Efficacy of cefiderocol- vs colistin-containing regimen for treatment of bacteraemic ventilator-associated pneumonia caused by carbapenem-resistant Acinetobacter baumannii in patients with COVID-19.

INTRODUCTION: Ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii (CRAB) in patients hospitalized in intensive care units (ICUs) is an important and challenging complication, including in patients with coronavirus disease 2019 (COVID-19). Considering the poor lung penetration of most antibiotics, including intravenous colistin due to the poor pharmacokinetics/pharmacodynamics at the infection site, the choice of the best antibiotic regimen is still being debated. METHODS: This single-centre, observational study was conducted from March 2020 to August 2022, and included all patients hospitalized consecutively with VAP and concomitant bloodstream infection due to CRAB in the COVID-ICU. The main goal of the study was to evaluate risk factors associated with survival or death at 30 days from VAP onset. A propensity score for receiving therapy was added to the model. RESULTS: During the study period, 73 patients who developed VAP and concomitant positive blood cultures caused by CRAB were enrolled in the COVID-ICU. Of these patients, 67 (91.7%) developed septic shock, 42 (57.5%) had died at 14 days and 59 (80.8%) had died at 30 days. Overall, 54 (74%) patients were treated with a colistin-containing regimen and 19 (26%) were treated with a cefiderocol-containing regimen. Cox regression analysis showed that chronic obstructive pulmonary disease and age were independently associated with 30-day mortality. Conversely, cefiderocol-containing regimens and cefiderocol + fosfomycin in combination were independently associated with 30-day survival, as confirmed by propensity score analysis. CONCLUSIONS: This real-life study in patients with bacteraemic VAP caused by CRAB provides useful suggestions for clinicians, showing a possible benefit of cefiderocol and its association with fosfomycin.

Direct antimicrobial susceptibility testing (AST) from positive blood cultures using Microscan system for early detection of bacterial resistance phenotypes.

Antimicrobial Susceptibility Testing is mandatory for Bloodstream Infections management in order to establish appropriate antimicrobial therapy. Herein we evaluated new approach based on AST results directly from positive blood cultures, using Microscan WA to carry out rapid phenotypical profile of antibiotic resistance. Our investigations allow to reduce time versus traditional results.

Varicella zoster immunity loss in multiple sclerosis patient treated with ocrelizumab.

Ocrelizumab is a novel humanized anti-CD20 antibody used for treatment of relapsing remitting and primary progressive multiple sclerosis with evidence of inflammatory activity. Guidelines suggest assessing vaccination status and eventually vaccinate patients with multiple sclerosis before new disease modifying therapy initiation. However, there are not any specific recommendations about vaccinal immunity reassessment after ocrelizumab injection. We describe the case of a patient who loss varicella zoster vaccinal immunity after the first ocrelizumab infusion. It is advisable to reassess vaccinal immunity to isolate non-immune patients and to adopt suitable preventive measures, including close contacts vaccination and avoidance of contacts with active infection.

Predictors of incomplete viral response and virologic failure in patients with acute and early HIV infection. Results of Italian Network of ACuTe HIV InfectiON (INACTION) cohort.

