Durability, safety, and efficacy of rilpivirine in clinical practice: results from the SCOLTA Project.

Rilpivirine is associated with a good efficacy and safety profile. However, data from real-life settings are scarce. METHODS: We investigated the durability, safety and efficacy of Rilpivirine-based antiretroviral therapy in a prospective, observational, multicenter study. RESULTS: We enrolled 499 HIV-infected patients, 360 (72.1%) males, mean age 43.4 ± 10.5 years, mean CD4 600 ± 327 cell/µL, mean HIV-RNA 3.80 ± 1.15 log10 cp/mL. After a median follow up of 16 months, 81 (16.2%) interruptions were reported, 36 (7.2%) of which for adverse events (16 of grade ≥3), most commonly neurological and gastrointestinal. We observed virological failures in only 8 (1.6%) patients. Naive patients showed a significant reduction in eGFR at week 24, 48 and 72 and in total cholesterol (TC)/HDL ratio at week 48 (p=0.007). In patients switching from PI we found a significant decrease at week 24 and 48 in TC and triglycerides at week 24, 48 and 72. eGFR showed a significant decrease at week 48 and 72. TC/HDL ratio showed a statistically significant decrease at week 24 (p=0.0008) and 72 (p=0.04). A significant increase at week 24 and 48 in AST and ALT values was observed. Patients switching from TDF/FTC/EFV showed a reduction in HDL, total cholesterol and triglycerides at week 24 and 48 and in eGFR at all follow up times. TC/HDL ratio showed a significant decrease at week 48 (p=0.01). CDC stage C and antiretroviral-experience (especially Protease Inhibitors) were associated with RPV discontinuation. CONCLUSION: In conclusion, our data confirm Rilpivirine efficacy, safety and tolerability with improvement in lipid profile. Although hepatic and renal events rarely caused discontinuation, liver and kidney parameters should be monitored.

Impact of circulating resistance-associated mutations on HIV pre-exposure prophylaxis (PrEP) efficacy: Modeling from antiretroviral resistance cohort analysis (ARCA) national database.

BACKGROUND: PrEP with FTC/TDF has shown great efficacy in preventing new HIV infections but issues remain (low adherence, high costs, toxicity and resistance development). No data are available about the impact of circulating Resistance-Associated Mutations (RAMs) on its efficacy. OBJECTIVES: describe the prevalence of FTC and/or TDF-related RAMs in Italian HIV-infected population and their potential impact on PrEP efficacy. STUDY DESIGN: ARCA is a national database that collects data about RAMs and epidemiological correlates from sites throughout Italy; it was queried about the prevalence of these RAMs in the last decade. PrEP efficacy was adjusted for a dynamic score based on RAMs prevalence. Absolute and relative risk increases (ARI and RRI) and number needed to harm (NNH) were calculated after this score. RESULTS: the query retrieved 3579 HAART-naïve and 5781 experienced subjects. Resistance to TDF is low and more common among naïve MSM in the area of Milan (where it topped to 14.3%), without other significant differences. If good adherence is not attained, RRI for receptive anal sex increases by 16% (in naïve) and 93.4% (in experienced MSM). NNH is largely above 10000 except for having receptive anal sex with a HAART-experienced MSM on a failing treatment (970). CONCLUSIONS: according to this model, PrEP may be introduced in Italy without general concerns, but efficacy may be partly reduced in young MSM having sex in Rome and Milan.

Statins and Aspirin use in HIV-infected people: gap between European AIDS Clinical Society guidelines and clinical practice: the results from HIV-HY study.

