Hepatitis B Virus Drug Resistance

A systematic review of Hepatitis B virus (HBV) drug and vaccine escape mutations in Africa: a call for urgent action

“…However, 101 screening of HBsAg is not routinely performed in many settings in Africa, with lack of 102 implementation at least partially driven by cost and lack of programmes for HBV 103 treatment outside the setting of HIV coinfection. HBV infected patients either remain 104 untreated (most typical in the setting of monoinfection), or are exposed to antiviral 105 drugs without proper monitoring and often intermittently, putting them at risk of 106 developing RAMs (more likely in the setting of HIV coinfection) [4, [7][8][9][10]. 107 108 HBV is a DNA virus that replicates via an RNA intermediate, with reverse 109 transcriptase (RT) catalysing the transcription of RNA into DNA [7].…”

“…In Africa, the choice of 116 agent is usually limited to 3TC and TDF. Emergence of mutations happens because 117 the RT enzyme is error-prone and lacks the proofreading function required to repair 118 errors during transcription [7]; when these mutations confer a selective advantage by 119 allowing the virus to escape the effect of drug therapy, they will become amplified in 120 the viral population. Some RAMs confer resistance to one agent only, while others 121 are associated with resistance to several agents (Fig 1).…”

“…Some RAMs confer resistance to one agent only, while others 121 are associated with resistance to several agents (Fig 1). 122 and five from the wider literature [7,[15][16][17][18]. 129 130 3TC was originally seen as a major breakthrough in treating HBV [19].…”

“…However, it is 131 now known to have a low genetic barrier to resistance and its long-term 132 effectiveness is limited as a result of resistance mutations in the 'YMDD' motif 133 (tyrosine, methionine, aspartate, aspartate; amino acids 203-206) in domain C of the 134 viral polymerase (Pol). These occur with associated upstream compensatory 135 mutations in Pol domains A, B and in the B-C interdomain [7,15,16]. Among chronic 136 HBV monoinfected patients, incidence of HBV resistance to 3TC is as high as 20% 137 per year.…”

“…142 143 TDF is widely used in treatment of both HIV and HBV and is generally well tolerated. 144 TDF has a high genetic barrier to resistance and maintains effective suppression of 145 HBV in both monoinfected and HIV/HBV coinfected individuals [5,7,10,21,22]. 146…”