Dataset Information

Brief Report: Changes in Levels of Inflammation After Antiretroviral Treatment During Early HIV Infection in AIDS Clinical Trials Group Study A5217.

ABSTRACT: BACKGROUND:We evaluated the changes in the levels of soluble biomarkers of inflammation and coagulation and T-cell activation among participants of AIDS Clinical Trials Group Study A5217 who were started on antiretroviral therapy (ART) within the first 6 months of HIV infection. METHODS:Cryopreserved specimens were obtained pre-ART (week 0), at the time of virologic suppression (week 36), and at 36 weeks after treatment interruption (week 72). Levels of D-dimer, C-reactive protein (CRP), and soluble CD14 (sCD14) were measured in plasma, whereas T-cell activation levels, defined as the frequencies of CD4 and CD8 T cells coexpressing HLA-DR and CD38, were measured in peripheral blood mononuclear cells. RESULTS:D-dimer levels were significantly lower at viral suppression (P = 0.031), whereas CRP and sCD14 levels remained similar to pre-ART levels. At viral suppression, levels of the soluble markers did not correlate with each other. CD4 T-cell counts pre-ART tended to modestly correlate with levels of D-dimer (r = 0.35; P = 0.058) and CRP (r = 0.33; P = 0.078). At 36 weeks after treatment interruption (week 72), D-dimer levels returned back to pre-ART levels. However, CD8 T-cell activation was significantly lower than pre-ART levels (35.8% at week 0 vs 28.9% at week 72; P = 0.004). CONCLUSIONS:Among the A5217 participants who started ART within the first 6 months of HIV infection, high levels of sCD14 and CRP remain similar to pre-ART levels, suggesting that immune damage occurring in the initial stages of infection persists despite short-term virologic suppression.

SUBMITTER: Macatangay BJ

PROVIDER: S-EPMC5393630 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Brief Report: Changes in Levels of Inflammation After Antiretroviral Treatment During Early HIV Infection in AIDS Clinical Trials Group Study A5217.

Macatangay Bernard J BJ Yang Ming M Sun Xin X Morton Jessica J De Gruttola Victor V Little Susan S Hogan Christine C Rinaldo Charles R CR

Journal of acquired immune deficiency syndromes (1999) 20170501 1

<h4>Background</h4>We evaluated the changes in the levels of soluble biomarkers of inflammation and coagulation and T-cell activation among participants of AIDS Clinical Trials Group Study A5217 who were started on antiretroviral therapy (ART) within the first 6 months of HIV infection.<h4>Methods</h4>Cryopreserved specimens were obtained pre-ART (week 0), at the time of virologic suppression (week 36), and at 36 weeks after treatment interruption (week 72). Levels of D-dimer, C-reactive protein ...[more]

PMID: 28198712

Similar Datasets

Project description:BackgroundDetectable HIV-1 in body compartments can lead to transmission and antiretroviral resistance. Although sex differences in viral shedding have been demonstrated, mechanisms and magnitude are unclear. We compared RNA levels in blood, genital-secretions and saliva; and drug resistance in plasma and genital-secretions of men and women starting/changing antiretroviral therapy (ART) in the AIDS Clinical Trials Group (ACTG) 5077 study.MethodsBlood, saliva and genital-secretions (compartment fluids) were collected from HIV-infected adults (≥ 13 years) at 14 United-States sites, who were initiating or changing ART with plasma viral load (VL) ≥ 2,000 copies/mL. VL testing was performed on all compartment fluids and HIV resistance genotyping on plasma and genital-secretions. Spearman rank correlations were used to evaluate concordance and Fisher's and McNemar's exact tests to compare VL between sexes and among compartments.ResultsSamples were available for 143 subjects; 36% treated (23 men, 29 women) and 64% 'untreated' (40 men, 51 women). RNA detection was significantly more frequent in plasma (100%) than genital-secretions (57%) and saliva (64%) (P<0.001). A higher proportion of men had genital shedding versus women (78% versus 41%), and RNA detection was more frequent in saliva versus genital-secretions in women when adjusted for censoring at the limit of assay detection. Inter-compartment fluid VL concordance was low in both sexes. In 22 (13 men, 9 women) paired plasma-genital-secretion genotypes from treated subjects, most had detectable resistance in both plasma (77%) and genital-secretions (68%). Resistance discordance was observed between compartments in 14% of subjects.ConclusionsHIV shedding and drug resistance detection prior to initiation/change of ART in ACTG 5077 subjects differed among tissues and between sexes, making the gold standard blood-plasma compartment assessment not fully representative of HIV at other tissue sites. Mechanisms of potential sex-dependent tissue compartmentalization should be further characterized to aid in optimizing treatment and prevention of HIV transmission.Trial registrationClinicalTrials.gov NCT00007488.