OBJECTIVES: To investigate the use of statins and acetylsalicylic acid (ASA) in HIV people in clinical practice. DESIGN: A multicenter, nationwide, prospective cohort study, including 1182 consecutive HIV patients was conducted. METHODS: Statin and ASA prescription was evaluated in primary and secondary cardiovascular disease prevention, according to the European AIDS Clinical Society (EACS) guidelines. RESULTS: Followed-up patients (998) were mostly males (70.9 %) with a mean age at enrolment of 46.5 years (SD 9.5). The mean time of follow-up was 3.3 years (SD 0.8). At the last follow-up visit, statins would have been recommended for 31.2 % and ASA for 16 % by EACS guidelines. Conversely, only 15.6 and 7.6 % of patients were on statin and ASA treatment, respectively; only 50.3 % of patients treated with statins achieved recommended low-density lipoprotein cholesterol (LDL-c) levels. At the last follow-up visit, agreement between statin therapy and EACS recommendation was 0.58 (95 % CI 0.52-0.63). The corresponding figure for ASA therapy was 0.50 (95 % CI 0.42-0.58), whereas the agreement for ASA therapy in secondary prevention was 0.59 (95 % CI 0.50-0.68). CONCLUSIONS: The prescription of statins and ASA in HIV-infected patients remains largely suboptimal, as only about 50 % of patients requiring statins and ASA are properly treated. Higher attention on this relevant issue and further investigation are warranted in this at risk population.

Darunavir-based dual therapy of treatment-experienced HIV-infected patients: analysis from a national multicenter database.

BACKGROUND: We assessed the virological response of dual therapy with DRV/r, plus raltegravir, maraviroc or etravirine, in virological failure patients and in virologically suppressed patients collected in the Italian Antiretroviral Resistance Database (ARCA). MATERIAL AND METHODS: The primary endpoint was the percentage of patients remaining free of virological failure (confirmed >50 copies/mL or any change in the regimen). Subjects had a resistance test and at least one follow-up visit. Observation was censored at last visit under dual therapy and survival analysis and proportional hazard models were used. RESULTS: Sixty-seven percent of the 221 patients started DRV/r with RAL, 20.4 % with ETV, and 12.2 % with MAR; 31.2 % virological failures were observed. At survival analysis, the overall proportion of failure was 29.2 % at 1 year and 33.8 % at 2 years. The proportion of failure was lower in patients starting with undetectable vs. detectable viral load (13.3 and 25.2 % vs. 37.4 and 38.8 % at 1 and 2 years, respectively, p = 0.001 for both analyses) and in patients treated with DRV 600 BID vs. 800 QD (HR: 0.56, 95 % CI: 0.31-0.99, p < 0.05). By regimen, the adjusted proportional model showed no significant difference among the three regimens. A significant lower risk of failure was associated with higher GSS (HIV-DB HR: 0.53, 95 % CI: 0.32-0.88, p = 0.014; Rega 0.60, 0.40-0.88, p < 0.01; ANRS 0.55, 0.34-0.90, p = 0.017), while a higher risk of failure with detectable HIV-RNA (3.02, 1.70-5.72, p < 0.001). CONCLUSIONS: Among experienced patients, the best candidates for dual-therapy regimens including DRV/r are those with undetectable viral load and higher GSS.

Muscle symptoms and creatine phosphokinase elevations in patients receiving raltegravir in clinical practice: Results from the SCOLTA project long-term surveillance.

Muscle alterations ranging from asymptomatic creatine phosphokinase (CPK) increases to rhabdomyolysis and central nervous system (CNS) symptoms have been reported in patients receiving raltegravir. Muscle symptoms and CPK increases were investigated in a cohort of HIV-infected patients receiving raltegravir-based antiretroviral therapy, and possible associated predictors were evaluated. The SCOLTA Project is a prospective, observational, multicentre study created to assess the incidence of adverse events in patients receiving new antiretroviral drugs in clinical practice. In total, 496 HIV-infected patients were enrolled [333 (67.1%) male]. CDC stage was C in 196 patients (39.5%). Mean age at enrolment was 45.9 ± 9.3 years. Median follow-up was 21 months. Twenty-six patients (5.2%) reported muscle symptoms (16 muscle pain and 17 weakness; 7 had both). Of 342 patients with normal baseline CPK values, 72 (21.1%) had a CPK increase. Seven patients (1.4%) discontinued raltegravir because of muscular events (three for muscle pain/weakness and four CPK increases). No cases of rhabdomyolysis were observed. Patients with muscle symptoms were more frequently receiving in their regimen than those not receiving atazanavir (P=0.04) and were more likely to also report CNS symptoms (P<0.0001). Significant predictors of muscle symptoms were CNS symptoms and use of atazanavir. Female sex was associated with a reduced risk of CPK increase. In conclusion, muscle symptoms and CPK elevations occurred frequently and caused most discontinuations due to adverse events. Their monitoring in patients receiving raltegravir should be considered, especially when co-administered with atazanavir or when CNS symptoms are also present.