OBJECTIVES: The aim of this study was to evaluate the factors that can influence an incomplete viral response (IVR) after acute and early HIV infection (AEHI). METHODS: This was a retrospective, observational study including patients with AEHI (Fiebig stages I-V) diagnosed between January 2008 and December 2014 at 20 Italian centres. IVR was defined by: (1) viral blip (51-1000 HIV-1 RNA copies/mL after achievement of < 50 HIV-1 RNA copies/mL); (2) virologic failure [> 1000 copies/mL after achievement of < 200 copies/mL, or ≥ 200 copies/mL after 24 weeks on an antiretroviral therapy (ART)]; (3) suboptimal viral response (> 50 copies/mL after 48 weeks on ART or two consecutive HIV-1 RNA levels with ascending trend during ART). Cox regression analysis was used to calculate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) for IVR. RESULTS: In all, 263 patients were studied, 227 (86%) males, with a median [interquartile range (IQR)] age of 38 (30-46) years. During a median follow-up of 13.0 (5.7-31.1) months, 38 (14.4%) had IVR. The presence of central nervous system (CNS) symptoms was linked to a higher risk of IVR (HR = 4.70, 95% CI: 1.56-14.17), while a higher CD4/CD8 cell count ratio (HR = 0.13, 95% CI: 0.03-0.51 for each point increase) and first-line ART with three-drug regimens recommended by current guidelines (HR = 0.40, 95% CI: 0.18-0.91 compared with other regimens including four or five drugs, older drugs or non-standard backbones) were protective against IVR. CONCLUSIONS: Patients with lower CD4/CD8 ratio and CNS symptoms could be at a higher risk of IVR after AEHI. The use of recommended ART may be relevant for improving short-term viral efficacy in this group of patients.

Evolution of transmitted HIV-1 drug resistance and viral subtypes circulation in Italy from 2006 to 2016.

OBJECTIVES: The aim was to evaluate the evolution of transmitted HIV-1 drug resistance (TDR) prevalence in antiretroviral therapy (ART)-naïve patients from 2006 to 2016. METHODS: HIV-1 sequences were retrieved from the Antiviral Response Cohort Analysis (ARCA) database and TDR was defined as detection of at least one mutation from the World Health Organization (WHO) surveillance list. RESULTS: We included protease/reverse transcriptase sequences from 3573 patients; 455 had also integrase sequences. Overall, 68.1% of the patients were Italian, the median CD4 count was 348 cells/µL [interquartile range (IQR) 169-521 cells/µL], and the median viral load was 4.7 log10 HIV-1 RNA copies/mL (IQR 4.1-5.3 log10 copies/mL). TDR was detected in 10.3% of patients: 6% carried mutations to nucleos(t)ide reverse transcriptase inhibitors (NRTIs), 4.4% to nonnucleos(t)ide reverse transcriptase inhibitors (NNRTIs), 2.3% to protease inhibitors (PIs), 0.2% to integrase strand transfer inhibitors (INSTIs) and 2.1% to at least two drug classes. TDR declined from 14.5% in 2006 to 7.3% in 2016 (P = 0.003): TDR to NRTIs from 9.9 to 2.9% (P = 0.003) and TDR to NNRTIs from 5.1 to 3.7% (P = 0.028); PI TDR remained stable. The proportion carrying subtype B virus declined from 76.5 to 50% (P < 0.001). The prevalence of TDR was higher in subtype B vs. non-B (12.6 vs. 4.9%, respectively; P < 0.001) and declined significantly in subtype B (from 17.1 to 8.8%; P = 0.04) but not in non-B subtypes (from 6.1 to 5.8%; P = 0.44). Adjusting for country of origin, predictors of TDR were subtype B [adjusted odds ratio (AOR) for subtype B vs. non-B 2.91; 95% confidence interval (CI) 1.93-4.39; P < 0.001], lower viral load (per log10 higher: AOR 0.86; 95% CI 0.75-0.99; P = 0.03), site in northern Italy (AOR for southern Italy/island vs. northern Italy, 0.61; 95% CI 0.40-0.91; P = 0.01), and earlier calendar year (per 1 year more recent: AOR 0.95; 95% CI 0.91-0.99; P = 0.02). CONCLUSIONS: The prevalence of HIV-1 TDR has declined during the last 10 years in Italy.

Natural NS5A inhibitor resistance associated substitutions in hepatitis C virus genotype 1 infected patients from Italy.

