John Walsh

Publications (20)110.14 Total impact

• Article: British HIV Association guidelines for the treatment of HIV-1-positive adults with antiretroviral therapy 2012.

  Ian Williams, Duncan Churchill, Jane Anderson, Marta Boffito, Mark Bower, Gus Cairns, Kate Cwynarski, Simon Edwards, Sarah Fidler, Martin Fisher, [......], Frank Post, Anton Pozniak, Caroline Sabin, Roy Trevelion, Andrew Ustianowski, John Walsh, Laura Waters, Edmund Wilkins, Alan Winston, Mike Youle
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  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.
  HIV Medicine 09/2012; 13 Suppl 2:1-85. · 3.01 Impact Factor
• Article: Biomarkers to monitor safety in people on art and risk of mortality.

  Loveleen Bansi, Brian Gazzard, Frank Post, Andrew Phillips, Margaret Johnson, Teresa Hill, Richard Gilson, Clifford Leen, John Walsh, Martin Fisher, Caroline Sabin
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  ABSTRACT: Though patients with HIV now have near normal life expectancies as a result of antiretroviral treatment, long-term adverse effects are of growing concern. Using time-updated laboratory measurements, we use several methods to derive a score that can be used to identify individuals at high risk of mortality. Patients who started highly active antiretroviral therapy after 2000 and had ≥1 CD4 count, viral load, and laboratory marker recorded after the date of starting highly active antiretroviral therapy were included in the analyses. Laboratory markers were stratified into quintiles and associations between each marker and mortality was assessed using Poisson regression. The estimates of the final model were used to construct a score for predicting short-term mortality. Several methods, including multiple imputation, were used for analyzing records with missing measurements. Of the 7232 patients included in this analysis, 247 died over 24,796 person-years of follow-up, giving an overall mortality rate of 1.00 (95% confidence interval: 0.87 to 1.12) per 100 person-years. Regardless of which method was used to deal with missing data, albumin, alkaline phosphatase, and hemoglobin were independently associated with mortality. Alanine transaminase was independently associated with mortality when patients with missing measurements were assumed to have measurements within the normal range. The C-statistics for all models ranged from 0.76 to 0.78. Measures of alanine transaminase, albumin, alkaline phosphatase, and hemoglobin in the normal range were predictive of mortality, and hence we suggest using a scoring system to predict mortality which relies on the raw values of these 4 laboratory markers.
  JAIDS Journal of Acquired Immune Deficiency Syndromes 02/2012; 60(1):51-8. · 4.43 Impact Factor
• Article: Does discordancy between the CD4 count and CD4 percentage in HIV-positive individuals influence outcomes on highly active antiretroviral therapy?

  Mark Gompels, David T Dunn, Andrew Phillips, Debbie Dooley, Andrew De Burgh Thomas, Jane Anderson, Frank Post, Deenan Pillay, Brian Gazzard, Teresa Hill, Margaret Johnson, Richard Gilson, Loveleen Bansi, Philippa Easterbrook, Martin Fisher, John Walsh, Chloe Orkin, Jonathan Ainsworth, Clifford Leen, Caroline Sabin
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  ABSTRACT: The CD4 count and CD4 percentage (CD4%) are both strong predictors of clinical disease progression in human immunodeficiency virus (HIV). Although individuals may show discordancy between their CD4 count and CD4%, the clinical relevance of this is unclear. Discordancy was defined where the CD4% was ≤10th percentile for a selected CD4 count range (referred to as low discordancy), within the central 80% range (concordant), or ≥90th percentile (high discordancy). Regression methods identified factors associated with low and high discordancy in untreated individuals and assessed the impact of discordancy on treatment responses to highly active antiretroviral therapy (HAART). High discordancy was associated with female sex, low viral load, and white ethnicity; low discordancy was associated with black or nonwhite ethnicity, older age, and injection drug use. Clinical event rates were higher in individuals with high discordancy starting HAART, but there was no association with subsequent HIV progression by 6 months after starting HAART. CD4 count increases remained lower, by 20 cells/mm(3), in individuals with low discordancy, and higher, by 27 cells/mm(3), in those with high discordancy. Overall discrepancies between the CD4/CD4% are small, confirming the use of absolute CD4 counts as a monitoring tool.
  The Journal of Infectious Diseases 02/2012; 205(4):540-7. · 6.41 Impact Factor
• Article: Lower Healthcare Costs Associated with the Use of a Single-Pill ARV Regimen in the UK, 2004-2008.

