Showing papers by "Chloe Orkin published in 2011"

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

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 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 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.

HIV-associated central nervous system diseases in the recent combination antiretroviral therapy era.

Abstract: BACKGROUND AND PURPOSE Data describing the incidence and survival of HIV-related central nervous system diseases (CNS-D) in recent years are sparse. METHODS 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. RESULTS 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. CONCLUSIONS An ongoing decline in the incidence of CNS-D has been observed in very recent years. Mortality following such a diagnosis remains high.

Antiretroviral therapy CNS penetration and HIV-1-associated CNS disease

Abstract: Objective: 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. Methods: 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. Results: 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. Conclusion: 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.

Long-term trends in CD4 cell counts and impact of viral failure in individuals starting antiretroviral therapy: UK Collaborative HIV Cohort (CHIC) study

Abstract: OBJECTIVE 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. METHODS Eligible participants from the UK Collaborative HIV Cohort (CHIC) were antiretroviralnaive 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. FINDINGS 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. CONCLUSIONS 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.

Outcomes in the First Year after Initiation of First-Line Haart among Heterosexual Men and Women in the Uk Chic Study:

Abstract: BACKGROUND We analysed the influence of gender on use and outcomes of first-line HAART in a UK cohort METHODS Analyses included heterosexuals starting HAART from 1998-2007 with pre-treatment CD4(+) T-cell count 500 copies/ml Virological suppression ( 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 RESULTS 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 38 years (IQR 20-62) At 6 and 12 months, 727% and 753% had VL≤50 copies/ml, with no large differences between genders at either time after adjustment for confounders (6 months, OR 092 [95% CI 076-113]; 12 months, OR 106 [95% CI 085-131]) Overall, 794% patients achieved virological suppression and 192% experienced virological rebound, without gender differences, although men had an increased risk of rebound after excluding pregnant women (adjusted relative hazard [RH] 133 [95% CI 104-171]) 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 -146 cells/mm(3) (95% CI -246--45) and -121 cells/mm(3) (95% CI -244-02) 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 072 [95% CI 063-083]) CONCLUSIONS 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

N-terminal-proB-type natriuretic peptide predicts cardiovascular disease events in HIV-infected patients

Abstract: Background: Cardiovascular disease (CVD) is increasing in HIV-infected patients. N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a significant predictor of CVD in the general population. We aimed to quantify the risk of CVD events associated with NT-proBNP at baseline in the Strategies for Management of Anti-Retroviral Therapy study. Methods: In a nested case-control study, NT-proBNP was measured at baseline in 186 patients who experienced a CVD event over an average of 2.8 years of follow-up and in 329 matched controls. Odds ratios (ORs) associated with baseline levels of NT-proBNP for CVD were estimated using conditional logistic regression. Results: At baseline median NT-proBNP [interquartile range (IQR)] was 48.1 (18.5, 112.9) pg/ml in patients who developed a CVD event and 25.7 (12.4, 50.2) pg/ml in controls. The unadjusted OR for the highest versus the lowest quartile was 3.7 [95% confidence interval (CI) 2.1-6.5, P < 0.0001 ]. After adjustment for baseline covariates and CVD risk factors, OR was 2.8 (95% CI 1.4-5.6, P=0.003); with additional adjustment for IL-6, high-sensitivity C-reactive protein and D-dimer, OR was 2.3 (95% CI 1.1-4.9, P=0.02). Conclusions: Higher levels of NT-proBNP are associated with increased risk of CVD in HIV patients after considering established CVD risk factors and markers for inflammation and thrombosis.

Responses to highly active antiretroviral therapy and clinical events in patients with a low CD4 cell count: late presenters vs. late starters

Abstract: OBJECTIVE 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. METHODS 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 350 cells/μL; starting HAART 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. RESULTS 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. CONCLUSION 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.

Uptake and outcome of combination antiretroviral therapy in men who have sex with men according to ethnic group: the UK CHIC Study

Abstract: Background:We investigated differences in retention in HIV care and uptake of combination antiretroviral therapy (cART) and treatment outcomes between different ethnic men who have sex with men (MSM) groups. Methods:MSM subjects with known ethnicity and ≥1 day follow-up from 1996 to 2009 in the UK Collaborative HIV Cohort Study were included. Black and minority ethnic (BME) men were categorized as: black; Indian/Pakistani/Bangladeshi; other Asian/Oriental; and other/mixed. Logistic regression was used to identify factors associated with treatment initiation within the 6 months after each CD4 count. HIV viral load, CD4 counts, discontinuation/switch of a drug in the initial cART regimen, and development of a new AIDS event/death at 6 and 12 months were also analyzed. Results:Of 16,406 MSM, 1818 (11.0%) were BME; 892 (49.1%) black, 139 (7.6%) Indian/Pakistani/Bangladeshi, 254 (13.9%) other Asian/Oriental, 532 (29.2%) other/mixed. The proportion of MSM with no follow-up after HIV diagnosis was higher among BME than white MSM (3.4% vs. 2.2%, P = 0.002). Permanent loss to follow-up was highest in the other/mixed and lowest in Indian/Pakistani/Bangladeshi groups (P = 0.02). Six thousand three hundred thirty-eight MSM initiated first cART from January 1, 2000, to January 1, 2009. In multivariable analyses, BME MSM were 18% less likely to initiate cART than white MSM with similar CD4 counts [adjusted odds ratio 0.82 (95% confidence interval: 0.74 to 0.91), P = 0.0001]. However, once on cART, there were no differences in virological, immunological, and clinical outcomes. Conclusions:This study demonstrates that despite BME MSM being a “minority within a minority” for those HIV infected, there are few ethnic disparities in access to and treatment outcomes in our setting.

Authors' response to Drs Scourfield, Jackson and Nelson: Letter to the Editor

Abstract: 1 Waters L, Fisher M, Anderson J et al. for the UK CHIC Steering Committee. Responses to highly active antiretroviral therapy and clinical events in patients with a low CD4 cell count: late presenters vs. late starters. HIV Med 2011; 12: 289–298. 2 Mocroft A, Reiss P, Kirk O et al. for the Opportunistic Infections Project Team of the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE). Is it safe to discontinue primary Pneumocystis jiroveci pneumonia prophylaxis in patients with virologically suppressed HIV infection and a CD4 cell count o200 cells/microL? Clin Infect Dis 2010; 51: 611–619. Erratum in: Clin Infect Dis 2010; 51: 1114.