Background HIV replication and immune activation may increase inflammation and coagulation biomarkers. Limited data exist comparing such biomarkers for those with and without HIV infection. Methods For those aged 45–76, high sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), D-dimer, and cystatin C were compared for 494 HIV-infected individuals in the Strategies for Management of Anti-Retroviral Therapy (SMART) study with 5,386 participants in the Multi-Ethnic Study of Atherosclerosis (MESA). For those aged 33–44, hsCRP and IL-6 were compared for 287 participants in SMART with 3,231 participants in the Coronary Artery Development in Young Adults (CARDIA) Study. Results hsCRP and IL-6 were 55% (p<0.001) and 62% (p<0.001) higher among HIV-infected participants compared to CARDIA. Compared to MESA, hsCRP, IL-6, D-dimer and cystatin C were 50%, 152%, 94%, and 27% higher (p<0.001 for each). For HIV-infected participants on ART with HIV-RNA levels ≤400 copies/mL, levels were higher (p<0.001) than the general population for all biomarkers (by 21% to 60%). Conclusions hsCRP, IL-6, D-dimer and cystatin C are elevated with HIV infection and remain so even after HIV-RNA levels are suppressed with ART. Further research is needed on the pathophysiology of HIV-induced activation of inflammatory and coagulation pathways in order to guide potential interventions.

Thomas Campbell and colleagues report findings of a randomized trial conducted in multiple countries regarding the efficacy of antiretroviral regimens with simplified dosing.

Objectives Among patients with HIV, the risk of death associated with different AIDS events has been quantified, but the risk of death associated with non-AIDS events has not been examined. We compared the risk of all-cause mortality following AIDS versus serious non-AIDS (SNA) events in SMART and ESPRIT. Design Data from 9,583 HIV-infected participants, 5,472 with CD4+ >350 cells/mm3 enrolled in SMART and 4,111 with CD4+ ≥300 cells/mm3 enrolled in ESPRIT were analyzed. Methods Cumulative mortality 6 months after AIDS and SNA (cardiovascular, renal, hepatic disease and malignancies) was estimated using the Kaplan-Meier method. Cox models were used to estimate hazard ratios (HRs) associated with AIDS and SNA on the risk of death overall and by treatment group within study. Results AIDS and SNA occurred in 286 and 435 participants with 47 (16%) and 115 (26%) subsequent deaths, respectively. Six-month cumulative mortality was 4.7% (95%CI:2.8–8.0) after experiencing an AIDS event and 13.4% (95%CI:10.5–17.0) after experiencing an SNA event. The adjusted HR for all-cause mortality for those who experienced AIDS versus those who did not was 4.9 (95%CI:3.6–6.8). The corresponding HR for SNA was 11.4 (95%CI:9.0–14.5) (p<0.001 for difference in HRs). Findings were similar for both treatment groups in SMART and both treatment groups in ESPRIT. Conclusions Among HIV-infected persons with higher CD4+ counts, SNA events occur more frequently and are associated with a greater risk of death than AIDS events. Future research should be aimed at comparing strategies to reduce morbidity and mortality associated with SNA events for HIV-infected persons.

Objective Compare the effectiveness, tolerability, and safety of three months of weekly rifapentine plus isoniazid under direct observation (3HP) vs. 9 months of daily isoniazid (9H) in HIV-infected persons. Design prospective, randomized, open-label non-inferiority trial Setting U.S., Brazil, Spain, Peru, Canada, and Hong Kong Participants HIV-infected persons who were tuberculin skin test positive or close contacts of tuberculosis cases. Intervention 3HP vs. 9H. Main Outcome Measures The effectiveness endpoint was tuberculosis; the non-inferiority margin was 0.75%. The tolerability endpoint was treatment completion; the safety endpoint was drug discontinuation due to adverse drug reaction. Results Median baseline CD4+ counts were 495 (IQR:389–675) and 538 (IQR:418–729) cells/mm3 in the 3HP and 9H arms, respectively (P=0.09). In the modified intention to treat analysis, there were two tuberculosis cases among 206 persons (517 person-years (p-y) of follow-up) in the 3HP arm (0.39 per 100 p-y) and six tuberculosis cases among 193 persons (481 p-y of follow-up) in the 9H arm (1.25 per 100 p-y). Cumulative tuberculosis rates were 1.01% vs. 3.50% in the 3HP and 9H arms, respectively (rate difference: −2.49%; upper bound of the 95% confidence interval (CI) of the difference: 0.60%). Treatment completion was higher with 3HP (89%) than 9H (64%) (P<0.001), and drug discontinuation due to an adverse drug reaction was similar (3% vs. 4%; P=0.79) in 3HP and 9H, respectively. Conclusions Among HIV-infected persons with median CD4+ count of approximately 500 cells/mm3, 3HP was as effective and safe for treatment of latent M. tuberculosis infection as 9H, and better tolerated. Trial Registration ClinicalTrials.gov (identifier: NCT00023452)

Summary Background Hematological abnormalities are common manifestations of advanced HIV-1 infection that could affect the outcomes of highly-active antiretroviral therapy (HAART). Although most HIV-1-infected individuals live in resource-constrained countries, there is little information about the frequency of hematological abnormalities such as anemia, neutropenia, and thrombocytopenia among individuals with advanced HIV-1 disease. Methods This study compared the prevalence of pre-antiretroviral therapy hematological abnormalities among 1571 participants in a randomized trial of antiretroviral efficacy in Africa, Asia, South America, the Caribbean, and the USA. Potential covariates for anemia, neutropenia, and thrombocytopenia were identified in univariate analyses and evaluated in separate multivariable models for each hematological condition. Results The frequencies of neutropenia (absolute neutrophil count ≤ 1.3 × 109/l), anemia (hemoglobin ≤ 10 g/dl), and thrombocytopenia (platelets ≤ 125 × 109/l) at initiation of antiretroviral therapy were 14%, 12%, and 7%, respectively, and varied by country (p < 0.0001 for each). In multivariable models, anemia was associated with gender, platelet count, and country; neutropenia was associated with CD4+ lymphocyte and platelet counts; and thrombocytopenia was associated with country, gender, and chronic hepatitis B infection. Conclusions Differences in the frequency of pretreatment hematological abnormalities could have important implications for the choice of antiretroviral regimen in resource-constrained settings.