13 results on '"Neaton, JD"'
Search Results
2. Association Between Single-Nucleotide Polymorphisms in HLA Alleles and Human Immunodeficiency Virus Type 1 Viral Load in Demographically Diverse, Antiretroviral Therapy-Naive Participants From the Strategic Timing of AntiRetroviral Treatment Trial.
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Ekenberg C, Tang MH, Zucco AG, Murray DD, MacPherson CR, Hu X, Sherman BT, Losso MH, Wood R, Paredes R, Molina JM, Helleberg M, Jina N, Kityo CM, Florence E, Polizzotto MN, Neaton JD, Lane HC, and Lundgren JD
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- Adult, Alleles, Anti-Retroviral Agents therapeutic use, Female, Genome-Wide Association Study, HIV Infections genetics, HIV Infections immunology, HIV Infections virology, HIV-1 isolation & purification, Histocompatibility Antigens Class I immunology, Host-Pathogen Interactions genetics, Host-Pathogen Interactions immunology, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Time Factors, Viral Load drug effects, Viral Load immunology, Anti-Retroviral Agents pharmacology, HIV Infections drug therapy, HIV-1 immunology, Histocompatibility Antigens Class I genetics, Viral Load genetics
- Abstract
The impact of variation in host genetics on replication of human immunodeficiency virus type 1 (HIV-1) in demographically diverse populations remains uncertain. In the current study, we performed a genome-wide screen for associations of single-nucleotide polymorphisms (SNPs) to viral load (VL) in antiretroviral therapy-naive participants (n = 2440) with varying demographics from the Strategic Timing of AntiRetroviral Treatment (START) trial. Associations were assessed using genotypic data generated by a customized SNP array, imputed HLA alleles, and multiple linear regression. Genome-wide significant associations between SNPs and VL were observed in the major histocompatibility complex class I region (MHC I), with effect sizes ranging between 0.14 and 0.39 log10 VL (copies/mL). Supporting the SNP findings, we identified several HLA alleles significantly associated with VL, extending prior observations that the (MHC I) is a major host determinant of HIV-1 control with shared genetic variants across diverse populations and underscoring the limitations of genome-wide association studies as being merely a screening tool., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
- Published
- 2019
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3. The Effect of Interrupted/Deferred Antiretroviral Therapy on Disease Risk: A SMART and START Combined Analysis.
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Borges ÁH, Neuhaus J, Sharma S, Neaton JD, Henry K, Anagnostou O, Staub T, Emery S, and Lundgren JD
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- Acquired Immunodeficiency Syndrome drug therapy, Adult, Anti-HIV Agents therapeutic use, Cardiovascular Diseases drug therapy, Disease Susceptibility, Female, HIV-1, Humans, Male, Middle Aged, Neoplasms, Proportional Hazards Models, Time-to-Treatment, Treatment Outcome, Anti-Retroviral Agents therapeutic use, CD4 Lymphocyte Count, HIV Infections drug therapy
- Abstract
Background: Pooled data from the SMART and START trials were used to compare deferred/intermittent versus immediate/continuous antiretroviral therapy (ART) on disease risk., Methods: Endpoints assessed were AIDS, serious non-AIDS (SNA), cardiovascular disease (CVD), cancer, and death. Pooled (stratified by study) hazard ratios (HRs) from Cox models were obtained for deferred/intermittent ART versus immediate/continuous ART; analyses were conducted to assess consistency of HRs across baseline-defined subgroups., Results: Among 10156 participants, there were 124 AIDS, 247 SNA, 117 cancers, 103 CVD, and 120 deaths. Interventions in each trial led to similar differences in CD4 count and viral suppression. Pooled HRs (95% confidence interval) of deferred/intermittent ART versus immediate/continuous ART were for AIDS 3.63 (2.37-5.56); SNA 1.62 (1.25-2.09); CVD 1.59 (1.07-2.37); cancer 1.93 (1.32-2.83); and death 1.80 (1.24-2.61). Underlying risk was greater in SMART than START. Given the similar HRs for each trial, absolute risk differences between treatment groups were greater in SMART than START. Pooled HRs were similar across subgroups., Conclusions: Treatment group differences in CD4 count and viral suppression were similar in SMART and START. Likely as a consequence, relative differences in risk of AIDS and SNA between immediate/continuous ART and deferred/intermittent ART were similar., Clinical Trials Registration: NCT00027352 and NCT00867048.
