Background
Women with HIV are more often infected with human papillomavirus (HPV) and are more prone to develop precancerous cervical lesions (squamous intraepithelial lesions, SIL) and invasive ...cervical cancer (ICC) than HIV‐negative women.
Objective
This scoping‐review analyses the impact of HIV on HPV prevalence, incidence and evolution to SIL and ICC.
Methods
We selected all PubMed systematic reviews and meta‐analyses published between January 2000 and July 2021 reporting data about HPV, cervical intraepithelial neoplasia (CIN), SIL and ICC prevalence, incidence and evolution in women with HIV. A hypothetical model comparing the history of HPV infection in HIV‐negative, combined antiretroviral therapy (cART)‐treated and ‐untreated women with HIV was built.
Results
Data from 11 meta‐analyses and 10 systematic reviews were selected, which included between 770 and 236 127 women with HIV. Women with HIV have a 3 to 6 times higher risk of being infected by HPV, of progression to high‐grade SIL (HSIL) and to ICC. These risks are exacerbated when the CD4 cell counts are low and when they are not using cART, whereas these risks are reduced by 20%–30% when they are optimally treated with cART and have had a suppressed HIV viral load for at least 2 years. In our model, we illustrated that optimal HIV treatment and preventing HIV reduce the number of ICC cases by 2.5 and 6 times, respectively.
Conclusions
Optimal treatment and care of HIV patients are essential to reduce their prevalence of ICC, as are preventive strategies which include HPV vaccination, cervical cancer screening strategies and treatment of HSIL.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose
As the COVID-19 pandemic continues, an increasing number of patients are afflicted by olfactory loss, a now well-recognized symptom of the disease. Though many patients seem to recover their ...sense of smell after a few weeks, a certain proportion of them seem to develop long-lasting olfactory disorder. Yet, as of October 2020, there is no recommended standardized treatment to reduce the risk of developing long-term olfactory disorder. In this pilot study, we investigated the efficacy and the safety of oral corticosteroids and olfactory training as a treatment for patients with persistent olfactory dysfunction as a result of COVID-19.
Methods
Non-hospitalized patients with a sudden loss of smell and a confirmed COVID-19 diagnosis were recruited by hospital call from February to April 2020. These participants were submitted to an extensive psychophysical testing in order to identify those with persistent dysosmia. Dysosmic patients were then treated either by a 10-day course of oral corticosteroids combined with olfactory training, or by olfactory training alone. All participants were subject to a second olfactory test after a mean of 10 weeks.
Results
72 subjects with documented COVID-19 infection performed the initial olfactory test, on average 5 weeks after losing their sense of smell. Amongst them, 27 (37.5%) patients showed persistent dysosmia and were all included in this study. Nine participants received oral corticosteroids and performed olfactory training (OCS + OT), while 18 performed olfactory training (OT) only. Only participants in the OCS + OT group had significantly improved their olfactory score and did so above the minimal clinically important difference for subjective improvement of smell (
p
= 0.007). Three of the participants who received oral corticosteroids reported minimal and transient side effects.
Conclusion
This pilot study may suggest the combination of a short course of oral corticosteroids and olfactory training is safe and may be beneficial in helping patients with enduring dysosmia recover from olfactory loss due to COVID-19. There is a crucial need for further investigation with larger cohorts to corroborate these findings.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
HPV infection may differ in women who are HIV-positive since birth (perinatally infected, P-HIV) and those who acquire HIV later in life (non-perinatally infected, NP-HIV). We assessed the HPV ...prevalence in relation to the HIV acquisition route and HPV vaccination status.
Case control study comparing 22 P-HIV with 22 NP-HIV patients. Cervical, anal and oral specimen were collected for HPV PCRs. The primary outcome was the prevalence of cervical, oral and anal HPV in P-HIV and NP-HIV patients. The secondary outcome was to identify risk factors for HPV infection. Comparative statistics for two independent groups, univariate and multivariable logistic regression analyses were used.
There were no differences between perinatally and non-perinatally infected women. Cervical dysplasia was found in 12/44 (27 %) patients and high-risk HPV (hrHPV) in 30 % of cervical (of which 89 % were hrHPV other than 16 and 18), in 3 % of oral and 65 % of anal specimens. All woman were using combined antiretroviral therapy (cART) and 64 % had HIVRNA < 20 cp/ml. A CD4 count <350/mm³ was associated with cytological abnormalities (OR: 13.52, p = 0.002) and with cervical HPV (OR: 6.11; p = 0.04); anal HPV was associated with a previous cervical dysplasia and concomitant cervical HPV infection. None of thirteen vaccinated patients had a 6/11/16/18 HPV infection.
In this small series of women under cART, we did not observe a difference in HPV infection in relation to the route of HIV acquisition. The high prevalence of hrHPV other than 16 and 18 support the use of a 9-valent vaccine.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background This study compares the management and outcome of high grade squamous intraepithelial lesions (HSIL) in HIV-positive and -negative women and identifies risk factors for treatment failure. ...Methods This retrospective, controlled study includes 146 HIV-positive women, matched for HSIL, age and year of diagnosis, with 146 HIV-negative women. Differences were analysed using parametric and non-parametric tests and Kaplan-Meier survival curves. A binary logistic regression was used to assess risk factors for treatment failure. Results Persistence of cervical disease was observed most frequently in HIV-positive women (42 versus 17%) (p < 0.001) and the cone biopsy margins were more often invaded in HIV-positive-women than in HIV-negative ones. (37 versus 16%; p < 0.05). HIV-positive women, with successful cervical treatment had better HIV disease control: with significantly longer periods of undetectable HIV viral loads (VL) (19 versus 5 months; p < 0.001) and higher CD4 counts (491 versus 320 cells/mm.sup.3; p < 0.001). HIV-positive women with detectable VL at the time of dysplasia had 3.5 times (95% IC: 1.5-8.3) increased risk of treatment failure. Being treated through ablative therapy was associated with a 7.4, four-fold (95% IC: 3.2-17.3) increased risk of treatment failure compared to conization Conclusion HIV-positive women have a higher risk of treatment failure of HSIL than do HIV-negative women, especially when ablative therapy is used and in women with poor control of their HIV infection. The management and the follow- up of HSIL's guidelines in this high-risk population should be adapted consequently: for HIV-positive women with uncontrolled viral load, excisional treatment should be the preferred therapy, whereas for women with undetectable viral load, CD4 + lymphocytes higher than 500 cells/mm.sup.3 and with a desire of pregnancy, ablative therapy may be considered. Keywords: HIV, HSIL, Treatment failure, CIN
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
We report a case of Argentine hemorrhagic fever diagnosed in a woman in Belgium who traveled from a disease-endemic area. Patient management included supportive care and combination therapy with ...ribavirin and favipiravir. Of 137 potential contacts, including friends, relatives, and healthcare and laboratory workers, none showed development of clinical symptoms of this disease.
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DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Aims
In the absence of a commonly agreed dosing protocol based on pharmacokinetic (PK) considerations, the dose and treatment duration for hydroxychloroquine (HCQ) in COVID‐19 disease currently vary ...across national guidelines and clinical study protocols. We have used a model‐based approach to explore the relative impact of alternative dosing regimens proposed in different dosing protocols for hydroxychloroquine in COVID‐19.
Methods
We compared different PK exposures using Monte Carlo simulations based on a previously published population pharmacokinetic model in patients with rheumatoid arthritis, externally validated using both independent data in lupus erythematous patients and recent data in French COVID‐19 patients. Clinical efficacy and safety information from COVID‐19 patients treated with HCQ were used to contextualize and assess the actual clinical value of the model predictions.
Results
Literature and observed clinical data confirm the variability in clinical responses in COVID‐19 when treated with the same fixed doses. Confounding factors were identified that should be taken into account for dose recommendation. For 80% of patients, doses higher than 800 mg day on day 1 followed by 600 mg daily on following days might not be needed for being cured. Limited adverse drug reactions have been reported so far for this dosing regimen, most often confounded by co‐medications, comorbidities or underlying COVID‐19 disease effects.
Conclusion
Our results were clear, indicating the unmet need for characterization of target PK exposures to inform HCQ dosing optimization in COVID‐19. Dosing optimization for HCQ in COVID‐19 is still an unmet need. Efforts in this sense are a prerequisite for best benefit/risk balance.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Atopobium vaginae is an anaerobic Gram-positive bacterium recognized as a causative agent of bacterial vaginosis and associated with preterm delivery. Invasive infection and bacteremia have been ...rarely reported. We describe the case of a woman expecting her firstborn child who presented with a A. vaginae bacteremia during labor. Identification was performed using 16S rRNA gene sequencing. Both maternal and fetal outcomes were favorable due to the maternal treatment with amoxicillin-clavulanic acid. We identified three other cases in the literature with different fetal outcome. The genetic diversity of A. vaginae should be further explored in order to reveal potential strains with differential pathogenic potential.
•Atopobium vaginae is a common cause of bacterial vaginosis and is associated with preterm birth.•A. vaginae invasive disease and especially bacteremia is infrequent.•We report a case of intrapartum A. vaginae bacteremia and review published cases.•A. vaginae identification issues are discussed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We report the case of a 38-year-old man with transient perivascular inflammation of the carotid artery syndrome that occurred in the course of covid-19. We describe for the first-time multimodal ...imaging features of the perivascular changes surrounding the carotid artery, and long-term follow-up by ultrasound. The imaging features observed on ultrasound, angiography-CT, MRI and FDG-Pet scan support the hypothesis of the inflammatory nature of the perivascular tissue thickening. The ultrasound follow-up confirmed the spontaneous resolution of the lesion, leaving on site some residual changes as sequelae. The good knowledge of the imaging features reported herein helps to recognize this entity in patients with covid-19.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Inherited CARD9 deficiency constitutes a primary immunodeficiency predisposing uniquely to chronic and invasive fungal infections. Certain mutations are shown to negatively impact CARD9 protein ...expression and/or NF-κB activation, but the underlying biochemical mechanism remains to be fully understood.
To investigate a possible founder origin of a known CARD9 R70W mutation in five families of Turkish origin. To explore the biochemical mechanism of immunodeficiency by R70W CARD9.
We performed haplotype analysis using microsatellite markers and SNPs. We designed a model system exploiting a gain-of-function (GOF) CARD9 L213LI mutant that triggers constitutive NF-κB activation, analogous to an oncogenic CARD11 mutant, to study NF-κB signaling and signalosome formation. We performed reporter assays, immunoprecipitation and confocal imaging on HEK cells overexpressing different CARD9 variants.
We identified a common haplotype, thus providing evidence for a common Turkish founder. CARD9 R70W failed to activate NF-κB and abrogated NF-κB activation by WT CARD9 and by GOF CARD9. Notably, R70W CARD9 also exerted negative effects on NF-κB activation by CARD10, CARD11, and CARD14. Consistent with the NF-κB results, the R70W mutation prevented GOF CARD9 to pull down the signalosome partner proteins BCL10 and MALT1. This reflected into drastic reduction of BCL10 filamentous assemblies in a cellular context. Indeed, structural analysis revealed that position R70 in CARD9 maps at the putative interface between successive CARD domains in CARD9 filaments.
The R70W mutation in CARD9 prevents NF-κB activation by inhibiting productive interactions with downstream BCL10 and MALT1, necessary for assembly of the filamentous CARD9-BCL10-MALT1 signalosome.
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