Pneumocystis jirovecii pneumonia in breast cancer mimicking SARS-CoV-2 pneumonia during pandemic.

Pneumocystis jirovecii pneumonia (PJP) is one of the most common HIV-related opportunistic infection. Apart from HIV patients, subjects treated with an associated therapy of high doses glucocorticoids and immunosuppressive drugs should be considered at risk. SARS-CoV-2 has become worldly known as the responsible of the pandemic that hit the world in late 2019 and that is still ongoing. Italy, and especially Brescia, was one of the area most struck by the pandemic, with a significant number of cases being reported (more than 112,648 as of October 2021). The diagnosis of SARS-CoV-2 is mainly based on RT-PCR assays performed on nasopharyngeal swab, X-ray of the chest and clinical manifestations. We describe two cases of PJP in two immunocompromised patients with breast cancer who were admitted at Spedali Civili of Brescia hospital, Italy, with an initial diagnosis of SARS-CoV-2 pneumonia, despite testing negative to RT-PCR on nasopharyngeal swabs. We also retrospectively reassessed all cases of pneumonia deemed as SARS-CoV-2-related upon admission and then converted to PJP as the final diagnosis. We describe the two following cases to emphasize that clinicians should always be alert about PJP, even during the SARS-CoV-2 pandemic, and avoid focusing on COVID-19 exclusively. PJP should always be considered as a differential diagnosis in patients, particularly if immunosuppressed, with an X-ray or TC of the chest suggestive of interstitial pneumonia and a negative SARS-CoV-2 RT-PCR on nasopharyngeal swabs.

Effectiveness of kidney transplantation in HIV-infected recipients under combination antiretroviral therapy: a single-cohort experience (Brescia, Northern Italy).

PURPOSE: Kidney transplantation was recently introduced for the treatment of end stage renal disease (ESRD) in HIV-infected patients. We report the results of the first 28 procedures at our centre. METHODS: A retrospective study was conducted on HIV-infected patients evaluated for kidney transplantation between January 2005 and October 2016. Patients were selected and monitored by the kidney transplantation and infectious diseases teams, according to the national protocol. RESULTS: 60 patients were evaluated; 32 entered the list and 28 were transplanted. Median CD4+ count was 337 cell/µL at transplantation and 399 cell/µL 12 months thereafter. HIV RNA was undetectable at transplantation in 27/28 patients and became undetectable within 24 weeks in the only patient starting antiretroviral combination therapy (cART) after surgery. Four patients experienced virological failure, but reached again undetectability after cART regimen change. At last available point of follow-up (median 126.1 weeks), HIV RNA was undetectable in all patients. Three patients experienced AIDS-defining events. We observed a cumulative number of 19 acute rejections in 16 patients (median time from transplantation to first rejection 5.2 weeks). Survival rate was 82.1%. To avoid pharmacokinetics (PK) interactions, cART regimen was changed from a protease inhibitor (PI)/non-nucleoside reverse transcriptase inhibitor (NNRTI)-based to an integrase inhibitor (InSTI)-based regimen in 11/20 alive patients with functioning graft. CONCLUSIONS: Kidney transplantation appears to be safe in HIV-infected patients carefully selected. As previously reported, we observed a high incidence of acute rejection. We expect that the recent implementation of the immunosuppressive protocols will allow a better immunologic control. Moreover, the introduction of InSTI permits a better strategy of cART, with lower incidence of PK interactions with immunosuppressive drugs.

Comparison between the gold standard DXA with calcaneal quantitative ultrasound based-strategy (QUS) to detect osteoporosis in an HIV infected cohort

ABSTRACT Introduction: Osteoporosis represents one of the most frequent comorbidity among HIV patients. The current standard method for osteoporosis diagnosis is dual-energy X-ray absorptiometry. Calcaneal quantitative ultrasound can provide information about bone quality. The aims of this study are to compare these two methods and to evaluate their ability to screen for vertebral fracture. Methods: This cross-sectional study was conducted in HIV patients attending the Clinic of Infectious and Tropical Diseases of Brescia during 2014 and who underwent lumbar/femoral dual-energy X-ray absorptiometry, vertebral fracture assessment and calcaneal quantitative ultrasound. The assessment of osteoporosis diagnostic accuracy was performed for calcaneal quantitative ultrasound and for vertebral fracture comparing them with dual-energy X-ray absorptiometry. Results: We enrolled 73 patients and almost 48% of them had osteoporosis with at least one of the method used. Vertebral fracture were present in 27.4%. Among patients with normal bone measurements, we found vertebral fracture in proportion between 10% and 30%. If we used calcaneal quantitative ultrasound method and/or X-ray as screening, the percentages of possible savable dual-energy X-ray absorptiometry ranged from 12% to 89% and misclassification rates ranged from 0 to 24.6%. A combined strategy, calcaneal quantitative ultrasound and X-Ray, identified 67% of patients with low risk of osteoporosis, but 16.4% of patients were misclassified. Conclusions: We observed that patients with osteoporosis determined by calcaneal quantitative ultrasound and/or dual-energy X-ray absorptiometry have higher probability to undergo vertebral fracture, but neither of them can be used for predicting vertebral fracture. Use of calcaneal quantitative ultrasound for screening is a reasonable alternative of dual-energy X-ray absorptiometry since our study confirm that none strategy is clearly superior, but both screen tools must be always completed with X-ray.

Comparison between the gold standard DXA with calcaneal quantitative ultrasound based-strategy (QUS) to detect osteoporosis in an HIV infected cohort.

INTRODUCTION: Osteoporosis represents one of the most frequent comorbidity among HIV patients. The current standard method for osteoporosis diagnosis is dual-energy X-ray absorptiometry. Calcaneal quantitative ultrasound can provide information about bone quality. The aims of this study are to compare these two methods and to evaluate their ability to screen for vertebral fracture. METHODS: This cross-sectional study was conducted in HIV patients attending the Clinic of Infectious and Tropical Diseases of Brescia during 2014 and who underwent lumbar/femoral dual-energy X-ray absorptiometry, vertebral fracture assessment and calcaneal quantitative ultrasound. The assessment of osteoporosis diagnostic accuracy was performed for calcaneal quantitative ultrasound and for vertebral fracture comparing them with dual-energy X-ray absorptiometry. RESULTS: We enrolled 73 patients and almost 48% of them had osteoporosis with at least one of the method used. Vertebral fracture were present in 27.4%. Among patients with normal bone measurements, we found vertebral fracture in proportion between 10% and 30%. If we used calcaneal quantitative ultrasound method and/or X-ray as screening, the percentages of possible savable dual-energy X-ray absorptiometry ranged from 12% to 89% and misclassification rates ranged from 0 to 24.6%. A combined strategy, calcaneal quantitative ultrasound and X-Ray, identified 67% of patients with low risk of osteoporosis, but 16.4% of patients were misclassified. CONCLUSIONS: We observed that patients with osteoporosis determined by calcaneal quantitative ultrasound and/or dual-energy X-ray absorptiometry have higher probability to undergo vertebral fracture, but neither of them can be used for predicting vertebral fracture. Use of calcaneal quantitative ultrasound for screening is a reasonable alternative of dual-energy X-ray absorptiometry since our study confirm that none strategy is clearly superior, but both screen tools must be always completed with X-ray.

Trigger-oriented HIV testing at Internal Medicine hospital Departments in Northern Italy: an observational study (Fo.C.S. Study).

BACKGROUND: Early detection of undiagnosed HIV infected patients is of paramount importance. The attitude of Italian hospital-based Internal Medicine physicians to prescribe HIV testing following the detection of HIV-associated signs, symptoms and behaviours (triggers) has been reported to be poor. The aim of the study is to quantify the extent of the missed opportunities for early HIV diagnosis in Internal Medicine Departments (IMD). METHODS: Patients admitted to IMD of a General University Hospital in Italy in March-June 2013 were interviewed using a structured questionnaire investigating the presence of triggers for HIV testing, including patient's characteristics, symptoms and conditions associated with HIV infection. HIV tests performed during hospitalisation were recorded. RESULTS: HIV testing was performed in 73 (6.6%) out of 1113 hospitalisations (1072 patients), providing positive results in three cases (4.1%). All of them presented ≥1 triggers. Conversely, 853 triggers were identified in 528 hospitalisations with at least one trigger (47.4%). The proportion of hospitalisations where an HIV testing was prescribed was 3.1%, 9.5% and 16.0% in the presence of zero, one-to-two or more triggers, respectively. Age <70 years, female gender, length of hospital stay, haematological disease, HBV infection, multiple sexual partners and lymphadenopathy were predictors of HIV testing by logistic regression analysis. CONCLUSIONS: Although chances of an HIV test being performed in patients hospitalised in IMD increases along with the number of triggers, the number of tests being performed in people presenting with triggers is unacceptably low and requires educational interventions in order to obtain individual and public health advantages.

Incidence of cardiovascular events in HIV-positive patients compared to general population over the last decade: a population-based study from 2000 to 2012.

