Detection of SARS-CoV-2 in Saliva and Nasopharyngeal Swabs According to Viral Variants.

The genome of the Omicron variant of concern (VOC) contains more than 50 mutations, many of which have been associated with increased transmissibility, differing disease severity, and the potential to elute immune responses acquired after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination or infection with previous VOCs. Due to a better tropism for the upper respiratory tract, it was suggested that the detection of the Omicron variant could be preferred in saliva, compared to nasopharyngeal swabs (NPS). Our objective was to compare the SARS-CoV-2 levels in saliva fluid and NPS to estimated Ct values, according to the main SARS-CoV-2 variants circulating in France since the beginning of 2021. We analyzed 1,289 positive reverse transcription-polymerase chain reaction (RT-PCR) results during the three major waves: Alpha, Delta, and Omicron. NPS and saliva sampling were performed for 909 (71%) and 380 (29%) cases, respectively. The Ct values were significantly lower in the NPS samples than in the saliva samples for the three main VOCs. Still, the difference was less pronounced with the Omicron variant than for the Alpha and Delta variants. In contrast, in the saliva samples, Ct values were significantly lower for the Omicron variant than for the Delta (difference of -2.7 Ct) and the Alpha (difference of -3.0 Ct) variants, confirming a higher viral load in saliva. To conclude, the higher viral load in saliva was evidenced for the Omicron variant, compared to the Alpha and Delta variants, suggesting that established diagnostic methods might require revalidation with the emergence of novel variants. IMPORTANCE Established methods for SARS-CoV-2 diagnostics might require revalidation with the emergence of novel variants. This is important for screening strategy programs and for the investigation of the characteristics of new variants in terms of tropism modification and increased viral burden leading to its spread. SARS-CoV-2 RT-PCR screening on saliva samples reported lower but acceptable performance, compared to nasopharyngeal samples. Due to a better tropism for the upper respiratory tract, it was suggested that the detection of the Omicron variant could be preferred in saliva, compared to nasopharyngeal swabs. Our study analyzed 1,289 positive RT-PCR results during the three major waves in France: Alpha, Delta, and Omicron. Our findings also showed a higher viral load in saliva for the Omicron variant, compared to the Alpha and Delta variants.

[Aspects virologiques, diagnostic et variants du SARS-CoV-2]. / Virological aspects, diagnostic tools and variants of SARS-CoV-2.

VIROLOGICAL ASPECTS, DIAGNOSTIC TOOLS AND VARIANTS OF SARS-COV-2 SARS-CoV-2 is an enveloped non-segmented linear single-stranded positive RNA virus. The envelope carries the protein spike (S) which recognizes the ACE2 receptor on the target cell and allows entry of the virus. The numerous mutations on the S protein are at the origin of a great genetic diversity, involved in the species barrier and the escape from neutralizing antibodies. The main mode of transmission is respiratory. The virus replicates 24 hours after infection and the viral RNA is detected by direct diagnostic techniques as the reference technique is RT-PCR on a nasopharyngeal sample. To expand screening, RT-PCR on saliva samples and antigenic tests have been developed. The majority of patients develop specific antibodies within 10-15 days which are detectable by serological methods. It is recommended to combine the search for anti-N and anti-S antibodies. The viral genome has great plasticity and variants emerged from the summer of 2020. There are several classifications, including that of the WHO, which assigns each variant a Greek letter. Finally, Santé publique France has deployed an epidemiological surveillance system of variants using PCR screening and sequencing.

ASPECTS VIROLOGIQUES, DIAGNOSTIC ET VARIANTS DU SARS-COV-2 Le SARS-CoV-2 est un virus enveloppé à ARN monocaténaire linéaire non segmenté de polarité positive. L'enveloppe porte la protéine Spike (S) qui reconnaît le récepteur ACE2 sur la cellule cible et permet l'entrée du virus. Les nombreuses mutations sur la protéine S sont à l'origine d'une grande diversité génétique, impliquées dans le franchissement de la barrière d'espèce et l'échappement aux anticorps neutralisants. Le mode de transmission principal est respiratoire. Le virus réplique dès vingt-quatre heures après l'infection, et l'ARN viral est détecté par les techniques de diagnostic direct ; la technique de référence est la RT-PCR sur prélèvement nasopharyngé. Pour élargir le dépistage, la RT-PCR sur prélèvement salivaire et les tests antigéniques ont été développés. La majorité des patients développent des anticorps spécifiques en dix à quinze jours, qui sont détectables par les méthodes sérologiques ; il est recommandé de combiner la recherche des anticorps anti-N (nucléocapside) et anti-S. Le génome viral est doté d'une grande plasticité, et des variants ont émergé dès l'été 2020. Il en existe plusieurs classifications dont celle de l'Organisation mondiale de la santé qui attribue à chaque variant une lettre grecque. Enfin, Santé publique France a déployé un système de surveillance épidémiologique de ces variants à l'aide de techniques de criblage et de séquençage.

