The proportion with undetectable HBV at one year (59%) was lower than useful handbook the proportion found in HIV negative patients receiving TDF for treatment of HBV infection. For example, a multicentre cohort study found that, of 54 HIV-negative patients treated with TDF and FTC, 60% of whom were HBeAg positive, the probability of attaining an undetectable HBV viral load was 76% at one year and 94% at two years. [30] Similarly, in a large randomised controlled trial comparing TDF with adefovir, Marcellin found 93% of 250 HBeAg negative and 76% of 176 HBeAg positive patients randomised to TDF had an undetectable viral load (<400 copies/mL) at 48 weeks (97% and 83% respectively of those still on TDF at 48 weeks) [31]. In the latter study, ten patients (2.

3%) had virological breakthrough (defined in that study as detectable HBV after an undetectable result or an increase in HBV viral load by a factor of ten from nadir). [31] Of the 550 patients in the current study, we identified 12 (2.4%) with a rise in HBV viral load on TDF treatment (although at least five of these 12 had less than a one log rise from nadir) which is comparable to HBV-monoinfected patients. However other published data in coinfected patients have found far higher rates, for example 9 (17%) of 52 patients followed up for a median of 34 months in one retrospective cohort study (which was not included in the current meta-analysis as data on HBV viral load suppression was only given at the end of follow-up and not at yearly time points) [32]. The high rate of virological suppression and low rate of breakthrough may be related to the low chance of developing TDF-resistance mutations.

In HBV/HIV coinfected patients treated with lamivudine as the only drug active against HBV, resistance develops in about 90% after four years [33] whereas mutations associated with TDF resistance, such as the combination of rtL180M, rtM204V/I and rtA194T [34] or N236T with A181V, [35] have only rarely been seen and are of uncertain significance [36]�C[38]. No statistically significant effect of prior 3TC/FTC exposure or of concomitant 3TC/FTC use was found and thus no evidence to support the hypotheses that prior exposure may make subsequent treatment less effective or that concomitant use of 3TC/FTC may give a higher rate of suppression.

However given the modest number of patients available for inclusion in the meta-analysis, the confidence intervals were wide and we could not exclude the possibility of moderately strong effects in either direction. In HIV-negative patients TDF monotherapy is as effective for HBV as combination therapy with TDF and 3TC/FTC Carfilzomib with suppression rates (<400 copies/mL) of 81% at one year in both arms of an RCT using TDF alone or TDF/FTC combination therapy, and 88% and 85% respectively at three years [39], [40].