Assessing ChatGPT's Potential in HIV Prevention Communication: A Comprehensive Evaluation of Accuracy, Completeness, and Inclusivity.

With the advancement of artificial intelligence(AI), platforms like ChatGPT have gained traction in different fields, including Medicine. This study aims to evaluate the potential of ChatGPT in addressing questions related to HIV prevention and to assess its accuracy, completeness, and inclusivity. A team consisting of 15 physicians, six members from HIV communities, and three experts in gender and queer studies designed an assessment of ChatGPT. Queries were categorized into five thematic groups: general HIV information, behaviors increasing HIV acquisition risk, HIV and pregnancy, HIV testing, and the prophylaxis use. A team of medical doctors was in charge of developing questions to be submitted to ChatGPT. The other members critically assessed the generated responses regarding level of expertise, accuracy, completeness, and inclusivity. The median accuracy score was 5.5 out of 6, with 88.4% of responses achieving a score ≥ 5. Completeness had a median of 3 out of 3, while the median for inclusivity was 2 out of 3. Some thematic groups, like behaviors associated with HIV transmission and prophylaxis, exhibited higher accuracy, indicating variable performance across different topics. Issues of inclusivity were identified, notably the use of outdated terms and a lack of representation for some communities. ChatGPT demonstrates significant potential in providing accurate information on HIV-related topics. However, while responses were often scientifically accurate, they sometimes lacked the socio-political context and inclusivity essential for effective health communication. This underlines the importance of aligning AI-driven platforms with contemporary health communication strategies and ensuring the balance of accuracy and inclusivity.

Cutting Edge: Hyperinflammatory Monocytes Expressing CD56 Abound in Severe COVID-19 Patients.

Proinflammatory monocytes play a preponderant role in the development of a cytokine storm causing fatal consequences in coronavirus disease 2019 (COVID-19) patients, highlighting the importance of analyzing in more detail monocyte distribution in these patients. In this study, we identified an atypical monocyte subpopulation expressing CD56 molecules that showed a low level of HLA-DR and high level of l-selectin. They released higher amounts of TNF-α and IL-6 and expressed genes associated with an excessive inflammatory process. Remarkably, the frequency of CD56+ monocytes inversely correlated with that of CD16+ monocytes and a high CD56+/CD16+monocyte ratio was associated with both disease severity and mortality, as well as with serum concentration of type I IFN, a factor able to induce the appearance of CD56+ monocytes. In conclusion, severe COVID-19 is characterized by the abundance of hyperinflammatory CD56+ monocytes, which could represent a novel marker with prognostic significance and, possibly, a therapeutic target for controlling the inflammatory process occurring during COVID-19.

Donor-derived mold infections in lung transplant recipients: The importance of active surveillance.

Unexpected donor-derived fungal infections represent a rare but potentially fatal complication in lung transplant (Tx) recipients. Timely communication of the results of donor cultures and prompt treatment of recipients are crucial to mitigate the consequences of donor-derived transmissions. In this prospective cohort study, all consecutive patients who underwent lung transplantation from 2015 to 2022 were included. In December 2015, a Local Active Surveillance System has been implemented to provide biovigilance of donor culture results and optimize recipients' management. The aim of this study is to investigate the incidence of unexpected, mold-positive cultures among lung donors and the rate of transmission to recipients. Furthermore, management strategies and outcome of recipients with mold transmission are described. In case of isolation of the same mold in donor and recipient cultures, when possible, transmission was confirmed by dendrogram analysis. During the study period, 82 lung Tx were performed from 80 donors. The prevalence of donors with "unexpected" mold isolation from the respiratory tract was 3.75% (3/80). Isolated molds were Aspergillus niger, Rhizopus oryzae, and Aspergillus flavus. Transmissions occurred in all the three cases (100%) with a mean time of 5 days from lung Tx but none of the recipients developed invasive mold disease. Our Local Active Surveillance System allowed prompt recognition of lung donors unexpected mold colonization. Even though transmission occurred, introduction of early targeted antifungal therapy prevented potential catastrophic consequence of mold donor-derived infection in the immediate post-Tx period.

Navigating the Nexus: HIV and Breast Cancer-A Critical Review.