Darunavir-based dual therapy in HIV experienced patients.

BACKGROUND: We assessed the virological response of DRV/r-based dual therapy in drug-experienced patients included in the Italian antiretroviral resistance database (ARCA). MATERIALS AND METHODS: Patients included in the study were treated with DRV/r in association with raltegravir (RAL), etravirine (ETV) or maraviroc (MAR) following treatment failure(s) and with a resistance test and at least one follow-up visit available. Observation was censored at last visit under dual therapy and survival analysis and proportional hazard models were used, taking virological failure (confirmed >50 c/mL HIV-RNA) as the end-point. RESULTS: Of the total 221 patients included, 149 (67.4%) started DRV/r with RAL, 45 (20.4%) with ETV, 27 (12.2%) with MAR. Patients characteristics at the start of dual regimen were as follows: mean number of previous regimens, nine (IQR: 5-13); non-B subtype, 17 (7.7%); median CD4 count, 347 (IQR: 246-544); undetectable viral load, 74 (33.5%). Full DRV/r resistance was detected in one (0.5%, HIV-DB interpretation system), 13 (5.9%, ANRS) and 17 patients (7.7%, Rega). 69 virological failures (31.2%) were observed during follow-up. At survival analysis, the overall proportion of failure was 29.2% at one year and 33.8% at two years. The proportion of failure was lower in patients starting with undetectable versus detectable viral load (13.3% and 25.2% versus 37.4% and 38.8% at one and two years, respectively, p=0.001 for both analyses) and in patients treated with DRV 600 BID versus 800 QD (HR: 0, 56; 95% CI 0.31-0.99; p<0.05). By regimen, patients treated with DRV/r-RAL showed a non-significant lower proportion of failure (27.7% at one year, 32.0% at two years) if compared with DRV/r-MAR (35.9%, 47.1%) and DRV/r-ETV (34.1%, 34.1% at one and two years). In the adjusted proportional model, no significant difference among the three regimens was detected. A significant lower risk of failure was associated with higher overall GSS (HIV-DB HR: 0.53, 95% CI 0.32-0.88, p=0.014; Rega 0.60, 0.40-0.88, p<0.01; ANRS 0.55, 0.34-0.90, p=0.017), while a higher risk of failure was associated with detectable HIV-RNA (3.02, 1.70-5.72, p<0.001). CONCLUSIONS: Among experienced patients, the best candidates to dual-therapy regimens including DRV/r are those with undetectable viral load and higher GSS. The association with RAL is the most commonly used but no clear advantage with respect to ETV or MAR was observed in our dataset, possibly due to the limited sample size.

The role of baseline HIV-1 RNA, drug resistance, and regimen type as determinants of response to first-line antiretroviral therapy.

The factors influencing virological response to first-line combined antiretroviral therapy (cART) in an Italian cohort of HIV-1-infected patients were examined. Eligible patients were those enrolled in a national prospective observational cohort (Antiretroviral Resistance Cohort Analysis), starting first-line cART between 2001 and 2011 and who had at least one follow-up of HIV-1 RNA. The primary endpoint was virological success, defined as the first viral load <50 copies/ml. Time to events were analyzed by Kaplan-Meier analysis and Cox proportional hazard model. One thousand three hundred five patients met the study inclusion criteria. In a multivariable model adjusting for transmission mode, presence of transmitted drug resistance, baseline CD4(+) cell count, viral subtype, and type of NRTI backbone employed, independent predictors of virological success were higher baseline viral load (≥500,000 vs. <100,000 HR 0.52; P < 0.001), a weighted genotypic susceptibility score (wGSS) <3 (HR 0.58; P = 0.003), male sex (HR 0.76 P = 0.001), and type of initial third drug employed (integrase inhibitor vs. boosted protease inhibitors HR 3.23; P < 0.001). In the subset with HIV-1 RNA >100,000 copies/ml, virologic success was only associated with the use of integrase inhibitors in the first cART regimen. Independent predictors of immunological success were baseline CD4(+) cell count and wGSS <3. High baseline HIV-1 RNA, predicted activity of the first-line regimen based on genotypic resistance testing, gender, and use of new agents were found to predict time to achieve virological success. The type of initial nucleoside analog backbone was not found to predict virological response.

