Heather J Ribaudo

Harvard Medical School, Boston, Massachusetts, United States

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Publications (95)906.49 Total impact

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    ABSTRACT: Objective: This article compares the effects of initiating three contemporary antiretroviral therapy (ART) regimens on progression of carotid artery intima-media thickness (IMT) over 3 years. Design: Randomized clinical trial. Setting: Multicenter (26 institutions). Patients: ART-naive HIV-infected individuals (n = 328) without known cardiovascular disease or diabetes mellitus. Intervention: Random assignment to tenofovir/emtricitabine along with atazanavir/ritonavir (ATV/r), darunavir/ritonavir (DRV/r), or raltegravir (RAL). Main outcome measures: Right-sided carotid IMT was evaluated by B-mode ultrasonography before ART initiation, and then after 48, 96, and 144 weeks. Comparisons of yearly rates of change in carotid IMT used mixed-effects linear regression models that permitted not only evaluation of the effects of ART on carotid IMT progression but also how ART-associated changes in traditional risk factors, bilirubin, and markers of HIV infection were associated carotid IMT progression. Results: HIV-1 RNA suppression rates were high in all arms (>85%) over 144 weeks. Modest increases in triglycerides and non-high-density lipoprotein cholesterol levels were observed in the protease inhibitor-containing arms compared with decreases with RAL. In contrast, carotid IMT progressed more slowly on ATV/r [8.2, 95% confidence interval (5.6, 10.8) μm/year] than DRV/r [12.9 (10.3, 15.5) μm/year, P = 0.013]; changes with RAL were intermediate [10.7 (9.2, 12.2) μm/year, P = 0.15 vs. ATV/r; P = 0.31 vs. DRV/r]. Bilirubin and non-high-density lipoprotein cholesterol levels appeared to influence carotid IMT progression rates. Conclusion: In ART-naive HIV-infected individuals at low cardiovascular disease risk, carotid IMT progressed more slowly in participants initiating ATV/r than those initiating DRV/r, with intermediate changes associated with RAL. This effect may be due, in part, to hyperbilirubinemia.
    AIDS (London, England) 09/2015; 29(14):1775-83. DOI:10.1097/QAD.0000000000000762 · 5.55 Impact Factor
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    ABSTRACT: Background. Some patients are not prescribed atazanavir over concern about possible jaundice. Atazanavir-associated hyperbilirubinemia correlates with UGT1A1 rs887829 genotype. We examined bilirubin-related discontinuation of atazanavir in participants from AIDS Clinical Trials Group study A5257. Methods. Discriminatory properties of UGT1A1 T/T genotype for predicting bilirubin-related atazanavir discontinuation through 96 weeks after antiretroviral initiation were estimated. Results. Genetic analyses involved 1450 participants, including 481 who initiated randomized atazanavir/ritonavir. Positive predictive values of rs887829 T/T for bilirubin-related discontinuation of atazanavir (with 95% confidence intervals) were 20% (9% - 36%) in Black, 60% (32% - 84%) in White, and 29% (8% - 58%) in Hispanic participants; Negative predictive values were 97% (93% - 99%), 95% (90% - 98%), and 97% (90% - 100%), respectively. Conclusions. Bilirubin-related discontinuation of atazanavir was rare in participants not homozygous for rs887829 T/T, regardless of race/ethnicity. We hypothesize that the higher rate of discontinuation among White participants homozygous for rs887829 T/T may reflect differences in physical manifestations of jaundice by race/ethnicity. Selective avoidance of atazanavir initiation among individuals with T/T genotypes would markedly reduce the likelihood of bilirubin-related discontinuation of atazanavir while allowing atazanavir to be prescribed to the majority of individuals. This genetic association will also affect atazanavir/cobicistat.
