Anti-spike antibody level is associated with the risk of clinical progression among subjects hospitalized with COVID-19 pneumonia: results from a retrospective cohort study.

PURPOSE: Antibodies against SARS-CoV-2 spike (anti-S) may confer protection against symptomatic COVID-19. Whether their level predicts progression among those with COVID-19 pneumonia remains unclear. METHODS: We conducted a retrospective cohort study to assess predictors of anti-S levels and whether anti-S titer is associated with death or mechanical ventilation (MV). Adults hospitalized for COVID-19 pneumonia between July 2021 and July 2022 were enrolled if anti-S had been measured within 72 h of admission. Predictors of anti-S level were explored using multivariable quantile regression. The association between anti-S levels and 30-day death/MV was investigated via multivariable logistic regression. Analyses were stratified by vaccine status. RESULTS: The median anti-S level was 1370 BAU/ml in 328 vaccinated and 15.5 BAU/ml in 206 unvaccinated individuals. Among the vaccinated, shorter symptom duration (p = 0.001), hematological malignancies (p = 0.002), and immunosuppressive therapy (p = 0.004) were associated with lower anti-S levels. In the unvaccinated group, symptom duration was the only predictor of anti-S levels (p < 0.001). After 30 days, 134 patients experienced death or MV. Among vaccinated individuals, higher anti-S levels correlated significantly with lower death/MV risk (per log2 increase, OR 0.88, 95%CI 0.81-0.97), irrespective of age and solid malignancies. Among unvaccinated, a marginally protective effect was observed (OR 0.86, 95%CI 0.73-1.01), independent of age, immunosuppressive therapy, and diabetes. Adjustment for monoclonal antibody treatment strengthened the association (OR 0.81, 95%CI 0.68-0.96). CONCLUSION: This study suggests that levels of anti-S antibodies can predict critical or fatal outcomes in COVID-19 pneumonia patients, regardless of vaccination. Whether anti-S Ab could guide risk assessment and vaccination boosting merits further evaluation.

In-label, off-label prescription, efficacy and tolerability of dalbavancin: report from a National Registry.

PURPOSE: Although dalbavancin is currently approved for the treatment of ABSSIs, several studies suggest its efficacy and tolerance as long-term therapy for other off-label indications requiring prolonged intravenous antibiotic administration. METHODS: We conducted a prospective nationwide study of dalbavancin use in real-life settings for both approved and off-label indications analysing for each case the clinical and microbiological characteristics of infection the efficacy and safety of treatments. RESULTS: During the study period (from December 2018 to July 2021), the ID specialists from 14 different centres enrolled 223 patients treated with dalbavancin [141 males (63%) and 82 females (37%); male/female ratio 1.72; mean age 59 (SD 17.2) years, (range 15-96). Most patients in the study population (136/223; 61.0%) came from community rather than health care facilities and most of them were visited in Infectious Diseases wards (93/223; 41.7%) and clinics (55/223; 24.7%) even though some patients were cured in other settings, such as surgery wards (18/223; 8.1%), orthopaedic wards (11/223; 4.9%), Emergency Rooms (7/223; 3.1%) and non-surgical other than ID wards (6/223; 2.7%). The most common ID diagnoses were osteomyelitis (44 cases/223; 19.7%; of which 29 acute and 15 chronic osteomyelitis), cellulitis (28/223; 12.5%), cutaneous abscess (23/223; 10.3%), orthopaedic prosthesis-associated infection (22/223; 9.9%), surgical site infection (20/223; 9.0%) and septic arthritis (15/223; 6.7%). CONCLUSION: In conclusion, by virtue of its PK/PD properties, dalbavancin represents a valuable option to daily in-hospital intravenous or outpatient antimicrobial regimens also for off-label indications requiring a long-term treatment of Gram-positive infections.

BCGitis after Bacille Calmette-Guerin intravesical administration from two referral centers: clinical characteristics and risk factors.