Decreasing cardiovascular risk in HIV infection between 2005 and 2011.

Cardiovascular risk profile was compared in 765 Italian HIV-infected outpatients enrolled in 2005 and in 765 individually age-matched and sex-matched patients enrolled in 2011. Median Framingham risk score was 8.6% in 2005 vs. 7.9% in 2011 (P = 0.04); metabolic syndrome was present in 40.3% vs. 33.4% (P = 0.006). Blood glucose, triglycerides, prevalence of smokers, and lipodystrophy were all significantly lower in 2011 (all P < 0.0001). Cardiovascular risk improved over a 6-year period in Italian HIV-infected patients.

Dolutegravir in antiretroviral-experienced patients with raltegravir- and/or elvitegravir-resistant HIV-1: 24-week results of the phase III VIKING-3 study.

BACKGROUND: The pilot phase IIb VIKING study suggested that dolutegravir (DTG), a human immunodeficiency virus (HIV) integrase inhibitor (INI), would be efficacious in INI-resistant patients at the 50 mg twice daily (BID) dose. METHODS: VIKING-3 is a single-arm, open-label phase III study in which therapy-experienced adults with INI-resistant virus received DTG 50 mg BID while continuing their failing regimen (without raltegravir or elvitegravir) through day 7, after which the regimen was optimized with ≥1 fully active drug and DTG continued. The primary efficacy endpoints were the mean change from baseline in plasma HIV-1 RNA at day 8 and the proportion of subjects with HIV-1 RNA <50 c/mL at week 24. RESULTS: Mean change in HIV-1 RNA at day 8 was -1.43 log10 c/mL, and 69% of subjects achieved <50 c/mL at week 24. Multivariate analyses demonstrated a strong association between baseline DTG susceptibility and response. Response was most reduced in subjects with Q148 + ≥2 resistance-associated mutations. DTG 50 mg BID had a low (3%) discontinuation rate due to adverse events, similar to INI-naive subjects receiving DTG 50 mg once daily. CONCLUSIONS: DTG 50 mg BID-based therapy was effective in this highly treatment-experienced population with INI-resistant virus. CLINICAL TRIALS REGISTRATION: www.clinicaltrials.gov (NCT01328041) and http://www.gsk-clinicalstudywww.gsk-clinicalstudyregister.com (112574).

Safety and durability in a cohort of HIV-1 positive patients treated with once and twice daily darunavir-based therapy (SCOLTA Project).

OBJECTIVE: To evaluate safety and durability of once-daily and twice-daily darunavir/ritonavir (DRV/r)-based treatment in HIV patients in clinical practice. METHODS: The Surveillance Cohort Long-Term Toxicity Antiretrovirals (SCOLTA) project is a prospective, observational, multicenter cohort created to assess the incidence of adverse events in patients receiving new antiretroviral drugs. Twenty-five Italian infectious diseases centers enroll patients and collect their data through this on-line system. Periodical evaluations of these patients, including physical examination and laboratory tests, were performed at baseline and every 6 months. RESULTS: Four hundred and twenty-nine patients were enrolled since May 2006. Eighty-five patients (19.8%) were prescribed once-daily DRV/r; 31 of them were treatment-naïve (36.5%). Among 54 (63.5%) treatment-experienced patients, 21 (38.9%) had undetectable viral load and started once-daily DRV/r as a simplification regimen. Patients on twice-daily regimen were older, more frequently lipodystrophic, HCV-coinfected, and in CDC stage C. In the following 24 months of follow-up, the viral load steadily decreased as well as the CD4 cell count rose. The reason for discontinuation did not significantly differ between groups. Mean blood glucose (BG) change from baseline did not show significant difference between groups, as well as high density lipoprotein cholesterol (HDL-C), triglycerides (TGL) and alanine transaminase (ALT). The survival curve shows that patients in the once-daily regimen withdrew treatment more frequently than those on twice-daily regimen (Log Rank Chi(2)P=0.009). CONCLUSION: Our study showed that DRV/r administrated both once daily or twice daily was safe and well tolerated with few discontinuations due to adverse events.