    09/2015; 2(3). DOI:10.1093/ofid/ofv085
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    ABSTRACT: Background: Combination antiretroviral therapy (ART) suppresses HIV-1 replication, but does not restore CD4 T-cell counts in all individuals. To investigate the effects of maraviroc on HIV-1 persistence and the relations between virologic and immunologic parameters in individuals with incomplete CD4 T-cell recovery, we performed a prospective, open-label pilot trial in which maraviroc was added to a suppressive ART regimen for 24 weeks. Design: A5256 was a single-arm trial in which individuals on suppressive ART with incomplete CD4 T-cell recovery added maraviroc for 24 weeks. Methods: We quantified low-level, residual viremia in plasma and total HIV-1 DNA and 2-long terminal repeat (2-LTR) circles in peripheral blood mononuclear cells before and after maraviroc intensification. We also evaluated markers of CD4 and CD8 T-cell immune activation (%CD38HLA-DR) and apoptosis (%caspase3/Bcl-2). Results: No effect of maraviroc was found on the probability of detectable plasma viremia (≥1 copy/ml; n = 31, exact McNemar P = 1.0) or detectable 2-LTR circles (n = 28, P = 0.25) or on total HIV-1 DNA (n = 28, 90% confidence interval -0.1, +0.3 log10 copies/10 CD4 T-cells). Premaraviroc HIV-1 DNA levels were inversely related to premaraviroc %CD38HLA-DR CD4 T-cells (Spearman = -0.52, P = 0.004), and lower premaraviroc HIV-1 DNA levels were associated with larger decreases in %CD38HLA-DR CD4 T-cells during maraviroc intensification (Spearman = 0.44, P = 0.018). Conclusion: In individuals on suppressive ART with incomplete CD4 T-cell recovery, maraviroc intensification did not affect measures of HIV-1 persistence but did decrease persistent CD4 T-cell immune activation especially in individuals with low preintensification levels of HIV-1 DNA.
    AIDS 07/2015; 29(16):1. DOI:10.1097/QAD.0000000000000810 · 5.55 Impact Factor
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    ABSTRACT: HIV-infected men and women who choose to conceive risk infecting their partners. To inform safer conception programs we surveyed HIV risk behavior prior to recent pregnancy amongst South African, HIV-infected women (N = 209) and men (N = 82) recruited from antenatal and antiretroviral clinics, respectively, and reporting an uninfected or unknown-HIV-serostatus pregnancy partner. All participants knew their HIV-positive serostatus prior to the referent pregnancy. Only 11 % of women and 5 % of men had planned the pregnancy; 40 % of women and 27 % of men reported serostatus disclosure to their partner before conception. Knowledge of safer conception strategies was low. Around two-thirds reported consistent condom use, 41 % of women and 88 % of men reported antiretroviral therapy, and a third of women reported male partner circumcision prior to the referent pregnancy. Seven women (3 %) and two men (2 %) reported limiting sex without condoms to peak fertility. None reported sperm washing or manual insemination. Safer conception behaviors including HIV-serostatus disclosure, condom use, and ART at the time of conception were not associated with desired pregnancy. In light of low pregnancy planning and HIV-serostatus disclosure, interventions to improve understandings of serodiscordance and motivate mutual HIV-serostatus disclosure and pregnancy planning are necessary first steps before couples or individuals can implement specific safer conception strategies.
