Neuroprotective Potential of Bacopa monnieri: Modulation of Inflammatory Signals.

BACKGROUND: To date, much evidence has shown the increased interest in natural molecules and traditional herbal medicine as alternative bioactive compounds to fight many inflammatory conditions, both in relation to immunomodulation and in terms of their wound healing potential. Bacopa monnieri is a herb that is used in the Ayurvedic medicine tradition for its anti-inflammatory activity. OBJECTIVE: In this study, we evaluate the anti-inflammatory and regenerative properties of the Bacopa monnieri extract (BME) in vitro model of neuroinflammation. METHODS: Neuronal SH-SY5Y cells were stimulated with TNFα and IFNγ and used to evaluate the effect of BME on cell viability, cytotoxicity, cytokine gene expression, and healing rate. RESULTS: Our results showed that BME protects against the Okadaic acid-induced cytotoxicity in SH-SY5Y cells. Moreover, in TNFα and IFNγ primed cells, BME reduces IL-1ß, IL-6, COX-2, and iNOS, mitigates the mechanical trauma injury-induced damage, and accelerates the healing of wounds. CONCLUSION: This study indicates that BME might become a promising candidate for the treatment of neuroinflammation.

Atypical Sites of Lymphadenopathy after Anti-COVID-19 Vaccine: Ultrasound Features.

Background and Objectives: Several authors have reported cervical and axillary lymphadenopathies as known side effects following anti-COVID-19 vaccine administration. Few data are available about atypical locations of post-anti-COVID-19 vaccine lymphadenopathy. In this investigation, we evaluated the incidence and prevalence of postvaccine lymphadenopathy ultrasound (US) features in atypical sites. Materials and Methods: In this retrospective study, we retrospectively selected 64 patients on whom US was performed between January and October 2021 due to COVID-19 vaccine-related lymphadenopathy. We investigated lymph node anatomical sites, presence, number, size, shape, cortical profile, hilum outline, superb microvascular imaging (SMI), and elastosonography. Results: A total of 170 nodes were assessed. Atypical location was demonstrated in 5/64 patients (7.8%). In all these cases, atypical nodal involvement was associated with lymphadenopathy in a typical site (axillary, supraclavicular) ipsilateral to the vaccine injection site. Two patients presented lymphadenopathy in the infraclavicular station (3.1%), one in the pectoralis major muscle (1.6%), one in the left arm (1.6%), and one in the nuchal site (1.6%). All lymphadenopathies were oval-shaped, with a median size of 0.9 ± 0.2 cm. US features included a symmetric cortex with hilum evidence (4/6, 60%), vascular signal at SMI in both the hilar region and periphery of lymph node (5/6, 83.3%), and a US elastography pattern resembling that of adjacent tissues (5/6, 83.3%). The median age of patients with lymphadenopathies in an atypical location was 23 years. The main type of vaccine associated with lymph node appearance in atypical sites was Moderna's mRNA-1273 (60% of patients, 4/6 lymph nodes accounting for 66.7% among atypical locations). Conclusion: Post-COVID-19 vaccine administration lymphadenopathies in an atypical location represent an intense immune response to antigenic stimuli and they may show alarming US traits superimposed on malignant pathologies, which may complicate the patient's clinical and diagnostic pathway. Despite no distinctive US features between reactive post-COVID-19 vaccination and malignant lymph nodes being available, careful examination of atypical lymph node locations associated with accurate knowledge of patients' clinical background and delay of US exam to four to six weeks after vaccine injection should be considered.

Iron Dyshomeostasis in COVID-19: Biomarkers Reveal a Functional Link to 5-Lipoxygenase Activation.

Coronavirus disease 2019 (COVID-19) is characterized by a broad spectrum of clinical symptoms. After acute infection, some subjects develop a post-COVID-19 syndrome known as long-COVID. This study aims to recognize the molecular and functional mechanisms that occur in COVID-19 and long-COVID patients and identify useful biomarkers for the management of patients with COVID-19 and long-COVID. Here, we profiled the response to COVID-19 by performing a proteomic analysis of lymphocytes isolated from patients. We identified significant changes in proteins involved in iron metabolism using different biochemical analyses, considering ceruloplasmin (Cp), transferrin (Tf), hemopexin (HPX), lipocalin 2 (LCN2), and superoxide dismutase 1 (SOD1). Moreover, our results show an activation of 5-lipoxygenase (5-LOX) in COVID-19 and in long-COVID possibly through an iron-dependent post-translational mechanism. Furthermore, this work defines leukotriene B4 (LTB4) and lipocalin 2 (LCN2) as possible markers of COVID-19 and long-COVID and suggests novel opportunities for prevention and treatment.