Bacillus Calmette-Guerin (BCG) is commonly and safely used as intravesical instillation to treat bladder cancer. Adverse effects are widely described in case report and series with a broad range of clinical presentations known as "BCGitis". Moreover, microbiological identification is often inconclusive leading to diagnostic uncertainty and no standardisation of definitions is available. We retrospectively collected all cases of BCGitis (n=19) after BCG intravesical administration occurred in 2 major Italian hospitals in the last 10 years. Median age was 71.8 years and among comorbidities hypertension affected 60% of patients. The delay in the onset of symptoms was < one week and an inverse correlation was observed between the number of instillations and the time to the onset of symptoms. Moreover, a febrile presentation was the commonest clinical symptom (85%) and an interstitial or micronodular pattern at chest X-ray or CT scan was found positive in about 70% and 90% of cases, respectively. Larger cohorts are needed in order to inform clinically relevant algorythms for this uncommon disease.

miRNA Expression Profiling in Subcutaneous Adipose Tissue of Monozygotic Twins Discordant for HIV Infection: Validation of Differentially Expressed miRNA and Bioinformatic Analysis.

Combined AntiRetroviral Treatments (cARTs) used for HIV infection may result in varied metabolic complications, which in some cases, may be related to patient genetic factors, particularly microRNAs. The use of monozygotic twins, differing only for HIV infection, presents a unique and powerful model for the controlled analysis of potential alterations of miRNAs regulation consequent to cART treatment. Profiling of 2578 mature miRNA in the subcutaneous (SC) adipose tissue and plasma of monozygotic twins was investigated by the GeneChip® miRNA 4.1 array. Real-time PCR and ddPCR experiments were performed in order to validate differentially expressed miRNAs. Target genes of deregulated miRNAs were predicted by the miRDB database (prediction score > 70) and enrichment analysis was carried out with g:Profiler. Processes in SC adipose tissue most greatly affected by miRNA up-regulation included (i) macromolecular metabolic processes, (ii) regulation of neurogenesis, and (iii) protein phosphorylation. Furthermore, KEGG analysis revealed miRNA up-regulation involvement in (i) insulin signaling pathways, (ii) neurotrophin signaling pathways, and (iii) pancreatic cancer. By contrast, miRNA up-regulation in plasma was involved in (i) melanoma, (ii) p53 signaling pathways, and (iii) focal adhesion. Our findings suggest a mechanism that may increase the predisposition of HIV+ patients to insulin resistance and cancer.

HPV 16 and 18 contribute to development of anal dysplasia in HIV infection irrespective of gender and sexual orientation.

OBJECTIVES: The aim of the present study was too investigate prevalence and persistence of human papilloma virus (HPV) and cytological abnormalities (CAs) in the anal swabs of people living with HIV (PLWH): men who have sex with men (MSM), men who have sex with women (MSW) and women (W). METHODS: Between March 2010 and January 2019, an anal swab for cytological and HPV genotyping tests was offered to all PLWH attending our clinic. Logistic regression analysis was conducted to identify predictors of infection. RESULTS: In all, 354 PLWH were screened: 174 MSM, 90 MSW and 61 W. Prevalence of at least one high-risk (HR) HPV was higher in MSM (91%) and W (85%) than in MSW (77%) (P < 0.05). Cytological abnormalities were found in 21.1% of the entire population. At multivariable regression analysis a lower risk for HPV infection was found for W than for MSM [odds ratio = 0.24 (95% confidence interval: 0.115-0.513)] and for MSW than for MSM [0.37 (0.180-0.773)] and there was a significantly higher risk of CAs in PLWH with HPV 16 and 18 [3.3 (1.04-10.49)]. A total of 175 PLWH (103 MSM, 33 MSW and 26 W) had at least one follow-up visit (T1) after a median (interquartile range) follow-up of 3.6 (2.1-5.7) years. The acquisition rate of HR-HPV was high, with 66.7% of PLWH negative for HR-HPV at T0 who became positive at T1 (P < 0.001). The prevalence of CAs was stable (20.6%). A significant association between CAs at T1 and persistence of HPV-16 and/or 18 was found (P < 0.05). CONCLUSIONS: HPV 16 and 18 are associated with the presence and development of CAs irrespective of sexual orientation.