Symmetric ambulatory arterial stiffness index and 24-h pulse pressure in HIV infection: results of a nationwide cross-sectional study.

OBJECTIVE: HIV infection has been associated with increased cardiovascular risk. Twenty-four-hour ambulatory blood pressure (BP) is a more accurate and prognostically relevant measure of an individual's BP load than office BP, and the ambulatory BP-derived ambulatory arterial stiffness index (AASI) and symmetric AASI (s-AASI) are established cardiovascular risk factors. METHODS: In the setting of the HIV and HYpertension (HIV-HY) study, an Italian nationwide survey on high BP in HIV infection, 100 HIV-infected patients with high-normal BP or untreated hypertension (72% men, age 48 ±â€Š10 years, BP 142/91 ±â€Š12/7 mmHg) and 325 HIV-negative individuals with comparable age, sex distribution, and office BP (68% men, age 48 ±â€Š10 years, BP 141/90 ±â€Š11/8 mmHg) underwent 24-h ambulatory BP monitoring. RESULTS: Despite having similar office BP, HIV-infected individuals had higher 24-h SBP (130.6 ±â€Š14 vs. 126.4 ±â€Š10 mmHg) and pulse pressure (49.1 ±â€Š9 vs. 45.9 ±â€Š7 mmHg, both P < 0.001), and a lower day-night reduction of mean arterial pressure (14.3 ±â€Š9 vs. 16.3 ±â€Š7%, P = 0.025). Both s-AASI and AASI were significantly higher in HIV patients (s-AASI, 0.22 ±â€Š0.18 vs. 0.11 ±â€Š0.15; AASI, 0.46 ±â€Š0.22 vs. 0.29 ±â€Š0.17; both P <0.001). In a multivariate regression, s-AASI was independently predicted by HIV infection (ß = 0.252, P <0.001), age, female sex, and 24-h SBP. In HIV patients, s-AASI had an inverse relation with CD4 cell count (Spearman's ρ -0.24, P = 0.027). CONCLUSION: Individuals with HIV infection and borderline or definite hypertension have higher symmetric AASI and 24-h systolic and pulse pressures than HIV-uninfected controls matched by office BP. High ambulatory BP may play a role in the HIV-related increase in cardiovascular risk.

Duration of first-line antiretroviral therapy with tenofovir and emtricitabine combined with atazanavir/ritonavir, efavirenz or lopinavir/ritonavir in the Italian ARCA cohort.

OBJECTIVES: To explore the durability of three first-line tenofovir/emtricitabine-based regimens in combination with atazanavir/ritonavir, efavirenz or lopinavir/ritonavir in HIV-1-infected patients. PATIENTS AND METHODS: A retrospective, longitudinal, multicentre analysis of adult patients enrolled in the Antiretroviral Resistance Cohort Analysis (ARCA), a national prospective observational cohort of HIV-1-infected patients followed up at more than 100 clinical and laboratory units in Italy. Patients eligible were those starting first-line antiretroviral therapy between 1 June 2004 and 15 April 2011 and who were followed up for at least 6 months. The primary endpoint was durability, defined as the time from antiretroviral therapy initiation to first treatment modification. Time-dependent events were analysed by the Kaplan-Meier approach and the Cox proportional hazard model. RESULTS: There are 26,000 HIV-infected patients in the ARCA database, of whom 1654 met study inclusion criteria. Six hundred and thirty-nine (38.6%) received efavirenz, 321 (19.4%) received atazanavir/ritonavir and 694 (41.9%) received lopinavir/ritonavir as a first-line regimen. Over a total observation period of 88 months, equivalent to more than 2805 person-years of follow-up, 618 patients underwent treatment modification. Lopinavir/ritonavir, given twice daily, was associated with a higher discontinuation rate than efavirenz- and atazanavir-based regimens [hazard ratio (HR) 1.83, 95% confidence interval (CI) 1.56-2.15, P = 0.001]. Comparing the once-daily regimens, the rate of discontinuation of efavirenz was higher than that of atazanavir/ritonavir (HR 1.39, 95% CI 1.06-1.83, P = 0.016). CONCLUSIONS: Significant differences in treatment duration were observed among the three studied regimens. Once-daily regimens exhibited greater durability than the twice-daily regimen. Among the specific regimens examined, tenofovir/emtricitabine plus atazanavir/ritonavir showed the greatest durability.