    AIDS and Behavior 06/2015; 19(12). DOI:10.1007/s10461-015-1050-x · 3.49 Impact Factor
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    ABSTRACT: Antiretroviral therapy initiation for HIV-1 infection is associated with 2% to 6% loss of bone mineral density (BMD). To evaluate the effect of vitamin D3 plus calcium supplementation on bone loss associated with antiretroviral therapy initiation. 48-week prospective, randomized, double-blind, placebo-controlled study. (ClinicalTrials.gov: NCT01403051). 39 AIDS Clinical Trials Group units. Adults with antiretroviral therapy-naive HIV. BMD by dual-energy x-ray absorptiometry, 25-hydroxyvitamin D levels, and other laboratory assessments. 165 eligible patients were randomly assigned (79 received vitamin D3 plus calcium and 86 received placebo). The study groups were well-balanced at baseline: 90% were men, 33% were non-Hispanic black, and the median CD4 count was 0.341 × 109 cells/L. At 48 weeks, the percentage of decline in total hip BMD was smaller in the vitamin D3 plus calcium group than in the placebo group: Medians were -1.36% (interquartile range [IQR], -3.43% to 0.50%) and -3.22% (IQR, -5.56% to -0.88%), respectively (P = 0.004). Similar results were seen at the lumbar spine. At 48 weeks, 90% of patients achieved HIV-1 RNA levels less than 50 copies/mL. Levels of 25-hydroxyvitamin D3 increased with vitamin D3 plus calcium but not with placebo: Median change was 61.2 nmol/L (IQR, 36.4 to 94.3) versus 1.7 nmol/L (IQR, -13.2 to 10.7) (P < 0.001). Overall, 103 patients (62%) reported 1 or more adverse event, with similar distribution between groups; no cases of hypercalcemia and 1 case of nephrolithiasis were reported in the placebo group. No international sites were included, and follow-up was only 48 weeks. Vitamin D3 plus calcium supplementation mitigates the BMD loss seen with initiation of efavirenz/emtricitabine/tenofovir disoproxil fumarate. National Institute of Allergy and Infectious Diseases, Bristol-Myers Squibb, and Gilead Sciences.
    Annals of internal medicine 06/2015; 162(12):815-824. DOI:10.7326/M14-1409 · 17.81 Impact Factor
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    ABSTRACT: Discrepancies between HIV-1 RNA results assayed by different FDA-approved platforms have been reported. Plasma samples collected from 332 randomly selected clinical trial participants during second year of antiretroviral treatment were assayed with 3 FDA-approved platforms: UltraSensitive Roche Amplicor Monitor, v1.5 [Monitor], Abbott RealTime HIV-1 Test/m2000 [Abbott] and Roche TaqMan HIV-1 Test, v2.0 [TaqMan]. Samples from 61 additional participants with confirmed HIV-1 RNA >50 c/mL during trial follow-up were also included. Endpoints were HIV-1 RNA quantification ≤ vs. >50 c/mL at an individual sample level (primary) and determination of confirmed virologic failure (VF) from longitudinal samples. 389 participants had results obtained from all assays on at least one sample (median=6). Proportions of results >50 c/mL were 19% [Monitor], 22% [TaqMan] and 25% [Abbott]. Despite indication of strong agreement (Cohen's kappa: 0.76-0.82), Abbott was more likely to detect HIV-1 RNA >50 c/mL than Monitor (matched pair odds ratio [mOR]=4.2; modified Obuchowski p<0.001) and TaqMan (mOR=2.1; p<0.001); TaqMan was more likely than Monitor (mOR=2.6; p<0.001). Although strong agreement in classifying VF across assay comparisons (kappa: 0.75-0.92), at a 50 c/mL threshold, differences in the probability of VF classification (in the same direction as primary) were apparent (all McNemar's p<0.007). At a 200 c/mL VF threshold, no differences between assays were apparent (all p>0.13). Despite strong agreement among assays, significant differences were observed with respect to detecting HIV-1 RNA >50 c/mL and identifying VF at the 50 c/mL threshold. This has important implications for the definition of VF in clinical trials and clinical practice. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