Compassionate Use of Remdesivir in Children With Severe COVID-19.

OBJECTIVES: Remdesivir shortens time to recovery in adults with severe coronavirus disease 2019 (COVID-19), but its efficacy and safety in children are unknown. We describe outcomes in children with severe COVID-19 treated with remdesivir. METHODS: Seventy-seven hospitalized patients <18 years old with confirmed severe acute respiratory syndrome coronavirus 2 infection received remdesivir through a compassionate-use program between March 21 and April 22, 2020. The intended remdesivir treatment course was 10 days (200 mg on day 1 and 100 mg daily subsequently for children ≥40 kg and 5 mg/kg on day 1 and 2.5 mg/kg daily subsequently for children <40 kg, given intravenously). Clinical data through 28 days of follow-up were collected. RESULTS: Median age was 14 years (interquartile range 7-16, range <2 months to 17 years). Seventy-nine percent of patients had ≥1 comorbid condition. At baseline, 90% of children required supplemental oxygen and 51% required invasive ventilation. By day 28 of follow-up, 88% of patients had a decreased oxygen-support requirement, 83% recovered, and 73% were discharged. Among children requiring invasive ventilation at baseline, 90% were extubated, 80% recovered, and 67% were discharged. There were 4 deaths, of which 3 were attributed to COVID-19. Remdesivir was well tolerated, with a low incidence of serious adverse events (16%). Most adverse events were related to COVID-19 or comorbid conditions. Laboratory abnormalities, including elevations in transaminase levels, were common; 61% were grades 1 or 2. CONCLUSIONS: Among 77 children treated with remdesivir for severe COVID-19, most recovered and the rate of serious adverse events was low.

Compassionate Use of Remdesivir for Patients with Severe Covid-19.

BACKGROUND: Remdesivir, a nucleotide analogue prodrug that inhibits viral RNA polymerases, has shown in vitro activity against SARS-CoV-2. METHODS: We provided remdesivir on a compassionate-use basis to patients hospitalized with Covid-19, the illness caused by infection with SARS-CoV-2. Patients were those with confirmed SARS-CoV-2 infection who had an oxygen saturation of 94% or less while they were breathing ambient air or who were receiving oxygen support. Patients received a 10-day course of remdesivir, consisting of 200 mg administered intravenously on day 1, followed by 100 mg daily for the remaining 9 days of treatment. This report is based on data from patients who received remdesivir during the period from January 25, 2020, through March 7, 2020, and have clinical data for at least 1 subsequent day. RESULTS: Of the 61 patients who received at least one dose of remdesivir, data from 8 could not be analyzed (including 7 patients with no post-treatment data and 1 with a dosing error). Of the 53 patients whose data were analyzed, 22 were in the United States, 22 in Europe or Canada, and 9 in Japan. At baseline, 30 patients (57%) were receiving mechanical ventilation and 4 (8%) were receiving extracorporeal membrane oxygenation. During a median follow-up of 18 days, 36 patients (68%) had an improvement in oxygen-support class, including 17 of 30 patients (57%) receiving mechanical ventilation who were extubated. A total of 25 patients (47%) were discharged, and 7 patients (13%) died; mortality was 18% (6 of 34) among patients receiving invasive ventilation and 5% (1 of 19) among those not receiving invasive ventilation. CONCLUSIONS: In this cohort of patients hospitalized for severe Covid-19 who were treated with compassionate-use remdesivir, clinical improvement was observed in 36 of 53 patients (68%). Measurement of efficacy will require ongoing randomized, placebo-controlled trials of remdesivir therapy. (Funded by Gilead Sciences.).

Latent tuberculosis infection screening in persons newly-diagnosed with HIV infection in Italy: A multicentre study promoted by the Italian Society of Infectious and Tropical Diseases.

BACKGROUND: The Italian Society of Infectious and Tropical Diseases performed a survey on the application of guidelines for the management of persons living with HIV (PLWH), to evaluate current practice and the yield of screening for latent tuberculosis infection (LTBI) in newly-diagnosed PLWH; in addition, the offer of preventive therapy to LTBI individuals and the completion rate were analysed. MATERIALS AND METHODS: Newly-diagnosed PLWH in nine centres were evaluated retrospectively (2016/2017) using binary and multinomial logistic regression to identify factors associated with LTBI diagnostic screening and QuantiFERON (QFT) results. RESULTS: Of 801 patients evaluated, 774 were studied after excluding active TB. LTBI tests were performed in 65.5%. Prescription of an LTBI test was associated with being foreign-born (odds ratio (OR) 3.19, p < 0.001), older (for 10-year increments, OR 1.22, p = 0.034), and having a CD4 count <100 cells/mm3 vs ≥500 cells/mm3 (OR 2.30, p = 0.044). LTBI was diagnosed in 6.5% of 495 patients evaluated by QFT. Positive results were associated with being foreign-born (relative risk ratio (RRR) 30.82, p < 0.001), older (for 10-year increments, RRR 1.78, p = 0.003), and having a high CD4 count (for 100 cells/mm3 increments, RRR 1.26, p < 0.003). Sixteen LTBI individuals started TB preventive therapy and eight completed it. CONCLUSIONS: LTBI screening is inconsistently performed in newly-diagnosed PLWH. Furthermore, TB preventive therapy is not offered to all LTBI individuals and compliance is poor.

The effect of primary drug resistance on CD4+ cell decline and the viral load set-point in HIV-positive individuals before the start of antiretroviral therapy.

OBJECTIVE: To evaluate the effect of primary resistance and selected polymorphic amino-acid substitutions in HIV reverse transcriptase and protease on the CD4 cell count and viral load set point before the start of antiretroviral treatment. DESIGN: Prospective cohort study. METHODS: A total of 6180 individuals with a resistance test prior to starting antiretroviral treatment accessing care in HIV clinics across Europe who had at least one viral load and one CD4+ test available were included in the analysis. The impact of amino-acid substitutions variants on viral load and CD4+ trends was investigated using linear mixed models. Clusters of mutations were studied using principal component analysis. RESULTS: Overall, the detection of any primary resistance was not associated with either the speed of CD4+ cell decline or the viral load set point. However, transmitted nucleoside reverse transcriptase inhibitor and protease inhibitor resistance appeared to be weakly associated with lower viral load set points, as were the polymorphic G16E or Q92K protease mutations. There was some evidence suggesting that these effects varied according to HIV subtype, with the effects of transmitted nucleoside reverse transcriptase inhibitor and protease resistance being particularly marked among individuals with a subtype B virus. A cluster of five polymorphic protease substitutions at position 20, 13, 36, 69 and 89 was associated with less steep CD4+ cell declines and lower viral load set points. CONCLUSION: Although we found little evidence for an association between primary resistance and CD4+ speed of decline and viral load set point, the potential role of polymorphic protease (alone or in clusters) and their interplay with HIV subtype needs to be further evaluated.

Brief Report: Peripheral Monocyte/Macrophage Phenotypes Associated With the Evolution of Cognitive Performance in HIV-Infected Patients.

BACKGROUND: The contribution of monocyte activation in the development of HIV-associated neurocognitive disorders is not completely understood. This study aimed to explore the predictive value of peripheral monocyte/macrophage (M/M) phenotypes on the evolution of cognitive performance in a population of virologically suppressed HIV-infected patients. SETTING: Prospective, observational, longitudinal study. METHODS: HIV-1-infected patients with HIV-RNA <50copies/mL for >12 months underwent neuropsychological examination at baseline and after 1 year. Cognitive performance was evaluated using Z-transformed scores, and neurocognitive impairment (NCI) was defined according to Frascati criteria. Peripheral M/M phenotypes (classic CD14CD16, intermediate CD14CD16, and nonclassic CD14CD16) and specific surface activation markers (eg, CD163, CD11b, and CD38) were evaluated using flow cytometry at baseline. Predictive value of peripheral M/M phenotypes on the evolution of cognitive performance over 1-year follow-up was also evaluated. RESULTS: Overall, 54 patients [85.2% men, median age 50 years (range 27-60 years), 27.8% hepatitis C virus coinfected, 48.1% with past AIDS-defining events, median nadir CD4 83 cells/µL (range 1-334), median baseline CD4 547 cells/µL (range 136-1652)] were enrolled. Proportion of patients with NCI was low, accounting for 13% at baseline and 16.5% after 1 year (P = 0.687). Memory was the only single domain in which decreased performance after 1 year was observed (-0.25 Z-score, P = 0.025). In patients with significant decrease (≥0.5 SD) in memory performance (n = 20), significantly lower CD14CD16CD163 (% CD14CD16) (P = 0.038) and higher CD14CD38 (% CD14) (P = 0.030) levels were observed. CONCLUSIONS: In virologically suppressed HIV-infected patients, the evolution of memory performance could be linked to the expression of certain peripheral activated M/M phenotypes. Such associations should be verified in larger populations over the long term.

Characterizing Non-Tuberculous Mycobacteria Infection in Bronchiectasis.

Chronic airway infection is a key aspect of the pathogenesis of bronchiectasis. A growing interest has been raised on non-tuberculous mycobacteria (NTM) infection. We aimed at describing the clinical characteristics, diagnostic process, therapeutic options and outcomes of bronchiectasis patients with pulmonary NTM (pNTM) disease. This was a prospective, observational study enrolling 261 adult bronchiectasis patients during the stable state at the San Gerardo Hospital, Monza, Italy, from 2012 to 2015. Three groups were identified: pNTM disease; chronic P. aeruginosa infection; chronic infection due to bacteria other than P. aeruginosa. NTM were isolated in 32 (12%) patients, and among them, a diagnosis of pNTM disease was reached in 23 cases. When compared to chronic P. aeruginosa infection, patients with pNTM were more likely to have cylindrical bronchiectasis and a "tree-in-bud" pattern, a history of weight loss, a lower disease severity and a lower number of pulmonary exacerbations. Among pNTM patients who started treatment, 68% showed a radiological improvement, and 37% achieved culture conversion without recurrence, while 21% showed NTM isolation recurrence. NTM isolation seems to be a frequent event in bronchiectasis patients, and few parameters might help to suspect NTM infection. Treatment indications and monitoring still remain an important area for future research.

Prognostic Value of the Fibrosis-4 Index in Human Immunodeficiency Virus Type-1 Infected Patients Initiating Antiretroviral Therapy with or without Hepatitis C Virus.

OBJECTIVE: To evaluate the Fibrosis (FIB)-4 index as a predictor of major liver-related events (LRE) and liver-related death (LRD) in human immunodeficiency virus (HIV) type-1 patients initiating combination antiretroviral therapy (cART). DESIGN: Retrospective analysis of a prospective cohort study. SETTING: Italian HIV care centers participating to the ICONA Foundation cohort. PARTICIPANTS: Treatment-naive patients enrolled in ICONA were selected who: initiated cART, had hepatitis C virus (HCV) serology results, were HBsAg negative, had an available FIB-4 index at cART start and during follow up. METHODS: Cox regression models were used to determine the association of FIB4 with the risk of major LRE (gastrointestinal bleeding, ascites, hepatic encephalopathy, hepato-renal syndrome or hepatocellular carcinoma) or LRD. RESULTS: Three-thousand four-hundred seventy-five patients were enrolled: 73.3% were males, 27.2% HCV seropositive. At baseline (time of cART initiation) their median age was 39 years, had a median CD4+ T cell count of 260 cells/uL, and median HIV RNA 4.9 log copies/mL, 65.9% had a FIB-4 <1.45, 26.4% 1.45-3.25 and 7.7% >3.25. Over a follow up of 18,662 person-years, 41 events were observed: 25 major LRE and 16 LRD (incidence rate, IR, 2.2 per 1,000 PYFU [95% confidence interval, CI 1.6-3.0]). IR was higher in HCV seropositives as compared to negatives (5.9 vs 0.5 per 1,000 PYFU). Higher baseline FIB-4 category as compared to <1.45 (FIB-4 1.45-3.25: HR 3.55, 95% CI 1.09-11.58; FIB-4>3.25: HR 4.25, 1.21-14.92) and time-updated FIB-4 (FIB-4 1.45-3.25: HR 3.40, 1.02-11.40; FIB-4>3.25: HR 21.24, 6.75-66.84) were independently predictive of major LRE/LRD, after adjusting for HIV- and HCV-related variables, alcohol consumption and type of cART. CONCLUSIONS: The FIB-4 index at cART initiation, and its modification over time are risk factors for major LRE or LRD, independently of infection with HCV and could be used to monitor patients on cART.