The feature of Metabolic Syndrome in HIV naive patients is not the same of those treated: results from a prospective study.

Metabolic Syndrome (MS) is a common disorder combining obesity, dyslipidemia, hypertension, and insulin resistance. Its prevalence among HIV-infected people is still debated. Besides, how antiretroviral therapy and HIV infection per se are related to MS is still unclear. All treatment-naïve patients attending scheduled visits at CISAI group hospitals between January and December 2007 were eligible for the study. Patients without MS at enrolment were followed-up for 3 years or until they developed MS, diagnosed according to the National Cholesterol Education Program (NCEP) definition. The main objective was to assess the 3-years incidence of MS. MS was evaluated for 188 subjects. Out of them, 62 (33.0%) had started HAART at enrolment, whereas 67 (35.6%) more started during the observation. 59 (31.4%) were still treatment-naive at the study end. MS was newly diagnosed in 14 patients. The incidence was 2.60 cases/100 person-years (95% CI 1.47-4.51), 2.75 (1.11-5.72) among HAART-naïve patients and 2.65 (1.23-5.03) in subjects on HAART. Blood pressure did not change in the study period, whereas in naive patients the HDL level significantly lowered (median -6.0 vs. 4.0, P<0.0001) compared to HAART-treated patients. Triglicerides increased significantly in HAART subjects (median 12.0 vs. 1.0, P=0.02), as well as blood glucose (median 6.0 vs. 1.0, P=0.01). In our population, the overall MS incidence was low and largely similar in patients who started HAART or remained naive. However, the feature of MS was different in the two groups, suggesting that in untreated and treated patients MS developed through different metabolic pathways.

A prognostic model for estimating the time to virologic failure in HIV-1 infected patients undergoing a new combination antiretroviral therapy regimen.

BACKGROUND: HIV-1 genotypic susceptibility scores (GSSs) were proven to be significant prognostic factors of fixed time-point virologic outcomes after combination antiretroviral therapy (cART) switch/initiation. However, their relative-hazard for the time to virologic failure has not been thoroughly investigated, and an expert system that is able to predict how long a new cART regimen will remain effective has never been designed. METHODS: We analyzed patients of the Italian ARCA cohort starting a new cART from 1999 onwards either after virologic failure or as treatment-naïve. The time to virologic failure was the endpoint, from the 90th day after treatment start, defined as the first HIV-1 RNA > 400 copies/ml, censoring at last available HIV-1 RNA before treatment discontinuation. We assessed the relative hazard/importance of GSSs according to distinct interpretation systems (Rega, ANRS and HIVdb) and other covariates by means of Cox regression and random survival forests (RSF). Prediction models were validated via the bootstrap and c-index measure. RESULTS: The dataset included 2337 regimens from 2182 patients, of which 733 were previously treatment-naïve. We observed 1067 virologic failures over 2820 persons-years. Multivariable analysis revealed that low GSSs of cART were independently associated with the hazard of a virologic failure, along with several other covariates. Evaluation of predictive performance yielded a modest ability of the Cox regression to predict the virologic endpoint (c-index≈0.70), while RSF showed a better performance (c-index≈0.73, p < 0.0001 vs. Cox regression). Variable importance according to RSF was concordant with the Cox hazards. CONCLUSIONS: GSSs of cART and several other covariates were investigated using linear and non-linear survival analysis. RSF models are a promising approach for the development of a reliable system that predicts time to virologic failure better than Cox regression. Such models might represent a significant improvement over the current methods for monitoring and optimization of cART.

No pol mutation is associated independently with the lack of immune recovery in patients infected with HIV and failing antiretroviral therapy.