  Eduard J Beck, Sundhiya Mandalia, Roshni Sangha, Mike Youle, Ray Brettle, Mark Gompels, Margaret Johnson, Anton Pozniak, Achim Schwenk, Stephen Taylor, John Walsh, Ed Wilkins, Ian Williams, Brian Gazzard
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  ABSTRACT: AIM: Investigate the cost and effects of a single-pill versus two- or three pill first-line antiretroviral combinations in reducing viral load, increasing CD4 counts, and first-line failure rate associated with respective regimens at 6 and 12 months. METHODS: Patients on first-line TDF+3TC+EFV, TDF+FTC+EFV, Truvada®+EFV or Atripla® between 1996-2008 were identified and viral load and CD4 counts measured at baseline, six and twelve months respectively. Factors that independently predicted treatment failure at six and twelve months were derived using multivariate Cox's proportional hazard regression analyses. Use and cost of hospital services were calculated at six and twelve months respectively. RESULTS: All regimens reduced viral load to below the limit of detection and CD4 counts increased to similar levels at six and twelve months for all treatment regimens. No statistically significant differences were observed for rate of treatment failure at six and twelve months. People on Atripla® generated lower healthcare costs for non-AIDS patients at £5,340 (£5,254 to £5,426) per patient-semester and £9,821 (£9,719 to £9,924) per patient-year that was £1,344 (95%CI £1,222 to £1,465) less per patient-semester and £1,954 (95%CI £1,801 to £2,107) less per patient-year compared with Truvada®+EFV; healthcare costs for AIDS patients were similar across all regimens. CONCLUSION: The single pill regimen is as effective as the two- and three-pill regimens of the same drugs, but if started as first-line induction therapy there would be a 20% savings on healthcare costs at six and 17% of costs at twelve months compared with Truvada®+EFV, that generated the next lowest costs.
  PLoS ONE 01/2012; 7(10):e47376. · 4.09 Impact Factor
• Article: HIV-associated central nervous system diseases in the recent combination antiretroviral therapy era.

  Lucy Garvey, Alan Winston, John Walsh, Frank Post, Kholoud Porter, Brian Gazzard, Martin Fisher, Clifford Leen, Deenan Pillay, Teresa Hill, Margaret Johnson, Richard Gilson, Jane Anderson, Philippa Easterbrook, Loveleen Bansi, Chloe Orkin, Jonathan Ainsworth, Andrew N Phillips, Caroline A Sabin
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  ABSTRACT: Data describing the incidence and survival of HIV-related central nervous system diseases (CNS-D) in recent years are sparse. Between 1996 and 2007, adult subjects without previous CNS-D within a large UK cohort were included (n=30,954). CNS-D were HIV encephalopathy (HIVe), progressive multifocal leucoencephalopathy (PML), cerebral toxoplasmosis (TOXO) and cryptococcal meningitis (CRYP). Associations between demographic, clinical and laboratory parameters with incidence and survival of CNS-D were evaluated using Poisson regression analysis and Kaplan-Meier techniques. Six hundred and thirteen new CNS-D occurred in 574 subjects (HIVe:187, PML:113, TOXO:184, CRYP:129). Incidence of all CNS-D declined from 13.1 per 1000 PY in 1996/1997 to 1.0 per 1000 PY in 2006/2007 (P=0.0001). Current CD4+ cell count below 200 cells/ul and plasma HIV RNA above 100,000 copies/ml were independently associated with the development of CNS-D. Calendar year 1996/1997, older age, prior AIDS diagnosis and PML diagnosis were significantly associated with shorter survival. An ongoing decline in the incidence of CNS-D has been observed in very recent years. Mortality following such a diagnosis remains high.
  European Journal of Neurology 03/2011; 18(3):527-34. · 3.69 Impact Factor
• Article: Outcomes in the first year after initiation of first-line HAART among heterosexual men and women in the UK CHIC Study.

