Determinants of survival in adult HIV patients on antiretroviral therapy in Eastern Uttar Pradesh: A prospective study

Background & objectives: The National AIDS Control Organization (NACO) of India has been providing free ARV (antiretroviral) drugs since 2004. b0 y 2012, 486,173 patients had received treatment through the antiretroviral therapy (ART) centres. The objective of this observational study was to assess the factors determining survival of patients on ART under routine programme conditions in an ART centre in north India five years after its inception. Methods: Treatment naive HIV positive patients who were enrolled in the ART centre between May 2009 and May 2010 and started on ART as per the Revised NACO guidelines 2009, were included in the study and outcome was assessed after two years of follow up. Results: A total of 1689 patients were included in the analysis, of whom 272 (16.10%) expired, 205 (12.13%) were lost to follow up (LFU), 526 (31.14%) were transferred out to other facilities and 686 (40.63%) were alive at the end of two years. Majority (92%) of the deaths occurred in the first six months of therapy. Age >30 yr, male gender, poor functional status, haemoglobin level <11 g/dl, body weight <45 kg and CD4 count <100/μl at baseline had significantly higher relative hazard of death. Most LFU also occurred in the first six months and these patients had significantly low CD4 count, weight, haemoglobin level and higher number of patients in Stages III and IV as compared to those who survived. Interpretation & conclusions: The study findings revealed poor survival in the first six months of therapy especially in those with severe immunosuppression. This emphasizes the need for early enrolment into the programme. The high LFU occurring early after initiation of therapy suggests the urgent need to build an efficient patient retrieval system in the programme

TGIF1 Gene Silencing in Tendon-Derived Stem Cells Improves the Tendon-to-Bone Insertion Site Regeneration

Background/Aims: The slow healing process of tendon-to-bone junctions can be accelerated via implanted tendon-derived stem cells (TDSCs) with silenced transforming growth interacting factor 1 (TGIF1) gene. Tendon-to-bone insertion site is the special form of connective tissues derivatives of common connective progenitors, where TGF-β plays bidirectional effects (chondrogenic or fibrogenic) through different signaling pathways at different stages. A recent study revealed that TGF-β directly induces the chondrogenic gene Sox9. However, TGIF1 represses the expression of the cartilage master Sox9 gene and changes its expression rate against the fibrogenesis gene Scleraxis (Scx). Methods: TGIF1 siRNA was transduced or TGIF1 was over-expressed in tendon-derived stem cells. Following suprapinatus tendon repair, rats were either treated with transduced TDSCs or nontransduced TDSCs. Histologic examination and Western blot were performed in both groups. Results: In this study, the silencing of TGIF1 significantly upregulated the chondrogenic genes and markers. Similarly, TGIF1 inhibited TDSC differentiation into cartilage via interactions with TGF-β-activated Smad2 and suppressed the phosphorylation of Smad2. The area of fibrocartilage at the tendon-bone interface was significantly increased in the TGIF1 (-) group compared with the control and TGIF1-overexpressing groups in the early stages of the animal model. The interface between the tendon and bone showed a increase of new bone and fibrocartilage in the TGIF1 (-) group at 4 weeks. Fibrovascular scar tissue was observed in the TGIF1-overexpressing group and the fibrin glue only group. Low levels of fibrocartilage and fibrovascular scar tissue were found in the TDSCs group. Conclusion: Collectively, this study shows that the tendon-derived stem cell modified with TGIF1 gene silencing has promising effects on tendon-to-bone healing which can be further explored as a therapeutic tool in regenerative medicine