    Journal of clinical microbiology 06/2015; 53(8). DOI:10.1128/JCM.00801-15 · 3.99 Impact Factor
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    ABSTRACT: Background: There is a need to prevent or minimize bone loss associated with antiretroviral treatment (ART) initiation. We compared maraviroc (MVC)- to tenofovir disoproxil fumarate (TDF)-containing ART. Methods: This was a double-blind, placebo-controlled trial. ART-naive subjects with human immunodeficiency virus type 1 RNA load (viral load [VL]) >1000 copies/mL and R5 tropism were randomized to MVC 150 mg or TDF 300 mg once daily (1:1), stratified by VL <100 000 or ≥100 000 copies/mL and age <30 or ≥30 years. All subjects received darunavir 800 mg, ritonavir 100 mg, and emtricitabine 200 mg daily. Dual-energy X-ray absorptiometry scanning was done at baseline and week 48. The primary endpoint was percentage change in total hip bone mineral density (BMD) from baseline to week 48 in the as-treated population. Results: We enrolled 262 subjects. A total of 259 subjects (130 MVC, 129 TDF) contributed to the analyses (91% male; median age, 33 years; 45% white, 30% black, 22% Hispanic). Baseline median VL was 4.5 log10 copies/mL and CD4 count was 390 cells/µL. The decline in hip BMD (n = 115 for MVC, n = 109 for TDF) at week 48 was less with MVC (median [Q1, Q3] of -1.51% [-2.93%, -0.11%] vs -2.40% [-4.30%, -1.32%] for TDF (P < .001). Lumbar spine BMD decline was also less with MVC (median -0.88% vs -2.35%; P < .001). Similar proportions of subjects in both arms achieved VL ≤50 copies/mL in as-treated and ITT analyses. Conclusions: MVC was associated with less bone loss at the hip and lumbar spine compared with TDF. MVC may be an option to attenuate ART-associated bone loss. Clinical trials registration: NCT01400412.
    Clinical Infectious Diseases 06/2015; 61(7). DOI:10.1093/cid/civ455 · 8.89 Impact Factor
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    ABSTRACT: Background: Specific antiretroviral therapy (ART) medications and the severity of human immunodeficiency virus (HIV) disease before treatment contribute to bone mineral density (BMD) loss after ART initiation. Methods: We compared the percentage change in BMD over 96 weeks in 328 HIV-infected, treatment-naive individuals randomized equally to tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) plus atazanavir/ritonavir (ATV/r), darunavir/ritonavir (DRV/r), or raltegravir (RAL). We also determined whether baseline levels of inflammation markers and immune activation were independently associated with BMD loss. Results: At week 96, the mean percentage changes from baseline in spine and hip BMDs were similar in the protease inhibitor (PI) arms (spine: -4.0% in the ATV/r group vs -3.6% in the DRV/r [P = .42]; hip: -3.9% in the ATV/r group vs -3.4% in the DRV/r group [P = .36]) but were greater in the combined PI arms than in the RAL arm (spine: -3.8% vs -1.8% [P < .001]; hip: -3.7% vs -2.4% [P = .005]). In multivariable analyses, higher baseline concentrations of high-sensitivity C-reactive protein, interleukin 6, and soluble CD14 were associated with greater total hip BMD loss, whereas markers of CD4(+) T-cell senescence and exhaustion (CD4(+)CD28(-)CD57(+)PD1(+)) and CD4(+) T-cell activation (CD4(+)CD38(+)HLA-DR(+)) were associated with lumbar spine BMD loss. Conclusions: BMD losses 96 weeks after ART initiation were similar in magnitude among patients receiving PIs, ATV/r, or DRV/r but lowest among those receiving RAL. Inflammation and immune activation/senescence before ART initiation independently predicted subsequent BMD loss.