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- 2019
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4. Interleukin 6 Is a Stronger Predictor of Clinical Events Than High-Sensitivity C-Reactive Protein or D-Dimer During HIV Infection.
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Borges ÁH, O'Connor JL, Phillips AN, Neaton JD, Grund B, Neuhaus J, Vjecha MJ, Calmy A, Koelsch KK, and Lundgren JD
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- Adult, Antifibrinolytic Agents, Cohort Studies, Female, Humans, Male, Middle Aged, Prognosis, Sensitivity and Specificity, Survival Analysis, C-Reactive Protein analysis, Fibrin Fibrinogen Degradation Products analysis, HIV Infections diagnosis, HIV Infections pathology, Interleukin-6 blood
- Abstract
Background: Interleukin 6 (IL-6), high-sensitivity C-reactive protein (hsCRP), and D-dimer levels are linked to adverse outcomes in human immunodeficiency virus (HIV) infection, but the strength of their associations with different clinical end points warrants investigation., Methods: Participants receiving standard of care in 2 HIV trials with measured biomarker levels were followed to ascertain all-cause death, non-AIDS-related death, AIDS, cardiovascular disease (CVD), and non-AIDS-defining malignancies. Hazard ratios (HRs) and 95% confidence intervals (CIs) of each end point for quartiles and log2-transformed IL-6, hsCRP, and D-dimer levels were calculated using Cox models. Marginal models modelling multiple events tested for equal effects of biomarker levels on different end points., Results: Among 4304 participants, there were 157 all-cause deaths, 117 non-AIDS-related deaths, 101 AIDS cases, 121 CVD cases, and 99 non-AIDS-defining malignancies. IL-6 was more strongly associated with most end points, compared with hsCRP. IL-6 appeared to be a stronger predictor than D-dimer for CVD and non-AIDS-defining malignancies, but 95% CIs overlapped. Independent associations of IL-6 were stronger for non-AIDS-related death (HR, 1.71; 95% CI, 1.43-2.04) and all-cause death (HR, 1.56; 95% CI, 1.33-1.84) and similar for CVD (HR, 1.35; 95% CI, 1.12-1.62) and non-AIDS-defining malignancies (HR, 1.30; 95% CI, 1.06-1.61). There was heterogeneity of IL-6 (P < .001) but not hsCRP (P = .15) or D-dimer (P = .20) as a predictor for different end points., Conclusions: IL-6 is a stronger predictor of fatal events than of CVD and non-AIDS-defining malignancies. Adjuvant antiinflammatory and antithrombotic therapies should be tested in HIV-infected individuals., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)
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- 2016
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5. Increase in 2-long terminal repeat circles and decrease in D-dimer after raltegravir intensification in patients with treated HIV infection: a randomized, placebo-controlled trial.
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Hatano H, Strain MC, Scherzer R, Bacchetti P, Wentworth D, Hoh R, Martin JN, McCune JM, Neaton JD, Tracy RP, Hsue PY, Richman DD, and Deeks SG
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- Antiretroviral Therapy, Highly Active, Biomarkers blood, Drug Administration Schedule, Female, HIV Infections blood, HIV Infections virology, HIV-1 drug effects, Humans, Male, Middle Aged, Raltegravir Potassium, Treatment Outcome, Virus Replication drug effects, Fibrin Fibrinogen Degradation Products metabolism, HIV Infections drug therapy, HIV Integrase Inhibitors administration & dosage, HIV Long Terminal Repeat genetics, HIV-1 genetics, Pyrrolidinones administration & dosage
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Background: The degree to which human immunodeficiency virus (HIV) continues to replicate during antiretroviral therapy (ART) is controversial. We conducted a randomized, double-blind, placebo-controlled study to assess whether raltegravir intensification reduces low-level viral replication, as defined by an increase in the level of 2-long terminal repeat (2-LTR) circles., Methods: Thirty-one subjects with an ART-suppressed plasma HIV RNA level of <40 copies/mL and a CD4(+) T-cell count of ≥350 cells/mm(3) for ≥1 year were randomly assigned to receive raltegravir 400 mg twice daily or placebo for 24 weeks. 2-LTR circles were analyzed by droplet digital polymerase chain reaction at weeks 0, 1, 2, and 8., Results: The median duration of ART suppression was 3.8 years. The raltegravir group had a significant increase in the level of 2-LTR circles, compared to the placebo group. The week 1 to 0 ratio was 8.8-fold higher (P = .0025) and the week 2 to 0 ratio was 5.7-fold higher (P = .023) in the raltegravir vs. placebo group. Intensification also led to a statistically significant decrease in the D-dimer level, compared to placebo (P = .045)., Conclusions: Raltegravir intensification resulted in a rapid increase in the level of 2-LTR circles in a proportion of subjects, indicating that low-level viral replication persists in some individuals even after long-term ART. Intensification also reduced the D-dimer level, a coagulation biomarker that is predictive of morbidity and mortality among patients receiving treatment for HIV infection.
