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  • Phillips, Andrew  (92)
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  • 1
    Language: English
    In: The Journal of infectious diseases, 01 February 2007, Vol.195(3), pp.410-5
    Description: Production of herpes simplex virus (HSV)-specific interferon- gamma by peripheral-blood mononuclear cells (PBMCs) of HSV-seropositive healthy donors and human immunodeficiency virus-infected persons was determined by use of ELISPOT. The mean +/- SD number of spot-forming cells/10(6) PBMCs was 314 +/- 74 in 11 healthy donors, 360 +/- 69 in 3 long-term nonprogressors (LTNPs), 186 +/- 52 in 9 newly diagnosed patients, and 181 +/- 59 in 33 patients who were receiving highly active antiretroviral therapy (HAART) for a median period of 30 months (range, 1-109 months). In 9 patients monitored prospectively while receiving virologically and immunologically successful first-line HAART, the number of spot-forming cells increased by 5.6/month (95% confidence interval, 1.2-9.9 [P=.01]) and 21.3/100 CD4 cells/mm(3) gained (95% confidence interval, 13.8-28.7 [P〈.0001]). Responses were correlated with LTNP status and CD4 cell count.
    Keywords: HIV ; Anti-HIV Agents -- Therapeutic Use ; HIV Infections -- Complications ; Herpes Simplex -- Complications ; Simplexvirus -- Immunology ; T-Lymphocytes -- Immunology
    ISSN: 0022-1899
    E-ISSN: 15376613
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  • 2
    Language: English
    In: Archives of internal medicine, 2005, Vol.165(4), pp.416-423
    Description: BACKGROUND: Although the incidence of most AIDS events declines after initiation of highly active antiretroviral therapy (HAART), this decline is more rapid for some conditions than others. We herein describe the decline in incidence of AIDS-defining events among 12,574 antiretroviral-naive individuals who started HAART in the Antiretorviral Therapy Cohort Collaboration and determined whether the rate of decline is similar for events with different etiologies. METHODS: Rates of AIDS were calculated for the periods 0 to 3, 4 to 6, 7 to 12, 13 to 24, and 25 to 36 months after starting HAART. Changes in incidence over time were investigated using Poisson regression. RESULTS: During 22 958 person-years of follow-up, 928 AIDS events developed (25.3% viral, 24.6% bacterial, 20.7% fungal, 8.1% protozoal, and 21.2% other). The incidence of any AIDS event declined from 129.3 (95% confidence interval [CI], 116.7-141.8) per 1000 person-years in the first 3 months to 13.2 (95% CI, 9.4-17.0) in the third year after starting HAART (P 〈.001). The rate of decline in incidence was greatest for events with a viral etiology (87.0% per year) and lowest for those with a fungal etiology (54.0% per year). In the third year, fungal events represented 37.0% of AIDS events that occurred. After adjustment for the CD4 count and human immunodeficiency virus 1 RNA level, changes in the incidence of bacterial and viral events from months 0 to 6 and 7 to 12 remained significant, suggesting that changes in these markers did not fully explain the changes in incidence seen. CONCLUSION: Although the incidence of all AIDS-defining events decreased substantially after starting HAART, the pattern of decline was most pronounced for events with a viral etiology
    Keywords: Medicine;
    ISSN: 0003-9926
    ISSN: 1538-3679
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  • 3
    Language: English
    In: The Journal of infectious diseases, 01 September 2006, Vol.194(5), pp.633-41
    Description: Limited data exist on factors predicting the development of opportunistic infections (OIs) at higher-than-expected CD4(+) cell counts in human immunodeficiency virus (HIV) type 1-infected adults. Multivariate Poisson regression models were used to determine factors related to the development of groups of OIs above their respective traditional upper CD4(+) cell count thresholds: group 1 (〉or=100 cells/ microL), OIs caused by cytomegalovirus, Mycobacterium avium complex, and Toxoplasma gondii; group 2 (〉or=200 cells/ microL), Pneumocystis pneumonia and esophageal candidiasis; and group 3 (〉or=300 cells/ microL), pulmonary and extrapulmonary tuberculosis. In groups 1, 2, and 3, 71 of 9,219, 125 of 7,934, and 36 of 7,838 patients, respectively, developed 〉or=1 intragroup OI. The