Incidence and factors associated with the risk of sexually transmitted diseases in HIV-infected people seen for care in Italy: data from the Icona Foundation cohort.

Objectives: The aims of this study were to identify temporal trends in the incidence of sexually transmitted diseases (STDs) in a cohort of HIV-infected people and to evaluate factors associated with the risk of a new STD diagnosis. Methods: All HIV-infected patients in the Icona Foundation Study cohort enrolled after 1998 were included in this study. STD incidence rates (IRs) were calculated and stratified by calendar period. Predictors of STDs were identified using a Poisson regression model with sandwich estimates for standard errors. Results: Data for 9168 participants were analysed [median age 37.3 (range 18-81) years; 74% male; 30% men who have sex with men (MSM)]. Over 46 736 person-years of follow-up (PYFU), 996 episodes of STDs were observed [crude IR 21.3/1000 PYFU; 95% confidence interval (CI) 20.0-22.6/1000 PYFU]. In multivariable Poisson regression analysis, MSM [rate ratio (RR) 3.03; 95% CI 2.52-3.64 versus heterosexuals], calendar period (RR 1.67; 95% CI 1.42-1.97 for 2008-2012 versus 1998-2002), HIV RNA > 50 HIV-1 RNA copies/mL (RR 1.44; 95% CI 1.19-1.74 versus HIV RNA ≤ 50 copies/mL) and a current CD4 count < 100 cells/μL (RR 4.66; 95% CI 3.69-5.89; P < 0.001 versus CD4 count > 500 cells/μL) were associated with an increased risk of STDs. In contrast, older age (RR 0.82 per 10 years older; 95% CI 0.77-0.89) and being currently on ART (RR 0.38; 95% CI 0.33-0.45) compared with being ART-naïve or on a treatment interruption were associated with a lower risk of developing STDs. Conclusions: An increase in the incidence of STDs was observed in more recent years. Interventions to prevent STDs and potential spread of HIV should target the younger population, MSM and people currently not receiving ART

Is physician assessment of alcohol consumption useful in predicting risk of severe liver disease among people with HIV and HIV/HCV co-infection?

Background: Alcohol consumption is a known risk factor for liver disease in HIV-infected populations. Therefore, knowledge of alcohol consumption behaviour and risk of disease progression associated with hazardous drinking are important in the overall management of HIV disease. We aimed at assessing the usefulness of routine data collected on alcohol consumption in predicting risk of severe liver disease (SLD) among people living with HIV (PLWHIV) with or without hepatitis C infection seen for routine clinical care in Italy. Methods: We included PLWHIV from two observational cohorts in Italy (ICONA and HepaICONA). Alcohol consumption was assessed by physician interview and categorized according to the National Institute for Food and Nutrition Italian guidelines into four categories: abstainer; moderate; hazardous and unknown. SLD was defined as presence of FIB4 > 3.25 or a clinical diagnosis of liver disease or liver-related death. Cox regression analysis was used to evaluate the association between level of alcohol consumption at baseline and risk of SLD. Results: Among 9542 included PLWHIV the distribution of alcohol consumption categories was: abstainers 3422 (36%), moderate drinkers 2279 (23%), hazardous drinkers 637 (7%) and unknown 3204 (34%). Compared to moderate drinkers, hazardous drinking was associated with higher risk of SLD (adjusted hazard ratio, aHR = 1.45; 95% CI: 1.03-2.03). After additionally controlling for mode of HIV transmission, HCV infection and smoking, the association was attenuated (aHR = 1.32; 95% CI: 0.94-1.85). There was no evidence that the association was stronger when restricting to the HIV/HCV co-infected population. Conclusions: Using a brief physician interview, we found evidence for an association between hazardous alcohol consumption and subsequent risk of SLD among PLWHIV, but this was not independent of HIV mode of transmission, HCV-infection and smoking. More efforts should be made to improve quality and validity of data on alcohol consumption in cohorts of HIV/HCV-infected individuals

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 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 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

Non-AIDS defining cancers in the D:A:D Study-time trends and predictors of survival : a cohort study