Nontuberculous Mycobacteria in Noncystic Fibrosis Bronchiectasis.

During the past decades, a growing interest has been raised in evaluating nontuberculous mycobacteria (NTM) in patients with noncystic fibrosis bronchiectasis (NCFBE). This paper reviews several aspects of the correlations between NTM and NCFBE, including pathogenesis, radiological features, diagnosis, and management. Bronchiectasis and NTM lung disease are connected, but which one comes first is still an unresolved question. The rate of NTM lung disease in NCFBE varies through the studies, from 5% to 30%. The most frequent species isolated is MAC. NCFBE patients affected by NTM infection frequently present coinfections, including both other different NTM species and microorganisms, such as P. aeruginosa. Once a diagnosis of NTM disease has been reached, the initiation of therapy is not always mandatory. NTM species isolated, patients' conditions, and disease severity and its evolution should be considered. Risk factors for disease progression in NCFBE patients with NTM are low body mass index, cavitary disease, consolidations, and macrolide resistance at presentation.

Risk of Severe Non AIDS Events Is Increased among Patients Unable to Increase their CD4+ T-Cell Counts >200+/µl Despite Effective HAART.

BACKGROUND: Immunological non-response (INR) despite virological suppression is associated with AIDS-defining events/death (ADE). Little is known about its association with serious non-AIDS-defining events (nADE). METHODS: Patients highly-active antiretroviral therapy (HAART) with <200 CD4+/µl and achieving HIV-RNA <50 copies/ml within 12 (±3) months were categorized as INR if CD4+ T-cell count at year 1 was <200/µl. Predictors of nADE (malignancies, severe infections, renal failure--ie, estimated glomerular filtration rate <30 ml/min, cardiovascular events and liver decompensation) were assessed using multivariable Cox models. Follow-up was right-censored in case of HAART discontinuation or confirmed HIV-RNA>50. RESULTS: 1221 patients were observed for a median of 3 (IQR: 1.3-6.1) years. Pre-HAART CD4+ were 77/µl (IQR: 28-142) and 56% of patients had experienced an ADE. After 1 year, CD4+ increased to 286 (IQR: 197-387), but 26.1% of patients were INR. Thereafter, 86 nADE (30.2% malignancies, 27.9% infectious, 17.4% renal, 17.4% cardiovascular, 7% hepatic) were observed, accounting for an incidence of 1.83 events (95%CI: 1.73-2.61) per 100 PYFU. After adjusting for measurable confounders, INR had a significantly greater risk of nADE (HR 1.65; 95%CI: 1.06-2.56). Older age (per year, HR 1.03; 95%CI: 1.01-1.05), hepatitis C co-infection (HR 2.09; 95%CI: 1.19-3.7), a history of previous nADE (HR 2.16; 95%CI: 1.06-4.4) and the occurrence of ADE during the follow-up (HR 2.2; 95%CI: 1.15-4.21) were other independent predictors of newly diagnosed nADE. CONCLUSIONS: Patients failing to restore CD4+ to >200 cells/µl run a greater risk of serious nADE, which is intertwined or predicted by AIDS progression. Improved management of this fragile population and innovative therapy able to induce immune-reconstitution are urgently needed. Also, our results strengthen the importance of earlier diagnosis and HAART introduction.

