Ojectives Among a subgroup of participants in the Strategies for Management of Antiretroviral Therapy (SMART) Trial that were naïve to antiretroviral therapy (ART) or off ART (≥6 months) at study entry, risk of AIDS and serious non-AIDS events was increased for participants who deferred ART compared to those randomized to (re)initiate ART immediately. Our objective was to determine whether ART initiation in this group reduced markers of inflammation and coagulation that have been associated with increased mortality risk in SMART. Changes in these biomarkers have been described after stopping ART, but not after starting ART in SMART. Methods Stored specimens for 254 participants (126 DC and 128 VS) who were naïve to ART or off ART (≥6 months) were analyzed for interleukin-6 (IL-6), high sensitivity C-reactive protein (hsCRP) and D-dimer at baseline and months 2 and 6. Results At month 6, 62% of VS group had HIV RNA <400copies/mL and median CD4 count was 190 cells/mm3 higher than for the DC group (590 vs. 400 cells/mm3). Compared with DC, the VS group had 32% (95%CI: 19 to 43%) lower D-dimer levels at month 6 (p<0.001); differences were not significant for hsCRP or IL-6 levels. Conclusions In this randomized comparison of immediate versus delayed ART initiation, D-dimer, but not IL-6 and hsCRP, declined significantly after starting ART. Further studies are needed to determine whether improvements in D-dimer are associated with reduced risk of clinical disease, and whether adjunct treatments used in combination with ART can reduce inflammation among individuals with HIV infection.

IntroductionThe use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals.Materials and MethodsA set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed.ResultsNone of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR-145 correlated with nadir CD4+ T cell count.DiscussionNo associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection.

Clinically evident metastases to the thyroid gland are rarely found antemortem. A case of a 59-year-old woman with a history of rectal carcinoma, who presented with low back pain and a mass in the right lobe of her thyroid gland, is presented. The tumour of the thyroid was found to be metastatic adenocarcinoma from her previous rectal cancer. Other synchronous metastases were noted in her lumbar spine and kidneys.The clinical finding of metastases to the thyroid gland is rare, particularly from a colorectal primary. One must consider, however, the possibility of a tumour of the thyroid gland representing a secondary malignancy in any patient with a prior history of cancer.

No abstract

No abstract