strongest predictor of an OI in groups 1 and 2 was current CD4(+) cell count (for group 1, incidence rate ratio [IRR] per 50% lower CD4(+) cell count, 5.37 [95% confidence interval {CI}, 3.71-7.77]; for group 2, 4.28 [95% CI, 2.98-6.14]). Injection drug use but not current CD4(+) cell count predicted risk in group 3. Use of antiretroviral treatment was associated with a lower incidence of OIs in all groups, likely by reducing HIV-1 RNA levels (IRR per 1-log(10) copies/mL higher HIV-1 RNA levels for group 1, 1.50 [95% CI, 1.15-1.95]; for group 2, 1.68 [95% CI, 1.40-2.02]; and for group 3, 1.89 [95% CI, 1.40-2.54]). Although the absolute incidence is low, the current CD4(+) cell count and HIV-1 RNA level are strong predictors of most OIs in patients with high CD4(+) cell counts.
    Keywords: Cd4 Lymphocyte Count ; AIDS-Related Opportunistic Infections -- Epidemiology
    ISSN: 0022-1899
    E-ISSN: 15376613
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  • 4
    Language: English
    In: The Lancet, 2010, Vol.375(9715), pp.639-639
    Description: The second analysis cited, from NA ACCORD,3 found higher hazard ratios apparently favouring early ART initiation, but there are unresolved questions about whether there is a bias in the analysis favouring early ART.5 Additionally, as pointed out in the DHHS guidelines, interpretation of all analyses from observational studies is limited by the potential for bias due to unmeasured confounders, which could plausibly explain the effects seen.
    Keywords: Medicine
    ISSN: 0140-6736
    E-ISSN: 1474-547X
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  • 5
    Language: English
    In: The Journal of infectious diseases, 15 February 2012, Vol.205(4), pp.540-7
    Description: 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.
    Keywords: Antiretroviral Therapy, Highly Active ; Anti-HIV Agents -- Administration & Dosage ; Drug Monitoring -- Methods ; HIV Infections -- Drug Therapy
    ISSN: 00221899
    E-ISSN: 1537-6613
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  • 6
    Language: English
    In: PLoS ONE, 01 January 2013, Vol.8(7), p.e69266
    Description: Non-nucleoside reverse transcriptase inhibitor (NNRTI)-resistant mutants have been shown to emerge after interruption of suppressive NNRTI-based antiretroviral therapy (ART) using routine testing. The aim of this study was to quantify the risk of resistance by sensitive testing and correlate the detection of resistance with NNRTI concentrations after treatment interruption and virologic responses after treatment resumption.Resistance-associated mutations (RAMs) and NNRTI concentrations were studied in plasma from 132 patients who interrupted suppressive ART within SMART. RAMs were detected by Sanger sequencing, allele-specific PCR, and ultra-deep sequencing. NNRTI concentrations were measured by sensitive high-performance liquid chromatography.Four weeks after NNRTI interruption, 19/31 (61.3%) and 34/39 (87.2%) patients showed measurable nevirapine (〉0.25 ng/ml) or efavirenz (〉5 ng/ml) concentrations, respectively. Median eight weeks after interruption, 22/131 (16.8%) patients showed ≥1 NNRTI-RAM, including eight patients with NNRTI-RAMs detected only by sensitive testing. The adjusted odds ratio (OR) of NNRTI-RAM detection was 7.62 (95% confidence interval [CI] 1.52, 38.30; p = 0.01) with nevirapine or efavirenz concentrations above vs. below the median measured in the study population. Staggered interruption, whereby nucleos(t)ide reverse transcriptase inhibitors (NRTIs) were continued for median nine days after NNRTI interruption, did not prevent NNRTI-RAMs, but increased detection of NRTI-RAMs (OR 4.25; 95% CI 1.02, 17.77; p = 0.03). After restarting NNRTI-based ART (n = 90), virologic suppression rates 〈400 copies/ml were 8/13 (61.5%) with NNRTI-RAMs, 7/11 (63.6%) with NRTI-RAMs only, and 51/59 (86.4%) without RAMs. The ORs of re-suppression were 0.18 (95% CI 0.03, 0.89) and 0.17 (95% CI 0.03, 1.15) for patients with NNRTI-RAMs or NRTI-RAMs only respectively vs. those without RAMs (p = 0.04).Detection of resistant mutants in the rebound viremia after interruption of efavirenz- or nevirapine-based ART affects outcomes once these drugs are restarted. Further studies are needed to determine RAM persistence in untreated patients and impact on newer NNRTIs.
