Factors Associated with D-Dimer Levels in HIV-Infected Individuals

Matti A Ristola on työryhmän jäsen.Peer reviewe

Adjudicated morbidity and mortality outcomes by age among individuals with HIV infection on suppressive antiretroviral therapy

Background: Non-AIDS conditions such as cardiovascular disease and non-AIDS defining cancers dominate causes of morbidity and mortality among persons with HIV on suppressive combination antiretroviral therapy. Accurate estimates of disease incidence and of risk factors for these conditions are important in planning preventative efforts. Methods: With use of medical records, serious non-AIDS events, AIDS events, and causes of death were adjudicated using pre-specified criteria by an Endpoint Review Committee in two large international trials. Rates of serious non-AIDS which include cardiovascular disease, end-stage renal disease, decompensated liver disease, and non-AIDS cancer, and other serious (grade 4) adverse events were determined, overall and by age, over a median follow-up of 4.3 years for 3,570 participants with CD4cell count 300 cells/mm3 who were taking antiretroviral therapy and had an HIV RNA level ≤500 copies/mL. Cox models were used to examine the effect of age and other baseline factors on risk of a composite outcome of all-cause mortality, AIDS, or serious non-AIDS. Results: Five-year Kaplan-Meier estimates of the composite outcome, overall and by age were 8.3% (overall), 3.6%

Haemoglobin and anaemia in the SMART study

Background: Data from randomized trials on the development of anaemia after interruption of therapy are not well-described. Methods: A total of 2,248 patients from the SMART study were included. We used Cox proportional hazards models to investigate development of new (12 mg/dl for females and <= 14 mg/dl for males) or worsening (8 mg/dl if anaemic at randomization) anaemia and Poisson regression analyses to explore the relationship between anaemia and the development of AIDS, death or non-AIDS events. Results: Overall, 759 patients developed new or worsening anaemia: 420/1,106 (38.0%) in the drug conservation (DC) arm and 339/1127 (30.1%) in the viral suppression (VS) arm (P<0.0001). At 4 months after randomization, patients in the DC arm had a significantly increased risk of developing new or worsening anaemia (adjusted relative hazard 1.56, 95% CI 1.28-1.89). Currently anaemic patients had an increased incidence of AIDS (adjusted incidence rate ratio [IRR] 2.31, 95% CI 1.34-3.98), death (adjusted IRR 2.19, 95% CI 1.23-3.87) and non-AIDS events (adjusted IRR 2.98, 95% CI 2.01-4.40) compared to non-anaemic patients. Conclusions: Patients who interrupted combination anti-retroviral therapy had a higher risk of new or worsening anaemia. Anaemic patients had a higher incidence of AIDS, non-AIDS defining events or deaths, possibly due to deteriorating health and subclinical disease

HIV replication, inflammation, and the effect of starting antiretroviral therapy on plasma asymmetric dimethylarginine, a novel marker of endothelial dysfunction

Background: HIV infection is associated with premature development of cardiovascular disease. Understanding the effects of HIV replication on endothelial dysfunction and platelet activation may identify treatment targets to reduce cardiovascular disease risk. Methods: A subgroup of HIV-infected participants in the Strategies for Management of Antiretroviral Therapy study off antiretroviral therapy (ART) at entry enabled a randomized comparison of immediate versus deferred ART initiation of changes in asymmetric dimethylarginine (ADMA), soluble CD40 ligand (sCD40L), and P-selectin levels. Results: At study entry, median (interquartile range) levels of ADMA, sCD40L, and P-selectin were 0.57 (0.49–0.66) µg/mL, 251 (135–696) µmol/L, and 34 (28–44) pg/mL. Compared to those randomized to deferral of ART (n = 114), participants randomized to immediate ART (n = 134) had 10.3% lower ADMA levels (P = 0.003) at 12 months; treatment differences in sCD40L (95% confidence interval: -17% to 44%; P = 0.53) and P-selectin (95% confidence interval: -10% to 10%; P = 0.95) were not significant. The difference in ADMA for those assigned immediate ART compared with those assigned ART deferral was greater among younger patients and those with higher levels of high-sensitivity C-reactive protein and D-dimer (

Boosted protease inhibitors and the electrocardiographic measures of QT and PR durations