  Tristan J Barber, Anna Maria Geretti, Jane Anderson, Achim Schwenk, Andrew N Phillips, Loveleen Bansi, Richard Gilson, Teresa Hill, John Walsh, Martin Fisher, [......], Philippa Easterbrook, Brian Gazzard, Adrian Palfreeman, Chloe Orkin, Clifford Leen, Mark Gompels, David Dunn, Valerie Delpech, Deenan Pillay, Caroline A Sabin
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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
• Source

  Available from: Jane Anderson

  Article: Cost-effectiveness of early treatment with first-line NNRTI-based HAART regimens in the UK, 1996-2006.

  Eduard J Beck, Sundhiya Mandalia, Gary Lo, Peter Sharott, Mike Youle, Jane Anderson, Guy Baily, Ray Brettle, Martin Fisher, Mark Gompels, George Kinghorn, Margaret Johnson, Brendan McCarron, Anton Pozniak, Alan Tang, John Walsh, David White, Ian Williams, Brian Gazzard
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  ABSTRACT: Calculate time to first-line treatment failure, annual cost and cost-effectiveness of NNRTI versus PIboosted first-line HAART regimens in the UK, 1996-2006. Population costs for HIV services are increasing in the UK and interventions need to be effective and efficient to reduce or stabilize costs. 2NRTIs + NNRTI regimens are cost-effective regimens for first-line HAART, but these regimens have not been compared with first-line PI(boosted) regimens. Times to first-line treatment failure and annual costs were calculated for first-line HAART regimens by CD4 count when starting HAART (2006 UK prices). Cost-effectiveness of 2NRTIs+NNRTI versus 2NRTIs+PI(boosted) regimens was calculated for four CD4 strata. 55% of 5,541 people living with HIV (PLHIV) started HAART with CD4 count ≤ 200 cells/mm3, many of whom were Black Africans. Annual treatment cost decreased as CD4 count increased; most marked differences were observed between starting HAART with CD4 ≤ 200 cells/mm3 compared with CD4 count >200 cells/mm3. 2NRTI+PI(boosted) and 2NRTI+NNRTI regimens were the most effective regimens across the four CD4 strata; 2NRTI + NNRTI was cost-saving or cost-effective compared with 2NRTI + PI(boosted) regimens. To ensure more effective and efficient provision of HIV services, 2NRTI+NNRTI should be started as first-line HAART regimen at CD4 counts ≤ 350 cell/mm3, unless specific contra-indications exist. This will increase the number of PLHIV receiving HAART and will initially increase population costs of providing HIV services. However, starting PLHIV earlier on cost-effective regimens will maintain them in better health and use fewer health or social services, thereby generating fewer treatment and care costs, enabling them to remain socially and economically active members of society. This does raise a number of ethical issues, which will have to be acknowledged and addressed, especially in countries with limited resources.
  PLoS ONE 01/2011; 6(5):e20200. · 4.09 Impact Factor
• Source

  Available from: Jane Anderson

  Article: Impact of late diagnosis and treatment on life expectancy in people with HIV-1: UK Collaborative HIV Cohort (UK CHIC) Study.

  Margaret May, Mark Gompels, Valerie Delpech, Kholoud Porter, Frank Post, Margaret Johnson, David Dunn, Adrian Palfreeman, Richard Gilson, Brian Gazzard, [......], John Walsh, Martin Fisher, Chloe Orkin, Jonathan Ainsworth, Loveleen Bansi, Andrew Phillips, Clifford Leen, Mark Nelson, Jane Anderson, Caroline Sabin
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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.
• Source

  Available from: Mark Gompels

  Article: The cost-effectiveness of early access to HIV services and starting cART in the UK 1996-2008.

