We analyzed the effect of time to initiation of antiretroviral therapy (ART) after diagnosis on the probability of HIV-1 transmission events (HIV-TE) in naïve HIV-1-infected men having sex with men ...(MSM).
Mathematical model.
We used discrete event simulation modeling to estimate the probability of HIV-TE in the first 8 weeks after ART initiation; we varied ART initiation from D0 to D28 after simulated "diagnosis". The model inputs used sexual behavior parameters from the MSM population of the START trial, and transmission rates per-sex act and HIV-1 RNA from recent meta-analyses. HIV-1 RNA decay curves were modeled from the databases of Single (efavirenz EFV v dolutegravir DTG), Spring-2 (raltegravir RAL v DTG), and Flamingo (darunavir/ritonavir DRVr v DTG) trials.
We found that the number of HIV-TE per index patient in the first 8 weeks after ART initiation increased linearly for same-day ART to initiation on day 28. Small but statistically significant advantages of integrase strand transfer inhibitors (INSTI) over EFV and DRVr were found.
Rapid, if not same-day initiation of INSTI-based ART to newly diagnosed HIV-infected MSM has the potential for substantial public health benefits related to decreases in HIV-TE.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Initiation of antiretroviral therapy (ART) for HIV infection using regimens that include integrase strand transfer inhibitors (INSTIs) is associated with a faster decline in HIV-1 RNA than what is ...observed with regimens that are anchored by other ART drug classes. We compared the impact of ART regimens that include dolutegravir (DTG), raltegravir (RAL), efavirenz (EFV), or darunavir/ritonavir (DRV/r), in treatment naïve men who have sex with men (MSM) on the probability of HIV-1 sexual transmission events (HIV-TE).
Mathematical model.
We used discrete event simulation modeling to estimate HIV-TE during the first 8 weeks after initiation of ART. HIV-1 RNA decay in men was modeled from the databases of three clinical trials: Single (DTG vs. EFV), Spring-2 (DTG vs. RAL) and Flamingo (DTG vs. DRV/r).
All regimens substantially reduced the number of HIV-TE compared to no treatment. DTG led to fewer HIV-TE than its comparator in each of the three trials: 22.72% fewer transmissions than EFV; 0.52% fewer transmissions than RAL; and 38.67% fewer transmissions than DRV/r. The number of patients needed to treat with DTG to prevent one transmission event instead of comparator was 48 vs EFV, 2,194 vs RAL, and 31 vs DRV/r.
Unsurprisingly, this mathematical model showed that all regimens reduced HIV-TE compared to no treatment. The results also suggest that that initial use of INSTIs, by virtue of their superior viral decay kinetics, have the potential to reduce HIV-1 horizontal transmission following initiation of ART in naïve MSM.
ClinicalTrials.gov NCT03183154.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This is a case of a man aged 40 years with a past medical history of smoking, hypertension, polycythemia vera, intellectual disability, and schizophrenia who presented with generalized headaches, ...progressive loss of balance, and visual disturbance for 1 month.
Head computed tomography and magnetic resonance imaging revealed a right cerebellar hematoma associated to heterogenous lesion with cystic components and flow-voids in the right cerebellar hemisphere. A ventriculoperitoneal shunt was placed with partial improvement of symptoms. Further vascular studies confirmed presence of a vascular nidus with significant arteriovenous shunting. The patient later required intervention for cerebellar arteriovenous malformation (AVM) removal. Microscopic evaluation of the lesion showed the AVM nidus, as well as large, vacuolated stromal cells and numerous thin-walled vessels. Immunostaining with inhibin and S-100 highlighted the stromal cells with numerous lipid-containing vacuoles. The earlier mentioned findings were consistent with the diagnosis of an AVM with coexistent hemangioblastoma of the right cerebellar hemisphere.
Coexistence of hemangioblastomas and AVMs are extremely rare, and only 3 cases have been reported previously in the literature.
Hepatic steatosis is a common condition found in the liver of hepatitis C virus (HCV)-infected patients, contributing to more severe forms of liver disease. In addition, the human immunodeficiency ...virus (HIV) may accelerate this process. Alternatively, several immune checkpoint proteins have been reported to be upregulated and correlated with disease progression during HCV and HIV infections. In steatosis, a detrimental immune system activation has been established; however, the role of the immune checkpoints has not been addressed so far. Thus, this study aimed to evaluate the association between plasma immune checkpoint proteins at baseline (before antiviral therapy) with hepatic steatosis index (HSI) increase at the end of follow-up (∼ five years after sustained virologic response (SVR)). We performed a multicenter retrospective study in 62 patients coinfected with HIV/HCV who started antiviral therapy. Immune checkpoint proteins were analyzed at baseline using a Luminex 200TM analyzer. The statistical association analysis was carried out using Generalized Linear Models (GLM) and Partial Least Squares Discriminant Analysis (PLS-DA). Fifty-three percent of the patients showed HSI increase from baseline to the end of follow-up. Higher immune checkpoint protein levels of BTLA, CD137(4–1BB), CD80, GITR, LAG-3, and PD-L1 before HCV therapy were associated with a long-term increase in HSI after successful HCV therapy, suggesting a potential predictive role for early detection of progression towards steatosis in HIV/HCV-coinfected patients.
Shorter duration of symptoms before remdesivir has been associated with better outcomes. Our goal was to evaluate variables associated with the need of ICU admission in a cohort of hospitalized ...patients for COVID-19 under remdesivir including the period from symptoms onset to remdesivir.
We conducted a retrospective multicentric study analysing all patients admitted with COVID-19 in 9 Spanish hospitals who received treatment with remdesivir in October 2020. The main outcome was the need of ICU admission after 24 h of the first dose of remdesivir.
In our cohort of 497 patients, the median of days from symptom onset to remdesivir was 5 days, and 70 of them (14.1%) were later admitted into ICU. The clinical outcomes associated with ICU admission were days from symptoms onset (5 vs. 6; p = 0.023), clinical signs of severe disease (respiratory rate, neutrophil count, ferritin levels and very-high mortality rate in SEIMC-Score) and the use of corticosteroids and anti-inflammatory drugs before ICU. The only variable significatively associated with risk reduction in the Cox-regression analyses was ≤ 5 days from symptoms onset to RDV (HR: 0.54, CI95%: 0.31-0.92; p = 0.024).
For patients admitted to the hospital with COVID-19, the prescription of remdesivir within 5 days from symptoms onset diminishes the need of ICU admission.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
During the past decade, liposomal amphotericin B has been used with increasing frequency to treat visceral leishmaniasis (VL). The World Health Organization convened a workshop to review current ...knowledge and to develop guidelines for liposomal amphotericin B use for VL. In Europe, liposomal amphotericin B is widely used to treat VL. In Africa and Asia, the VL disease burden is high and drug access is poor; liposomal amphotericin B is available only through preferential pricing for nonprofit groups in East Africa. Clinical trials and experience demonstrate high efficacy and low toxicity for liposomal amphotericin B (total dose, 20 mg/kg) in immunocompetent patients with VL. Combination trials in areas with antileishmanial drug resistance, and treatment and secondary prophylaxis trials in VL-human immunodeficiency virus-coinfected patients, are important to safeguard the current armamentarium and to optimize regimens. The public health community should work to broaden access to preferential liposomal amphotericin B pricing by public sector VL treatment programs.
The incidence of stroke in human immunodeficiency virus (HIV)-infected individuals has been well analyzed in recent epidemiological studies. However, little is known about the specific contribution ...of hepatitis C virus (HCV) infection to stroke among HIV-infected individuals. The aims of this study were to analyze trends in the incidence rates of stroke in HIV-infected individuals during the combination antiretroviral (cART) era in Spain and to categorize them by the presence or absence of HCV coinfection. We analyzed hospital discharges with a diagnosis of stroke in Spain according to ICD-9-CM during 1997-2013. The study period was divided into four calendar periods (1997-1999, 2000-2003, 2004-2007, and 2008-2013). Patients were classified according to HCV serology. The number of HIV-infected patients was estimated based on data from the National Centre of Epidemiology. We calculated incidence rates (events per 10,000 patient-years) and in-hospital case fatality rates (CFR). The incidence of hemorrhagic stroke (HS) decreased in HIV-monoinfected patients (15.8 1997-1999 to 6.5 2008-2013; P<0.001) and increased in HIV/HCV-coinfected patients (1.3 1997-1999 to 5.5 2008-2013; P<0.001). The incidence of ischemic stroke (IS) decreased in HIV-monoinfected patients (27.4 1997-1999 to 21.7 2008-2013; P = 0.005) and increased in HIV/HCV-coinfected patients (1.8 1997-1999 to 11.9 2008-2013; P<0.001). The CFR was 3.3 times higher for HS than for IS for the whole study period. The CFR of HS in HIV-monoinfected patients decreased significantly (47.4% 1997-1999 to 30.6% 2008-2013; P = 0.010) but did not change significantly among HIV/HCV-coinfected patients (41.4% 1997-1999 to 44.7% 2008-2013; P = 0.784). The CFR of IS in the whole HIV-infected population decreased significantly (14.6% 1997-1999 to 10.9% 2008-2013; P = 0.034), although no significant differences were found when each group was analyzed separately. In conclusion, after the introduction of cART, HS and IS rates decreased in HIV-monoinfected individuals, but increased steadily in HIV/HCV-coinfected individuals.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The objective of our study was to assess the prevalence and incidence of HEV in people living with HIV (PLWH) in a Spanish national cohort.
Retrospective longitudinal study including PLWH recruited ...in the cohort of adult HIV-infected patients of the AIDS Research Network in follow-up at 28 Spanish hospitals with available serum samples in 2014 and 2015. All samples were tested for HEV IgG, IgM, and RNA. Samples with detectable HEV viral loads were genotyped. Prevalence and incidence of HEV infection were calculated.
The study sample comprised 845 PLWH. At baseline, 101 patients were positive for HEV IgG antibodies (11.9%), none had HEV IgM antibodies, and 2 presented detectable HEV RNA (0.23%). Forty-two seroconverted for IgG, supposing a cumulative incidence of 5.7%. One subject was positive for IgM (0.13%), and 2 showed detectable HEV RNA (0.27%). One case was infected by the emergent HEV genotype 3ra.
Our study identifies one case of HEV 3ra genotype infection, the main host of which is rabbit, showing a potential zoonotic role of this emerging genotype in Spain.
We report on the first autopsy performed on a neonate with congenital Zika syndrome in Puerto Rico. A term male was born to a mother with confirmed Zika virus infection; he had a prenatal diagnosis ...of microcephaly and multiple cerebral calcifications, among other anomalies, and a normal male karyotype (determined by amniocentesis). He required neonatal resuscitation at birth and died at 2 days ofage. At autopsy, his head circumference was only 1.5 standard deviations below the mean, not fulfilling the criteria for microcephaly. He presented scissor legs, clenched and hyperflexed hands, and multiple contractures (arthrogryposis). The central nervous system findings were consistent with Zika encephalopathy: ventriculomegaly, lissencephaly, and severe encephalic degeneration with numerous dystrophic calcifications, among other findings. These anomalies were most likely secondary to congenital ZV infection. Although prenatally diagnosed with microcephaly, he did not fulfill the criteria after birth, which fact indicates the need for reassessment of the definition of microcephaly as it applies to patients exposed prenatally to the ZV.
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