Pidotimod and Immunological Activation in Individuals Infected with HIV.

BACKGROUND: The improvements in HIV infection therapy and the large availability of antiretroviral drugs have led to an increased survival among HIV infected people, and simultaneously to a raised morbidity and mortality due to not-AIDS-related events in this group compared to the general population. An increased systemic inflammation and a persistent immune activation play a pivotal role in determining high rates of non-AIDS comorbidities. In the last years, many natural or synthetic immunomodulatory molecules acting by different mechanisms have been conceived. Pidotimod is a synthetic dipeptide molecule showing immunomodulatory properties. The aim of this pilot study was to evaluate the effects of Pidotimod supplementation on residual inflammation in HIV infected population. METHODS: Forty HIV positive individuals under cART were enrolled: 30 were treated with Pidotimod supplementation (study group) and 10 served as control group (without Pidotimod supplementation). For all participants, Cystatin C, PCR, ESR, microalbuminuria, TNF-α, INF-γ, IL-4, IL-10, IL1ß, IL-18 and IL-2 were measured at enrolment (T0), 4 weeks after of Pidotimod supplementation (T1), and 4 weeks after completing supplementation (T2). RESULTS: In HIV positive participants treated with Pidotimod, the evaluation of cytokine levels showed that IL-10, IFN gamma, and IL-4 were significantly higher at enrolment compared to the control group. The increase under Pidotimod treatment persisted after supplementation suspension, while the pro-inflammatory cytokines levels were reduced. Salivary IgA also increased during 4 weeks of supplementation and persisted at 4 weeks after completing supplementation. On the other hand, the Cystatin C and microalbuminuria levels decreased over time, at a greater extent the Cystatin C serum levels. CONCLUSION: The study findings showed that the HIV population receiving Pidotimod achieved a rebalancing of pro-inflammatory and anti-inflammatory cytokines as well as a significant reduction in cystatin C levels. The treatment further allowed for an increase in salivary IgA levels at all the analyzed times, as a secondary event to a remodulation of the immunological status obtained with pidotimod. This approach could represent a new way to design new intervention strategies aimed at improving the persistent immune activation status in the virologically suppressed HIV population.

Circulating extracellular vesicles as new inflammation marker in HIV infection.

BACKGROUND: Extracellular vesicles, released by cell pullulation, are surrounded by a phospholipid bilayer and carry proteins as well and genetic material. It has been shown that extracellular vesicles mediate intercellular communication in several conditions, such as inflammation, immunodeficiency, tumor growth, and viral infections. Here, we analyzed circulating levels of extracellular vesicles in order to clarify their role in chronic inflammation mechanisms characterizing HIV patients. METHODS: We analyzed and subtyped circulating levels of extracellular vesicles, through a recently developed flow cytometry method. In detail, endothelial-derived extracellular vesicles (CD31+/CD41a-/CD45-, EMVs), extracellular vesicles stemming from leukocytes (CD45+, LMVs) and platelets (CD41a+/CD31+) were identified and enumerated. Moreover, we analyzed the extracellular vesicle protein cargo with proteomic analysis. RESULTS: Circulating levels of total extracellular vesicles, EMVs and LMVs were significantly lower in the HIV+ patients than in healthy subjects, whereas platelet-derived extracellular vesicles resulted higher in patients than in the healthy population. Proteomic analysis showed the upregulation of gammaIFN and IL1α, and down-regulation of OSM, NF-kB, LIF, and RXRA signaling resulted activated in this patients. CONCLUSION: These data demonstrate, for the first time that HIV infection induces the production of extracellular vesicles containing mediators that possibly feed the chronic inflammation and the viral replication. These two effects are connected as the inflammation itself induces the viral replication. We, therefore, hypothesize that HIV infection inhibits the production of extracellular vesicles that carry anti-inflammatory molecules.

Prevalence and predictors of malignancies in HIV patients: results of a retrospective multicentric Italian cohort.

We report the sharp reduction in the incidence of AIDS defining cancers in a multicentric, retrospective study carried out since 1991 and involving six Infectious Diseases Units spread across Italy. However, due to the parallel increase in non-AIDS defining cancers, cancer incidence was not reduced. Focusing on predictors of death in HIV-positive patients with neoplastic disease, multivariate models revealed that males as well as drug abusers were independently associated with a poor clinical outcome.