OBJECTIVES: Genetic variability in NS5A is associated with different levels of resistance to the currently licensed NS5A inhibitors. The aim of this study was to detect NS5A inhibitor resistance associated substitutions (RASs) in hepatitis C virus (HCV) genotype 1 (GT1) patients who are naive to direct-acting HCV antivirals. METHODS: Amplification, Sanger sequencing and phylogenetic analysis of the HCV NS5A region were performed on plasma obtained from 122 consecutive patients with HCV chronic infection attending four different clinics in Italy. RESULTS: NS5A inhibitor RASs were detected in 14/61 (23.0%) HCV GT1b and 3/61 (4.9%) HCV GT1a infected patients (p 0.007). The pan-genotypic RAS Y93H was detected in 1 (1.6%) GT1a and 4 (6.6%) GT1b patients. GT1a sequences clustered into two different clades with RASs detected in 1/34 (2.9%) clade I and 2/27 (7.4%) clade II sequences. CONCLUSIONS: Although the impact of naturally occurring NS5A RASs might be limited with upcoming pan-genotypic treatment regimens, this information is still useful to map naturally occurring HCV variants in different geographic areas in the context of current HCV therapy.

Reference curves for CD4 T-cell count response to combination antiretroviral therapy in HIV-1-infected treatment-naïve patients.

OBJECTIVES: The aim of this work was to provide a reference for the CD4 T-cell count response in the early months after the initiation of combination antiretroviral therapy (cART) in HIV-1-infected patients. METHODS: All patients in the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) cohort who were aged ≥ 18 years and started cART for the first time between 1 January 2005 and 1 January 2010 and who had at least one available measurement of CD4 count and a viral load ≤ 50 HIV-1 RNA copies/mL at 6 months (± 3 months) after cART initiation were included in the study. Unadjusted and adjusted references curves and predictions were obtained using quantile regressions. RESULTS: A total of 28 992 patients were included in the study. The median CD4 T-cell count at treatment initiation was 249 [interquartile range (IQR) 150, 336] cells/µL. The median observed CD4 counts at 6, 9 and 12 months were 382 (IQR 256, 515), 402 (IQR 274, 543) and 420 (IQR 293, 565) cells/µL. The two main factors explaining the variation of CD4 count at 6 months were AIDS stage and CD4 count at cART initiation. A CD4 count increase of ≥ 100 cells/mL is generally required in order that patients stay 'on track' (i.e. with a CD4 count at the same percentile as when they started), with slightly higher gains required for those starting with CD4 counts in the higher percentiles. Individual predictions adjusted for factors influencing CD4 count were more precise. CONCLUSIONS: Reference curves aid the evaluation of the immune response early after antiretroviral therapy initiation that leads to viral control.

Higher rates of triple-class virological failure in perinatally HIV-infected teenagers compared with heterosexually infected young adults in Europe.

OBJECTIVES: The aim of the study was to determine the time to, and risk factors for, triple-class virological failure (TCVF) across age groups for children and adolescents with perinatally acquired HIV infection and older adolescents and adults with heterosexually acquired HIV infection. METHODS: We analysed individual patient data from cohorts in the Collaboration of Observational HIV Epidemiological Research Europe (COHERE). A total of 5972 participants starting antiretroviral therapy (ART) from 1998, aged < 20 years at the start of ART for those with perinatal infection and 15-29 years for those with heterosexual infection, with ART containing at least two nucleoside reverse transcriptase inhibitors (NRTIs) and a nonnucleoside reverse transcriptase inhibitor (NNRTI) or a boosted protease inhibitor (bPI), were followed from ART initiation until the most recent viral load (VL) measurement. Virological failure of a drug was defined as VL > 500 HIV-1 RNA copies/mL despite ≥ 4 months of use. TCVF was defined as cumulative failure of two NRTIs, an NNRTI and a bPI. RESULTS: The median number of weeks between diagnosis and the start of ART was higher in participants with perinatal HIV infection compared with participants with heterosexually acquired HIV infection overall [17 (interquartile range (IQR) 4-111) vs. 8 (IQR 2-38) weeks, respectively], and highest in perinatally infected participants aged 10-14 years [49 (IQR 9-267) weeks]. The cumulative proportion with TCVF 5 years after starting ART was 9.6% [95% confidence interval (CI) 7.0-12.3%] in participants with perinatally acquired infection and 4.7% (95% CI 3.9-5.5%) in participants with heterosexually acquired infection, and highest in perinatally infected participants aged 10-14 years when starting ART (27.7%; 95% CI 13.2-42.1%). Across all participants, significant predictors of TCVF were those with perinatal HIV aged 10-14 years, African origin, pre-ART AIDS, NNRTI-based initial regimens, higher pre-ART viral load and lower pre-ART CD4. CONCLUSIONS: The results suggest a beneficial effect of starting ART before adolescence, and starting young people on boosted PIs, to maximize treatment response during this transitional stage of development.