Despite significant advances in the management of antiretroviral therapy (ART), leading to improved life expectancy for people living with HIV (PLWH), the incidence of non-AIDS-defining cancers, including breast cancer, has emerged as a critical concern. This review synthesizes current evidence on the epidemiology of breast cancer among HIV-infected individuals, highlighting the potential for an altered risk profile, earlier onset, and more advanced disease at diagnosis. It delves into the molecular considerations underpinning the relationship between HIV and breast cancer, including the role of immunosuppression, chronic inflammation, and gene expression alterations. Additionally, it examines the complexities of managing breast cancer in the context of HIV, particularly the challenges posed by ART and anticancer agents' cross-toxicities and drug-drug interactions. The review also addresses survival disparities, underscoring the need for improved cancer care in this population. By identifying gaps in knowledge and areas requiring further research, this review aims to illuminate the complexities of HIV-associated breast cancer, fostering a deeper understanding of its epidemiology, molecular basis, and clinical management challenges, thereby contributing to better outcomes for individuals at the intersection of these two conditions. This narrative review systematically explores the intersection of HIV infection and breast cancer, focusing on the impact of HIV on breast cancer risk, outcomes, and treatment challenges.

Network perturbation analysis in human bronchial epithelial cells following SARS-CoV2 infection.

BACKGROUND: SARS-CoV2, the agent responsible for the current pandemic, is also causing respiratory distress syndrome (RDS), hyperinflammation and high mortality. It is critical to dissect the pathogenetic mechanisms in order to reach a targeted therapeutic approach. METHODS: In the present investigation, we evaluated the effects of SARS-CoV2 on human bronchial epithelial cells (HBEC). We used RNA-seq datasets available online for identifying SARS-CoV2 potential genes target on human bronchial epithelial cells. RNA expression levels and potential cellular gene pathways have been analyzed. In order to identify possible common strategies among the main pandemic viruses, such as SARS-CoV2, SARS-CoV1, MERS-CoV, and H1N1, we carried out a hypergeometric test of the main genes transcribed in the cells of the respiratory tract exposed to these viruses. RESULTS: The analysis showed that two mechanisms are highly regulated in HBEC: the innate immunity recruitment and the disassembly of cilia and cytoskeletal structure. The granulocyte colony-stimulating factor (CSF3) and dynein heavy chain 7, axonemal (DNAH7) represented respectively the most upregulated and downregulated genes belonging to the two mechanisms highlighted above. Furthermore, the carcinoembryonic antigen-related cell adhesion molecule 7 (CEACAM7) that codifies for a surface protein is highly specific of SARS-CoV2 and not for SARS-CoV1, MERS-CoV, and H1N1, suggesting a potential role in viral entry. In order to identify potential new drugs, using a machine learning approach, we highlighted Flunisolide, Thalidomide, Lenalidomide, Desoximetasone, xylazine, and salmeterol as potential drugs against SARS-CoV2 infection. CONCLUSIONS: Overall, lung involvement and RDS could be generated by the activation and down regulation of diverse gene pathway involving respiratory cilia and muscle contraction, apoptotic phenomena, matrix destructuration, collagen deposition, neutrophil and macrophages recruitment.

New generation biologics for the treatment of psoriasis and psoriatic arthritis. State of the art and considerations about the risk of infection.

Psoriasis is a chronic immune-mediated disease characterized by inflammation of skin (psoriasis) or joints (psoriatic arthritis) or both, resulting from a dysregulation in particular of the T helper (Th)17 functions. There is no available cure for psoriasis, and a life-long treatment is needed to control signs and symptoms. Research interest is high around the newest biological drugs approved for the treatment of moderate to severe psoriasis and psoriatic arthritis, and especially drugs blocking the IL-23/IL-17 axis. Our aim is to review the new biological drugs for the treatment of psoriasis and their adverse effects, focusing on the risk of infections.

Chilblains-like lesions and SARS-CoV-2 in children: An overview in therapeutic approach.