  Eduard J Beck, Sundhiya Mandalia, Roshni Sangha, Peter Sharott, Mike Youle, Guy Baily, Ray Brettle, Mark Gompels, Margaret Johnson, Brendan McCarron, Ed Ong, Anton Pozniak, Achim Schwenk, Stephen Taylor, John Walsh, Ed Wilkins, Ian Williams, Brian Gazzard
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  ABSTRACT: To calculate use, cost and cost-effectiveness of people living with HIV (PLHIV) starting routine treatment and care before starting combination antiretroviral therapy (cART) and PLHIV starting first-line 2NRTIs+NNRTI or 2NRTIs+PI(boosted), comparing PLHIV with CD4≤200 cells/mm3 and CD4>200 cells/mm3. Few studies have calculated the use, cost and cost-effectiveness of routine treatment and care before starting cART and starting cART above and below CD4 200 cells/mm3. Use, costs and cost-effectiveness were calculated for PLHIV in routine pre-cART and starting first-line cART, comparing CD4≤200 cells/mm3 with CD4>200 cells/mm3 (2008 UK prices). cART naïve patients CD4≤200 cells/mm3 had an annual cost of £6,407 (95%CI £6,382 to £6,425) PPY compared with £2,758 (95%CI £2,752 to £2,761) PPY for those with CD4>200 cells/mm3; cost per life year gained of pre-cART treatment and care for those with CD4>200 cells/mm3 was £1,776 (cost-saving to £2,752). Annual cost for starting 2NRTIs+NNRTI or 2NRTIs+PI(boosted) with CD4≤200 cells/mm3 was £12,812 (95%CI £12,685-£12,937) compared with £10,478 (95%CI £10,376-£10,581) for PLHIV with CD4>200 cells/mm3. Cost per additional life-year gained on first-line therapy for those with CD4>200 cells/mm3 was £4639 (£3,967 to £2,960). PLHIV starting to use HIV services before CD4≤200 cells/mm3 is cost-effective and enables them to be monitored so they start cART with a CD4>200 cells/mm3, which results in better outcomes and is cost-effective. However, 25% of PLHIV accessing services continue to present with CD4≤200 cells/mm3. This highlights the need to investigate the cost-effectiveness of testing and early treatment programs for key populations in the UK.
  PLoS ONE 01/2011; 6(12):e27830. · 4.09 Impact Factor
• Article: Data linkage reduces loss to follow-up in an observational HIV cohort study.

  Teresa Hill, Loveleen Bansi, Caroline Sabin, Andrew Phillips, David Dunn, Jane Anderson, Philippa Easterbrook, Martin Fisher, Brian Gazzard, Richard Gilson, Margaret Johnson, Clifford Leen, Chloe Orkin, Achim Schwenk, John Walsh, Alan Winston, Abdel Babiker, Valerie Delpech
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  ABSTRACT: To ascertain the degree of loss to follow-up in a cohort and to identify its predictors. Human immunodeficiency virus (HIV)-infected individuals without CD4 cell counts for a year or more were defined as potentially lost to follow-up (LFU). Multivariable Poisson regression models identified the risk factors for potential LFU. Multivariable logistic regression models compared demographic and clinical characteristics of those who returned for care and those permanently LFU. Of 16,595 patients under follow-up, 43.6% were potentially LFU at least once. Of these, 39.8% were considered permanently LFU and 60.2% were seen again after 1 year. Of 9,766 episodes when patients were potentially LFU, 59% resulted in the patient returning for care at the same clinic or at a different clinic. Compared with those permanently LFU, patients returning were more likely to have started highly active antiretroviral therapy, to have higher CD4 counts and viral loads, to be younger, and to have had more CD4 tests before LFU. They were less likely to have had a previous episode of potential LFU. A substantial proportion of patients in the UK Collaborative HIV Cohort study are potentially LFU. Data linkage identifies patients returning for care at different centers. Recognition of factors associated with LFU may help reduce this important source of bias in observational databases.
  Journal of clinical epidemiology 03/2010; 63(10):1101-9. · 2.96 Impact Factor
• Article: The effects of a nucleoside-sparing antiretroviral regimen on the pharmacokinetics of ritonavir-boosted darunavir in HIV type-1-infected patients.

