditionally non-AIDS-related morbidities has increased. We investigated trends over time in all-cause mortality and for specific causes of death in people with HIV from 1999 to 2011. Methods Individuals from the Data collection on Adverse events of anti-HIV Drugs (D:A:D) study were followed up from March, 1999, until death, loss to follow-up, or Feb 1, 2011, whichever occurred first. The D:A:D study is a collaboration of 11 cohort studies following HIV-1-positive individuals receiving care at 212 clinics in Europe, USA, and Australia. All fatal events were centrally validated at the D:A:D coordinating centre using coding causes of death in HIV (CoDe) methodology. We calculated relative rates using Poisson regression. Findings 3909 of the 49 731 D:A:D study participants died during the 308 719 person-years of follow-up (crude incidence mortality rate, 12·7 per 1000 person-years [95% CI 12·3–13·1]). Leading underlying causes were: AIDS-related (1123 [29%] deaths), non-AIDS-defining cancers (590 [15%] deaths), liver disease (515 [13%] deaths), and cardiovascular disease (436 [11%] deaths). Rates of all-cause death per 1000 person-years decreased from 17·5 in 1999–2000 to 9·1 in 2009–11; we saw similar decreases in death rates per 1000 person-years over the same period for AIDS-related deaths (5·9 to 2·0), deaths from liver disease (2·7 to 0·9), and cardiovascular disease deaths (1·8 to 0·9). However, non-AIDS cancers increased slightly from 1·6 per 1000 person-years in 1999–2000 to 2·1 in 2009–11 (p=0·58). After adjustment for factors that changed over time, including CD4 cell count, we detected no decreases in AIDS-related death rates (relative rate for 2009–11 vs 1999–2000: 0·92 [0·70–1·22]). However, all-cause (0·72 [0·61–0·83]), liver disease (0·48 [0·32–0·74]), and cardiovascular disease (0·33 [0·20–0·53) death rates still decreased over time. The percentage of all deaths that were AIDS-related (87/256 [34%] in 1999–2000 and 141/627 [22%] in 2009–11) and liver-related (40/256 [16%] in 1999–2000 and 64/627 [10%] in 2009–11) decreased over time, whereas non-AIDS cancers increased (24/256 [9%] in 1999–2000 to 142/627 [23%] in 2009–11). Interpretation Recent reductions in rates of AIDS-related deaths are linked with continued improvement in CD4 cell count. We hypothesise that the substantially reduced rates of liver disease and cardiovascular disease deaths over time could be explained by improved use of non-HIV-specific preventive interventions. Non-AIDS cancer is now the leading non-AIDS cause and without any evidence of improvement. Funding Oversight Committee for the Evaluation of Metabolic Complications of HAART, with representatives from academia, patient community, US Food and Drug Administration, European Medicines Agency and consortium of AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, ViiV Healthcare, Merck, Pfizer, F Hoffmann-La Roche, and Janssen Pharmaceuticals.
    The Lancet 07/2014; 384(9939):241–248. · 39.21 Impact Factor
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    ABSTRACT: The link between CNS penetration of antiretrovirals and AIDS-defining neurologic disorders remains largely unknown.METHODS: HIV-infected, antiretroviral therapy-naive individuals in the HIV-CAUSAL Collaboration who started an antiretroviral regimen were classified according to the CNS Penetration Effectiveness (CPE) score of their initial regimen into low (<8), medium (8-9), or high (>9) CPE score. We estimated "intention-to-treat" hazard ratios of 4 neuroAIDS conditions for baseline regimens with high and medium CPE scores compared with regimens with a low score. We used inverse probability weighting to adjust for potential bias due to infrequent follow-up.RESULTS: A total of 61,938 individuals were followed for a median (interquartile range) of 37 (18, 70) months. During follow-up, there were 235 cases of HIV dementia, 169 cases of toxoplasmosis, 128 cases of cryptococcal meningitis, and 141 cases of progressive multifocal leukoencephalopathy. The hazard ratio (95% confidence interval) for initiating a combined antiretroviral therapy regimen with a high vs low CPE score was 1.74 (1.15, 2.65) for HIV dementia, 0.90 (0.50, 1.62) for toxoplasmosis, 1.13 (0.61, 2.11) for cryptococcal meningitis, and 1.32 (0.71, 2.47) for progressive multifocal leukoencephalopathy. The respective hazard ratios (95% confidence intervals) for a medium vs low CPE score were 1.01 (0.73, 1.39), 0.80 (0.56, 1.15), 1.08 (0.73, 1.62), and 1.08 (0.73, 1.58).CONCLUSIONS: We estimated that initiation of a combined antiretroviral therapy regimen with a high CPE score increases the risk of HIV dementia, but not of other neuroAIDS conditions.