    The Journal of Infectious Diseases 05/2015; 212(8). DOI:10.1093/infdis/jiv194 · 6.00 Impact Factor
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    ABSTRACT: Background. It is unclear whether the integrase inhibitor raltegravir (RAL) reduces inflammation and immune activation compared with ritonavir-boosted protease inhibitors (PIs). Methods. In a prospective, randomized, multicenter clinical trial that included 328 human immunodeficiency type 1 (HIV-1)-infected, treatment-naive participants were randomized to receive tenofovir disoproxil fumarate-emtricitabine (TDF/FTC) plus atazanavir/ritonavir (ATV/r), darunavir/ritonavir (DRV/r), or RAL. A total of 234 participants (71%) with HIV-1 RNA levels <50 copies/mL by week 24 were included. Plasma biomarkers of inflammation and coagulation that were analysed included high-sensitivity C-reactive protein, interleukin-6 (IL-6), GlycA, D-dimer, soluble CD14 (sCD14), sCD163, and sIL-2r; blood cellular markers included %CD38+DR+ of T-cell subsets and %CD14+CD16+ and%CD14(dim)CD16+ monocyte subsets. Changes from baseline were examined at earlier (24 or 48 weeks) and later (96 weeks) time points, with 95% confidence intervals on fold-change. Pairwise treatment groups were compared using Wilcoxon rank sum tests, with P values adjusted for false discovery rate control. Results. Changes in biomarkers varied by regimen during the 96 weeks of follow-up as follows: hsCRP declined with ATV/r and RAL, IL-6 declined only with RAL, and GLycA decreased in all groups. D-dimer declined with ATV/r and DRV/r and was unchanged with RAL. Markers of T-cell activation and sCD163 (but not sCD14 and CD14-+CD16+) declined in all groups. Conclusions. Despite some differences in specific markers of inflammation and immune activation between the antiretroviral therapy (ART) regimens, we found no consistent evidence that the reduction of inflammation and immune activation with ART initiation was different between RAL and PI-based regimens. Clinical Trials Registration. NCT00811954 and NCT00851799.
    Clinical Infectious Diseases 04/2015; 61(4). DOI:10.1093/cid/civ327 · 8.89 Impact Factor
  • Jeffrey L Lennox · Raphael J Landovitz · Heather J Ribaudo ·

    Annals of internal medicine 03/2015; 162(6):461-462. DOI:10.7326/L15-5066-3 · 17.81 Impact Factor
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    ABSTRACT: Background. Metabolic effects following combination antiretroviral therapy (cART) vary by regimen type. Changes in metabolic effects were assessed following cART in the ACTG A5257 study, and correlated with plasma ritonavir trough concentrations (C24). Methods. Treatment-naïve adult subjects were randomized to ritonavir boosted atazanavir or darunavir, or raltegravir based cART. Changes in lipids and other metabolic outcomes over time were estimated. Differences between arms were estimated with 97.5% confidence intervals and compared using pairwise Student's T-tests. Associations between ritonavir C24 and lipid changes at week-48 were evaluated via linear regression. Results. Analyses included 1797 subjects with baseline fasting data. Baseline lipid profiles and metabolic syndrome rates (∼21%) were similar across arms. Comparable increases occurred in total cholesterol, triglycerides, and LDL-cholesterol with the boosted protease inhibitors (PI); each PI had greater increases relative to raltegravir (all P≤0.001 at week-96). Metabolic syndrome incident rates by week-96 (∼22%) were not different across arms. Ritonavir C24 were not different by arm (P=0.89), (median 69 ng/mL and 74 ng/mL in the atazanavir and darunavir arms respectively) and were not associated with changes in lipid measures (all P>0.1). Conclusions. Raltegravir produced the most favorable lipid profile. Metabolic syndrome rates were high at baseline and increased to the same degree in all arms. Ritonavir C24 was not different in the PI arms and had no relationship with the modest but comparable increases in lipids observed with either atazanavir or darunavir. The long-term clinical significance of the lipid changes noted with the PIs relative to raltegravir deserves further evaluation.