  Lucy Garvey, Ngaire Latch, Otto W Erlwein, Nicola E Mackie, John Walsh, George Scullard, Myra O McClure, Laura Dickinson, David Back, Alan Winston
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  ABSTRACT: Nucleoside-sparing combination antiretroviral therapy (cART) regimens might be an attractive therapeutic option for HIV type-1 (HIV-1)-infected patients; however, the pharmacokinetic profiles of such regimens are frequently unknown. Fourteen HIV-1-infected patients (age 21-55 years, 64% male) on stable cART with plasma HIV RNA <50 copies/ml entered this Phase I pharmacokinetic study. In period 1, patients received tenofovir/emtricitabine/-darunavir/ritonavir (300/200/800/100 mg) all once daily. During period 2, raltegravir 400 mg twice daily was added to the regimen and in period 3 tenofovir/emtricitabine was discontinued. At steady state, intensive pharmacokinetic sampling was undertaken. Differences in the geometric mean ratio (GMR) for pharmacokinetic parameters between periods 2 versus 1 and period 3 versus 1 were assessed for darunavir and ritonavir (period 3 versus 2 for raltegravir). No statistically significant differences in pharmacokinetic parameters were observed between period 2 versus period 1. During period 3, darunavir GMR (95% confidence interval) values for trough and maximum plasma concentration (C(trough) and C(max)), area under the plasma concentration-time curve (AUC) and elimination half-life (t(1/2)) were 0.64 ng/ml (0.44-0.93), 1.05 ng/ml (0.90-1.24), 0.92 ng h/ml (0.78-1.08) and 0.69 h (0.46-1.05), respectively, when compared with period 1. No statistically significant changes were observed in ritonavir or raltegravir pharmacokinetic parameters. Darunavir C(trough)<550 ng/ml (the minimum effective concentration for protease-resistant HIV viral isolates) was observed in four patients during period 3 only. No clinically significant safety concerns were reported. Darunavir C(trough) is reduced by 36% when administered without tenofovir/emtricitabine in HIV-1-infected patients. This interaction might be of clinical significance in the management of individuals with protease-resistant HIV viral isolates.
  Antiviral therapy 01/2010; 15(2):213-8. · 3.16 Impact Factor
• Source

  Available from: Jane Anderson

  Article: Rising population cost for treating people living with HIV in the UK, 1997-2013.

  Sundhiya Mandalia, Roshni Mandalia, Gary Lo, Tim Chadborn, Peter Sharott, Mike Youle, Jane Anderson, Guy Baily, Ray Brettle, Martin Fisher, [......], George Kinghorn, Margaret Johnson, Brendan McCarron, Anton Pozniak, Alan Tang, John Walsh, David White, Ian Williams, Brian Gazzard, Eduard J Beck
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  ABSTRACT: The number of people living with HIV (PLHIV) is increasing in the UK. This study estimated the annual population cost of providing HIV services in the UK, 1997-2006 and projected them 2007-2013. Annual cost of HIV treatment for PLHIV by stage of HIV infection and type of ART was calculated (UK pounds, 2006 prices). Population costs were derived by multiplying the number of PLHIV by their annual cost for 1997-2006 and projected 2007-2013. Average annual treatment costs across all stages of HIV infection ranged from £17,034 in 1997 to £18,087 in 2006 for PLHIV on mono-therapy and from £27,649 in 1997 to £32,322 in 2006 for those on quadruple-or-more ART. The number of PLHIV using NHS services rose from 16,075 to 52,083 in 2006 and was projected to increase to 78,370 by 2013. Annual population cost rose from £104 million in 1997 to £483 million in 2006, with a projected annual cost between £721 and £758 million by 2013. When including community care costs, costs increased from £164 million in 1997, to £683 million in 2006 and between £1,019 and £1,065 million in 2013. Increased number of PLHIV using NHS services resulted in rising UK population costs. Population costs are expected to continue to increase, partly due to PLHIV's longer survival on ART and the relative lack of success of HIV preventing programs. Where possible, the cost of HIV treatment and care needs to be reduced without reducing the quality of services, and prevention programs need to become more effective. While high income countries are struggling to meet these increasing costs, middle- and lower-income countries with larger epidemics are likely to find it even more difficult to meet these increasing demands, given that they have fewer resources.
  PLoS ONE 01/2010; 5(12):e15677. · 4.09 Impact Factor
• Article: Virological response to initial antiretroviral regimens containing abacavir or tenofovir.