Use of efavirenz or atazanavir/ritonavir is associated with better clinical outcomes of HAART compared to other protease inhibitors: routine evidence from the Italian MASTER Cohort.

Randomized trials and observational cohorts reported higher rates of virological suppression after highly active antiretroviral therapy (HAART) including efavirenz (EFV), compared with boosted protease inhibitors (PIs). Correlations with immunological and clinical outcomes are unclear. Patients of the Italian MASTER cohort who started HAART from 2000 to 2010 were selected. Outstanding outcome (composite outcome for success (COS)) was introduced. We evaluated predictors of COS (no AIDS plus CD4+ count >500/mm(3)plus HIV-RNA <500 copies/mL) and of eight single outcomes either at month 6 or at year 3. Multivariable logistic regression was conducted. There were 6259 patients selected. Patients on EFV (43%) were younger, had greater CD4+ count, presented with AIDS less frequently, and more were Italians. At year 3, 90% of patients had HIV RNA <500 copies/mL, but only 41.4% were prescribed EFV, vs. 34.1% prescribed boosted PIs achieved COS (p <0.0001). At multivariable analysis, patients on lopinavir/ritonavir had an odds ratio of 0.70 for COS at year 3 (p <0.0001). Foreign origin and positive hepatitis C virus-Ab were independently associated with worse outcome (OR 0.54, p <0.0001 and OR 0.70, p 0.01, respectively). Patients on boosted PIs developed AIDS more frequently either at month 6 (13.8% vs. 7.6%, p <0.0001) or at year 3 (17.1% vs. 13.8%, p <0.0001). At year 3, deaths of patients starting EFV were 3%, vs. 5% on boosted PIs (p 0.008). In this study, naïve patients on EFV performed better than those on boosted PIs after adjustment for imbalances at baseline. Even when virological control is achieved, COS is relatively rare. Hepatitis C virus-positive patients and those of foreign origin are at risk of not obtaining COS.

The incidence of AIDS-defining illnesses at a current CD4 count ≥ 200 cells/µL in the post-combination antiretroviral therapy era.

BACKGROUND: Few studies consider the incidence of individual AIDS-defining illnesses (ADIs) at higher CD4 counts, relevant on a population level for monitoring and resource allocation. METHODS: Individuals from the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) aged ≥14 years with ≥1 CD4 count of ≥200 µL between 1998 and 2010 were included. Incidence rates (per 1000 person-years of follow-up [PYFU]) were calculated for each ADI within different CD4 strata; Poisson regression, using generalized estimating equations and robust standard errors, was used to model rates of ADIs with current CD4 ≥500/µL. RESULTS: A total of 12 135 ADIs occurred at a CD4 count of ≥200 cells/µL among 207 539 persons with 1 154 803 PYFU. Incidence rates declined from 20.5 per 1000 PYFU (95% confidence interval [CI], 20.0-21.1 per 1000 PYFU) with current CD4 200-349 cells/µL to 4.1 per 1000 PYFU (95% CI, 3.6-4.6 per 1000 PYFU) with current CD4 ≥ 1000 cells/µL. Persons with a current CD4 of 500-749 cells/µL had a significantly higher rate of ADIs (adjusted incidence rate ratio [aIRR], 1.20; 95% CI, 1.10-1.32), whereas those with a current CD4 of ≥1000 cells/µL had a similar rate (aIRR, 0.92; 95% CI, .79-1.07), compared to a current CD4 of 750-999 cells/µL. Results were consistent in persons with high or low viral load. Findings were stronger for malignant ADIs (aIRR, 1.52; 95% CI, 1.25-1.86) than for nonmalignant ADIs (aIRR, 1.12; 95% CI, 1.01-1.25), comparing persons with a current CD4 of 500-749 cells/µL to 750-999 cells/µL. DISCUSSION: The incidence of ADIs was higher in individuals with a current CD4 count of 500-749 cells/µL compared to those with a CD4 count of 750-999 cells/µL, but did not decrease further at higher CD4 counts. Results were similar in patients virologically suppressed on combination antiretroviral therapy, suggesting that immune reconstitution is not complete until the CD4 increases to >750 cells/µL.