BACKGROUND:Non-AIDS defining cancers (NADC) are an important cause of morbidity and mortality in HIV-positive individuals. Using data from a large international cohort of HIV-positive individuals, we described the incidence of NADC from 2004-2010, and described subsequent mortality and predictors of these.METHODS:Individuals were followed from 1st January 2004/enrolment in study, until the earliest of a new NADC, 1st February 2010, death or six months after the patient's last visit. Incidence rates were estimated for each year of follow-up, overall and stratified by gender, age and mode of HIV acquisition. Cumulative risk of mortality following NADC diagnosis was summarised using Kaplan-Meier methods, with follow-up for these analyses from the date of NADC diagnosis until the patient's death, 1st February 2010 or 6 months after the patient's last visit. Factors associated with mortality following NADC diagnosis were identified using multivariable Cox proportional hazards regression.RESULTS:Over 176,775 person-years (PY), 880 (2.1%) patients developed a new NADC (incidence: 4.98/1000PY [95% confidence interval 4.65, 5.31]). Over a third of these patients (327, 37.2%) had died by 1st February 2010. Time trends for lung cancer, anal cancer and Hodgkin's lymphoma were broadly consistent. Kaplan-Meier cumulative mortality estimates at 1, 3 and 5 years after NADC diagnosis were 28.2% [95% CI 25.1-31.2], 42.0% [38.2-45.8] and 47.3% [42.4-52.2], respectively. Significant predictors of poorer survival after diagnosis of NADC were lung cancer (compared to other cancer types), male gender, non-white ethnicity, and smoking status. Later year of diagnosis and higher CD4 count at NADC diagnosis were associated with improved survival. The incidence of NADC remained stable over the period 2004-2010 in this large observational cohort.CONCLUSIONS:The prognosis after diagnosis of NADC, in particular lung cancer and disseminated cancer, is poor but has improved somewhat over time. Modifiable risk factors, such as smoking and low CD4 counts, were associated with mortality following a diagnosis of NADC

A marked decrease of HIV 1 viremia in a population of potential transmitters in the 1997-2007 interval reduced the proportion of acute seroconverters but minimally affected the transmission of drug resistance

BACKGROUND: HIV-1 viremia is a major determinant of HIV-1 transmission at population level. We analysed the relationship between viremia levels of drug-experienced patients as potential transmitters (PTs), number of HIV-1 seroconversions and transmitted drug resistance (TDR) in newly diagnosed drug-naive patients (NDs) by an ecological longitudinal study. METHODS: We evaluated 95,832 HIV-1 RNA results from 4,615 treated patients followed at \u2018L. Sacco\u2019 Hospital during 1997-2007. HIV-1 RNA levels and CD4 cells for these patients ranged from 1.69 to 6.63 Log cp/ml and from 0 to 988 cells/\uf06dL. NDs, enrolled from 2002 to 2007, were 369, 103 of whom were seroconverters (SCs, 27.9%). HIV-1 RNA levels and CD4 cells for these patients ranged from 3.09 to 6.48 Log cp/ml and from 3 to 1,870 cells/\uf06dL. Pol sequences were obtained either by commercial kits or an home-made procedure. Resistance mutations were identified from 2008 IAS-USA list. Differences among proportions and temporal trends were tested using the chi-square and the Cochran-Armitage test, respectively. RESULTS: PTs were 72.2% males; modality of infection was 37.8%, 34.9% and 22.6% for IDUs, HEs MSMs, respectively. By dividing the study period in 5 biennial intervals the proportions of patients below 3 Log HIV-1 RNA significant increased from 49.5%, 56.6%, 66.1%, 70.0% to 81.6% overtime (p<.0001). NDs were males in 83.7% of cases; MSMs and HEs represented 51.7% and 44.4% of cases, respectively. When considering three biennial intervals in the year period \u201802-\u201907 for ND patients, a significant SCs decrease could be detected (from 35.3% in \u201902-\u201903 to 19.2% in \u201906-\u201907, p=.0057). Among individuals with established infection, MSM risk factor and female gender rose, although not significantly, from 58.8% to 68.0% and from 9.3% to 17.1% in the same interval. No changes were observed regarding other characteristics. Overall, TDR was 12.2% (45/369; 18.4% in SCs and 9.7% in NDs), fluctuating from 15.2% to 10.9% and 11.5% in the study period. Of note, 67.4% (29/45) of patients with TDR were MSMs. No primary resistance was detected in female SCs, while it was 11.5% (3/26) in female with unknown duration of infection. Among individuals with TDR, MSMs were 83.3% (15/18) for SCs and 56% (14/25) for individuals with established infection. CONCLUSIONS: This surveillance of an Italian metropolitan area at high prevalence of HIV-1 infection indicates that first generation HAART, as well as new potent antiretroviral combinations, achieved a marked reduction of HIV-1 viremia, reducing the proportions of SCs among NDs overtime. Nonetheless, TDR in na\uefve patients remained at substantial level and clustered in males who acquired HIV-1 infection through sex with man, thus representing an ongoing public health concern

Low prevalence of primary mutations associated to drug resitance in antiretroviral-naive patients at initiation of HAART.