The impact of homocysteine, B12, and D vitamins levels on functional neurocognitive performance in HIV-positive subjects.

BACKGROUND: The correlation among high levels of total homocysteine, low levels of B12vitamin, and neurocognitive impairment in HIV negative patients has been the main research topic in some of the latest reviews. The aim of this study was to examine if the alteration of homocysteine, B12 vitamin, and D vitamins plasma levels was present in HIV-positive, and their relationship with cognitive function. METHODS: 57 HIV infected were enrolled and underwent the serum measurement of homocysteine, B12, and D vitamins. The neurocognitive evaluation investigated 5 cognitive domains, through a neuropsychological battery test RESULTS: Homocysteine was found to be elevated in 70.2% of cases, B12 vitamin mean levels were low in 8 participants (14.0%), and 8 patients had D hypovitaminosis (14.0%). Abnormal homocysteine levels were associated with worse performance of verbal fluency (p = 0.003) and worse executive function (Stroop E test p = 0.040). The 25-OH D hypovitaminosis was associated with worse performances in executive functions in three different tests: Stroop E (p = 0.049), Trail B (p = 0.035), and Wais Digit Span (p = 0.042). Pathological levels of B12 Vitamin were also associated to worse performances in executive functions (Trail B Test and Wais Digit Span respectively p = 0.002 and 0.029) and with a lower speed in psychomotor processing (Peg Board Test on dominant hand, p = 0.014). CONCLUSIONS: In this study serum homocysteine, B12, and D vitamin levels are associated with neurocognitive performances; in fact low performance neurocognitive was correlated with hyperhomocysteine and low B12vitamin, and D vitamin levels. Evidence of the alteration of these parameters could facilitate the early identification of a neurocognitive impairment.

Use of quantitative ultrasound as bone mineral density evaluation in an Italian female population living with HIV: A real-life experience.

This is a multicenter cross-sectional study where we aimed to detect the rate of osteopenia/osteoporosis in an HIV female population (WLWHIV) by means of "heel quantitative ultrasound" (QUS) measurement. We enrolled 273 patients, mean age 48.1 years, 36% menopausal, 96% on combination antiretroviral therapy (cART). Calcaneal measure of bone mass index by QUS revealed osteopenia and osteoporosis in 76 (27.8%) and 16 (5.9%) WLWHIV. Our data underline the correlation between low QUS parameters and traditional risk factors for osteoporosis rather than with cART exposure, thus suggesting the crucial importance of detection and correction of traditional risk factors for osteoporosis in WLWHIV.

Prevalence of anal, oral, penile and urethral Human Papillomavirus in HIV infected and HIV uninfected men who have sex with men.

Aims of the study were to evaluate Human Papillomavirus (HPV) and type-specific prevalence in four anatomical sites in HIV infected men who have sex with men (MSM) compared with HIV uninfected MSM. Participants were recruited among the attendees of Infectious Diseases Clinics in Central Italy. A trained medical practitioner collected by interview sociodemographic data and information on medical history, sexual behavior, and drug use. Swabs from anal canal, oral cavity, urethral mucosa, and coronal sulcus were tested for HPV DNA and genotyping. Ninety MSM were enrolled, 45 subjects within each group. Overall, 48.9% MSM were HPV positive and prevalence was higher in HIV infected men (60.0% vs 37.8%, P = 0.035). HPV at multiple anatomic sites occurred in 59.1% MSM, with 34.1% and 22.7% at two and three sites, respectively. Prevalence of anal, coronal sulcus, oral, and urethral HPV was 96.3%, 37%, 21.6%, and 18.5% in HIV infected MSM, and 70.6%, 70.6%, 29.4%, and 23.5% among HIV uninfected. A similar proportion of HIV infected and uninfected MSM (59.2% and 58.8%) carried at least one high-risk genotype. Prevalence of types covered by nonavalent vaccine was 77.8% in HIV infected compared with 82.3% in HIV uninfected MSM. HPV 58 and 16 were mostly detected in HIV positive (43.7% and 31.2%) and negative MSM (50.0% and 40.0%). HPV detection rate underlined the high vulnerability of MSM to acquire multisite infections, characterized by various genotype combinations. Since nonavalent vaccine could have prevented 80% of HPV infections, study findings support the implementation of vaccination programs among MSM.

Prevalence of HPV infection among HIV-positive and HIV-negative women in Central/Eastern Italy: Strategies of prevention.