HIV-1 subtype is an independent predictor of reverse transcriptase mutation K65R in HIV-1 patients treated with combination antiretroviral therapy including tenofovir.

Subtype-dependent selection of HIV-1 reverse transcriptase resistance mutation K65R was previously observed in cell culture and small clinical investigations. We compared K65R prevalence across subtypes A, B, C, F, G, and CRF02_AG separately in a cohort of 3,076 patients on combination therapy including tenofovir. K65R selection was significantly higher in HIV-1 subtype C. This could not be explained by clinical and demographic factors in multivariate analysis, suggesting subtype sequence-specific K65R pathways.

Future research and collaboration: the "SINERGIE" project on HCV (South Italian Network for Rational Guidelines and International Epidemiology).

The SINERGIE (South Italian Network for Rational Guidelines and International Epidemiology) project is intended to set up a collaborative network comprising virologists, clinicians and public health officials dealing with patients affected by HCV disease in the Calabria Region. A prospective observational data-base of HCV infection will be developed and used for studies on HCV natural history, response to treatment, pharmaco-economics, disease complications, and HCV epidemiology (including phylogenetic analysis). With this approach, we aim at improving the identification and care of patients, focusing on upcoming research questions. The final objective is to assist in improving care delivery and inform Public Health Authorities on how to optimize resource allocation in this area.

Lung cancer in HIV-infected patients: the experience in Brescia from 1999 to 2009.

Lung cancer (LC) is the most common cancer among the non AIDS-defining malignancies in the highly active antiretroviral therapy (HAART) era. We described 23 HIV infected patients with a LC diagnosis followed in the Clinic of Tropical and Infectious Diseases of Brescia during the period of 1999-2009. All of these patients except two (n = 21, 91.3%) were cigarette smokers and all had at least one risk factor for developing cancer of the lung, or predisposing comorbidities, such as a COPD (chronic obstructive pulmonary disease) or a previous pneumonia. The median age at LC diagnosis was 53.6 years (range 21.2-71.4 years). Adenocarcinoma and squamous cell carcinoma were diagnosed in 10 cases (43.5%) respectively. In 21 subjects (91.3%) cancer was detected at stage IV with metastases. The median survival was 5.95 months. Greater intervention focused on the cessation of smoking is necessary, as well as the implementation of closer screening policies, especially in HIV-positive subjects with LC risk factors.

Evolution of transmitted HIV-1 drug resistance in HIV-1-infected patients in Italy from 2000 to 2010.

Prevalence and predictors of transmitted drug resistance (TDR), defined as the presence of at least one WHO surveillance drug resistance mutation (SDRM), were investigated in antiretroviral-naïve HIV-1-infected patients, with a genotypic resistance test (GRT) performed ≤6 months before starting cART between 2000 and 2010. 3163 HIV-1 sequences were selected (69% subtype B). Overall, the prevalence of TDR was 12% (13.2% subtype B, 9% non-B). TDR significantly declined overall and for the single drug classes. Older age independently predicted increased odds of TDR, whereas a more recent GRT, a higher HIV-RNA and C vs. B subtype predicted lower odds of TDR.