SARS-CoV-2 (Severe Acute Respiratory Syndrome, Coronavirus, type 2) is the virus responsible for the global pandemic of Coronavirus disease 2019 (COVID-19) that began in China in December 2019. The variability of nasal olfactory symptoms in pediatric patients is interlinked with possible warning signs, including respiratory, gastrointestinal, ocular, or dermatological symptoms. Skin findings in patients with COVID-19 can range from petechiae to papulovesicular rashes to diffuse urticaria and can be confused with rashes of non-COVID-19 conditions. These lesions typically appear early during COVID-19 and are thought to be secondary to viral replication or circulating cytokines. Herein, we discuss two pediatric cases, presenting with skin lesions, which tested positive for SARS-CoV-2, thus, briefly reviewing current literature for similar reports and related management. Although these lesions heal spontaneously in most cases, an adequate "targeted" therapeutic approach can shorten the time and the discomfort of the skin disease.

Favourable course in a cohort of Parkinson's disease patients infected by SARS-CoV-2: a single-centre experience.

The COVID-19 outbreak has had a dramatic impact on the healthcare system due to the rapid, worldwide spread of the virus, highlighting several considerations on the best management of infected patients and also potential risks and prognostic factors in patients with pre-existing chronic diseases exposed to the virus. Neurodegenerative disorders are known to be chronic, disabling diseases that imply a higher vulnerability to infections, and for this reason, it has been suggested that SARS-CoV-2 infection may have a worse course in these patients. In the present study, we report our experience with 12 patients affected by Parkinson's disease (PD) who became infected with SARS-Cov-2 due to a COVID-19 outbreak in a care residency, and thus hospitalised in our COVID hospital. Most of the PD patients had a long disease duration and multiple comorbidities even though SARS-CoV-2 manifestations were mild, and none required intensive care. Despite lung conditions, most of our PD patients had mild symptoms: 7 patients were clinically asymptomatic (58.3%); 3 patients had fever, cough, and myalgia (25%) and 2 patients had dyspnoea (16%) that needed high-flow oxygen therapy. Few complications related to PD were seen. All patients were discharged after a mean hospitalisation period of 30 days. Mortality rate during hospitalisation was zero. Our findings suggest that SARS-CoV-2 infection does not have a poor prognosis in patients with PD. More extensive data and evaluations, however, are needed to confirm our data, and caution is warranted.

Management of pernio-like cutaneous manifestations in children during the outbreak of COVID-19.

During the outbreak of COVID-19 many pernio-like lesions have been increasingly reported. The aim of the study is to describe our management of these skin manifestations and to evaluate a possible correlation to SARS-CoV-2 infection. All patients underwent clinical and laboratory tests to detect a possible underlying connective disease and also to specific SARS-CoV-2 investigations such as oropharyngeal swab and IgG-IgM serology. Nine patients aged between 5 and 15 years old were evaluated. Skin lesions observed were purplish, erythematous and oedematous, in some cases painful and itchy. Six out of nine had respiratory and systemic symptoms (cough, nasal congestion, chills, fever, and asthenia) that preceded cutaneous findings of approximately 2 weeks. Concerning blood exams, three out of nine had D-dimer weakly increased, four had ANA positivity: two with a title 1:160, one with 1:320, and one with 1:5120 and a speckled pattern. The latter patient had also ENA SS-A positive and RF positivity, confirmed at a second check, so as to allow us to make a diagnosis of connective tissue disease. Four out of nine had aPL positivity (IgM). Reactants acute phase were all negative. Oropharyngeal swabs and serology tests for SARS-CoV-2 was negative (borderline in one patient for IgM). No treatment was needed. Even if we do not have enough data to prove it, we hypothesize a correlation between pernio-like lesions and SARS-CoV-2 infection for an increased number of these lesions described during the pandemic and also because such manifestations appeared when temperatures were mild and patients were at home in isolation for the lockdown. Many questions remain open about interaction host-virus.

Malignant melanoma in HIV: Epidemiology, pathogenesis, and management.