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
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  • 7
    Language: English
    In: PLoS ONE, 01 January 2013, Vol.8(2), p.e55312
    Description: There is interest in expanding ART to prevent HIV transmission, but in the group with the highest levels of ART use, men-who-have-sex-with-men (MSM), numbers of new infections diagnosed each year have not decreased as ARTcoverage has increased for reasons which remain unclear.We analysed data on the HIV-epidemic in MSM in the UK from a range of sources using an individual-based simulation model. Model runs using parameter sets found to result in good model fit were used to infer changes in HIV-incidence and risk behaviour.HIV-incidence has increased (estimated mean incidence 0.30/100 person-years 1990-1997, 0.45/100 py 1998-2010), associated with a modest (26%) rise in condomless sex. We also explored counter-factual scenarios: had ART not been introduced, but the rise in condomless sex had still occurred, then incidence 2006-2010 was 68% higher; a policy of ART initiation in all diagnosed with HIV from 2001 resulted in 32% lower incidence; had levels of HIV testing been higher (68% tested/year instead of 25%) incidence was 25% lower; a combination of higher testing and ART at diagnosis resulted in 62% lower incidence; cessation of all condom use in 2000 resulted in a 424% increase in incidence. In 2010, we estimate that undiagnosed men, the majority in primary infection, accounted for 82% of new infections.A rise in HIV-incidence has occurred in MSM in the UK despite an only modest increase in levels of condomless sex and high coverage of ART. ART has almost certainly exerted a limiting effect on incidence. Much higher rates of HIV testing combined with initiation of ART at diagnosis would be likely to lead to substantial reductions in HIV incidence. Increased condom use should be promoted to avoid the erosion of the benefits of ART and to prevent other serious sexually transmitted infections.
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
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  • 8
    In: AIDS, 2015, Vol.29(14), pp.1855-1862
    Description: BACKGROUND:: Increased rates of testing, with early antiretroviral therapy (ART) initiation, represent a key potential HIV-prevention approach. Currently, in MSM in the United Kingdom, it is estimated that 36% are diagnosed by 1 year from infection, and the ART initiation threshold is at CD4 cell count 350/μl. We investigated what would be required to reduce HIV incidence in MSM to below 1 per 1000 person-years (i.e. 〈535 new infections per year) by 2030, and whether this is likely to be cost-effective. METHODS:: A dynamic, individual-based simulation model was calibrated to multiple data sources on HIV in MSM in the United Kingdom. Outcomes were projected according to future alternative HIV testing and ART initiation scenarios to 2030, considering also potential changes in levels of condomless sex. RESULTS:: For ART use to result in an incidence of close to 1/1000 person-years requires the proportion of all HIV-positive MSM with viral suppression to increase from below 60% currently to 90%, assuming no rise in levels of condomless sex. Substantial increases in HIV testing, such that over 90% of men are diagnosed within a year of infection, would increase the proportion of HIV-positive men with viral suppression to 80%, and it would be 90%, if ART is initiated at diagnosis. The scenarios required for such a policy to be cost-effective are presented. CONCLUSION:: This analysis provides targets for the proportion of all HIV-positive MSM with viral suppression required to achieve substantial reductions in HIV incidence.