The present cross-sectional-study aimed to determine the prevalence of human papillomavirus (HPV)-genotypes among human immunodeficiency virus (HIV)-positive and -negative women in Central/Eastern Italy, and to identify the optimal strategies for effective HPV-prevention in each group. A representative sample of HIV-negative (150/200) and -positive (50/200) women, who underwent cervico-vaginal-swabbing. Swabs were analysed for a cytological screening and for a HPV-DNA-genotyping-test. A total of 66/200 swabs resulted HPV-positive. The overall HPV-prevalence was 33% with a higher prevalence in the HIV-positive-group (48%) compared with the HIV-negative-group (28%). The most frequent genotypes were: 16, 31, 52, 58, 66, 73 and 89. Furthermore, the prevalence of specific genotypes was different in each group. The results of the present study indicate that HIV infection appears to be an independent risk factor for HPV-infection. In addition, HPV-infection is more common and more likely to persist in HIV-positive compared with in HIV-negative women. The optimal way to counteract HPV infection is through primary prevention. The stage of immunity (cluster of differentiation 4-level) at the time of the HPV-screening is one of the most important parameters for detection of susceptibility to HPV-infection and to evaluate the response to the HPV-vaccine in HIV-positive women. It may be used to determine the sub-group of HIV-positive women that are more prone to HPV-infections or that exhibit a partial response to the HPV-vaccine. At present, a novel type of vaccine with 9-genotypes is available and in the near future, it may serve an essential role in the prevention of HPV infections.

Cytokines, Hepatic Fibrosis, and Antiretroviral Therapy Role in Neurocognitive Disorders HIV Related.

The HIV may trigger a process of neuronal loss and axonal degeneration throughout the brain, which is carried on by the immune system releasing of proinflammatory cytokines, so that chronic inflammation associated with dysregulated innate immune response, glial cell dysfunction, and adverse antiretroviral therapy (ART) effect play an important role causing milder HIV-associated neurocognitive disorders or asymptomatic neurocognitive impairment. All patients have been tested for neurocognitive functioning through a comprehensive, five-domain neuropsychological battery performed in the study. Human cytokine (interleukin [IL]-6, IL-8, IL-18, and tumor necrosis factor [TNF]-α) and brain-derived neurotrophic factor serum levels were quantified using ELISAs, and the hepatic fibrosis was estimated using the noninvasive Fibrosis 4 (FIB-4) score. The study showed a group of 40 HIV-infected individuals and it was observed that almost 40% of HIV+ individuals, even if clinically asymptomatic, displayed some degree of neurocognitive dysfunction, compared to normative performance standards, at least in two cognitive areas. The functions affected the most were memory, attention, executive function, and psychomotor processing speed. Three cytokines (IL-6, IL-8, and IL-18) to be significantly linked to test results in specific neurocognitive domain were found. Treatments with nucleoside reverse transcriptase inhibitor plus non-nucleoside reverse transcriptase inhibitor alone were instead associated with poor neurocognitive outcome, especially in verbal fluency, fine motility, and Zung Depression Scale. Elevated value of FIB-4 score showed an opposite connection with cognitive performance as well, underlining the direct association between hepatic steatosis and neurocognitive deficit. The cytokine panel and the FIB-4 score can predict presence or worsening of neurocognitive functions in HIV-infected individuals. An ART switch can be suggested according to the neurocognitive domain involved the most, advising a therapy with protease inhibitors or/and integrase inhibitors to improve fluency, executive functions, and to prevent depression.

High prevalence of human papillomavirus type 58 in HIV infected men who have sex with men: A preliminary report in Central Italy.

Human papillomavirus (HPV) infection and type-specific prevalence at anal, oral, coronal sulcus, and urethral mucosa in fifty HIV positive men having sex with men (MSM) were evaluated; patients were enrolled in a non-metropolitan area of Central Italy. Clinical and socio-demographic information, drug, and sexual behaviors were obtained for each participant. HPV was detected by PCR from an overall of 200 specimens, and genotyping was performed by both Restriction Fragment Length Polymorphism analysis and sequencing. HPV DNA was found in 60.0% (n = 30) of HIV positive MSM, and prevalence was higher at anal canal (n = 28, 56.0%) compared to all the other anatomical sites (χ(2) test P < 0.01) of coronal sulcus (n = 11, 22.0%), oral (n = 8, 16.0%), and urethral mucosa (n = 5, 10.0%). We found 63.3% (n = 19) of MSM with at least one high-risk genotype, and HPV-58 was more frequently detected (n = 9, 47.4%) respect to HPV-16 (n = 6, 31.6%). This is the first report on HPV detected at four anatomical sites involved in sexual practices in HIV positive MSM. We found an unusual distribution of oncogenic genotypes with an exceeding prevalence of HPV-58 respect to HPV-16. Hence, the recently licensed nonavalent vaccine should be suitable to prevent a larger number of infections caused by potentially emerging high-risk genotypes.