Factors influencing the normalization of CD4+ T-cell count, percentage and CD4+/CD8+ T-cell ratio in HIV-infected patients on long-term suppressive antiretroviral therapy.

We evaluated factors associated with normalization of the absolute CD4+ T-cell counts, per cent CD4+ T cells and CD4+/CD8+ T-cell ratio. A multicentre observational study was carried out in patients with sustained HIV-RNA <50 copies/mL. Outcomes were: CD4-count >500/mm(3) and multiple T-cell marker recovery (MTMR), defined as CD4+ T cells >500/mm(3) plus%CD4 T cells >29%plus CD4+/CD8+ T-cell ratio >1. Kaplan-Meier survival analysis and Cox regression analyses to predict odds for achieving outcomes were performed. Three hundred and fifty-two patients were included and followed-up for a median of 4.1 (IQR 2.1-5.9) years, 270 (76.7%) achieving a CD4+ T-cell count >500 cells/mm(3) and 197 (56%) achieving MTMR. Using three separate Cox models for both outcomes we demonstrated that independent predictors were: both absolute CD4+ and CD8+ T-cell counts, %CD4+ T cells, a higher CD4+/CD8+ T-cell ratio, and age. A likelihood-ratio test showed significant improvements in fitness for the prediction of either CD4+ >500/mm(3) or MTMR by multivariable analysis when the other immune markers at baseline, besides the absolute CD4+ count alone, were considered. In addition to baseline absolute CD4+ T-cell counts, pretreatment %CD4+ T cells and the CD4+/CD8+ T-cell ratio influence recovery of T-cell markers, and their consideration should influence the decision to start antiretroviral therapy. However, owing to the small sample size, further studies are needed to confirm these results in relation to clinical endpoints.

Specific prebiotics modulate gut microbiota and immune activation in HAART-naive HIV-infected adults: results of the "COPA" pilot randomized trial.

Intestinal mucosal immune system is an early target for human immunodeficiency virus type 1 (HIV-1) infection, resulting in CD4(+) T-cell depletion, deterioration of gut lining, and fecal microbiota composition. We evaluated the effects of a prebiotic oligosaccharide mixture in highly active antiretroviral therapy (HAART)-naive HIV-1-infected adults. In a pilot double-blind, randomized, placebo-controlled study, 57 HAART-naive HIV-1-infected patients received a unique oligosaccharide mixture (15 or 30 g short chain galactooligosaccharides/long chain fructooligosaccharides/pectin hydrolysate-derived acidic oligosaccharides (scGOS/lcFOS/pAOS) daily) or a placebo for 12 weeks. Microbiota composition improved significantly with increased bifidobacteria, decreased Clostridium coccoides/Eubacterium rectale cluster, and decreased pathogenic Clostridium lituseburense/Clostridium histolyticum group levels upon prebiotic supplementation. In addition, a reduction of soluble CD14 (sCD14), activated CD4(+)/CD25(+) T cells, and significantly increased natural killer (NK) cell activity when compared with control group were seen in the treatment group. The results of this pilot trial highly significantly show that dietary supplementation with a prebiotic oligosaccharide mixture results in improvement of the gut microbiota composition, reduction of sCD14, CD4(+) T-cell activation (CD25), and improved NK cell activity in HAART-naive HIV-infected individuals.

The evolving burden of HIV infection compared with other chronic diseases in northern Italy.

