Objective
The aim of the study was to examine the rates and predictors of treatment modification following combination antiretroviral therapy (cART) failure in Asian patients with HIV enrolled in the TREAT Asia HIV Observational Database (TAHOD).
Methods
Treatment failure (immunological, virological and clinical) was defined by World Health Organization criteria. Countries were categorized as high or low income by World Bank criteria.
Results
Among 2446 patients who initiated cART, 447 were documented to have developed treatment failure over 5697 person‐years (7.8 per 100 person‐years). A total of 253 patients changed at least one drug after failure (51.6 per 100 person‐years). There was no difference between patients from high‐ and low‐income countries [adjusted hazard ratio (HR) 1.02; P=0.891]. Advanced disease stage [Centers for Disease Control and Prevention (CDC) category C vs. A; adjusted HR 1.38, P=0.040], a lower CD4 count (≥51 cells/μL vs. ≤50 cells/μL; adjusted HR 0.61, P=0.022) and a higher HIV viral load (≥400 HIV‐1 RNA copies/mL vs. <400 copies/mL; adjusted HR 2.69, P<0.001) were associated with a higher rate of treatment modification after failure. Compared with patients from low‐income countries, patients from high‐income countries were more likely to change two or more drugs (67%vs. 49%; P=0.009) and to change to a protease‐inhibitor‐containing regimen (48%vs. 16%; P<0.001).
Conclusions
In a cohort of Asian patients with HIV infection, nearly half remained on the failing regimen in the first year following documented treatment failure. This deferred modification is likely to have negative implications for accumulation of drug resistance and response to second‐line treatment. There is a need to scale up the availability of second‐line regimens and virological monitoring in this region.
Leptin plays a role in regulating the body weight in mice. Injection of recombinant mouse leptin expressed in Escherichia coli reduced the food intake and body weight in normal, ob/ob and diet-induced obesity mice. Hyperglycemia, hyperinsulinemia and hypothermia can also be corrected in ob/ob mice after leptin injection. Leptin is a 16-kDa secretory protein comprising 167 amino acids produced in adipose tissue and is secreted to blood stream. In this study, a recombinant mouse leptin was generated and purified from a baculovirus expression system. This protein was used to identify putative ligands using a phage library of random peptides. Three leptin-binding phage clones were found, which were characterized by DNA sequencing and ELISA methods. The amino acid sequences of the reactive peptides are: LAYCSDPVRCLVWWY, MFWISAVSFVDHALV and LVLVLSAFLCCGVG. All three clones bound to recombinant human and mouse leptins. These peptides may be useful tools to study leptin-receptor interaction, food intake and body weight regulation.
The preparation of flagellin (FLA) from Salmonella adelaide and Boivin antigen (BA) from Vibrio cholerae is described. These two antigens differed chemically from each other and showed marked differences in their degradability by mouse intestinal juice in vitro and in their fate in the intact mouse when given intravenously. Unlike BA, FLA was rapidly degraded in intestinal juice and readily sequestered and degraded by the liver. The suitability of these antigens in oral absorption studies is discussed.
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