Multidrug-resistant Neisseria gonorrhoeae failing treatment with ceftriaxone and doxycycline in France, November 2017.

We report a multidrug-resistant Neisseria gonorrhoeae urogenital and pharyngeal infection with ceftriaxone resistance and intermediate resistance to azithromycin in a heterosexual woman in her 20s in France. Treatment with ceftriaxone plus doxycycline failed for the pharyngeal localisation. Whole-genome sequencing of isolate F90 identified MLST1903, NG-MAST ST3435, NG-STAR233, and relevant resistance determinants. F90 showed phenotypic and genotypic similarities to an internationally spreading multidrug-resistant and ceftriaxone-resistant clone detected in Japan and subsequently in Australia, Canada and Denmark.

Short article: Hepatitis B virus status in children born to HIV/HBV coinfected women in a French hospital: a cross-sectional study.

OBJECTIVES: We assessed hepatitis B virus (HBV) status in children born to HIV/HBV coinfected women with large access to antiretroviral therapy. METHODS: All HIV/HBV coinfected pregnant women from 01 January 2000 to 01 January 2012 were included in the retrospective study (NCT02044068). Antiretroviral therapy during pregnancy and injection of HBV immunoglobulin/vaccine to newborns was recorded. We assessed HBV status of children aged at least 2 years. RESULTS: Twenty-one women (35 children) were studied. Twenty-six children (74%) had HBsAb: 22 had received immunoglobulin and 24 had received a complete vaccine (with immunoglobulin in 21 cases); their mothers had been administered lamivudine or tenofovir/emtricitabine during eight and nine pregnancies, respectively. Eight children (23%) were negative for HBsAg, HBsAb, and HBcAb: four (11.5%) had received immunoglobulin and a complete vaccine; in two children, it was not known whether they had received an immunoglobulin injection; in one child, the vaccine was incomplete; and in the last one, it was not known whether he had received immunoglobulin/vaccine. Their mothers had been administered lamivudine or tenofovir/emtricitabine during five and two pregnancies, respectively. No infant has chronic HBV infection (HBsAg) after prenatal mothers' antiretroviral therapy combined with a complete postnatal HBV protection. One child had HBcAb and HBsAb: it was not known whether she had received an immunoglobulin injection; the vaccine was incomplete. The mother had been administered lamivudine during the last trimester of pregnancy. CONCLUSION: Antiretroviral therapy in HBV/HIV coinfected women following current national HBV guidelines may prevent mother-to-child-transmission of HBV. Negativity of surrogate markers of vaccine-induced protection is frequent; large studies on long-term protection are needed.

Hepatitis B virus (HBV) status of children born to HIV/HBV co-infected women in a French hospital: a cross-sectional study.

INTRODUCTION: Human Immunodeficiency Virus (HIV) Mother-To-Child-Transmission (MTCT) and prevention by combined antiretroviral therapy (cART) have been extensively studied. Hepatitis B Virus (HBV) MTCT from HIV/HBV co-infected women and prevention by antiretroviral therapy with dual activity have been poorly studied. The aim of the study was to assess HBV MTCT from HIV/HBV co-infected women in a developed country with a large access to cART. MATERIALS AND METHODS: HIV/HBV co-infected pregnant women attending the Obstetrics Department from 1st January 2000 to 1st January 2012 could be included in the study (NCT02044068). Antiretroviral therapy during pregnancy, injection of immunoglobulin and/or vaccine to newborns was retrospectively recorded. We assessed HBV status of children at least as old as two years. RESULTS: Forty nine (9.2%) from 530 HIV-infected women followed in the hospital were HIV/HBV co-infected. 34 (69.4%) had given birth to 57 children in the hospital. 13 of these women (22 children) were lost-to-follow-up, 21 women (35 children) could be studied. Twenty six children (74.3%) had HBs Ab at a protective level, 22 of them had received immunoglobulin at birth; 24 had received a complete vaccine schedule during the first six months of life (with immunoglobulin in 21 cases). The women had been given lamivudine or tenofovir/emtricitabine during eight and nine pregnancies respectively. Eight children (22.8%) were tested negative for HBs Ag, HBs Ab and HBc Ab: 4 (11.4%) had received immunoglobulin and a complete vaccine schedule; in two children, immunoglobulin was uncertain; in one child, the vaccine schedule was incomplete; in the last one, data about immunoglobulin and the vaccine schedule were lacking. The women had been given lamivudine or tenofovir/emtricitabine during five and two pregnancies respectively. One child had HBc Ab and HBs Ab, immunoglobulin was uncertain and the vaccine schedule was incomplete. The woman had been given lamivudine during the last trimester. CONCLUSIONS: Three quarters of the children were protected. HBs Ab were negative in more than a tenth of the children who had received immunoglobulin and a complete vaccine schedule, questioning on long-term protection and underlining the need of control.

Higher specificity of nucleic acid sequence-based amplification isothermal technology than of real-time PCR for quantification of HIV-1 RNA on dried blood spots.

Dried blood spots (DBS) are widely proposed as a plasma surrogate for monitoring antiretroviral treatment efficacy based on the HIV-1 RNA level (viral load [VL]) in resource-limited settings. Interfering coamplification of cell-associated HIV-1 DNA during reverse transcription (RT)-PCR can be avoided by using nucleic acid sequence-based amplification (NASBA) technology, which is based on an RNA template and isothermic conditions. We analyzed VL values obtained with DBS and plasma samples by comparing isothermic NASBA (NucliSENS EasyQ HIV-1 V2.0; bioMérieux) with real-time RT-PCR (Cobas TaqMan HIV-1 V2.0; Roche). Samples from 197 HIV-1-infected patients were tested (non-B subtypes in 51% of the cases). Nucleic acid extractions were performed by use of NucliSENS EasyMAG (bioMérieux) and Cobas AmpliPrep (Roche) before the NASBA and RT-PCR quantifications, respectively. Both quantification assays have lower limits of detection of 20 (1.3) and 800 (2.9) log10 copies/ml (log) in plasma and DBS, respectively. The mean (DBS minus plasma) differences were -0.39 and -0.46 log, respectively, for RT-PCR and NASBA. RT-PCR on DBS identified virological failure in 122 of 126 patients (sensitivity, 97%) and viral suppression in 58 of 70 patients (specificity, 83%), yielding 12 false-positive results (median, 3.2 log). NASBA on DBS identified virological failure in 85 of 96 patients (sensitivity, 89%) and viral suppression in 95 of 97 patients (specificity, 98%) and yielded 2 false-positive results (3.0 log for both). Both technologies detected HIV-1 RNA in DBS at a threshold of 800 copies/ml. This higher specificity of NASBA technology could avoid overestimation of poor compliance or the emergence of resistance when monitoring antiretroviral efficacy with the DBS method.

Stability and antiviral activity against human cytomegalovirus of artemisinin derivatives.

OBJECTIVES: Artesunate, a derivative of dihydroartemisinin, itself a product of artemisinin, inhibits the replication of cytomegalovirus in vitro. In vivo, artesunate undergoes rapid conversion into the active metabolite dihydroartemisinin. The in vitro stability of the compounds and the antiviral activity of dihydroartemisinin are of great concern for the interpretation of in vitro testing. The aim of the study was to measure artesunate conversion into dihydroartemisinin in culture medium and to evaluate the stability and antiviral activity of artemisinin derivatives, according to culture conditions. METHODS: Conversion of artesunate into dihydroartemisinin was measured in culture medium with or without fetal calf serum, in the presence or absence of fibroblast monolayers, at different times. The stability of artemisinin derivatives was determined in serum-enriched medium. Concentrations of each compound inhibiting viral DNA synthesis by 50% were determined in fibroblasts cultured in serum-free or serum-enriched medium, after addition of compound as a single dose or fractional doses. RESULTS: Conversion of artesunate into dihydroartemisinin in serum-free or serum-enriched medium was non-equimolar. The half-lives of artesunate, dihydroartemisinin and artemisinin were 10.3 ± 0.9, 5.2 ± 0.5 and 11.2 ± 1.2 h, respectively. Activity of dihydroartemisinin and artesunate was markedly reduced in serum-starved cells. Unexpectedly, dihydroartemisinin displayed a lower activity than artesunate. Addition of both compounds as fractional doses increased their activity. Artemisinin had no anticytomegaloviral activity. CONCLUSIONS: Artemisinin derivatives were shown to be unstable in vitro and their addition as fractional doses could partly compensate for this instability. Importantly, the cellular physiological condition was a determinant of their antiviral activity.

Dynamics of cytomegalovirus populations harbouring mutations in genes UL54 and UL97 in a haematopoietic stem cell transplant recipient.

We characterised by pyrosequencing, the dynamics of cytomegalovirus populations harbouring mutations A594V in gene UL97 and A834P and Q578H in gene UL54 in a haematopoietic stem cell transplant recipient. Unexpected re-emergence of A594V and decrease of A834P under CMX001 were shown to depend on both the selection pressure exerted by the antiviral treatments and the immune response.

Fully automated quantification of cytomegalovirus (CMV) in whole blood with the new sensitive Abbott RealTime CMV assay in the era of the CMV international standard.

Fully standardized reproducible and sensitive quantification assays for cytomegalovirus (CMV) are needed to better define thresholds for antiviral therapy initiation and interruption. We evaluated the newly released Abbott RealTime CMV assay for CMV quantification in whole blood (WB) that includes automated extraction and amplification (m2000 RealTime system). Sensitivity, accuracy, linearity, and intra- and interassay variability were validated in a WB matrix using Quality Control for Molecular Diagnostics (QCMD) panels and the WHO international standard (IS). The intra- and interassay coefficients of variation were 1.37% and 2.09% at 5 log10 copies/ml and 2.41% and 3.80% at 3 log10 copies/ml, respectively. According to expected values for the QCMD and Abbott RealTime CMV methods, the lower limits of quantification were 104 and <50 copies/ml, respectively. The conversion factor between international units and copies (2.18), determined from serial dilutions of the WHO IS in WB, was significantly different from the factor provided by the manufacturer (1.56) (P = 0.001). Results from 302 clinical samples were compared with those from the Qiagen artus CMV assay on the same m2000 RealTime system. The two assays provided highly concordant results (concordance correlation coefficient, 0.92), but the Abbott RealTime CMV assay detected and quantified, respectively, 20.6% and 47.8% more samples than the Qiagen/artus CMV assay. The sensitivity and reproducibility of the results, along with the automation, fulfilled the quality requirements for implementation of the Abbott RealTime CMV assay in clinical settings. Our results highlight the need for careful validation of conversion factors provided by the manufacturers for the WHO IS in WB to allow future comparison of results obtained with different assays.

Epidemiological, virological and clinical characteristics of HBV infection in 223 HIV co-infected patients: a French multi-centre collaborative study.

BACKGROUND: Chronic hepatitis B (CHB) is a clinical concern in human immunodeficiency virus (HIV)-infected individuals due to substantial prevalence, difficulties to treat, and severe liver disease outcome. A large nationwide cross-sectional multicentre analysis of HIV-HBV co-infected patients was designed to describe and identify parameters associated with virological and clinical outcome of CHB in HIV-infected individuals with detectable HBV viremia. METHODS: A multicenter collaborative cross-sectional study was launched in 19 French University hospitals distributed through the country. From January to December 2007, HBV load, genotype, clinical and epidemiological characteristics of 223 HBV-HIV co-infected patients with an HBV replication over 1000 IU/mL were investigated. RESULTS: Patients were mostly male (82%, mean age 42 years). Genotype distribution (A 52%; E 23.3%; D 16.1%) was linked to risk factors, geographic origin, and co-infection with other hepatitis viruses. This genotypic pattern highlights divergent contamination event timelines by HIV and HBV viruses. Most patients (74.7%) under antiretroviral treatment were receiving a drug with anti-HBV activity, including 47% receiving TDF. Genotypic lamivudine-resistance detected in 26% of the patients was linked to duration of lamivudine exposure, age, CD4 count and HIV load. Resistance to adefovir (rtA181T/V) was detected in 2.7% of patients. Advanced liver lesions were observed in 54% of cases and were associated with an older age and lower CD4 counts but not with viral load or genotype. Immune escape HBsAg variants were seldom detected. CONCLUSIONS: Despite the detection of advanced liver lesions in most patients, few were not receiving anti-HBV drugs and for those treated with the most potent anti-HBV drugs, persistent replication suggested non-optimal adherence. Heterogeneity in HBV strains reflects epidemiological differences that may impact liver disease progression. These findings are strong arguments to further optimize clinical management and to promote vaccination in HIV-infected patients.

Case report: benefits of quantitative polymerase chain reaction in the clinical management of herpes simplex virus 1 infection with prominent hepatitis and unusual secondary progression.

Herpes simplex virus (HSV) infection is rarely considered in the differential diagnosis of severe acute hepatitis and disseminated infection in immunocompetent adults. A case of disseminated HSV-1 infection in an 82-year-old woman initially presenting with neurological problems, signs of meningitis and prominent hepatitis was investigated. Initial diagnosis, monitoring, and follow-up were based on the application of molecular methods to cerebrospinal fluid, serum, and liver tissue samples from this patient. Following an initial full recovery, the patient presented delayed intracerebral haemorrhage and diffuse arthralgia. This atypical case, with delayed secondary progression, highlights the wide range of clinical features of HSV infection and the benefits of monitoring viral load by quantitative real-time polymerase chain reaction (PCR) during patient management.

High burden of non-influenza viruses in influenza-like illness in the early weeks of H1N1v epidemic in France.

BACKGROUND: Influenza-like illness (ILI) may be caused by a variety of pathogens. Clinical observations are of little help to recognise myxovirus infection and implement appropriate prevention measures. The limited use of molecular tools underestimates the role of other common pathogens. OBJECTIVES: During the early weeks of the 2009-2010 flu pandemic, a clinical and virological survey was conducted in adult and paediatric patients with ILI referred to two French University hospitals in Paris and Tours. Aims were to investigate the different pathogens involved in ILI and describe the associated symptoms. METHODS: H1N1v pandemic influenza diagnosis was performed with real time RT-PCR assay. Other viral aetiologies were investigated by the molecular multiplex assay RespiFinder19®. Clinical data were collected prospectively by physicians using a standard questionnaire. RESULTS: From week 35 to 44, endonasal swabs were collected in 413 patients. Overall, 68 samples (16.5%) were positive for H1N1v. In 13 of them, other respiratory pathogens were also detected. Among H1N1v negative samples, 213 (61.9%) were positive for various respiratory agents, 190 in single infections and 23 in mixed infections. The most prevalent viruses in H1N1v negative single infections were rhinovirus (62.6%), followed by parainfluenza viruses (24.2%) and adenovirus (5.3%). 70.6% of H1N1v cases were identified in patients under 40 years and none after 65 years. There was no difference between clinical symptoms observed in patients infected with H1N1v or with other pathogens. CONCLUSION: Our results highlight the high frequency of non-influenza viruses involved in ILI during the pre-epidemic period of a flu alert and the lack of specific clinical signs associated with influenza infections. Rapid diagnostic screening of a large panel of respiratory pathogens may be critical to define and survey the epidemic situation and to provide critical information for patient management.

Rotavirus rearranged genomic RNA segments are preferentially packaged into viruses despite not conferring selective growth advantage to viruses.

The rotavirus (RV) genome consists of 11 double-stranded RNA segments. Sometimes, partial sequence duplication of an RNA segment leads to a rearranged RNA segment. To specify the impact of rearrangement, the replication efficiencies of human RV with rearranged segments 7, 11 or both were compared to these of the homologous human wild-type RV (wt-RV) and of the bovine wt-RV strain RF. As judged by viral growth curves, rotaviruses with a rearranged genome (r-RV) had no selective growth advantage over the homologous wt-RV. In contrast, r-RV were selected over wt-RV during competitive experiments (i.e mixed infections between r-RV and wt-RV followed by serial passages in cell culture). Moreover, when competitive experiments were performed between a human r-RV and the bovine wt-RV strain RF, which had a clear growth advantage, rearranged segments 7, 11 or both always segregated in viral progenies even when performing mixed infections at an MOI ratio of 1 r-RV to 100 wt-RV. Lastly, bovine reassortant viruses that had inherited a rearranged segment 7 from human r-RV were generated. Although substitution of wt by rearranged segment 7 did not result in any growth advantage, the rearranged segment was selected in the viral progenies resulting from mixed infections by bovine reassortant r-RV and wt-RV, even for an MOI ratio of 1 r-RV to 10(7) wt-RV. Lack of selective growth advantage of r-RV over wt-RV in cell culture suggests a mechanism of preferential packaging of the rearranged segments over their standard counterparts in the viral progeny.

Antiviral activity of ganciclovir and artesunate towards human cytomegalovirus in astrocytoma cells.

Antimalarial drug artesunate inhibits cytomegalovirus (HCMV) replication in human fibroblasts. Astrocytes, the major cell type of the brain, support cytomegalovirus (HCMV) replication. The aim of the study was to assess the antiviral activity of artesunate in astrocytoma cell line U373MG in comparison with ganciclovir. The antiviral concentration inhibiting by 50% (IC(50)) the synthesis of viral DNA was measured by real-time PCR in parallel in U373MG and MRC-5 cells. Reference HCMV strains susceptible and resistant to ganciclovir, and clinical isolates were tested. Ganciclovir and artesunate had similar activity in U373MG cells and MRC-5 fibroblasts. The artesunate IC(50)s in U373MG cells (1.5-2.25 µM) were at least 36-fold lower than the 50% cytotoxicity concentrations. Then, the anti-HCMV activity of artesunate was demonstrated in a cancer cell line.

Rapid determination of antiviral drug susceptibility of human cytomegalovirus by real-time PCR.

A quantitative real-time PCR-based assay was developed for determination of cytomegalovirus (HCMV) susceptibility to antiviral drugs. After HCMV isolate-growth for 4 days, antiviral drug susceptibility was determined by measuring the reduction of intracellular HCMV DNA in the presence of increasing concentrations of either ganciclovir, or foscarnet or cidofovir. The 50% inhibitory concentration (IC(50)) was the drug concentration that reduced the number of HCMV genome copies by 50%. The IC(50) values were measured for seven HCMV reference strains sensitive or resistant to one or more antiviral drugs. The antiviral susceptibility of 21 HCMV isolates was then tested and the results were consistent with prior determination of their phenotype and/or genotype by plaque reduction assay and sequencing. The real-time PCR susceptibility assay reported here was found to be highly reproducible, simpler to perform than the plaque reduction assay, and amenable to use in the routine diagnostic virology laboratory.

Rearrangements of rotavirus genomic segment 11 are generated during acute infection of immunocompetent children and do not occur at random.

Group A rotaviruses are the main cause of viral gastroenteritis in infants. The viral genome consists of 11 double-stranded RNA (dsRNA) segments. Dysfunction of the viral RNA polymerase can lead to gene rearrangements, which most often consist of partial sequence duplication of a dsRNA segment. Gene rearrangements have been detected in vivo during chronic infection in immunodeficient children or in vitro during passages at a high multiplicity of infection in cell culture, suggesting that these replication conditions lead to selective advantages favoring the recovery of viruses with rearranged genes. During acute rotavirus infection, the replication level is high, but the occurrence of rearrangement events has never been reported. By the use of a reverse transcription-PCR assay specifically designed to detect small numbers of copies of rearranged forms of segment 11 in a high background of its standard counterpart, we detected 12 rearrangement events among 161 cases (7.5%) of acute rotavirus infection in immunocompetent children. Strikingly, in all but one case, rearrangement took place at the same location within the short direct repeat AUGU sequence. For the unique case with a different rearrangement pattern, the rearrangement occurred within the direct repeat ACAAGUC that was specific for this isolate. In conclusion, we report the occurrence of segment 11 rearrangements during acute rotavirus infection in immunocompetent children. We show that under such conditions of infection, the viral RNA polymerase generates rearrangements which occur not at random but within direct repeats which might constitute hot spots for RNA recombination.

Reactivation of lamivudine-resistant occult hepatitis B in an HIV-infected patient undergoing cytotoxic chemotherapy.

BACKGROUND: Reactivation of occult hepatitis B virus (HBV) infection is a well-known complication of cytotoxic chemotherapy. Lamivudine prophylaxis is recommended to reduce the incidence and severity of hepatitis in this context. CASE REPORT: An HIV-infected patient positive for HBs antigen became positive for HBc antibody alone under lamivudine given as part of antiretroviral therapy. He was treated with chemotherapy for non-Hodgkin's lymphoma while under lamivudine. Then, he developed HBV-related hepatitis that led to delay chemotherapy. He received adefovir that induced a dramatic decline in HBV DNA load and a normalisation of hepatic enzyme levels. However, the patient died of a relapse of lymphoma. Retrospective analysis of stored plasma samples showed evidence of lamivudine-resistant occult hepatitis before the onset of chemotherapy and reactivation of the HBV mutant. CONCLUSION: To our knowledge, this is the first report of occult hepatitis reactivation due to lamivudine-resistant mutant selected under lamivudine therapy in an HIV-infected patient. Our study underlines the need to carefully investigate lamivudine resistance in HIV-infected patients with occult infection under lamivudine therapy. Those patients should be monitored with the addition of anti-viral agents effective against the mutant strain.