The impact of hepatitis coinfection on immunological and virological responses to antiretroviral therapy and HIV disease progression among this Asian cohort are similar to that seen in Western countries. The longer-term impact of hepatitis coinfection on both HIV disease and liver disease morbidity and mortality needs to be monitored.

This study examined characteristics of HIV-infected patients in the TREAT Asia HIV Observational Database who were lost to follow-up (LTFU) from treatment and care. Time from last clinic visit to 31 March 2009 was analysed to determine the interval that best classified LTFU. Patients defined as LTFU were then categorised into permanently LTFU (never returned) and temporary LTFU (re-entered later), and these groups compared. A total of 3626 patients were included (71% male). No clinic visits for 180 days was the best-performing LTFU definition (sensitivity 90.6%, specificity 92.3%). During 7697 person-years of follow-up, 1648 episodes of LFTU were recorded (21.4 per 100-person-years). Patients LFTU were younger (P = 0.002), had HIV viral load ≥500 copies/mL or missing (P = 0.021), had shorter history of HIV infection (P = 0.048), and received no, single- or double-antiretroviral therapy, or a triple-drug regimen containing a protease inhibitor (P < 0.001). 48% of patients LTFU never returned. These patients were more likely to have low or missing haemoglobin (P < 0.001), missing recent HIV viral load (P < 0.001), negative hepatitis C test (P = 0.025), and previous temporary LTFU episodes (P < 0.001). Our analyses suggest that patients not seen at a clinic for 180 days are at high risk of permanent LTFU, and should be aggressively traced.

Glycine N-methyltransferase (GNMT) is a protein with multiple functions. Recently, two Italian siblings who had hepatomegaly and chronic elevation of serum transaminases were diagnosed to have GNMT deficiency caused by inherited compound heterozygosity of the GNMT gene with missence mutations. To evaluate the expression of GNMT in cell lines and tissues from hepatocellular carcinoma (HCC) patients, we produced two monoclonal antibodies (mAbs) 4-17 and 14-1 using two recombinant GNMT fusion proteins. M13 phage peptide display showed that the reactive epitopes of mAbs 4-17 and 14-1 were amino acid residues 11-15 and 272-276 of human GNMT, respectively. The dissociation constants of the binding between GNMT and mAbs were 1.7 x 10(-8) M for mAb 4-17 and 1.8 x 10(-9) M for mAb 14-1. Both mAbs can identify GNMT present in normal human and mouse liver tissues using Western blotting (WB) and immunohistochemical staining assay (IHC). In addition, WB with both mAbs showed that none of 2 hepatoblastoma and 5 HCC cell lines expressed GNMT. IHC demonstrated that 50% (13/26) of nontumorous liver tissues and 96% (24/25) of HCC tissues did not express GNMT. Therefore, the expression of GNMT was downregulated in human HCC.

BackgroundPneumocystis jiroveci pneumonia (PCP) prophylaxis is recommended for patients with CD4 counts of less than 200 cells/mm3. This study examines the proportion of patients in the TREAT Asia HIV Observational Database (TAHOD) receiving PCP prophylaxis, and its effect on PCP and mortality.MethodsTAHOD patients with prospective follow up had data extracted for prophylaxis using co-trimoxazole, dapsone or pentamidine. The proportion of patients on prophylaxis was calculated for each calendar year since 2003 among patients with CD4 counts of less than 200 cells/mm3. The effect of prophylaxis on PCP and survival were assessed using random-effect Poisson regression models.ResultsThere were a total of 4050 patients on prospective follow up, and 90% of them were receiving combination antiretroviral therapy. Of those with CD4 counts of less than 200 cells/mm3, 58% to 72% in any given year received PCP prophylaxis, predominantly co-trimoxazole. During follow up, 62 patients developed PCP (0.5 per 100 person-years) and 169 died from all causes (1.36/100 person-years). After stratifying by site and adjusting for age, CD4 count, CDC stage and antiretroviral treatment, those without prophylaxis had no higher risk of PCP, but had a significantly higher risk of death (incident rate ratio 10.8, p < 0.001). PCP prophylaxis had greatest absolute benefit in patients with CD4 counts of less than 50 cells/mm3, lowering mortality rates from 33.5 to 6.3 per 100 person-years.ConclusionsApproximately two-thirds of TAHOD patients with CD4 counts of less than 200 cells/mm3 received PCP prophylaxis. Patients without prophylaxis had significantly higher mortality, even in the era of combination ART. Although PCP may be under-diagnosed, these data suggest that prophylaxis is associated with important survival benefits.

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