OBJECTIVES: The aim of the study was to estimate the burden and direct costs of diseases in HIV-infected patients (either opportunistic illnesses or other chronic diseases) with respect to the HIV-uninfected population. These estimates will be useful for the projection of future direct costs of HIV care. PATIENTS AND METHODS: A population-based study was conducted in the Brescia Local Health Agency in northern Italy. An administrative database recorded diagnoses, deaths, drug prescriptions and health resource utilization for all medical and surgical patients in the region from 2003 to 2007. The study estimated the prevalence of HIV infection as well as HIV-related mortality and annual cost per patient, and compared mortality and costs related to HIV infection with those for a set of 15 other chronic diseases. The standardized hazard ratio (SHR) and standardized mortality ratio (SMR) were obtained using an indirect standardization method. RESULTS: The prevalence of HIV infection increased from 218 per 100,000 inhabitants in 2003 to 263 per 100,000 in 2007. Although mortality rates decreased markedly (from 24 per 1000 HIV-infected patients in 2003 to 16 per 1000 in 2007), the data show that mortality was still higher in HIV-infected patients compared with the general population in the most recent years (SMR 8.8 in 2007). In each year included in the study, HIV-infected patients had higher rates of care-seeking for chronic diseases, including liver diseases (SHR>8), neuropathy, oesophagus-gastro-duodenum diseases, serious psychiatric disorders and renal failure (SHR approximately 3 for each). Also, the rate of medical attendance for neoplasias, chronic pulmonary disease, diabetes, and cardiovascular disease increased over time in HIV-infected patients compared with the general population. Ranking diseases in order of their total cost to the health system, HIV infection ranked 12th, with total costs of €28.6 million in 2007. Ranking in order of cost per patient, HIV infection ranked third, with a cost per patient of €9894 in 2007. HIV-infected patients with concomitant chronic diseases had higher average costs. The cost per patient in 2007 was €8104 for HIV-infected patients without other chronic diseases, €9908 for HIV infection plus cardiovascular disease, €11,370 for HIV infection plus chronic liver disease and €12,013 for HIV infection plus neoplasias. CONCLUSIONS: The prevalence and population cost of people living with HIV are likely to increase as a result of prolonged survival, aging of HIV-infected patients and increased risk of other chronic diseases. In the near future, HIV infection will rank as one of the most costly chronic diseases. Prevention strategies need to be more widely adopted to control the growing burden of the HIV epidemic and other chronic diseases affecting HIV-infected patients.

Favourable evolution of virological and immunological profiles in treated and untreated patients in Italy in the period 1998-2008.

BACKGROUND: This study provides an estimate of the proportion of HIV-positive patients in Italian clinics showing an 'adverse prognosis' (defined as a CD4 count ≤ 200 cells/µL or an HIV RNA >50 HIV-1 RNA copies/mL) over time, and investigates whether this proportion varied according to patients' characteristics. METHODS: We estimated the annual proportion of patients with a CD4 count ≤ 200 cells/µL or HIV RNA > 50 copies/mL out of the total number of patients in the Icona Foundation cohort seen in any given year, both overall and after stratifying by demographical and treatment status groups. Generalized estimating equation models for Poisson regression were applied. RESULTS: In 1998-2008, the prevalence of patients with a CD4 count ≤ 200 cells/µL decreased from 14 to 6% [adjusted relative risk (RR) 0.86/year; 95% confidence interval (CI) 0.84-0.88; P<0.0001]. The prevalence of HIV RNA > 50 copies/mL decreased from 66 to 40% (adjusted RR 0.95/year; 95% CI 0.95-0.96; P<0.0001) in all patients and from 38 to 12% in the subgroup of patients who had previously received antiretroviral therapy (ART) for ≥ 6 months (adjusted RR 0.89/year; 95% CI 0.88-0.90; P<0.0001). CONCLUSIONS: There was a substantial increase in the success rate of ART in Italy in 1998-2008, resulting in a lower percentage of patients with adverse prognosis in recent years. The use of ART seemed to be the most important determinant of viral load outcome, regardless of mode of transmission. Although injecting drug users showed a less marked improvement in CD4 cell count over time than other risk groups, they showed a similar improvement in detectable viral load.