Project description:BackgroundHigh-throughput approaches are increasingly being used to identify genetic associations across multiple phenotypes simultaneously. Here, we describe a pilot analysis that considered multiple on-treatment laboratory phenotypes from antiretroviral therapy-naive patients who were randomized to initiate antiretroviral regimens in a prospective clinical trial, AIDS Clinical Trials Group protocol A5202.Participants and methodsFrom among 5 9545 294 polymorphisms imputed genome-wide, we analyzed 2544, including 2124 annotated in the PharmGKB, and 420 previously associated with traits in the GWAS Catalog. We derived 774 phenotypes on the basis of context from six variables: plasma atazanavir (ATV) pharmacokinetics, plasma efavirenz (EFV) pharmacokinetics, change in the CD4+ T-cell count, HIV-1 RNA suppression, fasting low-density lipoprotein-cholesterol, and fasting triglycerides. Permutation testing assessed the likelihood of associations being by chance alone. Pleiotropy was assessed for polymorphisms with the lowest P-values.ResultsThis analysis included 1181 patients. At P less than 1.5×10, most associations were not by chance alone. Polymorphisms with the lowest P-values for EFV pharmacokinetics (CYPB26 rs3745274), low-density lipoprotein -cholesterol (APOE rs7412), and triglyceride (APOA5 rs651821) phenotypes had been associated previously with those traits in previous studies. The association between triglycerides and rs651821 was present with ATV-containing regimens, but not with EFV-containing regimens. Polymorphisms with the lowest P-values for ATV pharmacokinetics, CD4 T-cell count, and HIV-1 RNA phenotypes had not been reported previously to be associated with that trait.ConclusionUsing data from a prospective HIV clinical trial, we identified expected genetic associations, potentially novel associations, and at least one context-dependent association. This study supports high-throughput strategies that simultaneously explore multiple phenotypes from clinical trials' datasets for genetic associations.

Project description:BackgroundThe association of inflammatory biomarkers with clinical events after antiretroviral therapy initiation is unclear.MethodsA5202 randomized 1857 treatment-naive subjects to abacavir/lamivudine or tenofovir-DF/emtricitabine with efavirenz or atazanavir/ritonavir. Substudy A5224s measured inflammatory biomarkers on subjects with available plasma from baseline and week 24 or 96. An exploratory analysis of the association of high-sensitivity C-reactive protein, interleukin-6 (IL-6), soluble receptors of tumor necrosis factor α (sTNF)-RI, sTNF-RII, TNF-α, soluble vascular cellular adhesion molecules (sVCAM-1), and soluble intercellular adhesion molecules (sICAM-1) with times to AIDS and to non-AIDS events used Cox proportional hazards models.ResultsAnalysis included 244 subjects; 85% men and 48% white non-Hispanic with median age 39 years, HIV-1 RNA of 4.6 log10 copies per milliliter, and CD4 of 240 cells per microliter. Overall, 13 AIDS events (9 opportunistic infections, 3 AIDS-cancers, and 1 recurrent bacterial pneumonia) and 18 non-AIDS events (6 diabetes, 4 cancers, 3 cardiovascular, and 5 pneumonias) occurred. Higher baseline IL-6, sTNF-RI, sTNF-RII, and sICAM-1 were significantly associated with increased risk of AIDS-defining events. Adjustment for baseline HIV-1 RNA did not change results, whereas adjusting for baseline CD4 count left only sTNF-RI and sICAM-1 significantly associated with increased risk. Time-updated values of IL-6, sTNFR-I and II, and sICAM-1 were also associated with an increased risk. For non-AIDS events, only higher baseline high-sensitivity C-reactive protein was significantly associated with increased risk, whereas higher IL-6 was marginally associated with higher risk. Analyses of time-updated biomarker values showed tumor necrosis factor α to be significantly associated with increased risk, even after adjustment for antiretroviral therapy, and CD4 count or HIV-1 RNA.ConclusionsHigher levels of several inflammatory biomarkers were independently associated with increased risk of AIDS and non-AIDS events.

Dataset Information

Brief Report: Changes in Levels of Inflammation After Antiretroviral Treatment During Early HIV Infection in AIDS Clinical Trials Group Study A5217.

Publications

Brief Report: Changes in Levels of Inflammation After Antiretroviral Treatment During Early HIV Infection in AIDS Clinical Trials Group Study A5217.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets