Acute hepatitis B virus infection despite vaccination in a patient treated by infliximab: a case report.

BACKGROUND: Despite an effective vaccine, hepatitis B remains a major global health problem due to its significant morbidity and mortality. Vaccination in immunosuppressed patients such as those treated for an inflammatory bowel disease (IBD) can be less effective. This case describes an uncommon original diagnosis of an acute hepatitis B infection occurring in a vaccinated but immunocompromised IBD patient under long-term infliximab treatment. A low anti-HBs titer and the presence of HBsAg escape mutations are possible hypotheses to explain this unexpected infection. CASE PRESENTATION: A 28-year-old Caucasian male, regularly followed-up for a Crohn's disease treated by infliximab, was regularly screened for sexually transmissible infections because of at-risk behaviors. Despite a correct immunization scheme against hepatitis B virus (HBV), an active HBV infection was diagnosed during one of those screenings. Retrospective testing of a sample collected 6 months earlier was in favor of an evolution from an acute hepatitis B toward a chronic hepatitis B. The patient has always had a low anti-HBs antibody levels (near the threshold of 10 IU/L) possibly explaining his infection. In addition, HBV sequencing revealed a genotype A2 HBV strain, carrying the sD144A substitution on the S protein, known as a potential immune escape variant. Dual therapy combining tenofovir disoproxil fumarate and emtricitabine, active against HBV but also efficient as an HIV pre-exposure prophylaxis, was initiated. Ten months after treatment initiation, all surrogate biochemical and virological endpoints for HBV functional cure were achieved. Treatment and periodical monitoring are being maintained. CONCLUSION: Emphasis should be placed on HBV screening, vaccination and regular monitoring of patients under long-term immunosuppressive therapy, particularly those with at-risk behaviors.

Mitochondrial abnormalities in patients with HIV-HCV co-infection as compared to patients with HCV mono-infection.

INTRODUCTION: Mitochondrial dysfunction is a classic complication of HIV infection and its treatment and has also been reported in hepatitis C virus (HCV)-infected patients. Little is known about interactions between both viruses on mitochondrial metabolism. METHODS: We performed a cross-sectional study of HCV-infected patients who underwent liver biopsy as part of their routine care. Mitochondrial function was assessed by (a) liver morphological (histology) and functional (spectro-photometry) studies, and (b) serum lactate kinetics, oxygen uptake, and anaerobic threshold measurement during standardized incremental exercise. Three predefined groups of patients were compared. RESULTS: Thirty-eight HCV-infected patients were included: 13 not HIV infected (group 1), 7 with HIV co-infection and low nucleoside reverse transcriptase inhibitor (NRTI) exposure (none over the last 2 years; group 2), and 18 with HIV co-infection and high NRTI exposure (group 3). On liver biopsies, respiratory chain complex IV activity was impaired, at 5 (2-7) nmol/min/mg substrates in group 1, 5 (3-8) in group 2, and 8 (2-13) in group 3 (normal values, 20-56). Maximal power output was diminished and anaerobic threshold occurred earlier in HIV-infected patients, regardless of NRTI exposure. CONCLUSION: HCV has deleterious effects on liver mitochondrial metabolism, notably on respiratory chain complex IV. No significant interaction with HIV was observed.

Enhanced immunovirological response in women compared to men after antiretroviral therapy initiation during acute and early HIV-1 infection: results from a longitudinal study in the French ANRS Primo cohort.

INTRODUCTION: Previous studies have reported better immunovirological characteristics in women compared with men after HIV seroconversion. We investigated whether differences persisted under long-term antiretroviral therapy (ART) in individuals treated since acute and early HIV-1 infection (AHI). METHODS: Data were obtained for 262 women and 1783 men enrolled between 1996 and 2017 in the French multicentre ANRS PRIMO cohort. We modelled the viral response, long-term immune recovery and HIV DNA decay in the 143 women and 1126 men who initiated ART within the first three months of infection. RESULTS: The participants were mostly white. The mean age was 37 years at AHI diagnosis. Pre-ART viral loads were lower in women than men, 5.2 and 5.6 log10 copies/mL (p = 0.001). After ART initiation, women more rapidly achieved viral suppression than men (adjusted hazard ratio: 1.33, 95% confidence interval 1.09 to 1.69). They also experienced a faster increase in CD4+ T-cell count and CD4:CD8 ratio during the first months of treatment. Sex-related differences in CD4+ T-cell counts were more pronounced with increasing age. This led to a sustained mean difference of 99 to 168 CD4+ T-cells/µL depending on age between women and men at 150 months of ART. Moreover, CD4:CD8 ratio of women was higher than that of men by 0.31, at 150 months of ART. There was no statistically significant difference between sexes for the levels of HIV DNA over time (mean estimate at the last modelling point: 1.9 log10 copies/106 PBMCs after 70 months of ART for both sexes). CONCLUSIONS: The high level of immune recovery and decrease in total HIV DNA levels achieved after ART initiation during AHI reinforce the importance of early diagnosis of HIV infection and immediate ART initiation. The immunological benefit of being female increased throughout prolonged ART duration, which may give women additional protection from adverse clinical events and premature ageing.