    Clinical Infectious Diseases 03/2015; 60(12). DOI:10.1093/cid/civ193 · 8.89 Impact Factor
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    ABSTRACT: Objective. ACTG A5230 evaluated lopinavir/ritonavir (LPV/r) monotherapy following virologic failure on first-line regimens in Africa and Asia. Methods. Eligible subjects had received first-line regimens for at least 6 months and had plasma HIV-1 RNA levels 1000-200,000copies/mL. All subjects received LPV/r 400/100mg twice daily. Virologic failure (VF) was defined as failure to suppress to <400 copies/mL by week 24, or confirmed rebound to >400 copies/mL at or after week 16 following confirmed suppression. Subjects with VF added emtricitabine 200mg/tenofovir 300mg (FTC/TDF) once daily. The probability of continued HIV-1 RNA <400 copies/mL on LPV/r-monotherapy through week 104 was estimated with a 95% confidence interval (CI); predictors of treatment success were evaluated with Cox proportional hazards models. Results. 123 subjects were enrolled. Four subjects died and 2 discontinued prematurely; 117 /123 (95%) completed 104 weeks. Through week 104, 49 subjects met the primary endpoint; 47 had VF, and 2 intensified treatment without VF. Of the 47 subjects with VF, 41 (33%) intensified treatment, and 39/41 subsequently achieved levels <400 copies/mL. The probability of continued suppression <400copies/mL over 104 weeks on LPV/r-monotherapy was 60% [95% CI 50%, 68%]; 80-85% maintained levels <400 copies/mL with FTC/TDF intensification as needed. Ultrasensitive assays on specimens with HIV-1 RNA level<400 copies/mL at weeks 24, 48 and 104 revealed that 61%, 62% and 65% were suppressed to <40 copies/mL, respectively. Conclusion. LPV/r monotherapy after first-line virologic failure with FTC/TDF intensification when needed provides durable suppression of HIV-1 RNA over 104 weeks.
    Clinical Infectious Diseases 02/2015; DOI:10.1093/cid/civ109 · 8.89 Impact Factor
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    ABSTRACT: Episodes of human immunodeficiency virus low-level viremia (LLV) are common in the clinical setting, but its association with antiretroviral therapy (ART) regimen and adherence remains unclear. Antiretroviral therapy adherence was evaluated in participants of the Research on Access to Care in the Homeless cohort by unannounced pill counts. Factors associated with increased risk of LLV include treatment with a protease inhibitor (PI)-based regimen (ritonavir-boosted PI vs nonnucleoside reverse-transcriptase inhibitor: adjusted hazard ratio [HR], 3.1; P = .01) and lower ART adherence over the past 3 months (HR, 1.1 per 5% decreased adherence, adjusted; P = .050). Patients with LLV may benefit from ART adherence counseling and potentially regimen modification.
    01/2015; 2(1):ofu119-ofu119. DOI:10.1093/ofid/ofu119
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    ABSTRACT: Efavirenz and abacavir are components of recommended first-line regimens for HIV-1 infection. We used genome-wide genotyping and clinical data to explore genetic associations with virologic failure among patients randomized to efavirenz-containing or abacavir-containing regimens in AIDS Clinical Trials Group (ACTG) protocols. Virologic response and genome-wide genotype data were available from treatment-naive patients randomized to efavirenz-containing (n=1596) or abacavir-containing (n=786) regimens in ACTG protocols 384, A5142, A5095, and A5202. Meta-analysis of association results across race/ethnic groups showed no genome-wide significant associations (P<5×10) with virologic response for either efavirenz or abacavir. Our sample size provided 80% power to detect a genotype relative risk of 1.8 for efavirenz and 2.4 for abacavir. Analyses focused on CYP2B genotypes that define the lowest plasma efavirenz exposure stratum did not show associations nor did analysis limited to gene sets predicted to be relevant to efavirenz and abacavir disposition. No single polymorphism is associated strongly with virologic failure with efavirenz-containing or abacavir-containing regimens. Analyses to better consider context, and that minimize confounding by nongenetic factors, may show associations not apparent here.