Effect of Probiotic Supplement on Cytokine Levels in HIV-Infected Individuals: A Preliminary Study.

UNLABELLED: Inflammation persists in patients infected with HIV. Reduction of inflammatory cytokines and microbial translocation might be one way that this could be managed. PURPOSE: The anti-inflammatory properties of certain probiotic strains prompted us to investigate whether a probiotic could reduce the inflammatory index of HIV-infected patients. METHODS: The study involved 30 HIV+ males on antiretroviral therapy, who were given one bottle of fermented milk Yakult Light® containing Lactobacillus casei Shirota (LcS) twice a day for four weeks. RESULTS: The probiotic LcS was associated with an increase of T lymphocytes and a significant increase of CD56+ cells (p = 0.04). There was also a significant decrease of mRNA levels of TGFß, IL-10 and IL-12 (p < 0.001) and IL-1ß expression (p < 0.001) and an increase of serum IL-23 (p = 0.03). In addition, decreased inflammation and cardiovascular risk were observed, as shown by a reduction of cystatin C (p < 0.001). CONCLUSIONS: These data provide preliminary evidence that probiotic supplementation may modulate certain immunological parameters and some of the cytokines that were analyzed. Thus, we propose that LcS may be an inexpensive and practical strategy to support the immune function of HIV+ patients.

Prevalence and predictors of malignancies in a polycentric cohort of HIV patients from Italy.

INTRODUCTION: HIV infected patients have a higher risk of developing cancer than the general population. Kaposi's sarcoma, non-Hodgkin's lymphoma, primary CNS lymphoma and invasive cervical cancers are considered as AIDS defining [1]. An increased incidence in recent years has been reported also for other malignancies after the introduction of cART [2,3]. MATERIALS AND METHODS: We performed a retrospective multicentric evaluation of all HIV infected patients with both AIDS and non-AIDS defining neoplasms at six Infectious Disease Units spread throughout Italy since 1991 through 2013. Cases were compared with equal number of controls without neoplasia followed at the same institutions, matched for length of HIV infection. RESULTS: Since 1991, 339 consecutive cases of malignancy were collected from the six convening centres, including approximately an equal proportion of AIDS (51.2%) and non-AIDS defining tumours. Mean prevalence of tumours among centres was 8.3% (r. 6.1%-9.6%). Mean age at tumour diagnosis was significantly lower than in controls (42.6±11.0 vs 46.8±10.6 years, respectively, p<0.0001). As to risk factors for HIV infection, approximately 1/4 (26.1%) of patients were drug abusers, in equal proportion as in controls. A remarkable higher proportion of cancer patients had CD4 T-cell counts <200 c/mmc at time of diagnosis (45.2% vs 13.3%, p<0.0001). Seventy percent of tumours occurred in males; 52.8% of tumour patients were diagnosed with AIDS before and 19.0% at the time of tumour diagnosis. Ninety (28.1%) tumour patients were dead at the time of data collection, a much higher proportion than among cases (12.9%, p<0.0001). Deaths among non-AIDS (20.8%) and AIDS defining tumour patients (35.0%) were significantly different (p=0.005). Predictors of AIDS defining tumours at the time of data collection were: male sex (57.9% vs 40.6%, p=0.004), CD4 T-cell counts <200 c/mmc (63.6% vs 44.1%, p<0.0001), whereas being cART treated at the time of tumour diagnosis was protective (38.0% vs 68.0%, p<0.0001). In the final multivariate model of logistic regression, male sex (OR=2.0, p=0.03) and not being cART treated (OR=2.5, p=0.001) held as independent predictors. CONCLUSIONS: Our retrospection revealed a considerably high proportion of non-AIDS defining tumours, apparently at rise in recent years. We registered high prevalence of tumours in each centre. Absence of cART seemed related with AIDS defining tumours: once more prevention of late presentation appeared the way to avoid worse prognosis in this setting.