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- 2013
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6. Higher levels of CRP, D-dimer, IL-6, and hyaluronic acid before initiation of antiretroviral therapy (ART) are associated with increased risk of AIDS or death.
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Boulware DR, Hullsiek KH, Puronen CE, Rupert A, Baker JV, French MA, Bohjanen PR, Novak RM, Neaton JD, and Sereti I
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- Acquired Immunodeficiency Syndrome drug therapy, Adult, Anti-Retroviral Agents therapeutic use, Biomarkers blood, Biomarkers metabolism, Case-Control Studies, Disease Progression, Female, Humans, Immune Reconstitution Inflammatory Syndrome blood, Immune Reconstitution Inflammatory Syndrome virology, Male, Middle Aged, Morbidity, RNA, Viral blood, Risk Factors, Acquired Immunodeficiency Syndrome blood, C-Reactive Protein metabolism, Fibrin Fibrinogen Degradation Products metabolism, HIV Infections blood, HIV Infections drug therapy, Hyaluronic Acid blood, Interleukin-6 blood
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Background: Substantial morbidity occurs during the first year of antiretroviral therapy (ART) in persons with advanced human immunodeficiency virus (HIV) disease despite HIV suppression. Biomarkers may identify high-risk groups., Methods: Pre-ART and 1-month samples from an initial ART trial were evaluated for biomarkers associated with AIDS events or death within 1-12 months. Case patients (n = 63) and control patients (n = 126) were 1:2 matched on baseline CD4 cell count, hepatitis status, and randomization date. All had ≥ 1 log(10) HIV RNA level decrease at 1 month., Results: Case patients had more frequent prior AIDS events, compared with control patients (P = .004), but similar HIV RNA levels at baseline. Pre-ART and 1-month C-reactive protein (CRP), D-dimer, and interleukin 6 (IL-6) levels and pre-ART hyaluronic acid (HA) levels were associated with new AIDS events or death (P ≤ .01). Patients who experienced immune reconstitution inflammatory syndrome (IRIS) events had higher pre-ART tumor necrosis factor α (TNF-α) and HIV RNA levels and significant 1-month increases in CRP, D-dimer, IL-6, interleukin 8, CXCL10, TNF-α, and interferon-γ levels, compared with patients who experienced non-IRIS events (P ≤ .03). Individuals with baseline CRP and HA levels above the cohort median (>2.1 mg/L and >50.0 ng/mL, respectively) had increased risk of AIDS or death (OR, 4.6 [95% CI, 2.0-10.3]; P < .001) and IRIS (OR, 8.7 [95% CI, 2.2-34.8] P = .002)., Conclusions: Biomarkers of Inflammation (CRP, IL-6), coagulation (D-dimer), and tissue fibrosis (HA) measured pre-ART and at 1 month are associated with higher risk of AIDS events, IRIS, or death, warranting additional study as risk stratification strategies.
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- 2011
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7. Plasma levels of soluble CD14 independently predict mortality in HIV infection.