    Pharmacogenetics and Genomics 11/2014; 25(2). DOI:10.1097/FPC.0000000000000106 · 3.48 Impact Factor
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    ABSTRACT: Background : Cellular markers of immune activation are strong predictors of disease progression and comorbidities in HIV infection. It is unclear whether soluble biomarkers of T cell (sIL-2r) and monocyte (MNC) activation (sCD14, sCD163) represent robust surrogate markers of cellular immune activation during the course of antiretroviral therapy (ART). Methods : In the ACTG A5260s study, Spearman correlations between biomarkers of T-cell and MNC activation and proinflammatory MNC (pMNCs) subsets were estimated at entry and 96 weeks in 328 HIV-infected treatment-naive subjects randomized equally to tenofovir/emtricitabine plus raltegravir or ritonavir-boosted atazanavir or darunavir. Analyses were restricted to 234 (71%) subjects who had HIV-1 RNA <50 copies/ml by week 24 and thereafter. Plasma and cellular immune markers were determined by ELISA and flow cytometry, respectively. Results: sIL-2r and sCD163 were significantly associated with T cell activation (% CD38+DR+ CD8 T cells) at entry and 96 weeks. sCD163 was also associated with both T cell activation and pMNCs (% CD14+CD16+ MNCs) after successful ART. sCD14 was significantly associated with T cell activation and pMNCs only at entry. After 96 weeks of ART, sIL-2r and sCD14 were not associated with cellular markers of pMNCs (Table). Conclusion: There were modest associations between all plasma markers of immune activation and cellular markers of T activation in viremic subjects. However, after successful ART, only sCD163 had a modest association with cellular markers of T cell activation. Plasma markers of immune activation may reflect different immune activation pathways with differential dependence on viral replication versus immune dysregulation that is not reversed with viral suppression by ART. Plasma Markers Week 0 Week 96 Cellular Markers sIL-2r sCD14 sCD163 sIL-2r sCD14 sCD163 % CD38+DR+ of CD8+ T cells (T cell activation) 0.36 (<0.001) 0.25 (<0.001) 0.38 (<0.001) 0.18 (0.011) 0.11 (0.11) 0.40 (<0.001) % CD14+CD16+ of MNCs (pMNCs) 0.07 (0.30) 0.27 (<0.001) 0.06 (0.38) -0.06 (0.40) 0.07 (0.32) 0.16 (0.022) % CD163+ of MNCs (pMNCs) -0.01 (0.90) 0.03 (0.65) -0.02 (0.78) -0.07 (0.29) -0.02 (0.81) -0.05 (0.52) 1Similar correlations on CD4+; 2associations with CD16 (h) CD14 (l) not apparent.
    IDWeek 2014 Meeting of the Infectious Diseases Society of America; 10/2014
  • J. L. Lennox · R. J. Landovitz · H. J. Ribaudo · I Ofotokun · L. H. Na · C. Godfrey ·

    Annals of internal medicine 10/2014; 161(7). · 17.81 Impact Factor

  • Annals of internal medicine 10/2014; 161(7):I-22. DOI:10.7326/P14-9035 · 17.81 Impact Factor
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    ABSTRACT: Nonnucleoside reverse transcriptase inhibitor-based antiretroviral therapy is not suitable for all treatment-naive HIV-infected persons.
