The proportion suppressed increased over time and reached 100% overall (Table 2). The number of patients in follow-up at each year declined, however of the 379 patients in studies with more than one year of selleck follow-up, individual patient data was available for 187 (49.3%) and in these patients dropping out (i.e. no later HBV viral load test result being available) was more likely at every time point for patients with suppressed HBV than for those with detectable HBV (non-significant �C data not shown). Virological rebound on TDF was rare, with no cases seen in 16 of 23 studies. Three studies reported a single patient with an increase in HBV viral load on TDF treatment, [17], [21], [25] three had two patients, [7], [14], [22] and one had three [8] though in three of these studies the size of the increases were not reported, in two the increases were very small (0.
1 to 0.3 log), and only two had patients with an increase of at least one log (one in each study). [7], [22] Unfortunately no discussion of these two cases was given, in particular there were no data on drug compliance and treatment adherence. The funnel plot (Figure 5) shows the standard error against the proportion undetectable at one year, with the vertical line marking the summary estimate of the treatment effect (derived using fixed-effect meta-analysis). [28] The plot is symmetrical with no suggestion of publication bias. There is considerable heterogeneity in the effect found in larger studies (appearing higher up on the graph with a lower standard error), with one apparent outlier with a low proportion undetectable despite large size (de Vries-Sluijs, [8] Group D).
Separate funnel plots of each arm in the analysis also show no publication bias (not shown). Repeating the regression analysis after excluding the outlier study arm and after excluding small studies (with less than ten patients) made no significant difference to the results. The model included a term for study design and showed that study design had no significant impact on the results, with p values of 0.76, 0.54 and 0.42 at 1, 2 and 3 years in the overall analysis. Figure 5 Funnel plot of standard error against proportion undetectable at one year �C all study arms (with pseudo 95% confidence limits).
Discussion This review of HBV/HIV coinfected patients treated with TDF results demonstrates lasting virological suppression of HBV replication to below the level of detection, with the proportion suppressed increasing to 100% over time, though with small numbers at later time points. Few patients experience virological failure on treatment. However several reservations should Anacetrapib be noted. Firstly most of the studies included were observational in design and patients dropping out were not well characterised. Secondly, in this meta-analysis we compare different treatment groups though allocation to these was randomised in only two studies.