An investigation was undertaken to determine whether specific pol mutations hinder long-term immune recovery regardless of virological response. In total, 826 patients with >50 HIV RNA copies/ml, who underwent genotypic resistance testing between 1 January 2000 and 31 December 2003 after >3 years of antiretroviral treatment, and were followed up for >3 years after genotypic resistance testing, were analyzed retrospectively. The outcome of the study was the lack of immune recovery after >3 years of follow-up, defined as a slope by linear regression <0. The viremia detectability ratio was defined as the number of HIV RNA values of >50 copies/ml divided by the number of HIV RNA measurements during follow-up. Logistic regression was used for univariable and multivariable analysis. Median (Q1, Q3) values at baseline were the following: age 40 (37, 45) years, years on antiretroviral therapy 4.45 (3.65, 5.47), HIV RNA 3.91 (3.39, 4.53) log(10) copies/ml, CD4+ T-cell 358 (211, 524)/µl. After 3.13 years of follow-up, 375 patients (45.4%) showed a lack of immune recovery. The risk of lack of immune recovery increased independently with increasing baseline CD4+ counts (OR=1.104 per 50-cell increase, 95% CI=1.069-1.142, P<0.0001), increasing viremia detectability ratio during follow-up (OR=1.145 per 0.1-unit increase, 95% CI=1.093-1.202, P<0.0001), and with earlier calendar years of resistance testing (overall effect: P=0.0007). In conclusion, no pol mutation is associated independently with the lack of immune recovery.

Is metabolic syndrome associated to HIV infection per se? Results from the HERMES study.

HERMES is a prospective study, including all treatment-naïve patients attending scheduled visits at hospitals in the CISAI group in 2007. The present cross-sectional analysis aims to assess the baseline prevalence and characteristics of Metabolic Syndrome (MS) in a population of HIV-positive treatment-naïve patients. MS was diagnosed using the National Cholesterol Education Program (NCEP) definitions. A total of 292 subjects were enrolled, median age was 37 years, 75% of them were males. The prevalence of MS was 12.3%. The most frequent trio of abnormalities that led to the diagnosis of MS was high blood pressure, triglycerides and HDL. Univariate analysis showed that MS was associated with the following variables: age, education, physical activity, advanced HIV disease (CDC stage C or HIV-RNA >100,000 copies + CD4 <100 cells/mm(3)). Higher educational levels remained protectively associated with MS in multivariate analysis. A higher risk of MS was also associated with advanced HIV disease. Actually, treatment-naïve HIV-positive patients in an advanced stage of the disease have a higher prevalence of abnormal levels of triglycerides, HDL cholesterol and blood glucose than those at a less advanced stage. These findings of the HERMES study suggest, therefore, that HIV infection per se is associated to MS.

Fosamprenavir/ritonavir in advanced HIV disease (TRIAD): a randomized study of high-dose, dual-boosted or standard dose fosamprenavir/ritonavir in HIV-1-infected patients with antiretroviral resistance.

BACKGROUND: APV102002 was an open-label study comparing a dual-boosted HIV-1 protease inhibitor (PI) [fosamprenavir/lopinavir/ritonavir (FPV/LPV/RTV; 1400 mg/533 mg/133 mg twice daily)] and a high dose of FPV/RTV 1400 mg/100 mg twice daily (HD-FPV/RTV) versus the standard FPV/RTV 700 mg/100 mg twice-daily (STD-FPV/RTV) regimen for 24 weeks. METHODS: Adult patients with prior failure to two or more PI-based regimens and on a failing PI regimen were randomized to STD-FPV/RTV (n = 24), HD-FPV/RTV (n = 25) or FPV/LPV/RTV (n = 25). The primary aim was to test week 24 superiority of HD-FPV/RTV and FPV/LPV/RTV over STD-FPV/RTV as measured by plasma HIV-1 RNA average area under the curve minus baseline (AAUCMB). RESULTS: There was no difference in the week 24 AAUCMB between the regimens. The proportion of patients with <50 copies/mL of plasma HIV RNA was 21%, 24% and 20%, respectively, by time to loss of virological response (TLOVR) analysis. High baseline drug resistance provided some explanation for the low efficacy. A lower baseline background drug resistance and higher fosamprenavir genotypic inhibitory quotient led to better antiviral responses. The plasma amprenavir trough concentartion (C(tau)) was 49% higher in the HD-FPV/RTV arm than in the STD-FPV/RTV arm and similar in the FPV/LPV/RTV and STD-FPV/RTV arms. The plasma lopinavir C(tau) was similar to historical data with standard LPV/RTV 400 mg/100 mg twice daily. All regimens were relatively well tolerated, although diarrhoea was more frequent in the HD-FPV/RTV and FPV/LPV/RTV arms, and hypertriglyceridaemia and increased total cholesterol were more common in the FPV/LPV/RTV arm. CONCLUSIONS: While the strategies of higher dose FPV/RTV and dual FPV/LPV/RTV were relevant at the time of study initiation, new therapies for antiretroviral-experienced patients make such strategies of limited interest. In addition, this study failed to demonstrate antiviral superiority of the HD-FPV/RTV or FPV/LPV/RTV regimen over the STD-FPV/RTV twice-daily regimen in highly treatment-experienced patients.

