This informs decisions regarding the need for therapy in patients with high CD4 cell counts and no indication for HAART, as well as the choice of drug treatment and the need for HCC screening if cirrhosis is present. Liver biopsy may provide additional information on the degree of inflammation and fibrosis and the presence of other pathology (e.g. steatosis) [121]. Assessment of fibrosis is essential before a decision is made to defer HBV and/or HIV treatment. Given the accelerated progression of fibrosis in coinfection, any CX-5461 ic50 patient with significant necroinflammation or fibrosis should be treated [120]. The

key determinants of who needs treatment for HBV are the HBV DNA level and the CD4 cell count. In HBV monoinfected patients, there is a good correlation between high HBV DNA levels, long-term histological progression to cirrhosis and the rate of HCC. It is PD0325901 presumed that this correlation also exists for coinfected persons but whether liver disease progresses at a lower HBV DNA level is unknown [123]. The accepted HBV DNA threshold for consideration for treatment is now >2000 IU/mL. In patients who have significant liver damage but low or undetectable HBV DNA levels, the possibility of HDV coinfection should be considered. The presence of HBV DNA without HBsAg, with or without HBcAb (occult HBV), is very rare and does not account for significant liver damage [119]. The CD4 cell count is integral to

deciding when to initiate HIV therapy. A threshold of 350 cells/μL is recommended by BHIVA and other international guidelines as

a level below which antiretrovirals are indicated in HIV-monoinfected persons [124]. Because of the negative effect of immune depletion on HBV progression, the availability of single drugs with high level dual activity, and the increased risk of liver-related deaths in patients with CD4 counts below 500 cells/μL, coinfected patients with CD4 counts between 350 and 500 cells/μL should also be treated with drugs PIK-5 active at suppressing both viruses [119]. 4.3.1.1 Recommendations • ALT elevation is less sensitive as an indicator of disease severity in coinfection and a level below the upper limit of normal should not be used as a reason to defer treatment if otherwise indicated. Normal levels should be considered as 30 IU/L for men and 19 IU/L for women (II). There are currently seven drugs that have been, or are soon to be, approved for use against HBV: four have additional HIV activity [lamivudine (3TC), emtricitabine (FTC), tenofovir and entecavir] and three are only active against HBV at licensed doses (interferon, adefovir and telbivudine). The data excluding anti-HIV activity for telbivudine are limited and monitoring of HIV viral load and repeat HIV genotyping pre-HAART initiation are advised. The efficacy of these drugs has been assessed in randomized trials extending out to 5 years in monoinfected patients [118].