    Neurology 06/2014; · 8.30 Impact Factor
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    ABSTRACT: Objectives The aim of the study was to statistically model the relative increased risk of cardiovascular disease (CVD) per year older in Data collection on Adverse events of anti-HIV Drugs (D:A:D) and to compare this with the relative increased risk of CVD per year older in general population risk equations.Methods We analysed three endpoints: myocardial infarction (MI), coronary heart disease (CHD: MI or invasive coronary procedure) and CVD (CHD or stroke). We fitted a number of parametric age effects, adjusting for known risk factors and antiretroviral therapy (ART) use. The best-fitting age effect was determined using the Akaike information criterion. We compared the ageing effect from D:A:D with that from the general population risk equations: the Framingham Heart Study, CUORE and ASSIGN risk scores.ResultsA total of 24 323 men were included in analyses. Crude MI, CHD and CVD event rates per 1000 person-years increased from 2.29, 3.11 and 3.65 in those aged 40–45 years to 6.53, 11.91 and 15.89 in those aged 60–65 years, respectively. The best-fitting models included inverse age for MI and age + age2 for CHD and CVD. In D:A:D there was a slowly accelerating increased risk of CHD and CVD per year older, which appeared to be only modest yet was consistently raised compared with the risk in the general population. The relative risk of MI with age was not different between D:A:D and the general population.Conclusions We found only limited evidence of accelerating increased risk of CVD with age in D:A:D compared with the general population. The absolute risk of CVD associated with HIV infection remains uncertain.
    HIV Medicine 06/2014; · 3.45 Impact Factor
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    ABSTRACT: No consensus exists on how to define abnormally rapid deterioration in renal function (Rapid Progression, RP). We developed an operational definition of RP in HIV-positive persons with baseline estimated glomerular filtration rate (eGFR) >90ml/min/1.73m2 (using Cockcroft Gault) in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study from 2004 to 2011. Two definitions were evaluated; RP definition A: An average eGFR decline (slope) >=5ml/min/1.73m2/year over four years of follow-up with >=3 eGFR measurements/year, last eGFR <90 ml/min/1.73m2 and an absolute decline >=5ml/min/1.73m2/year in two consecutive years. RP definition B: An absolute annual decline >=5ml/min/1.73m2/year in each year and last eGFR <90ml/min/1.73m2. Sensitivity analyses were performed considering two and three years' follow-up. The percentage with and without RP who went on to subsequently develop incident chronic kidney disease (CKD; 2 consecutive eGFRs <60ml/min/1.73m2 and 3 months apart) was calculated. 22,603 individuals had baseline eGFR >=90ml/min/1.73m2. 108/3655 (3.0%) individuals with >=4 years' follow-up and >=3 measurements/year experienced RP under definition A; similar proportions were observed when considering follow-up periods of three (n=195/6375; 3.1%) and two years (n=355/10756; 3.3%). In contrast under RP definition B, greater proportions experienced RP when considering two years (n=476/10756; 4.4%) instead of three (n=48/6375; 0.8%) or four (n=15/3655; 0.4%) years' follow-up. For RP definition A, 13 (12%) individuals who experienced RP progressed to CKD, and only (21) 0.6% of those without RP progressed to CKD (sensitivity 38.2% and specificity 97.4%); whereas for RP definition B, fewer RP individuals progressed to CKD. Our results suggest using three years' follow-up and at least two eGFR measurements per year is most appropriate for a RP definition, as it allows inclusion of a reasonable number of individuals and is associated with the known risk factors. The definition does not necessarily identify all those that progress to incident CKD, however, it can be used alongside other renal measurements to early identify and assess those at risk of developing CKD. Future analyses will use this definition to identify other risk factors for RP, including the role of antiretrovirals.