Cardiovascular diseases are currently a main cause of death among people living with HIV. This population-based study aimed to investigate the incidence of cardiovascular events (CVEs) in HIV-positive people and factors associated with CVEs. We performed a retrospective cohort study of the HIV-infected patients residing in the Local Health Authority of Brescia, northern Italy, from 2000 to 2012. Incidence of CVEs events in HIV-positive patients was compared with that expected in general population living in the same area, computing standardized incidence ratios (SIRs). CVEs-associated risk factors were assessed using Cox regression analysis and competing risk model of death. About 3766 HIV-infected patients were included in the study. Over the 12-year-period, we recorded 134 CVEs: 83 (61.9%) acute myocardial infarctions (CVE type-1), and 51 (38.1%) strokes (CVE type-2). A twofold increased risk (SIR = 2.02) of CVEs was found in HIV-infected patients compared to the general population. Notably, within male patients: for CVE type-1, SIR = 1.89, for CVE type-2 SIR = 2.25; within female patients: for CVE type-1, SIR = 2.91, for CVE type-2 SIR = 2.07. Age >45 years, male gender, diabetes, and total blood cholesterol >200 mg/dl were significantly associated with CVEs incidence (for all, p < .05). These results were confirmed using the competing risk model. Our cohort study confirmed the higher incidence of CVEs in HIV-positive patients, and put emphasis on the importance of traditional cardiovascular risk factors. Overall CVE risk in HIV-positive patients was twice as high as CVE risk in general population. We found a peculiar gender distribution, with a relative risk for CVE type-1 higher in HIV-positive females, and a higher CVE type-2 risk in male patients. More studies are needed in order to support these findings and to further highlight possible gender differences in the risk of developing CVEs in HIV-positive patients.

Neutrophil to Lymphocyte Ratio and Cardiovascular Disease Incidence in HIV-Infected Patients: A Population-Based Cohort Study.

Neutrophil to lymphocyte ratio (NLR) has been shown to predict occurrence of cardiovascular events in the general population. The aim of our study was to evaluate the role of NLR to predict major cardiovascular disease (CVD) events in HIV-infected subjects. We performed a retrospective cohort study of HIV-infected patients residing in the Local Health Authority (LHA) of Brescia, northern Italy, from 2000 to 2012. The incidence of CVD events in HIV-positive patients was compared with that expected in the general population living in the same area, computing standardized incidence ratios (SIRs). To evaluate the predictive role of NLR, univariate and multivariate Cox regression models were applied, computing hazard ratios (HRs). A total of 3766 HIV-infected patients (mean age 38.1 years, 71.3% males) were included (person-years 28768.6). A total of 134 CVD events occurred in 119 HIV-infected patients. A 2-fold increased risk (SIR 2.02) of CVD was found in HIV-infected patients compared to the general population. NLR levels measured at baseline and during follow-up were independently associated with CVD incidence, when also adjusting for both traditional CVD risk factors and HIV-related factors (HR 3.05 for NLR≥ 1.2). The area under the receiver operating characteristics (ROC) curve showed a modest, not statistically significant, increase, from 0.81 to 0.83, with addition of NLR to Framingham risk score model covariates. In conclusion an elevated NLR is a predictor of risk CVD in HIV-infected patients, independently from the traditional CVD risk factors.

Screening for Neurocognitive Impairment in HIV-Infected Individuals at First Contact after HIV Diagnosis: The Experience of a Large Clinical Center in Northern Italy.

Neurocognitive disorders are emerging, probably underestimated, complications in HIV-infected people. The aim of the study was to assess neurocognitive profiles of newly detected HIV-infected patients. We performed an observational retrospective single-cohort study. Illiterates and patients with neurologic symptoms or previous psychiatric diagnosis were excluded. Neuropsychological profiles were assessed using a validated battery of neuropsychological tests. We included 206 patients; with males representing the majority of them (85%). Risk factors for HIV acquisition were unprotected sexual intercourse (homo/bisexual in 39.8% and heterosexual in 60.2%). Thirty-nine patients (18.9%) were previous injection drug users, while 41 (19.9%) were alcohol abusers. Mean education was 11.1 years (SD--standard deviation--3.7). A high prevalence of HIV-associated neurocognitive disorders (HAND, 47.1%) was present in HIV-infected patients: particularly, asymptomatic neurocognitive impairment (ANI) was found in 30.6%, mild neurocognitive disorder (MND) in 15% and HIV-associated dementia (HAD) in 1.5%. Male gender, low degree of education, AIDS diagnosis and gepatitis B virus (HBV) co-infection were factors independently associated with HAND in a multivariable logistic regression model. Our data suggest that patient-specific factors and AIDS diagnosis have a certain kind of impact in HAND occurrence. A complete neuropsychological screening must be recommended in all patients at HIV-infection diagnosis.

Increase in standard cholesterol and large HDL particle subclasses in antiretroviral-naïve patients prescribed efavirenz compared to atazanavir/ritonavir.

BACKGROUND: Cardiovascular risk in HIV-infected patients is related, at least in part, to serum lipid alterations before and after HAART. Lipoprotein-particle subclasses may also have an effect, but comparative data after standard HAART regimens are limited. METHODS: This was a substudy of a trial in 91 antiretroviral-naïve patients randomized to tenofovir + emtricitabine + atazanavir/ritonavir (ATV/r) or efavirenz (EFV). Over-time trends from baseline to week 48 in total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), HDL particles (HDLp), and TC:HDL-C and TG:HDL-C ratios were analyzed by analysis of covariance (ANCOVA). Furthermore, confidence intervals for differences between the 2 groups at week 48 were calculated. Indications for lipid-lowering interventions and low HDL-C were also studied. RESULTS: ANCOVA showed that, with respect to patients receiving ATV/r, those prescribed efavirenz (EFV) had greater increases reported as mean differences in lipid values at week 48: 14 mg/dL (95% CI, 0.2 to 27) for TC, 14 mg/dL (95% CI, 4 to 25) for LDL-C, 5 mg/dL (95% CI, 2 to 9) for HDL-C, and 2.2 mg/dL (95% CI, 0.4 to 4) for large HDLp. Proportions of subjects with indications for lipid-lowering interventions and with HDL-C <40 mg/dL did not differ significantly. CONCLUSIONS: Patients prescribed EFV had greater increases in TC, LDL-C, and HDL-C. Although no significant differences were detected between the 2 groups for the TC:HDL ratio and for indications to start lipid-lowering interventions, large HDLp increased more in the EFV group compared to the ATV/r group, suggesting a protective effect associated with EFV use.

Malaria and hiv in adults: when the parasite runs into the virus.

Malaria and HIV/AIDS are among the principal causes of morbidity and mortality worldwide, particularly in resource-limited settings such as sub-Saharan Africa. Despite the international community's efforts to reduce incidence and prevalence of these diseases, they remain a global public health problem. Clinical manifestations of malaria may be more severe in HIV infected patients, which have higher risks of severe malaria and malaria related death. Co-infected pregnant women, children and international travelers from non-malaria endemic countries are at higher risk of clinical complications. However, there is a paucity and conflicting data regarding malaria and HIV co-infection, particularly on how HIV infection can modify the response to antimalarial drugs and about drug-interactions between antiretroviral agents and artemisinin-based combined regimens. Moreover, consulting HIV-infected international travelers and physicians specialized in HIV care and travel medicine should prescribe an adequate chemoprophylaxis in patients travelling towards malaria endemic areas and pay attention on interactions between antiretrovirals and antimalarial prophylaxis drugs in order to prevent clinical complications of this co-infection.This review aims to evaluate the available international literature on malaria and HIV co-infection in adults providing a critical comprehensive review of nowadays knowledge.

Virological effectiveness and CD4+ T-cell increase over early and late courses in HIV infected patients on antiretroviral therapy: focus on HCV and anchor class received.

BACKGROUND: The aim of this study was to explore the effects of HCV co-infection on virological effectiveness and on CD4+ T-cell recovery in patients with an early and sustained virological response after HAART. METHODS: We performed a longitudinal analysis of 3,262 patients from the MASTER cohort, who started HAART from 2000 to 2008. Patients were stratified into 6 groups by HCV status and type of anchor class. The early virological outcome was the achievement of HIV RNA <500 copies/ml 4-8 months after HAART initiation. Time to virological response was also evaluated by Kaplan-Meier analysis. The main outcome measure of early immunological response was the achievement of CD4+ T-cell increase by ≥100/mm3 from baseline to month 4-8 in virological responder patients. Late immunological outcome was absolute variation of CD4+ T-cell count with respect to baseline up to month 24. Multivariable analysis (ANCOVA) investigated predictors for this outcome. RESULTS: The early virological response was higher in HCV Ab-negative than HCV Ab-positive patients prescribed PI/r (92.2% versus 88%; p = 0.01) or NNRTI (88.5% versus 84.7%; p = 0.06). HCV Ab-positive serostatus was a significant predictor of a delayed virological suppression independently from other variables, including types of anchor class. Reactivity for HCV antibodies was associated with a lower probability of obtaining ≥100/mm3 CD4+ increase within 8 months from HAART initiation in patients treated with PI/r (62.2% among HCV Ab-positive patients versus 70.9% among HCV Ab-negative patients; p = 0.003) and NNRTI (63.7% versus 74.7%; p < 0.001). Regarding late CD4+ increase, positive HCV Ab appeared to impair immune reconstitution in terms of absolute CD4+ T-cell count increase both in patients treated with PI/r (p = 0.013) and in those treated with NNRTI (p = 0.002). This was confirmed at a multivariable analysis up to 12 months of follow-up. CONCLUSIONS: In this large cohort, HCV Ab reactivity was associated with an inferior virological outcome and an independent association between HCV Ab-positivity and smaller CD4+ increase was evident up to 12 months of follow-up. Although the difference in CD4+ T-cell count was modest, a stricter follow-up and optimization of HAART strategy appear to be important in HIV patients co-infected by HCV. Moreover, our data support anti-HCV treatment leading to HCV eradication as a means to facilitate the achievement of the viro-immunological goals of HAART.