People affected by immunodeficiency, and especially those infected by HIV, are burdened by a higher risk of developing malignancies. It has been estimated that the incidence of melanoma in HIV-infected people is 2.6-fold higher than in uninfected ones. In this group of patients, melanoma shows a more aggressive phenotype and poorer survival rates compared to HIV-negative people. Standard guidelines of diagnosis and care do not exist yet. Studies suggest high index of suspicion and a low threshold for biopsy in HIV-positive patients regardless of their CD4+ count and the use of standard surgical margins for re-excision procedures. In case of diagnosis of melanoma in HIV-positive patients, a thorough search for metastatic disease is recommended because of the more aggressive course of this cancer in HIV-positive patients. Moreover, to rapidly find out any recurrence or metastatic disease after treatment, these patients need a close follow-up, every 3 months, for the first 2 years and at least twice yearly thereafter. Although surgery remains the main therapeutic option, application of immune checkpoint-based immunotherapy is being studied and seems to be promising. The aim of this review is to present the current knowledge and future options for melanoma diagnosis and treatment in people living with HIV.

Vitamin D Status Modulates Inflammatory Response in HIV+ Subjects: Evidence for Involvement of Autophagy and TG2 Expression in PBMC.

Conflicting results on the involvement of vitamin D deficiency in inflammatory and immune response in HIV+ subjects are reported. We aimed to characterize the possible influence of vitamin D status on changes in expression of tissue transglutaminase gene (TGM2) and other genes involved in inflammatory response and autophagy in peripheral blood mononuclear cells (PBMC) from HIV+ subjects. HIV+ subjects (n = 57) under antiretroviral therapy (ART) and healthy controls (n = 40) were enrolled. mRNA levels of 1-alpha-hydroxylase (CYP27B1), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), TGM2, microtubule-associated protein 1A/1B-light chain 3 (LC3), autophagy-related 5 homolog (ATG5), and Beclin 1 (BECN1) were quantified by real-time PCR. In HIV+ subjects, 25(OH)D3 plasma levels were negatively correlated with time since HIV diagnosis. In PBMC from HIV+ subjects, increases in gene expression of TNF-α and IFN-γ in comparison to controls were observed. The highest increase in TNF-α transcripts was observed in HIV+ subjects with deficient 25(OH)D3 levels. Autophagy-related genes LC3, ATG5, and BECN1 were down-regulated in HIV+ subjects. Moreover, TGM2 transcripts were up-regulated in PBMC from HIV+ subjects with 25(OH)D3 deficiency. Changes observed in PBMC from HIV+ subjects appeared to be dependent on vitamin D status. The present results suggest that vitamin D deficiency is associated with changes in the expression of markers of inflammation and autophagy, resulting in immune cell dysfunction.

Epidemiology of the new HIV infections in a large university hospital of Southern Italy: the importance of increasing the culture of the HIV screening test in the prevention of late diagnosis.

BACKGROUND: the delay of HIV diagnosis represents an important risk of spreading HIV infection within the community and, at the same time, a loss of opportunity for undiagnosed subjects to start the antiretroviral therapy. OBJECTIVES: to evaluate the difference, over time, between early and late HIV diagnosis in a large University Hospital of Southern Italy and to emphasize the importance of spreading the culture of prevention, based on the improvement of the HIV screening test adherence, in order to reduce the incidence of late HIV diagnosis. DESIGN: retrospective cross-sectional study. SETTING AND PARTICIPANTS: all the HIV screening tests performed in the six-year period 2013-2018 by the HIV laboratory of a third-level University hospital of Sicily (Southern Italy) were considered. The tests were performed on four categories of patients: voluntary HIV screening participants, inpatients, outpatients, and healthcare workers. MAIN OUTCOME MEASURES: number of performed HIV tests and frequency of early and late HIV diagnosis in the studied categories of subjects. RESULTS: in the considered period, 16,290 HIV tests were performed and the new diagnosis, considering all the four categories of patients, were in total 72, of which the highest percentage (45.8%) concerned voluntary HIV screening participants showing a mean CD4+ level >350/µL (threshold to discriminate early or late infection), followed by inpatients (27.8%) and outpatients (26.4%) with a mean CD4+ levels <350/µL. Moreover, from 2013 to 2018, the detection of serological positivity on voluntary HIV screening participants showed a decrease of 12.5%, while there was a parallel increase of 18.2% in the inpatients group. In the outpatients, the serological positivity remains quite stable. Concerning sexual habits, in the voluntary HIV screening participants, more than half (55.5%) of the HIV positive subjects were homo-bisexuals, while in the inpatients and outpatients' groups the highest percentage (83.3%) were heterosexuals. CONCLUSIONS: in this study, the majority (45.8%) of the new HIV diagnosis were detected on voluntary HIV screening participants in an earlier phase of infection. However, adding the percentages of inpatients and outpatients, it results that more than half (54.2%) of the new diagnosis occurred in a more advanced phase of infection. For these reasons, it appears necessary to stress the importance of an early diagnosis, reachable only by the spread of an HIV screening culture through health education campaigns addressed to the entire population and, especially, to heterosexual category that was the most interested group in the late diagnosis.

