Introduction Tenofovir disoproxil fumarate (TDF) is widely recommended for treatment of chronic hepatitis B virus (HBV) infection because it is safe, affordable and has a high genetic barrier to resistance. TDF resistance associated mutations (RAMs) have been reported, but data are limited, particularly for Africa. We set out to identify potential RAMs in individuals with detectable HBV viraemia on TDF treatment. Methods We recruited adults with chronic HBV infection from Cape Town, South Africa, identifying individuals with a TDF resistance phenotype, defined as persistent HBV vireamia despite >12 months of TDF treatment. We sequenced HBV DNA using MiSeq Illumina with whole genome target enrichment, and sought potential TDF RAMs, based on a pre-defined list of polymorphisms. Results Among 66 individuals with chronic HBV (genotypes A and D), three met our clinical definition for TDF resistance, of whom two were coinfected with HIV. In one participant, the consensus HBV sequence contained nine polymorphisms that have been described in association with TDF resistance. Significant treatment non-adherence in this individual was unlikely, as HIV RNA was suppressed. TDF RAMs were also present in HBV sequences from the other two participants, but other factors including treatment non-adherence may also have had a role in failure of HBV DNA suppression in these cases. Discussion Our findings add to the evidence that RAMs in HBV reverse transcriptase may underpin a TDF resistant phenotype. This is the first time these RAMs have been reported from Africa in association with clinical evidence of TDF resistance.
Objectives: Prompted by international targets for elimination of hepatitis B virus (HBV), we set out to characterise individuals with HBV monoinfection vs. those coinfected with HBV/HIV, to evaluate the impact of therapy and to guide improvements in clinical care. Methods: We report observational data from a real world cross-sectional cohort of 115 adults with chronic hepatitis B infection (CHB), at a university hospital in Cape Town, South Africa. HIV coinfection was present in 39 (34%) subjects. We recorded cross-sectional demographic, clinical and laboratory data. Results: Compared to those with HIV coinfection, HBV monoinfected adults were less likely to be HBeAgpositive (p = 0.01), less likely to have had assessment with elastography (p < 0.0 0 01), and less likely to be on antiviral treatment (p < 0.0 0 01); they were more likely to have detectable HBV viraemia (p = 0.04), and more likely to have features of liver disease including moderate/severe thrombocytopaenia (p = 0.007), elevated bilirubin (p = 0.004), and elevated APRI score (p = 0.02). Three cases of hepatocellular carcinoma all arose in HBV monoinfection. Conclusions: Our data demonstrate that individuals with HBV monoinfection may be disadvantaged compared to those with HIV coinfection, highlighting potential systematic inequities in referral, monitoring and treatment.
Objective: Prompted by international targets for elimination of hepatitis B virus (HBV) infection, we performed a cross-sectional observational study of adults with chronic HBV (CHB) infection in South Africa, characterising individuals with HBV monoinfection vs. those coinfected with HBV/HIV, to evaluate the impact of therapy and to guide improvements in clinical care as guidelines for antiviral therapy change over time. Design: We prospectively recruited 115 adults with CHB, over a period of one year at a university hospital in Cape Town, South Africa. HIV coinfection was present in 39 (34%) subjects. We recorded cross-sectional demographic, clinical and laboratory data. Results: Adults with HBV monoinfection were comparable to those with HBV/HIV coinfection in terms of age, sex and body mass. HBeAg-positive status was more common among those with HIV coinfection (p=0.01). However, compared to HBV/HIV coinfection, HBV monoinfected patients were less likely to have had assessment with elastography (p<0.0001) and less likely to be on antiviral treatment (p<0.0001). The HBV monoinfected group was more likely to have detectable HBV viraemia (p=0.04), and features suggesting underlying liver disease including moderate/severe thrombocytopaenia (p=0.007), elevated bilirubin (p=0.004), and APRI score >2 (p=0.02). Three cases of hepatocellular carcinoma were documented, all in patients with HBV monoinfection. Conclusion: In this setting, individuals with HBV monoinfection are disadvantaged in terms of clinical assessment and appropriate antiviral therapy compared to those with HIV coinfection, associated with relatively worse liver health. Enhanced advocacy, education, resources and infrastructure are required to optimise interventions for CHB.
Introduction: Tenofovir disoproxil fumarate (TDF) is widely recommended for treatment of chronic hepatitis B virus (HBV) infection because it is safe, affordable and has a high genetic barrier to resistance. TDF resistance associated mutations (RAMs) have been reported, but data are limited, particularly for Africa. We set out to identify RAMs in individuals with detectable HBV viraemia on TDF treatment. Methods: We recruited adults with chronic HBV infection from Cape Town, South Africa, identifying individuals with a TDF resistance phenotype, defined as persistent HBV vireamia despite >12 months of TDF treatment. We sequenced HBV DNA using MiSeq Illumina with whole genome target enrichment, and analysed to determine the genotype and identify potential TDF RAMs, based on a pre-defined list of polymorphisms. Results: Among 66 individuals with chronic HBV, we identified three meeting our phenotypic definition for TDF resistance, of whom two were coinfected with HIV. The sequences grouped as genotypes A1 and D3. In one participant, the consensus HBV sequence had ten polymorphisms that have been described in association with TDF resistance. Significant treatment non-adherence in this individual was unlikely, as HIV RNA was suppressed. TDF RAMs were also present in HBV sequences from the other two participants, but other factors including treatment non-adherence may also have had a role in failure of HBV DNA suppression in these cases. Discussion: Our findings add to the evidence that RAMs in HBV RT can underpin a TDF resistant phenotype. This is the first time these RAMs have been reported from Africa in association with clinical evidence of TDF resistance.
Objectives: Prompted by international targets for elimination of hepatitis B virus (HBV), we set out to characterise individuals with HBV monoinfection vs. those coinfected with HBV/HIV, to evaluate the impact of therapy and to guide improvements in clinical care. Methods: We report observational data from a real world cross-sectional cohort of 115 adults with chronic hepatitis B infection (CHB), at a university hospital in Cape Town, South Africa. HIV coinfection was present in 39 (34%) subjects. We recorded cross-sectional demographic, clinical and laboratory data. Results: Compared to those with HIV coinfection, HBV monoinfected adults were less likely to be HBeAgpositive (p = 0.01), less likely to have had assessment with elastography (p < 0.0 0 01), and less likely to be on antiviral treatment (p < 0.0 0 01); they were more likely to have detectable HBV viraemia (p = 0.04), and more likely to have features of liver disease including moderate/severe thrombocytopaenia (p = 0.007), elevated bilirubin (p = 0.004), and elevated APRI score (p = 0.02). Three cases of hepatocellular carcinoma all arose in HBV monoinfection. Conclusions: Our data demonstrate that individuals with HBV monoinfection may be disadvantaged compared to those with HIV coinfection, highlighting potential systematic inequities in referral, monitoring and treatment.
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