Identifying HIV patients with an unfavorable cardiovascular risk profile in the clinical practice: results from the SIMONE study.

OBJECTIVE: To identify and characterize HIV-infected patients at higher cardiovascular risk in ordinary clinical settings. DESIGN: Multicenter, nationwide cross-sectional study. METHODS: Consecutive HIV-patients, attending scheduled visits at facilities involved in the Italian coordination group for the study of allergies and HIV infection (CISAI), were included between February and April, 2005. Their 10-year probability of acute coronary events was calculated using the Framingham Risk Score (FRS) as well as 3 other cardiovascular algorithms ("PROCAM", "PROGETTO CUORE", "SCORE"); Metabolic Syndrome (MS) was diagnosed according to the National Cholesterol Education Program definitions. An estimated 10-year CVD >or=10% and/or MS led to the diagnosis of high CV risk. We compared selected clinical features between high- and low-risk patients. RESULTS: A total of 1230 HIV infected patients (72% males, mean age of 43+/-9 years), 185 of whom treatment-naive, were evaluated. FRS gave the highest estimate of CV risk. The mean 10-year risk for acute coronary events according to FRS was 7.4+/-7.0. MS was present in 22% of the observed patients. Accordingly, 443 patients (36%) were classified at high risk. Twelve percent of the patients (n=142) had both a FRS >or=10% and a diagnosis of MS. The main single predictor of increased cardiovascular risk was smoking (60% of whole sample). A higher prevalence of clinically evident lipodystrophy and a higher CD4 T-cell counts were found both in patients with higher FRS and in patients with high FRS and MS (both p<0.001). CONCLUSIONS: The worst estimation of CV risk was obtained with the FRS algorithm. Clinical evidence of lipodystrophy and higher CD4 T-cell counts were closely associated to a worse cardiovascular risk profile.

Tenofovir renal safety in HIV-infected patients: results from the SCOLTA Project.

OBJECTIVE: To evaluate the prevalence and incidence of nephrotoxicity in HIV-infected patients enrolled in the SCOLTA Project tenofovir cohort and to identify possible risk factors. DESIGN: The SCOLTA Project is a prospective, observational, multicenter study involving 25 infectious disease departments in Italy created to assess the incidence of severe adverse events in patients receiving new antiretroviral drugs. PATIENTS: The SCOLTA Project tenofovir cohort includes a total of 754 HIV infected patients. RESULTS: Data including grade II-IV creatinine elevations according to ACTG scale were available in 354 patients, 237 (67%) males with a mean age of 40.1+/-7.6 years enrolled in the SCOLTA Project tenofovir cohort. During a mean follow up of 19.5+/-11.5 months creatinine elevations were reported in 9/354 (2.5%) patients, all males. Mean duration of tenofovir therapy at the event was 9.5+/-5 months. The overall incidence was 1.6 (95% CI 1.5-1.7) per 100 person-years (p-y) and 0.5 (95% CI 0.4-0.6) p-y for grade III. No grade IV creatinine elevations were reported. Patients with nephrotoxicity were older and more frequently male, HCV infected, in CDC stage C and their CD4 cell count was significantly lower than those without nephrotoxicity. No significant difference was found between tenofovir co-administered antiretroviral drugs. CONCLUSIONS: Both prevalence and incidence of nephrotoxicity were low in patients receiving tenofovir in a non-selected clinical setting. Renal injury in patients receiving tenofovir seems associated with the presence of co-morbidities and with advanced HIV infection.