Impact of detectable human cytomegalovirus DNAemia on viro-immunological effectiveness of HAART in HIV-infected patients naive to antiretroviral therapy.

Our objective was to explore whether positive human cytomegalovirus (HCMV) DNAemia at baseline impaired CD4+ T-cell increase after 1 year of HAART. A sub-study of a randomized clinical trial in selected patients with <200 cell/mm CD4+ at baseline was conducted. Six out of 30 patients had detectable HCMV DNAemia at baseline, all reaching HCMV suppression at week 52 after HAART (only 1 of them was treated with valgancyclovir). No significant differences were found between patients with detectable or undetectable HCMV DNAemia in terms of CD4+ T-cell increase and HIV RNA response to HAART. Although some data may favor HCVM pre-emptive therapy to decrease immune activation, our results do not indicate that this practice may increase CD4+ T-cell count after HAART. At the same time, HAART proved effective in reducing HCMV DNAemia without the need for a specific therapy.

Prospective evaluation of bone markers, parathormone and 1,25-(OH)2 vitamin D in HIV-positive patients after the initiation of tenofovir/emtricitabine with atazanavir/ritonavir or efavirenz.

BACKGROUND: Increased risk of fractures and osteoporosis have been associated with the use of antiretroviral drugs. There is a paucity of prospective evaluations of bone markers after the initiation of drugs currently recommended to treat HIV infection and results on the evolution of these markers are conflicting. Lastly, the effect of tenofovir on 1,25-(OH)2 vitamin D is uncertain. METHODS: We performed a prospective study on the evolution of bone markers, parathormone and 1,25-(OH)2 vitamin D before and after standard antiretroviral regimens. This was a sub-study of a trial conducted in antiretroviral-naïve patients randomized to tenofovir + emtricitabine in combination with either atazanavir/ritonavir (ATV/r) or efavirenz (EFV). Follow-up lasted 48 weeks. The following bone markers were analyzed: C-terminal cross-laps (CTx), osteocalcin (OC), osteoprotegerin (OPG), and receptor activator of nuclear factor κB ligand (RANKL). Mixed-factorial analysis of variance with random-coefficient general linear model was used to compare their trends over time and linear multivariable regression was performed with a backward selection method to assess predictors of their variations from baseline to week 48. Trends of parathormone and 1,25-(OH)2 vitamin D were also evaluated. RESULTS: Seventy-five patients were studied: 33 received EFV and 42 ATV/r. Significant increases were found for all markers except for RANKL. There was a significant direct association between CTx and OC increases. Multivariable analysis showed that higher glomerular filtration rate (estimated through cystatin C clearance) predicted greater OPG increase, while older age, higher HIV RNA at baseline and use of ATV/r predicted greater CTx increase. A significant increase of parathormone accompanied the evolution of the study markers. 1,25-(OH)2 vitamin D remained stable, though a seasonality variation was demonstrated. CONCLUSIONS: These data demonstrate CTx increase (bone resorption marker) corresponding to OC increase (bone formation marker) early upon HAART initiation. Moreover, predictors of bone marker increases have been suggested, possibly indicating that a stricter monitoring of bone health and pro-active interventions are needed in older patients, those with higher HIV RNA, prescribed ATV/r rather than EFV, and with decreased renal function at baseline. Further studies are needed to clarify the mechanisms responsible for up-regulation of bone turnover markers, as well as to understand if and what markers are best correlated or predictive of pathological fractures.