    BMC Nephrology 03/2014; 15(1):51. · 1.52 Impact Factor
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    ABSTRACT: Short-term zidovudine monotherapy (ZDVm) remains an option for some pregnant HIV-positive women not requiring treatment for their own health but may affect treatment responses once antiretroviral therapy (ART) is subsequently started. Data were obtained by linking two UK studies: the UK Collaborative HIV Cohort (UK CHIC) study and the National Study of HIV in Pregnancy and Childhood (NSHPC). Treatment responses were assessed for 2028 women initiating ART at least one year after HIV-diagnosis. Outcomes were compared using logistic regression, proportional hazards regression or linear regression. In adjusted analyses, ART-naive (n = 1937) and ZDVm-experienced (n = 91) women had similar increases in CD4 count and a similar proportion achieving virological suppression; both groups had a low risk of AIDS. In this setting, antenatal ZDVm exposure did not adversely impact on outcomes once ART was initiated for the woman's health.
    BMC Infectious Diseases 03/2014; 14(1):127. · 2.56 Impact Factor
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    ABSTRACT: Background. Tenofovir disoproxil fumarate (TDF) has been linked to renal impairment but the extent to which this impairment is reversible is unclear. We aimed to investigate the reversibility of renal decline on TDF.Methods. Cox Proportional Hazards models assessed factors associated with discontinuing TDF in those with >6 months exposure. In those who discontinued TDF, linear piecewise regression models estimated eGFR slopes (mL/min/1.73 m(2)/yr) before, during and after TDF exposure. Factors associated with not achieving eGFR recovery 6 months after discontinuing TDF were assessed using multivariable logistic regression.Results. We observed eGFR declines during TDF exposure (mean (95% CI) slopes -15.7 (-20.5, -10.9) during the first 3 months; -3.1(-4.6, -1.7) thereafter), and evidence of eGFR increases following discontinuation (12.5 (8.9, 16.1) during the first 3 months; 0.8 (0.1, 1.5) thereafter). Following TDF discontinuation, 38.6% of patients with eGFR decline did not experience recovery. A higher baseline eGFR, lower discontinuation eGFR and more prolonged TDF exposure were associated with increased risk of incomplete recovery at 6 months post-TDF discontinuation.Conclusions. This study shows that eGFR decline on TDF was not fully reversible in one third of patients, and suggests that prolonged TDF exposure at low eGFR should be avoided.
    The Journal of Infectious Diseases 02/2014; · 5.85 Impact Factor
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    ABSTRACT: Few data describe antiretroviral treatment (ART)-related adverse events when treatment is initiated at CD4 cell counts more than 350 cells/μl. We compared rates of laboratory-defined adverse events (LDAEs) according to CD4 cell count at initiation. A cohort study. ART-naive persons initiating ART from 2000 to 2010 were included. Chi-square, analysis of variance (ANOVA) and Kruskal-Wallis tests compared characteristics among those starting ART with a CD4 cell count of 350 or less, 351-499 and at least 500 cells/μl. Time-updated Poisson regression compared rates of LDAE in the three CD4 cell strata. Cox proportional hazard models compared risk of ART discontinuation. Nine thousand four hundred and six individuals were included: median age 37 years, 61% white, 80% men, median viral load 4.8 log copies/ml. Four hundred and forty-seven (4.9%) and 1099 (11.7%) started ART with a CD4 cell count at least 500 and 351-499 cells/μl, respectively. One thousand two hundred and eighty-three (13.6%) patients experienced at least one LDAE. The rate of LDAE did not differ between those starting ART with a CD4 cell count 351-499 and less than 350 cells/μl [relative rate 0.90, 95% confidence interval (CI) 0.74-1.09)], but an increased risk of ART discontinuation was observed (hazard ratio 1.58, 95% CI 1.10-2.27). Those starting ART at CD4 cell count at least 500 cells/μl had an increased rate of LDAE (relative rate 1.44, 95% CI 1.13-1.82) but were not more likely to discontinue ART (hazard ratio 1.15, 95% CI 0.64-2.09). This study demonstrates the need to consider ART-related toxicities when initiating therapy at CD4 cell counts at least 500 cells/μl. Although evidence from randomized controlled trials is awaited, the timing of ART initiation in terms of benefits and risks of ART remains an important question.
