Where ART is recommended (all patients with a CD4 count <350 cell

Where ART is recommended (all patients with a CD4 count <350 cells/μL), agents with HBV activity should be incorporated into the ART regimen. In patients with CD4 cell counts of MLN8237 concentration 350–500 cells/μL, in whom ART is not otherwise recommended, treatment for HBV infection may best be achieved by using a combined ART/HBV regimen. If ART is not required, that is in patients with CD4 counts of >500 cells/μL, the optimum strategy may be to use agents with exclusive HBV and no HIV activity so that HIV resistance is not induced; however, earlier initiation of ART should still be considered [118–123]. Awareness of the additive hepatotoxic risks of certain antiretroviral drugs

should be considered (e.g. nevirapine). HIV

therapy not indicated. If the CD4 count is above 500 cells/μL, the HBV DNA is below 2000 IU/L, the ALT is normal, and there is no fibrosis, treatment is not indicated and patients should be monitored on a 3–6-monthly basis. If the CD4 count is above 500 cells/μL and HBV therapy is indicated, the options are to use drugs only active against HBV, alone or in combination, or early introduction of antiretroviral drugs including tenofovir with FTC. Limited evidence exists on the use of pegylated interferon in coinfected persons [125] but it appears to be less effective and is associated with greater toxicity. However, resistance does not occur and a 12-month course of pegylated interferon is an option in a patient with GS-1101 clinical trial elevated ALT, low serum HBV DNA (<2 × 106 IU/L), and minimal liver fibrosis, especially if genotype A [119]. Lack of response, as judged by failure to reduce HBV DNA by 1 log10 by week 12 and to <2000 IU/L by week 24, should prompt discontinuation and consideration for antivirals [119,120]. Pegylated interferon should not be used in patients with decompensated cirrhosis [126]. Adefovir has been evaluated in coinfected persons and is active for both wild-type and 3TC-resistant virus but is less potent than tenofovir [127]. Nevertheless, at the dose used in HBV treatment, it does not affect HIV replication or select resistance mutations

that may limit future tenofovir use. It is therefore an option DAPT supplier in this situation, unlike tenofovir which must be used only with other ART agents [128,129]. Telbivudine has greater intrinsic activity than adefovir or 3TC but has also not been studied sufficiently in coinfection. Its efficacy is limited by the development of resistance (25% at 24 months in monoinfected persons), with cross-resistance to 3TC/FTC but not adefovir [118]. Adefovir and telbivudine select for nonoverlapping HBV resistance mutations. Entecavir, although previously thought to be devoid of antiretroviral effect, has been found to possess modest anti-HIV activity and can select for HIV rt M184 V [130]. This drug should not be used in the absence of fully suppressive antiretroviral therapy (ART). HIV therapy indicated.

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