BACKGROUND: There are contradictory reports regarding the effects of protease inhibitors on the ECG measures of QT and PR interval durations. The effect of interrupting use of protease inhibitors on QT and PR progression is also unknown. METHODS: This analysis included 3719 participants from the Strategies for Management of Antiretroviral Therapy (SMART) study, of whom 1879 were randomized to receive intermittent antiretroviral therapy (ART) (drug conservation group), whereas the rest received these drugs continuously (viral suppression group). Linear regression analysis was used to compare four ritonavir-boosted protease inhibitor (protease inhibitor/r) regimens [saquinavir (SQV/r), lopinavir (LPV/r), atazanavir (ATV/r), and other protease inhibitor/r], and nonboosted protease inhibitor regimens with nonnucleoside reverse transcriptase inhibitor (NNRTI) regimens for Bazett’s (QTcB) and Fredericia’s (QTcF) heart rate corrected QT and PR. Changes in QTcB, QTcF, and PR after 12 and 24 months of randomization were compared in the drug conservation group and viral suppression group. RESULTS: Average levels of QTcB, QTcF, and PR duration at entry were 415, 406, and 158 ms. At study entry, 49% of participants were taking an NNRTI (no protease inhibitor)-based regimen and 31% were prescribed a boosted protease inhibitor, the most common being LPV/r. After adjustment for baseline factors, QTcB and QTcF levels did not vary by boosted protease inhibitor group (P = 0.26 and P = 0.34, respectively). For those given any of the boosted protease inhibitors, QTcB was 1.5 ms lower than the NNRTI group (P = 0.04). Both boosted and nonboosted protease inhibitor-containing regimens were significantly associated (P <0.01 for each) with longer PR intervals compared to the NNRTI group. After adjustment, the difference between boosted protease inhibitors and the NNRTI group was 5.11 ms (P <0.01); for nonboosted protease inhibitors, this difference was 3.00 ms (P <0.01). Following ART interruption, PR duration declined for both the boosted and nonboosted protease inhibitor groups and compared to the viral suppression group, significant changes in PR interval were observed 24 months after ART interruption of boosted protease inhibitors (P <0.01). CONCLUSION: Different protease inhibitor-based regimens have a similar, minimal effect on QT compared to NNRTI-based regimens. All protease inhibitor-based regimens (boosted and nonboosted) were associated with prolongation of PR, and interruption of protease inhibitor regimens reduced the prolonged PR duration. Further research is needed to confirm the findings of this study and assess the clinical relevance of the differences

Inflammation predicts changes in high-density lipoprotein particles and apolipoprotein A1 following initiation of antiretroviral therapy

BACKGROUND:: The effects of HIV infection and antiretroviral therapy (ART) on usual lipid levels have been reported. The effects of initiating versus deferring ART on high-density and low-density lipoprotein particle (HDL-P and LDL-P, respectively) concentrations and apolipoprotein (Apo) levels are not well described. METHODS:: In a subgroup of participants not taking ART at study entry who were randomized in the Strategies for Management of Antiretroviral Therapy (SMART) trial to immediately initiate ART (\u27viral suppression group\u27) or to defer it (\u27drug conservation group\u27), lipoprotein particle concentrations and ApoA1 and ApoB levels were measured at baseline and at 2 and 6 months following randomization. RESULTS:: Compared with drug conservation group (n = 126), HDL-P and ApoA1 levels increased among viral suppression participants (n = 128) after starting ART. At 6 months, viral suppression participants had 13% higher total HDL-P (P \u3c 0.001) and 9% higher ApoA1 (P \u3c 0.001). LDL-P, very low density lipoprotein particle, and ApoB did not differ significantly between the viral suppression and drug conservation groups. Among viral suppression participants, predictors of HDL-P and ApoA1 increases included baseline levels of high-sensitivity C-reactive protein (hsCRP) and interleukin 6 (IL-6), but not HIV RNA level, CD4 cell count, or traditional cardiovascular disease risk factors. The effect of starting ART on changes in HDL-P and ApoA1 was greater for those with higher versus lower baseline levels of IL-6 (P = 0.001 and 0.08, respectively, for interaction) or hsCRP (P = 0.01 and 0.04, respectively, for interaction). CONCLUSION:: HDL-P and ApoA1 increase following ART initiation, to a degree that depends on the degree of inflammation present at entry. These findings suggest that activation of inflammatory pathways contribute to HIV-associated changes in HDL. © 2011 Wolters Kluwer Health Lippincott Williams & Wilkins