    AIDS (London, England) 02/2014; · 6.56 Impact Factor

Publication Stats

16k Citations
3,736.31 Total Impact Points


  • 2014
    • UK Department of Health
      Londinium, England, United Kingdom
  • 1998–2014
    • University College London
      • • Department of Infection and Population Health
      • • Department of Primary Care and Population Health (PCPH)
      Londinium, England, United Kingdom
  • 2011–2013
    • Imperial College London
      • Section of Infectious Diseases
      London, ENG, United Kingdom
    • University College Dublin
      • School of Medicine & Medical Science
      Dublin, L, Ireland
  • 2007–2013
    • University of Copenhagen
      • Copenhagen HIV Programme (CHIP)
      Copenhagen, Capital Region, Denmark
    • The Bracton Centre, Oxleas NHS Trust
      Дартфорде, England, United Kingdom
  • 2012
    • North Bristol NHS Trust
      Bristol, England, United Kingdom
    • Gezond Amsterdam
      Amsterdamo, North Holland, Netherlands
    • Guy's and St Thomas' NHS Foundation Trust
      Londinium, England, United Kingdom
  • 2010–2012
    • King's College London
      Londinium, England, United Kingdom
    • British HIV Association
      Londinium, England, United Kingdom
  • 2008–2012
    • Medical Research Council (UK)
      • MRC Clinical Trials Unit
      Londinium, England, United Kingdom
    • St George's, University of London
      Londinium, England, United Kingdom
    • Azienda Ospedaliera San Paolo - Polo Universitario
      Milano, Lombardy, Italy
    • Università degli Studi di Modena e Reggio Emilia
      Modène, Emilia-Romagna, Italy
  • 2006–2012
    • University of Bristol
      • School of Social and Community Medicine
      Bristol, England, United Kingdom
    • Public Health England
      Londinium, England, United Kingdom
    • Municipal Health Service of South Netherlands
      Dordt, South Holland, Netherlands
  • 1994–2012
    • Royal Free London NHS Foundation Trust
      • Department of Haematology
      Londinium, England, United Kingdom
    • University of London
      Londinium, England, United Kingdom
  • 2005–2011
    • Brighton and Sussex University Hospitals NHS Trust
      Brighton, England, United Kingdom
    • Chelsea and Westminster Hospital NHS Foundation Trust
      Londinium, England, United Kingdom
    • University of Milan
      Milano, Lombardy, Italy
    • Federal University of Minas Gerais
      Cidade de Minas, Minas Gerais, Brazil
    • International Society for Disease Surveillance
      Brighton, England, United Kingdom
    • Queen Mary, University of London
      • The Blizard Institute of Cell and Molecular Science
      London, ENG, United Kingdom
  • 2003–2011
    • UCL Eastman Dental Institute
      Londinium, England, United Kingdom
    • Copenhagen University Hospital Hvidovre
      Hvidovre, Capital Region, Denmark
    • University of New South Wales
      • Kirby Institute
      Kensington, New South Wales, Australia
  • 2005–2009
    • Université Victor Segalen Bordeaux 2
      Burdeos, Aquitaine, France
  • 2000–2008
    • University of Liverpool
      Liverpool, England, United Kingdom
  • 2004
    • University of Zurich
      Zürich, Zurich, Switzerland
  • 1999–2003
    • Goethe-Universität Frankfurt am Main
      • Center for Internal Medicine
      Frankfurt, Hesse, Germany
  • 2001
    • Brunel University
      • Health Economics Research Group
      London, ENG, United Kingdom
  • 1997
    • Johns Hopkins Bloomberg School of Public Health
      • Department of Epidemiology
      Baltimore, Maryland, United States
  • 1993–1997
    • The Haemophilia Society
      Londinium, England, United Kingdom
  • 1995
    • Imperial College Healthcare NHS Trust
      Londinium, England, United Kingdom