HIV-associated psoriasis: Epidemiology, pathogenesis, and management.

People living with HIV (PLWH) are affected by a higher incidence skin disorders, which are often associated with high morbidity and mortality. In particular, psoriasis affects PLWH severely and for a longer time than the general population. Human immunodeficiency virus (HIV) infection is characterized by a progressive decrease in CD4+ T-cell count, and it could seem paradoxical that psoriasis exacerbations are more frequent in this subset of patients than the general population, even though it is commonly observed at any stage of infection. For a long time, there have been limited therapeutic choices for PLWH affected by psoriasis. The introduction of the combined antiretroviral therapy dramatically changed the natural course of both HIV and psoriasis in PLWH, leading to an improvement of quality and duration of life. However, the clinical severity of psoriasis in PLWH often requires the use of immunosuppressant drugs. Knowledge about their safety and efficacy are limited to case-reports, small case-series and studies, therefore their use has not yet entered the routine. Further studies are needed to determine if immunosuppressive drugs can be safely and effectively used in PLWH affected by psoriasis and other autoimmune disorders.

Outbreak of Brucella melitensis infection in Eastern Sicily: risk factors, clinical characteristics and complication rate.

Brucellosis is one of the most common zoonoses in the world, especially in Southern Italy, where many cases are still recorded every year. 128 cases of brucellosis were observed in Messina (Sicily) in 2016, representing a tenfold increase in the number of cases of brucellosis expected. The aim of this multicenter retrospective study was to analyze clinical and microbiological aspects of a brucellosis outbreak in the province of Messina in 2016, the incidence of its complications and the treatment combinations applied. The principal transmission route was through the ingestion of unpasteurized fresh cheese. The mean latency period between the onset of the symptoms and diagnosis was 35.58±42.75 days. A late diagnosis increases the risk of developing complications. Drug-resistant strains of B. melitensis to Trimethoprim/ Sulfamethoxazole and Ciprofloxacin were found in blood cultures of 58.4% patients. Brucellosis is still present in Sicily. A diagnostic delay predisposes to complications requiring prolonged therapies. The finding of Brucella melitensis strains resistant to the most widespread treatments is worrisome and needs further investigation. Moreover, the use of alternative combination antibiotic therapy is recommended.

Risk factors of venous thrombo-embolism during cytomegalovirus infection in immunocompetent individuals. A systematic review.

Most of the effects and complications of cytomegalovirus (CMV) infection are still unknown, even though its tropism for the endothelium has been extensively investigated. In fact, CMV is suspected to be a cause of venous thrombo-embolism (VTE) since 1974, but there is still no consensus about the management of CMV-related thrombosis and how to prevent it. Cytomegalovirus-related thrombosis has been reported mostly in immunocompromised patients, rarely in immunocompetent individuals. In order to identify potential risk factors of CMV-related thrombosis, we performed a systematic review of the literature regarding immunocompetent patients with cytomegalovirus infection and thrombosis. We found 115 cases with a mean age of 37.36 years (SD ± 16.43 years). Almost half the female patients were assuming EP contraception at the time of the event, and almost half the patients were affected by a coagulation disorder. Interestingly, just two women and four men had no risk factor for thrombosis other than the CMV infection at the time of the event. In conclusion, coagulation disorders and EP contraception have to be taken into a great deal of consideration in patients with CMV infection, since they could be important risk factors for VTE. Knowing the correlation with coagulation disorders, the use of anticoagulation drugs cannot be considered overtreatment. It was not feasible to determine the usefulness of an antiviral treatment. Further studies, even randomized ones, are required to determine the usefulness of antiviral drugs and the real prevalence of CMV-related VTE.