OBJECTIVE: To assess the prevalence of mutations in the reverse-transcriptase (RT) and protease (PR) region in a cohort of chronically-infected HIV-positive patients requiring highly active antiretroviral therapy (HAART). METHODS: The study included 347 patients enrolled in the Italian Cohort of Antiretroviral Naive patients (I.CO.NA) who had to initiate HAART. The whole PR-region, and amino acids 1-320 of RT-region were sequenced from plasma samples at baseline. RESULTS: Median CD4-lymphocytes and HIV-RNA at baseline were 231 x 10(6) cells/l and 4.89 log(10) copies/ml; 307 of 347 (88.5%) patients carried no mutations in the RT region, whereas 40 (11.5%) carried one or more mutations associated with resistance to nucleoside-RT inhibitor (NRTI) (7.8%), or non-nucleoside-RTI (NNRTI) (4.9%), with four patients carrying mutations to both classes. Among mutations associated with high-level resistance to RTI, T215Y was found in only two patients, M184V in two cases, T69D and T215C in other two cases (one each), and K103N in only one patient, for a total of six patients (one carrying both T215Y and M184V) (1.7%). Seventy-six patients (21.9%) carried no mutations in the PR region, whereas 271 (78.1%) had one or more mutations. Primary mutations associated with substantial resistance to protease inhibitors were found in only five of 347 patients (1.4%) (M46V/L, I54V, V82A/I); all the other patients carried only secondary mutations (L10F/I/V, M36I, L63P, A71T/V, V77I). CONCLUSIONS: Prevalence of mutations associated with high-level resistance to antiretroviral drugs is low in HIV-infected patients with long-term infection. This suggests no preclusion in principle to any antiretroviral drug at the time of decision of the first therapeutic regimen

Evaluation of the prognostic value of impaired renal function on clinical progression in a large cohort of HIV-infected people seen for care in Italy

Whilst renal dysfunction, especially mild impairment (6090, 60-89, 90, 60-89, <60 ml/min, respectively, with an unadjusted HR of 2.49 (95%CI 1.56-3.97) for patients with eGFR <60 ml/min and 0.68 (95%CI 0.52-0.90) for eGFR 60-89. The risk of AIDS events was significantly lower in mild renal dysfunction group even after adjustment for HIV-related characteristics. Our data confirm that impaired renal function is an important risk marker for CCVD events in the HIV-population; importantly, even those with mild renal impairment (90<eGFR<60) seem to be at increased risk of cerebro-cardiovascular morbidity and mortality

Incidence and factors associated with the risk of sexually transmitted diseases in HIV-infected people seen for care in Italy: Data from the Icona Foundation cohort

Objectives The aims of this study were to identify temporal trends in the incidence of sexually transmitted diseases (STDs) in a cohort of HIV-infected people and to evaluate factors associated with the risk of a new STD diagnosis. Methods All HIV-infected patients in the Icona Foundation Study cohort enrolled after 1998 were included in this study. STD incidence rates (IRs) were calculated and stratified by calendar period. Predictors of STDs were identified using a Poisson regression model with sandwich estimates for standard errors. Results Data for 9168 participants were analysed [median age 37.3 (range 18\u201381) years; 74% male; 30% men who have sex with men (MSM)]. Over 46 736 person-years of follow-up (PYFU), 996 episodes of STDs were observed [crude IR 21.3/1000 PYFU; 95% confidence interval (CI) 20.0\u201322.6/1000 PYFU]. In multivariable Poisson regression analysis, MSM [rate ratio (RR) 3.03; 95% CI 2.52\u20133.64 versus heterosexuals], calendar period (RR 1.67; 95% CI 1.42\u20131.97 for 2008\u20132012 versus 1998\u20132002), HIV RNA > 50 HIV-1 RNA copies/mL (RR 1.44; 95% CI 1.19\u20131.74 versus HIV RNA 64 50 copies/mL) and a current CD4 count < 100 cells/\u3bcL (RR 4.66; 95% CI 3.69\u20135.89; P 500 cells/\u3bcL) were associated with an increased risk of STDs. In contrast, older age (RR 0.82 per 10 years older; 95% CI 0.77\u20130.89) and being currently on ART (RR 0.38; 95% CI 0.33\u20130.45) compared with being ART-na\uefve or on a treatment interruption were associated with a lower risk of developing STDs. Conclusions An increase in the incidence of STDs was observed in more recent years. Interventions to prevent STDs and potential spread of HIV should target the younger population, MSM and people currently not receiving ART