  Loveleen Bansi, Caroline Sabin, Richard Gilson, Brian Gazzard, Clifford Leen, Jane Anderson, David Dunn, Teresa Hill, Martin Fisher, Jonathan Ainsworth, Deenan Pillay, Margaret Johnson, John Walsh, Chloe Orkin, Philippa Easterbrook, Mark Gompels, Andrew Phillips
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  ABSTRACT: Patients with a baseline viral load >100,000 copies/mL receiving abacavir (ABC) as part of the nucleoside-backbone component of their first highly active antiretroviral therapy (HAART) regimen have been reported to have a greater failure rate than those receiving tenofovir (TDF). We analyzed short-term outcomes of the use of HAART combinations that included ABC or TDF. The mean 2-8-week change in viral load was calculated using linear regression. In total, 1136 patients started ABC, and 412 started TDF. After adjustment for baseline viral load and other factors, there was no difference in the change in viral load between the patients who started ABC and those who started TDF (0.03 [95% confidence interval, -0.07 to 0.12]) log copies/mL; P = .59). Furthermore, there was no evidence that this effect differed according to baseline viral load (P = .88 for the interaction between pre-HAART viral load and nucleoside started). Likewise, there was no difference in rates of virological failure between the 2 drugs at 24-48 weeks after starting HAART.
  The Journal of Infectious Diseases 09/2009; 200(5):710-4. · 6.41 Impact Factor
• Article: CD4 counts and the risk of systemic non-Hodgkin's lymphoma in individuals with HIV in the UK.

  Mark Bower, Martin Fisher, Teresa Hill, Iain Reeves, John Walsh, Chloe Orkin, Andrew N Phillips, Loveleen Bansi, Richard Gilson, Philippa Easterbrook, Margaret Johnson, Brian Gazzard, Clifford Leen, Deenan Pillay, Achim Schwenk, Jane Anderson, Kholoud Porter, Mark Gompels, Caroline A Sabin
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  ABSTRACT: Since the introduction of highly active antiretroviral therapy, there has been a decline in the incidence of non-Hodgkin's lymphoma among HIV-infected individuals. We described trends in the incidence of systemic non-Hodgkin's lymphoma in the UK CHIC Study from 1996-2006 and evaluated the association between immunosuppression and development of systemic non-Hodgkin's lymphoma: 286/23,155 (1.2%) individuals developed an AIDS-defining lymphoma (258 systemic). Younger age, receipt of highly active antiretroviral therapy and later calendar year were all independently associated with a reduced risk of systemic non-Hodgkin's lymphoma. A lower latest CD4 count was strongly associated with systemic non-Hodgkin's lymphoma, in patients who had (RR per log(2)(cells/mm(3)) higher: 0.62) and had not (0.70) received highly active antiretroviral therapy. Associations with other measures of immunosuppression, including nadir CD4 count, experience and duration of severe immunosuppression, were generally weaker. Earlier highly active anti-retroviral therapy initiation and wider access to HIV testing is advocated to reduce the risk of systemic non-Hodgkin's lymphoma.
  Haematologica 04/2009; 94(6):875-80. · 6.42 Impact Factor
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  Available from: Jane Anderson

  Article: British HIV Association Guidelines for the treatment of HIV-1-infected adults with antiretroviral therapy 2008.

  B G Gazzard, Jane Anderson, Abdel Babiker, Marta Boffito, Gary Brook, Gary Brough, Duncan Churchill, Ben Cromarty, Satyajit Das, Martin Fisher, [......], Devaki Nair, Barry Peters, Andrew Phillips, Deenan Pillay, Anton Pozniak, John Walsh, Ed Wilkins, Ian Williams, Matthew Williams, Mike Youle
  HIV Medicine 11/2008; 9(8):563-608. · 3.01 Impact Factor
• Article: Concomitant use of nonnucleoside analogue reverse transcriptase inhibitors and rifampicin in TB/HIV type 1-coinfected patients.