New and old complex recombinant HIV-1 strains among patients with primary infection in 1996-2006 in France: the French ANRS CO06 primo cohort study.

BACKGROUND: Prevalence of HIV-1 non-B subtypes has increased overtime in patients diagnosed at the time of primary infection (PHI) in France. Our objective was to characterize in detail non-B strains which could not be genetically classified into the known subtypes/Circulating Recombinant Forms (CRFs). METHODS: Among 744 patients enrolled in the ANRS PRIMO Cohort since 1996, 176 (23.7%) were infected with HIV-1 non-B strains. The subtype/CRF could not be identified in RT for 15 (2%). The V3-V5 env region was sequenced and 3 strains (04FR-KZS, 06FR-CRN, 04FR-AUK) were full-length sequenced. Phylogenetic and bootscan analyses were used to characterize the mosaic structures. RESULTS: Among V3-V5 sequences, 6 were divergent A, 2 distantly related to E or D, 2 C, 1 B and 2 remained unclassified. 04FR-KZS, isolated in a Congolese woman infected in France, clustered with 2 previously described viruses from the Democratic Republic of Congo. They represent CRF27_cpx involving A/E/G/H/J/K/U subtypes. 06FR-CRN, isolated in a homosexual Caucasian patient, was a B/C/U recombinant involving a Brazilian C strain. 04FR-AUK, isolated in a Congolese patient infected in France, was a A/K/CRF09/U recombinant clustering from gag to vif with HIV-1 MAL. Others PHI were further observed in 2006-2007 with 1 KZS and 5 CRN-like viruses, suggesting their spread in France. CONCLUSION: This study illustrates the increasing HIV-1 diversity in France associating new (06FR-CRN) and old (CRF27_cpx and "MAL-like" 04FR-AUK) strains, which are rare in their region of origin but may have a possible founder effect in France. Our results strengthen the French guidelines recommending viro-epidemiological surveillance of HIV-1 diversity.

Salvage therapy with amprenavir and ritonavir: prospective study in 17 heavily pretreated patients.

OBJECTIVE: To evaluate the safety profile and efficacy of salvage regimens containing amprenavir (APV) 600 mg twice daily and ritonavir (RTV) 200 mg twice daily. DESIGN: Prospective, single-center study. METHOD: The patient database of the department of infectious diseases was screened for patients who had failed at least two successive three-drug combinations. These patients were proposed to take APV and RTV in association with two to four other drugs. They were followed monthly for 6 months. RESULTS: Seventeen patients were included. They had been previously treated for 70 +/- 23 months. At baseline, viral load (VL) was 4.86 +/- 0.98 log10 copies/mL and CD4 187 +/- 145 10(6)/L. On week 24, using intent-to-treat analysis, VL decreased to 2.95 +/- 1.59 log10 copies/mL and CD4 increased to 365 +/- 210 10(6)/L. Nine patients (53%) had a VL < 2.3 log10 copies/mL. The most common adverse events were grade 1 or 2 diarrhea and an increase of cholesterol and triglyceride levels. Mean APV trough concentration was 1727 +/- 1749 ng/mL on week 24. CONCLUSION: These data show that the combination of low-dose RTV and reduced doses of APV is safe. This combination can be added to nonnucleoside analogs.

Alpha interferon administration during structured interruptions of combination antiretroviral therapy in patients with chronic HIV-1 infection: INTERVAC ANRS 105 trial.

Interferon-α administration during structured treatment interruptions (STIs) was studied in a phase III trial. We randomized 168 chronically infected HIV undetectable under combined antiretroviral therapy patients to have three STIs with or without α-interferon. The number of patients who had to resume treatment during post-STI follow-up was not significantly different between the two arms. Patients with a low CD4 nadir and a high baseline HIV-DNA had a higher risk of treatment resumption in the interferon arm.

