Hepatitis B virus coinfection in human immunodeficiency virus-infected patients: A review

Table 1 Characteristics of antiviral drugs for chronic hepatitis B in human immunodeficiency virus-infected patients

Characteristics	Interferon alfa-2b1	Pegylated interferon alfa-2a1	Lamivudine	Emtricitabine	Adefovir	Entecavir	Telbivudine	Tenofovir disoproxil fumarate
Antiviral effect	Immune modulation	Immune modulation	Interference of HBV DNA synthesis	Interference of HBV DNA synthesis	Interference of HBV DNA synthesis	Interference of HBV DNA synthesis	Interference of HBV DNA synthesis	Interference of HBV DNA synthesis
HIV-1activity	No	No	Yes	Yes	No, at low dose2	Yes	No7	Yes
Dosage and administration	10 million IU SC or IM 3 times a week	180 mg SC once a week	300 mg/d oral	200 mg/d oral	10 mg/d oral	0.5 mg/d oral5	600 mg/d oral	300 mg/d oral
Defined treatment duration	48 wk	48 wk	Indefinite	Indefinite	Indefinite	Indefinite	Indefinite	Indefinite
Undetectable HBV DNA	-	-	40%-84% at 1 yr	53% at 2 yr	8.6% and 5.7% at 36 wk 36 and 48, respectively8	38% by the end of study (mean follow-up, 74 wk)9	-	Up to 91% at 5 yr
HBeAg seroconversion	0%-20%	0%-20%	22%-35% at 1 yr	14% at 48 wk	9% at 144 wk	-	-	50% of TDF use; 57% of TDF plus FTC use at 5 yr
Tolerability	Poor	Poor	Excellent	Excellent	Good	Excellent	Good	Good
Major adverse events	Leukopenia, depression	Leukopenia, depression	-	-	Nephrotoxicity (3%)	-	-	Nephrotoxicity (1%-3%)
Viral resistance barrier	No	No	Low (50% at 2 yr and 90% at 4 yr)	Intermediate (18% at 2 yr)	High	High	-	High
HBV resistancemutations	No	No	M204I/VL180MA181T/VV173L	M204I/VL180MA181T/V	N236TA181T/V	M204I/V4L180MT184I/A/G/LS202I/GI169T	M204IA181T/V	A194T3A181T/VN236T
Cross-resistance to LAM	No	No	-	Yes	No	No	Yes	No
Interaction with other antiretrovirals	No	No	No	No	No	No	Zidovudine; stavudine6	Didanosine; atazanavir6

¹HBeAg positive subjects with CD4 cell counts of > 350 cells/μL and aminotransferase levels elevated to at least twice the upper limit of normal would probably achieve the greatest benefit from IFN-alfa therapy[70,71];

²While ADV (20 mg/d) does have minimal HIV-1 activity, the development of HIV-1 resistance mutations has not been demonstrated at low dose adefovir (10 mg/d)[72,80];

³TDF mutations have not been clearly associated with decreased anti-HBV efficacy[73];

⁴Presence of several mutations is necessary to decrease efficacy for ETV at a dose of 1 mg/d;

⁵1 mg/d for LAM-resistant HBV infection;

⁶LdT is a thymidine analogue that might interact with zidovudine or stavudine[74]. TDF can interact with didanosine by increasing the concentration of didanosine and impairing immunologic response[75]. It also decreases the concentration of atazanavir sulfate[76];

⁷LdT showed a potent anti-HBV activity in HIV-1-positive, hepatitis B e antigen-positive patients with high HBV viremia in a case report. However, a transient reduction in HIV-1 RNA between 2 and 3 log₁₀ copies/mL after 24 wk of telbivudine therapy was found in 2 of 3 patients although no genotypic resistance mutations to anti-HIV-1 were found[81]. In another study, no significant decline in HIV-1 RNA load or in the selection of genotypic or phenotypic resistance in HIV-1 RT was observed in 2 patients who received LdT treatment[77]. In vitro virologic analyses demonstrated that LdT had no activity against wild-type HIV and drug-resistant variants;

⁸In a prospective randomized, double-blind, placebo-controlled trial of 10 mg/d ADV vs 300 mg/d of TDF in subjects with HBV and HIV coinfection on stable ART, with serum HBV DNA > 100000 copies/mL, and plasma HIV-1 RNA < 10000 copies/mL, the mean time-weighted average change in serum HBV DNA from baseline to week 48 was -4.44log₁₀ copies/mL for TDF and -3.21log₁₀ copies/mL for ADV[78];

⁹In a small cohort of 13 patients with positive HBeAg and detectable HBV DNA who had received > 6 mo of TDF/FTC therapy, add-on ETV to TDF/FTC-experienced patients achieved undetectable HBV DNA load in 38% and normal ALT levels in 8 (62%)[79]. ADV: Adefovir dipivoxil; ETV: Entecavir; FTC: Emtricitabine; HBV: Hepatitis B virus; HBeAg: HBV envelope antigen; IM: Intramuscularly; LAM: Lamivudine; LdT: Telbivudine; SC: Subcutaneously; TDF: Tenofovir disoproxil fumarate.