  Leena Sathia, Ifeyinwa Obiorah, Graham Taylor, Onn Kon, Marie O'Donoghue, Sara Gibbins, John Walsh, Alan Winston
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  ABSTRACT: Pharmacokinetic interactions between rifampicin and nonnucleoside analogue reverse transcriptase inhibitors (NNRTIs) pose challenges in the treatment of TB/HIV coinfection. We describe NNRTI plasma concentrations (PC) and treatment outcomes in TB/HIV coinfected patients receiving rifampicin and NNRTIs concomitantly. Single center prospective data were collected on all TB/HIV-coinfected patients who received concomitant NNRTI and rifampicin between 2001 and 2005. Of 103 TB/HIV coinfected patients, 26 received concomitant rifampicin with efavirenz (EFV) and 17 with nevirapine (NVP). NNRTIs were commenced after rifampicin in 18/26 (69%) and 7/17 (41%) subjects treated with EFV and NVP, respectively. Of these 88% completed antituberculosis therapy. There were two (5%) deaths, both due to lymphoproliferative malignancy. Three (7%) patients transferred care or discontinued therapy. Of subjects 83% had normal liver function tests (LFTs) and 11% had Grade 1-2 and 6% Grade 3-4 LFT abnormalities during concomitant therapy. PCs were measured in 31 patients. The first PCs were within the therapeutic range in 5/7 on NVP 200 mg bd, 2/4 on NVP 300 mg bd, 3/7 EFV 600 mg od, and 7/13 on EFV 800 mg od. PCs were subtherapeutic in 4/11 (36%) and 3/20 (20%) subjects on NVP and EFV, respectively. No virological rebounds were observed. Of subjects receiving concomitant NVP or EFV with rifampicin, 64% and 80%, respectively, had therapeutic NNRTI PCs. Subtherapeutic PCs were not associated with virological failure. Good clinical outcomes and a low incidence of hepatotoxicity were observed.
  AIDS research and human retroviruses 08/2008; 24(7):897-901. · 2.18 Impact Factor
• Article: Changes in outcome of persons initiating highly active antiretroviral therapy at a CD4 count less than 50 Cells/mm3.

  Kholoud Porter, Sarah Walker, Teresa Hill, Jane Anderson, Clifford Leen, Margaret Johnson, Brian Gazzard, John Walsh, Martin Fisher, Chloe Orkin, Achim Schwenk, Richard Gilson, Philippa Easterbrook, Valerie Delpech, Caroline A Sabin
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  ABSTRACT: Although HIV treatment guidelines recommend highly active antiretroviral therapy (HAART) initiation before reaching a CD4 count of 200 cells/mm3, many people in resource-rich settings, and a substantial proportion in resource-limited settings, present at levels <50 cells/mm3. Using UK Collaborative HIV Cohort data, we assessed virologic response to HAART for antiretroviral-naive persons initiating therapy at a CD4 count <50 cells/mm3. We also investigated changes in the probability of having a viral level <400 copies/mL at 48 weeks over calendar time adjusting for gender, age, exposure category, ethnicity, baseline CD4 count and viral load, and whether the regimen contained a protease inhibitor. At 12, 24, 36, and 48 weeks, 80%, 83%, 85%, and 83% of participants, respectively, had a viral level <400 copies/mL. This proportion rose from 1997 to 1998, falling slightly in the most recent calendar period. By far the most important predictor of virologic suppression was calendar year of starting HAART (odds ratio [OR] = 2.49, 4.28, and 3.28 for 1999 to 2000, 2001 to 2002, and 2003 to 2005, respectively, compared with 1997 to 1998). Women were more likely to have a viral level <400 copies/mL at week 48 compared with men (OR = 1.74, 95% confidence interval [CI]: 1.07 to 3.02), as were older individuals (OR = 1.46, 95% CI: 1.11 to 1.96 for every 10 years older). There was marginal or no evidence that other factors were associated with outcome. The estimated corresponding probabilities of achieving a viral level <50 copies/mL at week 48 were 71%, 75%, and 79% for a woman aged 25, 35, and 45 years, respectively, initiating HAART in the most recent calendar period. The respective probabilities for a man at those ages were 68%, 73%, and 78%. These data, albeit under conditions of good infrastructure for care delivery, are a useful comparator for other populations starting therapy at similar levels of immunodeficiency and may be valuable for evaluating the success of antiretroviral therapy rollout programs.
  JAIDS Journal of Acquired Immune Deficiency Syndromes 02/2008; 47(2):202-5. · 4.43 Impact Factor
• Article: Risk of extensive virological failure to the three original antiretroviral drug classes over long-term follow-up from the start of therapy in patients with HIV infection: an observational cohort study.