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Sandler NG, Wand H, Roque A, Law M, Nason MC, Nixon DE, Pedersen C, Ruxrungtham K, Lewin SR, Emery S, Neaton JD, Brenchley JM, Deeks SG, Sereti I, and Douek DC
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- Adult, Biomarkers blood, CD4-Positive T-Lymphocytes, Case-Control Studies, Cause of Death, Fatty Acid-Binding Proteins blood, Humans, Lipopolysaccharides blood, Logistic Models, Male, Middle Aged, RNA, Viral, Young Adult, HIV Infections blood, HIV Infections mortality, Lipopolysaccharide Receptors blood
- Abstract
Background: Chronic human immunodeficiency virus (HIV) infection is associated with intestinal permeability and microbial translocation that contributes to systemic immune activation, which is an independent predictor of HIV disease progression. The association of microbial translocation with clinical outcome remains unknown., Methods: This nested case-control study included 74 subjects who died, 120 of whom developed cardiovascular disease and 81 of whom developed AIDS during the Strategies for Management of Anti-Retroviral Therapy (SMART) study with matched control subjects. Intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), soluble CD14 (sCD14), endotoxin core antibody (EndoCAb), and 16S ribosomal DNA (rDNA) were measured in baseline plasma samples., Results: Subjects with the highest quartile of sCD14 levels had a 6-fold higher risk of death than did those in the lowest quartile (95% confidence interval, 2.2-16.1; P<.001), with minimal change after adjustment for inflammatory markers, CD4(+) T cell count, and HIV RNA level. No other marker was significantly associated with clinical outcomes. I-FABP, LPS, and sCD14 were increased and EndoCAb was decreased in study subjects, compared with healthy volunteers. sCD14 level correlated with levels of IL-6, C-reactive protein, serum amyloid A and D-dimer., Conclusions: sCD14, a marker of monocyte response to LPS, is an independent predictor of mortality in HIV infection. Therapeutic attenuation of innate immune activation may improve survival in patients with HIV infection.
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- 2011
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8. A randomized factorial trial comparing 4 treatment regimens in treatment-naive HIV-infected persons with AIDS and/or a CD4 cell count <200 cells/μL in South Africa.
- Author
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Ratsela A, Polis M, Dhlomo S, Emery S, Grandits G, Khabo P, Khanyile T, Komati S, Neaton JD, Naidoo LC, Magongoa D, and Qolohle D
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- Acquired Immunodeficiency Syndrome complications, Acquired Immunodeficiency Syndrome immunology, Acquired Immunodeficiency Syndrome virology, Adult, Alkynes, Anti-HIV Agents adverse effects, CD4 Lymphocyte Count, Cyclopropanes, Didanosine adverse effects, Drug Therapy, Combination, Female, HIV genetics, Humans, Lamivudine adverse effects, Lopinavir, Male, RNA, Viral blood, South Africa, Stavudine adverse effects, Treatment Outcome, Zidovudine adverse effects, Acquired Immunodeficiency Syndrome drug therapy, Anti-HIV Agents therapeutic use, Benzoxazines therapeutic use, Didanosine therapeutic use, Lamivudine therapeutic use, Pyrimidinones therapeutic use, Ritonavir therapeutic use, Stavudine therapeutic use, Zidovudine therapeutic use
- Abstract
Background: Few randomized trials comparing antiretroviral therapy (ART) regimens have been conducted in resource-limited settings., Methods: In the Republic of South Africa, antiretroviral-naive human immunodeficiency virus (HIV)-infected individuals >14 years old with a CD4 cell count <200 cells/μL or a prior AIDS diagnosis were randomized to receive efavirenz (EFV) or lopinavir/ritonavir (LPV/r) with either zidovudine (ZDV) plus didanosine (ddI) or stavudine (d4T) plus lamivudine (3TC) in an open-label, 2-by-2 factorial study and followed up for the primary outcome of AIDS or death and prespecified secondary outcomes, including CD4 cell count and viral load changes, treatment discontinuation, and grade 4 events., Results: In total, 1771 persons were randomized and followed up for a median of 24.7 months. AIDS or death occurred in (1) 163 participants assigned EFV and 157 assigned LPV/r (hazard ratio [HR], 1.04 [95% confidence interval {CI}, 0.84-1.30]) and in (2) 170 participants assigned ZDV+ddI and 150 assigned d4T+3TC (HR, 1.15 [95% CI, 0.93-1.44]). HIV RNA levels were lower (P < .001) and CD4 cell counts were greater (P < .01) over follow-up for d4T+3TC versus ZDV+ddI. Rates of potentially life-threatening adverse events and overall treatment discontinuation were similar for d4T+3TC and ZDV+ddI; however, more participants discontinued d4T because of toxicity (12.6%) than other treatments (<5%)., Conclusion: EFV and LPV/r are effective components of first-line ART. The poorer viral and immune responses with ZDV+ddI and the greater toxicity-associated discontinuation rate with d4T+3TC suggest that these treatments be used cautiously as initial therapy., Trial Registration: ClinicalTrials.gov identifier: NCT00342355.
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- 2010
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9. Markers of inflammation, coagulation, and renal function are elevated in adults with HIV infection.
