Mutations associated with lamivudine‐resistance in therapy‐naïve hepatitis B virus (HBV) infected patients with and without HIV co‐infection: Implications for antiretroviral therapy in HBV and HIV co‐infected South African patients

Selabe, Selokela G.; Lukhwareni, Azwidowi; Song, E; Leeuw, Yeegan G.M.; Burnett, Rosemary J.; Mphahlele, M. Jeffrey

doi:10.1002/jmv.20974

Cited by 50 publications

(59 citation statements)

References 28 publications

(33 reference statements)

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“…Even though such findings are rare, a similar report is also available from South Africa where ~30% of the naive occult HBV/HIV co-infected patients harbored 3TC resistance [63]. Previously, we observed high prevalence of 3TC resistance among the HIV/HBV co-infected subjects of eastern India who are on prolonged ART [64].…”

Section: Discussionmentioning

confidence: 70%

Occult hepatitis B virus infection in HIV positive patients at a tertiary healthcare unit in eastern India

et al. 2017

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Occult HBV infection (OBI), defined by the presence of HBV DNA in absence of hepatitis B surface antigen (HBsAg), is a significant concern in the HIV-infected population. Of 441 HIV+/HBsAg- patients analyzed, the overall prevalence of OBI was 6.3% (28/441). OBI was identified in 21 anti-HBc positives (17.8%), as well as among those who lacked any HBV-specific serological markers (2.2%). Comparison with HIV/HBV co-infection revealed that the levels of CD4, ALT, and HBV DNA were significantly lower during occult infection. Discrete differences were also observed with respect to quasispecies divergence. Additionally, subgenotype D1 was most frequent in occult infection, while D2 was widespread during chronic infection. The majority (~90%) of occult D1 sequences had the sQ129R mutation in the surface gene. This study highlights several distinct features of OBI in India and underscores the need for additional HBV DNA screening in HIV-positive individuals.

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Section: Discussionmentioning

confidence: 70%

Occult hepatitis B virus infection in HIV positive patients at a tertiary healthcare unit in eastern India

et al. 2017

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“…Other studies have reported primary 3TC resistance due to rt181T/S substitutions [10]. HBV mutations also occur in the absence of 3TC therapy and are thought to occur naturally in HBV carriers who have not been treated with the drug, implying that pre-existing mutations may be transmitted or contribute toward early emergence of 3TC resistance during therapy [11, 12]. …”

Section: Introductionmentioning

confidence: 99%

HBV Genotypes and Drug Resistance Mutations in Antiretroviral Treatment-Naive and Treatment-Experienced HBV–HIV-Coinfected Patients

et al. 2017

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Background The presence of hepatitis B virus (HBV) resistance mutations upon initiation or during antiretroviral therapy (ART) in HIV co-infected patients is an important determinant of treatment response. The main objective of the study was to determine the prevalence of HBV resistance mutations in antiretroviral treatment-naïve and treatment-experienced HBV-HIV co-infected Ghanaian patients with detectable HBV viremia. Methods HBV-HIV co-infected patients who were ART-naïve or had received at least 9 months of lamivudine (3TC)-containing ART were enrolled in a cross-sectional study. Demographic and clinical data were collected and HBV DNA quantified. Partial HBV sequences were amplified by PCR and sequenced bi-directionally to obtain a 2.1-2.2 kb fragment for phylogenetic analysis of HBV genotypes and evaluation of drug resistance mutations. Results Of the 100 HBV-HIV co-infected study patients, 75 were successfully PCR-amplified, and 63 were successfully sequenced. Of these 63 patients, 27 (42.9%) were ART-experienced, and 58 (92.1%) had HBV genotype E. No resistance mutations were observed in the 36 ART-naïve patients, while 21 (77.8%) of 27 treatment-experienced patients had resistance mutations. All patients with resistance mutations had no tenofovir (TDF) in their regimens, and 80% of them had HIV RNA < 40 copies/mL. The 3TC resistance mutations rtL180M and rtM204V were observed in 10 (47.6%) of the 21 patients, while 5 patients (23.8%) had rtV173, rtL80I, and rtM204V mutations. Discussion A high proportion of HBV-HIV co-infected patients with detectable viremia on 3TC-containing ART had resistance mutations despite good ART adherence as determined by HIV RNA suppression. This study emphasizes the need for dual therapy as part of a fully suppressive ART in all HBV-HIV co-infected patients in Ghana.

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“…Of note, none of the 12 testing positive for HBV DNA was anti-HCV positive, a feature said to be associated with occult HBV in other settings [Cacciola et al, 1999]. On the other hand, with the availability of highly active antiretroviral treatment (HAART) in Africa in the recent years, the prevalence of lamivudine resistant mutants is increasing [Selabe et al, 2007]. Lamivudine resistant mutations have been reported to cause the amino acid substitutions in both the pol and envelope genes, thus affecting HBsAg and its detection [Ono-Nita et al, 1999;Yeh et al, 2000].…”

Section: Discussionmentioning

confidence: 97%

Validity of the rapid strip assay test for detecting HBsAg in patients admitted to hospital in Uganda

Seremba

Ocama

Opio

et al. 2010

Journal of Medical Virology

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Commercially available rapid strip assays (RSAs) for hepatitis B surface antigen (HBsAg) are used for most routine clinical testing in sub-Saharan Africa. This study evaluated the validity of RSA and a more sophisticated enzyme immunoassay (EIA) with confirmation by nucleic acid testing (NAT) in hospitalized patients in Uganda. Sera from 380 consecutive patients collected and tested for HBsAg and anti-HIV in Kampala, Uganda by RSA were sent frozen to Dallas for EIA including HBsAg, total anti-hepatitis B core, hepatitis B e antigen, and anti-HIV. NAT was performed on all HBsAg-positives and on a random sample of 102 patients that were HBsAg-negative by both assays. Overall, 31 (8%) were HBsAg positive by RSA while 50 (13%) were HBsAg-positive by EIA; 26 were concordant between the two assays. Of 55 HBsAg-positive patients, nearly all showed detectable serum hepatitis B virus (HBV) DNA by bDNA (46) or PCR (4) assay. The 26 patients who were HBsAg positive by both EIA and RSA had significantly higher median serum HBV DNA levels than the 24 patients who were HBsAg positive by EIA alone. An additional 12/102 (12%) HBsAg negative patients had very low serum HBV DNA levels by NAT. Several differences in expected results of serologic testing were observed in this large series of African patients. RSA HBsAg testing is less sensitive than EIA; even EIA failed to detect all HBV DNA positive sera. A more complex testing protocol than RSA alone will be needed in Africa to improve patient care.

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Mutations associated with lamivudine‐resistance in therapy‐naïve hepatitis B virus (HBV) infected patients with and without HIV co‐infection: Implications for antiretroviral therapy in HBV and HIV co‐infected South African patients

Cited by 50 publications

References 28 publications

Occult hepatitis B virus infection in HIV positive patients at a tertiary healthcare unit in eastern India

Occult hepatitis B virus infection in HIV positive patients at a tertiary healthcare unit in eastern India

HBV Genotypes and Drug Resistance Mutations in Antiretroviral Treatment-Naive and Treatment-Experienced HBV–HIV-Coinfected Patients

Validity of the rapid strip assay test for detecting HBsAg in patients admitted to hospital in Uganda

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