Trends in unsafe sex and influence of viral load among patients followed since primary HIV infection, 2000-2009.

BACKGROUND: In the current context of increasing unsafe sex, HIV incidence may have evolved, depending on HIV prevalence in sexual networks and, among HIV-infected persons who practice unsafe sex, on their infectivity and partners' HIV serostatus. We examined calendar trends in sexual behaviours at risk of HIV-1 transmission (SBR) among 967 adults followed since primary HIV infection (ANRS PRIMO cohort) and relationship with current treatments and viral load. METHODS: Patients completed since 2000 self-administered questionnaires on sexual practices every 6 months. SBR with HIV-negative/unknown partners were analyzed among 155 heterosexual women, 142 heterosexual men and 670 MSM by using logistic generalized estimating equation models (6656 visits). RESULTS: During 2000-2009, the frequency of SBR did not increase significantly among women with steady partners; risk factors were a low education level and alcohol/smoking use. Among heterosexual men with steady partners, the frequency of SBR doubled since 2006; during this period, the only associated factor was combined antiretroviral treatment for at least 6 months or viral load less than 400 copies/ml. Among MSM, SBR increased gradually over time; SBR with steady partners was associated with a low education level and alcohol use. SBR was more frequent among MSM with casual partners; no association with viral load was found. CONCLUSION: In France, recent trends and risk factors in unprotected sex with HIV-negative/unknown partners differ according to sex/sexual preference. The recent increase in SBR among heterosexual men with low viral load may be related to increasing awareness of the 'treatment-as-prevention' concept. The lack of association between SBR and viral load among MSM supports use of treatment-as-prevention as part of diversified prevention strategies.

Diabetes in patients with pasteurellosis.

From 1991 to 2003, 20 patients with pasteurellosis were admitted to our unit, of whom 2 died. They presented with cellulitis (n = 14), arthritis (n = 6), pneumonia (n = 3), subcutaneous abscess (n = 3), bursitis (n = 2), meningitis, otitis, sinusitis and uveitis. Underlying diseases included diabetes (n = 6) and malignancy (n = 5). Diabetes could be a predisposing condition for pasteurellosis.

Mitochondrial abnormalities in HIV-infected lipoatrophic patients treated with antiretroviral agents.

BACKGROUND: Lipodystrophy is now widely described in HIV infected patients under antiretroviral regimen with important psychological impact. But physiopathology of loss of fat mass is still debated and the role of mitochondrial impairment is not clearly defined. OBJECTIVE: To correlate clinical lipoatrophy (LA) in HIV patients with long-term treatment by nucleoside reverse transcriptase inhibitors (NRTIs) and muscular impairment related to mitochondrial dysfunction. METHODS: Ten consecutive patients with clinical LA and 10 nonlipodystrophic (NLD) individuals on antiretroviral therapy were included. Patients underwent the following investigations: dual-energy x-ray absorptiometry (DEXA) scanning and lactate kinetics during standardized exercise. The mitochondrial respiratory complex activity (III and IV) and histoenzymatic abnormalities (classified as none, mild, or severe) were evaluated on muscle tissue obtained by biopsy in deltoid muscle. RESULTS: Mean NRTI exposure was longer in the LA group than in the NLD group (81 +/- 30 months vs. 59 +/- 15 months), but mean protease inhibitor exposure was identical in both groups. Mean fat mass distribution for leg in the LA and NLD groups was 860 +/- 381 g versus 1895 +/- 999 g, respectively. The lactic acidosis threshold during exercise was reached in the LA group at lower workloads (mean: 45 +/- 17 W in the LA group vs. 68 +/- 11 W in the NLD group), and maximum power output exercise was restricted in LA patients (mean: 115 +/- 30 W vs. 153 +/- 28 W). Total complex activities in muscular tissue were lower in LA patients: the median (range) for complex III was 67 (1-128) versus 112 (28-143), and the median (range) for complex IV was 28 (1-70) versus 42 (1-75). Six patients had severe histoenzymatic abnormalities in the LA group versus none in the NLD group. CONCLUSION: Clinical LA, confirmed by DEXA, in long-term NRTI-treated patients was associated with muscular mitochondrial dysfunction as shown by rapid lactic acidemia increase, impairment of respiratory chain activity for complexes III and IV, and mitochondrial histoenzymatic abnormalities.