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Neuhaus J, Jacobs DR Jr, Baker JV, Calmy A, Duprez D, La Rosa A, Kuller LH, Pett SL, Ristola M, Ross MJ, Shlipak MG, Tracy R, and Neaton JD
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- Adult, Aged, Anti-HIV Agents therapeutic use, Biomarkers, C-Reactive Protein analysis, Cystatin C blood, Female, Fibrin Fibrinogen Degradation Products analysis, HIV Infections drug therapy, Humans, Interleukin-6 blood, Male, Middle Aged, Viral Load, Blood Coagulation Disorders pathology, HIV Infections complications, Inflammation pathology, Kidney Diseases pathology
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Background: Human immunodeficiency virus (HIV) replication and immune activation may increase inflammation and coagulation biomarkers. Limited data exist comparing such biomarkers in persons with and without HIV infection., Methods: For persons 45-76 years of age, levels of high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, D-dimer, and cystatin C were compared in 494 HIV-infected individuals in the Strategies for Management of Anti-Retroviral Therapy (SMART) study and 5386 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) study. For persons 33-44 years of age, hsCRP and IL-6 levels were compared in 287 participants in the SMART study and 3231 participants in the Coronary Artery Development in Young Adults (CARDIA) study., Results: hsCRP and IL-6 levels were 55% (P < . 001) and 62 (P < . 001) higher among HIV-infected participants than among CARDIA study participants. Compared with levels noted in MESA study participants, hsCRP, IL-6, D-dimer, and cystatin C levels were 50%, 152%, 94%, and 27% higher, respectively (P < . 001, for each), among HIV-infected participants. HIV-infected participants receiving antiretroviral therapy who had HIV RNA levels 400 copies/mL had levels higher (by 21% to 60%) (P < . 001) than those in the general population, for all biomarkers., Conclusions: hsCRP, IL-6, D-dimer, and cystatin C levels are elevated in persons with HIV infection and remain so even after HIV RNA levels are suppressed with antiretroviral therapy. Additional research is needed on the pathophysiology of HIV-induced activation of inflammatory and coagulation pathways, to guide potential interventions.
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- 2010
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10. High-density lipoprotein particles and markers of inflammation and thrombotic activity in patients with untreated HIV infection.
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Baker J, Ayenew W, Quick H, Hullsiek KH, Tracy R, Henry K, Duprez D, and Neaton JD
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- Adult, Case-Control Studies, Female, Fibrin Fibrinogen Degradation Products analysis, Fibrinogen analysis, HIV Infections complications, HIV Infections immunology, Humans, Intercellular Adhesion Molecule-1 blood, Interleukin-6 blood, Male, Middle Aged, Thrombosis blood, HIV Infections blood, Lipoproteins, HDL blood, Thrombosis virology
- Abstract
Background: Untreated human immunodeficiency virus (HIV) infection is associated with changes in blood lipids, inflammation, thrombotic activity, and increased risk for cardiovascular disease., Methods: We studied high-density lipoprotein particle (HDLp) concentrations and inflammatory (high-sensitivity C-reactive protein [hsCRP] and interleukin [IL] 6), endothelial activation (E-selectin and soluble intercellular adhesion molecule-1 [sICAM-1]), and thrombotic (fibrinogen and D-dimer) biomarkers in a group of 32 untreated HIV-infected and 29 uninfected persons. Differences in the levels of blood lipids and biomarkers by HIV status were examined before and after adjustment for age, sex, race/ethnicity, smoking status, body mass index, and the presence of hepatitis C., Results: HIV-infected participants, compared with uninfected participants, had lower HDL cholesterol (HDLc) levels (-26%) and HDLp numbers (-21%), with reductions in large (-50%) and small (-20%) HDLp, specifically (P < or = .01 for all). A trend was present for higher total cholesterol (P = .15 and triglyceride levels (P = .11) among individuals with HIV infection. Levels of IL-6, sICAM-1, and D-dimer were 65%-70% higher in HIV-infected participants (P < or = .02 for all). Covariate adjustment did not diminish these associations. For HIV-infected participants, total and small HDLp (respectively) tended to correlate inversely with levels of IL-6 (P = .08 and P = .02), sICAM-1 (P < .01 for both) and D-dimer (P = .03 and p < .01)., Conclusions: Persons with untreated HIV infection have lower HDLp (primarily large and small HDLp) and higher IL-6, sICAM-1, and D-dimer levels, and the relationship of these markers to HIV-mediated atherosclerotic risk requires further study.