Improved metabolic profile after switch to darunavir/ritonavir in HIV positive patients previously on protease inhibitor therapy.

Metabolic abnormalities associated with cumulative exposure to antiretroviral therapy have been linked to an increased risk of myocardial infarction in HIV positive individuals. The aim of this study was to evaluate whether the switch from lopinavir/ritonavir (LPV/r) or fosamprenavir/ritonavir (FPV/r) to darunavir/ritonavir (DRV/r) is able to improve the lipid profile. A total of 13 Caucasian subjects (7 from LPV/r and 6 from FPV/r) were enrolled in the study and received DRV/r at the dose of 800/100 mg, without change in their NRTI backbone. Viro-immunological parameters, triglycerides (TGs), total cholesterol (TCh), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, fasting glucose, HOMA-IR, indexes of hepatic and renal functionality, microalbuminuria and cystatin C were measured at baseline (T0), 3 months (T3), 6 months (T6), and 12 months (T12). The switch to DRV/r reduced levels of TCh, LDL, and TGs at T3. Similar improvements were confirmed further at T6 and at T12. A 14% increase in CD4+ count cells (P < 0.05) was observed. Serum cystatin C values showed a statistically significant decrease. After 12 months of switching to DRV/r from LPV/r or FPV/r, patients infected with HIV with TGs above 200 mg/dl, showed a 49% decrease in TGs, along with a 16% reduction of LDL and 19% reduction of TCh. Switching to DRV/r also improved immunological parameters, such as CD4+ cells count and cystatin C plasmatic levels, which may translate into a reduction of the cardiovascular risk. In conclusion, a switch to DRV/r should be considered in those HIV positive patients undergoing antiretroviral therapy, who also present abnormal lipid profiles.

Effect of antiviral therapy on pro-angiogenic hematopoietic and endothelial progenitor cells in HIV-infected people.

BACKGROUND: HIV infection is an independent risk factor for cardiovascular disease. HIV-sustained impairment of endothelial progenitor cells (EPCs) could contribute to this process, so that it is important to assess whether antiviral therapy (ART) is able to revert these abnormalities. METHODS: We quantified in 21 naïves and 34 treated patients two functionally distinct clonogenic progenitors which have been acknowledged important for vascular repair: the hematopoietic progenitor colony forming unit - endothelial cells (CFU-EC) and the true endothelial progenitor, the endothelial colony forming cells (ECFC). We correlated results obtained with conventional vascular risk factors and with HIV-related parameters. RESULTS: We found that these progenitors behaved differently in naive and treated patients. In particular, CFU-EC level was significantly low in all naive patients and slowly recovered during ART. In contrast, the ECFC level was abnormally high in naive patients while it decreased upon ART. The CFU-EC level was related to conventional cardiovascular risk factors, as reported in general population, but also to inflammatory indexes and CD4 cell count. In contrast, the ECFC number was exclusively related to viral replication activity and to CD4 cell count. CONCLUSIONS: In HIV-infected people, the levels of CFU-EC and ECFC are related to classical cardiovascular risk factors but, in addition, they are also significantly influenced by the infection itself and by antiviral therapy.

Short communication: proangiogenic hematopoietic cells in acute HIV infection.

Chronic HIV infection induces significant changes in the trafficking of circulating endothelial progenitor cells (EPCs). Specifically, it causes marked depletion of proangiogenic hematopoietic cells, the so-called colony-forming unit-endothelial cells (CFU-ECs). In this study we evaluated CFU-ECs in two subjects with acute HIV infection. We found that both patients already had a low CFU-EC level at the time of diagnosis. Nevertheless, after 6 months of antiretroviral therapy, the CFU-EC concentration reverted to normal values in both cases. HIV significantly depletes the CFU-EC compartment even in the early phase of infection, while 6-month therapy appears to be able to restore it.

Induction with ribavirin in a relapsing patient with chronic HCV hepatitis

In this case, a new possible strategy for treatment of hepatitis C virus (HCV) relapsing patients is described. The target of anti-HCV therapy is sustained viral response, but strategies for improving sustained viral response in relapsing patients would be useful, and ribavirin is crucial for obtaining viral response. Six weeks of induction therapy with ribavirin were used to improve efficacy of standard combined antiviral therapy in a patient relapsing to standard therapy. In the present case, the patient had undergone a retreatment with the same regimen with the exception of the six-week induction period with ribavirin. Use of induction therapy with ribavirin in this case has allowed for a sustained viral response without prolonging the interferon exposure time in retreatment.