Outbreak of Brucella melitensis infection in Eastern Sicily: risk factors, clinical characteristics and complication rate.

Brucellosis is one of the most common zoonoses in the world, especially in Southern Italy, where many cases are still recorded every year. 128 cases of brucellosis were observed in Messina (Sicily) in 2016, representing a tenfold increase in the number of cases of brucellosis expected. The aim of this multicenter retrospective study was to analyze clinical and microbiological aspects of a brucellosis outbreak in the province of Messina in 2016, the incidence of its complications and the treatment combinations applied. The principal transmission route was through the ingestion of unpasteurized fresh cheese. The mean latency period between the onset of the symptoms and diagnosis was 35.58 ± 42.75 days. A late diagnosis increases the risk of developing complications. Drug-resistant strains of B. melitensis to Trimethoprim/Sulfamethoxazole and Ciprofloxacin were found in blood cultures of 58.4% patients. Brucellosis is still present in Sicily. A diagnostic delay predisposes to complications requiring prolonged therapies. The finding of Brucella melitensis strains resistant to the most widespread treatments is worrisome and needs further investigation. Moreover, the use of alternative combination antibiotic therapy is recommended.

Expression of the OAS Gene Family Is Highly Modulated in Subjects Affected by Juvenile Dermatomyositis, Resembling an Immune Response to a dsRNA Virus Infection.

BACKGROUND: Juvenile dermatomyositis (JDM) is a systemic, autoimmune, interferon (IFN)-mediated inflammatory muscle disorder that affects children younger than 18 years of age. JDM primarily affects the skin and the skeletal muscles. Interestingly, the role of viral infections has been hypothesized. Mammalian 2'-5'-oligoadenylate synthetase (OAS) genes have been thoroughly characterized as components of the IFN-induced antiviral system, and they are connected to several innate immune-activated diseases. The main purpose of the paper is to define the potential interrelationship between the OAS gene family network and the molecular events that characterize JDM along with double-stranded RNA (dsRNA) molecular pathways. METHODS: We analyzed three microarray datasets obtained from the NCBI in order to verify the expression levels of the OAS gene family network in muscle biopsies (MBx) of JDM patients compared to healthy controls. Furthermore, From GSE51392, we decided to select significant gene expression profiles of primary nasal and bronchial epithelial cells isolated from healthy subjects and treated with polyinosinic-polycytidylic acid (poly(I:C)), a synthetic analog of double-stranded RNA (dsRNA), a molecular pattern associated with viral infection. RESULTS: The analysis showed that all OAS genes were modulated in JDM muscle biopsies. Furthermore, 99% of OASs gene family networks were significantly upregulated. Of importance, 39.9% of modulated genes in JDM overlapped with those of primary epithelial cells treated with poly(I:C). Moreover, the microarray analysis showed that the double-stranded dsRNA virus gene network was highly expressed. In addition, we showed that the innate/adaptive immunity markers were significantly expressed in JDM muscles biopsies. and that their levels were positively correlated to OAS gene family expression. CONCLUSION: OAS gene expression is extremely modulated in JDM as well as in the dsRNA viral gene network. These data lead us to speculate on the potential involvement of a viral infection as a trigger moment for this systemic autoimmune disease. Further in vitro and translational studies are needed to verify this hypothesis in order to strategically plan treatment interventions.

Tache Noire in a Patient with Acute Q Fever.

OBJECTIVE: To describe a rare case of acute Q fever with tache noire. CLINICAL PRESENTATION AND INTERVENTION: A 51-year-old man experienced acute Q fever showing tache noire, generally considered a pathognomonic sign of Mediterranean spotted fever (MSF) and MSF-like illness, but not a clinical feature of Q fever. The patient was treated with doxycycline 100 mg every 12 h. CONCLUSION: In the Mediterranean area, tache noire should be considered pathognomonic of MSF but it should not rule out Q fever. Clinical diagnosis should be supported by accurate laboratory diagnostic tests to guide proper management.

Monitoring Integration over Time Supports a Role for Cytotoxic T Lymphocytes and Ongoing Replication as Determinants of Reservoir Size.