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- 2010
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11. Inferior clinical outcome of the CD4+ cell count-guided antiretroviral treatment interruption strategy in the SMART study: role of CD4+ Cell counts and HIV RNA levels during follow-up.
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Lundgren JD, Babiker A, El-Sadr W, Emery S, Grund B, Neaton JD, Neuhaus J, and Phillips AN
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- AIDS-Related Opportunistic Infections epidemiology, AIDS-Related Opportunistic Infections mortality, Drug Administration Schedule, HIV Infections immunology, HIV Infections mortality, HIV Infections virology, Humans, Proportional Hazards Models, Treatment Outcome, Anti-HIV Agents administration & dosage, CD4 Lymphocyte Count, HIV genetics, HIV immunology, HIV Infections drug therapy, RNA, Viral blood
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Background and Methods: The SMART study compared 2 strategies for using antiretroviral therapy-drug conservation (DC) and viral suppression (VS)-in 5,472 human immunodeficiency virus (HIV)-infected patients with CD4+ cell counts >350 cells/microL. Rates and predictors of opportunistic disease or death (OD/death) and the relative risk (RR) in DC versus VS groups according to the latest CD4+ cell count and HIV RNA level are reported., Results: During a mean of 16 months of follow-up, DC patients spent more time with a latest CD4+ cell count <350 cells/microL (for DC vs. VS, 31% vs. 8%) and with a latest HIV RNA level >400 copies/mL (71% vs. 28%) and had a higher rate of OD/death (3.4 vs. 1.3/100 person-years) than VS patients. For periods of follow- up with a CD4+ cell count <350 cells/microL, rates of OD/death were increased but similar in the 2 groups (5.7 vs. 4.6/100 person-years), whereas the rates were higher in DC versus VS patients (2.3 vs. 1.0/100 person-years; RR, 2.3 [95% confidence interval, 1.5-3.4]) for periods with the latest CD4+ cell count >or= 350 cells/microL-an increase explained by the higher HIV RNA levels in the DC group., Conclusions: The higher risk of OD/death in DC patients was associated with (1) spending more follow-up time with relative immunodeficiency and (2) living longer with uncontrolled HIV replication even at higher CD4+ cell counts. Ongoing HIV replication at a given CD4+ cell count places patients at an excess risk of OD/death.
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- 2008
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12. Reply.
- Author
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Emery S, Lane HC, and Neaton JD
- Published
- 2000
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13. Primary prophylaxis with pyrimethamine for toxoplasmic encephalitis in patients with advanced human immunodeficiency virus disease: results of a randomized trial. Terry Beirn Community Programs for Clinical Research on AIDS.
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Jacobson MA, Besch CL, Child C, Hafner R, Matts JP, Muth K, Wentworth DN, Neaton JD, Abrams D, and Rimland D
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- AIDS-Related Opportunistic Infections mortality, Adult, Double-Blind Method, Female, Humans, Male, Middle Aged, Pneumonia, Pneumocystis complications, Pneumonia, Pneumocystis mortality, AIDS-Related Opportunistic Infections drug therapy, HIV Infections complications, Pyrimethamine adverse effects, Toxoplasmosis, Cerebral prevention & control
- Abstract
Pyrimethamine, 25 mg thrice weekly, was evaluated as primary prophylaxis for toxoplasmic encephalitis (TE) in a double-blind, randomized clinical trial in patients with human immunodeficiency virus (HIV) disease, absolute CD4 lymphocyte count of < 200/microL (or prior AIDS-defining opportunistic infection), and the presence of serum IgG to Toxoplasma gondii. Leucovorin was coadministered only for hematologic toxicity. There was a significantly higher death rate among patients receiving pyrimethamine (relative risk [RR], 2.5; 95% confidence interval [CI], 1.3-4.8; P = .006), even after adjusting for factors predictive of survival. The TE event rate was low in both treatment groups (not significant). Only 1 of 218 patients taking trimethoprim-sulfamethoxazole but 7 of 117 taking aerosolized pentamidine for prophylaxis against Pneumocystis carinii pneumonia developed TE (adjusted RR for the trimethoprim-sulfamethoxazole group, 0.16; 95% CI, 0.01-1.79; P = .14). Thus, for HIV-infected patients receiving trimethoprim-sulfamethoxazole, additional prophylaxis for TE appears unnecessary.
- Published
- 1994
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