Cancer incidence and mortality for all causes in HIV-infected patients over a quarter century: a multicentre cohort study.

BACKGROUND: We aimed to assess cancer incidence and mortality for all-causes and factors related to risk of death in an Italian cohort of HIV infected unselected patients as compared to the general population. METHODS: We conducted a retrospective (1986-2012) cohort study on 16 268 HIV infected patients enrolled in the MASTER cohort. The standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs) were computed using cancer incidence rates of Italian Cancer Registries and official national data for overall mortality. The risk factors for death from all causes were assessed using Poisson regression models. RESULTS: 1,195 cancer cases were diagnosed from 1986 to 2012: 700 AIDS-defining-cancers (ADCs) and 495 non-AIDS-defining-cancers (NADCs). ADC incidence was much higher than the Italian population (SIR = 30.8, 95% confidence interval 27.9-34.0) whereas NADC incidence was similar to the general population (SIR = 0.9, 95% CI 0.8-1.1). The SMR for all causes was 11.6 (11.1-12.0) in the period, and it decreased over time, mainly after 1996, up to 3.53 (2.5-4.8) in 2012. Male gender, year of enrolment before 1993, older age at enrolment, intravenous drug use, low CD4 cell count, AIDS event, cancer occurrence and the absence of antiretroviral therapy were all associated independently with risk of death. CONCLUSIONS: In HIV infected patients, ADC but not NADC incidence rates were higher than the general population. Although overall mortality in HIV infected subjects decreased over time, it is about three-fold higher than the general population at present.

Survival in HIV-infected patients after a cancer diagnosis in the cART Era: results of an italian multicenter study.

OBJECTIVES: We studied survival and associated risk factors in an Italian nationwide cohort of HIV-infected individuals after an AIDS-defining cancer (ADC) or non-AIDS-defining cancer (NADC) diagnosis in the modern cART era. METHODS: Multi-center, retrospective, observational study of HIV patients included in the MASTER Italian Cohort with a cancer diagnosis from January 1998 to September 2012. Malignancies were divided into ADC or NADC on the basis of the Centre for Disease Control-1993 classification. Recurrence of cancer and metastases were excluded. Survivals were estimated according to the Kaplan-Meier method and compared according to the log-rank test. Statistically significant variables at univariate analysis were entered in a multivariate Cox regression model. RESULTS: Eight hundred and sixty-six cancer diagnoses were recorded among 13,388 subjects in the MASTER Database after 1998: 435 (51%) were ADCs and 431 (49%) were NADCs. Survival was more favorable after an ADC diagnosis than a NADC diagnosis (10-year survival: 62.7%±2.9% vs. 46%±4.2%; p = 0.017). Non-Hodgkin lymphoma had lower survival rates than patients with Kaposi sarcoma or cervical cancer (10-year survival: 48.2%±4.3% vs. 72.8%±4.0% vs. 78.5%±9.9%; p<0.001). Regarding NADCs, breast cancer showed better survival (10-year survival: 65.1%±14%) than lung cancer (1-year survival: 28%±8.7%), liver cancer (5-year survival: 31.9%±6.4%) or Hodgkin lymphoma (10-year survival: 24.8%±11.2%). Lower CD4+ count and intravenous drug use were significantly associated with decreased survival after ADCs or NADCs diagnosis. Exposure to cART was found to be associated with prolonged survival only in the case of ADCs. CONCLUSIONS: cART has improved survival in patients with an ADC diagnosis, whereas the prognosis after a diagnosis of NADCs is poor. Low CD4+ counts and intravenous drug use are risk factors for survival following a diagnosis of ADCs and Hodgkin lymphoma in the NADC group.