  Andrew N Phillips, Clifford Leen, Alan Wilson, Jane Anderson, David Dunn, Achim Schwenk, Chloe Orkin, Teresa Hill, Martin Fisher, John Walsh, Deenan Pillay, Loveleen Bansi, Brian Gazzard, Philippa Easterbrook, Richard Gilson, Margaret Johnson, Caroline A Sabin
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  ABSTRACT: The long-term durability of viral-load suppression provided by the three original antiretroviral drugs is not well characterised. We estimated the proportion of patients who had extensive triple-class failure during long-term follow-up and examined characteristics associated with an increased rate of failure. 7916 patients who started antiretroviral therapy with three or more drugs were followed up from the time that therapy started until the last viral-load measure. Extensive triple-class virological failure was defined by failure of three subclasses of nucleoside reverse transcriptase inhibitors, a non-nucleoside reverse transcriptase inhibitor, and a ritonavir-boosted protease inhibitor. 167 patients developed extensive triple-class failure during 27 441 person-years of follow-up. The Kaplan-Meier estimate for the cumulative risk of extensive triple-class failure was 9.2% by 10 years (95% CI 5.0-13.4). There was evidence that this rate has decreased over time (adjusted hazard ratio 0.86 [0.77-0.96] per year more recent; p=0.006). Of the 167 patients with extensive triple-class failure, 101 (60%) subsequently had at least one viral load less than 50 copies per mL. The risk of death by 5 years from the time of extensive triple-class failure was 10.6% (2.4-18.8, nine deaths). We have shown that extensive virological failure of the three main classes of drugs occurs slowly in routine clinical practice. This finding has implications for the planning of treatment programmes in developing countries, where additional drugs outside these classes are unlikely to be available for some time.
  The Lancet 01/2008; 370(9603):1923-8. · 38.28 Impact Factor
• Article: Rate of AIDS diseases or death in HIV-infected antiretroviral therapy-naive individuals with high CD4 cell count.

  Andrew N Phillips, Brian Gazzard, Richard Gilson, Philippa Easterbrook, Margaret Johnson, John Walsh, Clifford Leen, Martin Fisher, Chloe Orkin, Jane Anderson, Deenan Pillay, Valerie Delpech, Caroline Sabin, Achim Schwenk, David Dunn, Mark Gompels, Teresa Hill, Kholoud Porter, Abdel Babiker
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  ABSTRACT: 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. Analysis of data from an ongoing HIV cohort study. 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 > or = 350 cells/microl among patients in the UK CHIC Study. 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/microl 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/microl compared with those with CD4 cell count > or = 650 cells/microl 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 > or = 350 cells/microl , 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. The trend of decreasing rate of AIDS and death with higher CD4 cell count is present throughout the CD4 cell count > or = 350 cells/microl range in ART-naive people.
  AIDS 08/2007; 21(13):1717-21. · 6.24 Impact Factor
• Article: Impact of late diagnosis and treatment on life expectancy in people with HIV-1: UK Collaborative HIV Cohort (UK CHIC) Study

  Margaret May, Mark Gompels, Valerie Delpech, Kholoud Porter, Frank Post, Margaret Johnson, David Dunn, Adrian Palfreeman, Richard Gilson, Brian Gazzard, [......], John Walsh, Martin Fisher, Chloe Orkin, Jonathan Ainsworth, Loveleen Bansi, Andrew Phillips, Clifford Leen, Mark Nelson, Jane Anderson, Caroline Sabin
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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.