    Annals of internal medicine 10/2014; 161(7):461-471. DOI:10.7326/M14-1084 · 17.81 Impact Factor
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    ABSTRACT: Background: The 2013 American College of Cardiology/American Heart Association (ACC/AHA) cholesterol guidelines are being applied to HIV-infected patients but have not been validated in this at-risk population, which is known to have a high prevalence of subclinical high-risk morphology (HRM) coronary atherosclerotic plaque. Objective: To compare recommendations for statins among HIV-infected subjects with/without HRM coronary plaque according to 2013 ACC/AHA versus 2004 Adult Treatment Panel III guidelines. Methods/design: Data from 108 HIV-infected subjects without known cardiovascular disease (CVD) or lipid-lowering treatment who underwent contrast-enhanced computed tomography angiography were analyzed. Recommendations for statin therapy according to 2013 versus 2004 guidelines were assessed among those with/without HRM coronary plaque. Results: Among all subjects, 10-year atherosclerotic cardiovascular disease (ASCVD) risk score was 3.3% (1.6, 6.6), yet 36% of subjects had HRM coronary plaque. Among those with HRM coronary plaque, statins would be recommended for 26% by 2013 guidelines versus 10% by 2004 guidelines (P=0.04). Conversely, among those without HRM coronary plaque, statins would be recommended for 19% by 2013 guidelines versus 7% by 2004 guidelines (P=0.005). In multivariate modeling, while 10-year ASCVD risk score related to HRM coronary plaque burden (P=0.02), so too did other factors not incorporated into 2013 guidelines. Conclusion: The 2013 ACC/AHA cholesterol guidelines recommend statin therapy for a higher percentage of subjects with and without HRM coronary plaque relative to 2004 guidelines. However, even by 2013 guidelines, statin therapy would not be recommended for the majority (74%) of HIV-infected subjects with subclinical HRM coronary plaque. Outcome studies are needed to determine the utility of new statin recommendations and the contribution of HRM coronary plaque to CVD events among HIVinfected subjects.
    AIDS (London, England) 09/2014; 28(14):2061-2070. DOI:10.1097/QAD.0000000000000360 · 5.55 Impact Factor
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    ABSTRACT: Background. Human immunodeficiency virus (HIV)-1 elite controllers (ECs) represent an ideal population to study the effects of HIV persistence on chronic inflammation in the absence of antiretroviral therapy (ART). Methods. Twenty inflammatory markers measured in cohorts of ECs, HIV suppressed noncontrollers, and HIV-uninfected controls were compared using rank-based tests and partial least squares discriminant analysis (PLSDA). Spearman correlations were determined among the inflammatory markers, residual viremia by the single-copy assay, and CD4[superscript +] T cell slope. Results. Significant differences were seen between cohorts in 15 of the soluble inflammatory markers. Human immunodeficiency virus-1 ECs were found to have the highest levels for all of the markers with the exception of RANTES. In particular, median levels of 7 inflammatory markers (soluble CD14 [sCD14], interferon [IFN]-γ, IFN-γ-inducible protein [IP]-10, interleukin [IL]-4, IL-10, sCD40L, and granulocyte-macrophage colony-stimulating factor) were twice as high in the HIV-1 ECs compared with either of the HIV-suppressed or uninfected groups. Multivariate PLSDA analysis of inflammatory markers improved differentiation between the patient cohorts, discerning gender differences in inflammatory profile amongst individuals on suppressive ART. Soluble markers of inflammation in ECs were not associated with either levels of residual HIV-1 viremia or CD4[superscript +] T cell decline. Conclusions. Despite maintaining relatively low levels of viremia, HIV-1 ECs had elevated levels of a set of key inflammatory markers. Additional studies are needed to determine whether ECs may benefit from ART and to further evaluate the observed gender differences.
    08/2014; 2(1):ofu117-ofu117. DOI:10.1093/ofid/ofu117

Publication Stats

5k Citations
906.49 Total Impact Points


  • 1999-2015
    • Harvard Medical School
      • Department of Medicine
      Boston, Massachusetts, United States
  • 2014
    • University of Massachusetts Boston
      Boston, Massachusetts, United States
    • Boston University
      Boston, Massachusetts, United States
  • 2008-2014
    • Harvard University
      • Department of Biostatistics
      Cambridge, Massachusetts, United States
  • 2007
    • Weill Cornell Medical College
      • Department of Public Health
      New York City, New York, United States
  • 2004-2007
    • Cornell University
      Итак, New York, United States
  • 2005
    • Vanderbilt University
      Nashville, Michigan, United States