The dynamics of HIV reservoir accumulation off antiretroviral therapy (ART) is underexplored. Levels of integrated HIV DNA in peripheral blood mononuclear cells (PBMCs) were longitudinally monitored before and after antiviral therapy. HIV integration increased over time in both elite controllers (ECs; n = 8) and noncontrollers (NCs; n = 6) before ART, whereas integration remained stable in patients on ART (n = 4). The median annual fold change was higher in NCs than in ECs and negatively correlated with CD4/CD8 T-cell ratio. Cytotoxic T lymphocyte (CTL) function as assessed by infected CD4 T-cell elimination (ICE) and granzyme B activity did not significantly change over time in ECs, suggesting that the gradual increase in integrated HIV DNA observed in ECs was not a result of progressive loss of immune-mediated control. Also, acutely infected (n = 7) but not chronically infected (n = 6) patients exhibited a significant drop in integrated HIV DNA 12 months after ART initiation. In conclusion, in the absence of ART, integrated HIV accumulates over time both in NCs and in ECs, at variable individual rates. Starting ART early in infection leads to a greater drop in integrated HIV DNA than does initiating treatment after years of infection. The increase in integrated HIV DNA over time suggests that early treatment may be of benefit in limiting HIV reservoirs. IMPORTANCE: The establishment of a latent reservoir represents a barrier to cure among HIV-infected individuals. The dynamics of HIV reservoir accumulation over time in patients before antiviral therapy is underexplored, in large part because it is difficult to accurately and reproducibly measure the size of HIV reservoir in this setting. In our study, we compared the dynamics of integrated HIV DNA over time in ECs and NCs before and after ART was initiated. We found that integrated HIV DNA levels progressively increase over time in the absence of ART, but with a higher, albeit variable, rate in NCs compared to ECs. In addition, integrated HIV DNA declines more dramatically when ART is initiated in acute rather than chronic HIV infection, suggesting important differences between acute and chronic infection. Our study highlights the role of HIV replication and CTL control in reservoir accumulation in sanctuary sites and why ART appears to be more effective in acute infection.

Cardiovascular risk and dyslipidemia among persons living with HIV: a review.

BACKGROUND: Aim of this review is to focus the attention on people living with HIV infection at risk of developing a cardiovascular event. What is or what would be the most suitable antiretroviral therapy? Which statin or fibrate to reduce the risk? How to influence behavior and lifestyles? DISCUSSION: Prevention of cardiovascular disease (CVD) risk remains the first and essential step in a medical intervention on these patients. The lifestyle modification, including smoking cessation, increased physical activity, weight reduction, and the education on healthy dietary practices are the main instruments. Statins are the cornerstone for the treatment of hypercholesterolemia. They have been shown to slow the progression or promote regression of coronary plaque, and could also exert an anti-inflammatory and immunomodulatory effect. However the current guidelines for the use of these drugs in general population are dissimilar, with important differences between American and European ones. The debate between American and European guidelines is still open and, also considering the independent risk factor represented by HIV, specific guidelines are warranted. Ezetimibe reduces the intestinal absorption of cholesterol. It is effective alone or in combination with rosuvastatin. It does not modify plasmatic concentrations of antiretrovirals. A number of experimental new classes of drugs for the treatment of hypercholesterolemia are being studied. Fibrates represent the first choice for treatment of hypertriglyceridemia, however, the renal toxicity of fibrates and statins should be considered. Omega 3 fatty acids have a good safety profile, but their efficacy is limited. Another concern is the high dose needed. Other drugs are acipimox and tesamorelin. Current antiretroviral therapies are less toxic and more effective than regimens used in the early years. Lipodistrophy and dyslipidemia are the main causes of long-term toxicities. Not all antiretrovirals have similar toxicities. Protease Inhibitors may cause dyslipidemia and lipodystrophy, while integrase inhibitors have a minimal impact on lipids profile, and no evidence of lipodystrophy. There is still much to be written with the introduction of new drugs in clinical practice. CONCLUSIONS: Cardiovascular risk among HIV infected patients, interventions on behavior and lifestyles, use of drugs to reduce the risk, and switch in antiretroviral therapy, remain nowadays major issues in the management of HIV-infected patients.