    Keywords: Cd4 Antigen ; Data Processing ; Antiretroviral Therapy ; Infection ; Sex ; Acquired Immune Deficiency Syndrome ; Human Immunodeficiency Virus ; Economics ; Simulation ; Homosexuality ; Infection ; Antiretroviral Agents ; Lentivirus ; Retroviridae ; Diseases/Injuries/Trauma ; AIDS and HIV ; Microorganisms & Parasites ; Cost-Effectiveness ; Economic Evaluation ; HIV ; HIV Diagnosis ; Mathematical Models ; Prevention ; Testing;
    ISSN: 0269-9370
    E-ISSN: 14735571
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  • 9
    In: International Journal of Epidemiology, 2017, Vol. 46(3), pp.797-797n
    Description: Many questions about the long-term effects of combination antiretroviral therapy (cART) on clinical 3 outcomes in people living with HIV (PLWH) and their impact on health systems remain unanswered. The 4 Collaboration of Observational HIV Epidemiological Research Europe (COHERE) was formed in 2005 to 5 pool and harmonize existing longitudinal data on people living with HIV in Europe, to answer key 6 research questions that could not be addressed adequately by individual cohorts. Key research 7 questions include long-term prognosis, rare outcomes, and variations across patient groups, settings 8 and health systems. COHERE uses the HIV Cohorts Data Exchange Protocol, a standardized and validated 9 method of data structure and transfer, to compile data from over 40 cohorts of PLWH residing in 10 Europe, representing 331 481 individuals, including 2808 children (〈13), representing 2 135 896 person- 11 years of follow-up. COHERE compiles data on clinical characteristics, antiretroviral therapy and other 12 medications, HIV seroconversion, opportunistic infections, laboratory results and socio demographic 13 data. External collaborators interested in conducting a project in COHERE should submit a project 14 proposal to the Regional Coordinating Centres in Bordeaux and Copenhagen for review by COHERE’s 15 governing bodies (see www.cohere.org for further information).
    Keywords: Medicine ; Public Health;
    ISSN: 0300-5771
    E-ISSN: 1464-3685
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  • 10
    Language: English
    In: PLoS ONE, 01 January 2014, Vol.9(5), p.e97340
    Description: To assess if a strategy of early ART to prevent HIV transmission is acceptable to ART naïve people with HIV with high CD4 counts.ASTRA is a UK multicentre, cross sectional study of 3258 HIV outpatients in 2011/12. A self-completed questionnaire collected sociodemographic, behavioral and health data, and attitudes to ART; CD4 count was recorded from clinical records.ART naïve participants with CD4 ≥350 cells/µL (n = 281) were asked to agree/disagree/undecided with the statements (i) I would want to start treatment now if this would slightly reduce my risk of getting a serious illness, and (ii) I would want to start treatment now if this would make me less infectious to a sexual partner, even if there was no benefit to my own health.Participants were 85% MSM, 76% white, 11% women. Of 281 participants, 49.5% and 45.2% agreed they would start ART for reasons (i) and (ii) respectively; 62.6% agreed with either (i) or (ii); 12.5% agreed with neither; 24.9% were uncertain. Factors independently associated (p〈0.1) with agreement to (i) were: lower CD4, more recent HIV diagnosis, physical symptoms, not being depressed, greater financial hardship, and with agreement to (ii) were: being heterosexual, more recent HIV diagnosis, being sexually active.A strategy of starting ART at high CD4 counts is likely to be acceptable to the majority of HIV-diagnosed individuals. Almost half with CD4 〉350 would start ART to reduce infectiousness, even if treatment did not benefit their own health. However a significant minority would not like to start ART either for modest health benefit or to reduce infectivity. Any change in approach to ART initiation must take account of individual preferences. Transmission models of potential benefit of early ART should consider that ART uptake may be lower than that seen with low CD4 counts.
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
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