Home as the new frontier for the treatment of COVID-19: the case for anti-inflammatory agents.

COVID-19, caused by SARS-CoV-2, is characterised by a broad spectrum of symptom severity that requires varying amounts of care according to the different stages of the disease. Intervening at the onset of mild to moderate COVID-19 symptoms in the outpatient setting would provide the opportunity to prevent progression to a more severe illness and long-term complications. As early disease symptoms variably reflect an underlying excessive inflammatory response to the viral infection, the use of anti-inflammatory drugs, especially non-steroidal anti-inflammatory drugs (NSAIDs), in the initial outpatient stage of COVID-19 seems to be a valuable therapeutic strategy. A few observational studies have tested NSAIDs (especially relatively selective COX-2 inhibitors), often as part of multipharmacological protocols, for early outpatient treatment of COVID-19. The findings from these studies are promising and point to a crucial role of NSAIDs for the at-home management of people with initial COVID-19 symptoms.

A Home-Treatment Algorithm Based on Anti-inflammatory Drugs to Prevent Hospitalization of Patients With Early COVID-19: A Matched-Cohort Study (COVER 2).

Background and Aim: While considerable success has been achieved in the management of patients hospitalized with severe coronavirus disease 2019 (COVID-19), far less progress has been made with early outpatient treatment. We assessed whether the implementation of a home treatment algorithm-designed based on a pathophysiologic and pharmacologic rationale-and including non-steroidal anti-inflammatory drugs, especially relatively selective cyclooxygenase-2 inhibitors and, when needed, corticosteroids, anticoagulants, oxygen therapy and antibiotics-at the very onset of mild COVID-19 symptoms could effectively reduce hospital admissions. Methods: This fully academic, matched-cohort study evaluated outcomes in 108 consecutive consenting patients with mild COVID-19, managed at home by their family doctors between January 2021 and May 2021, according to the proposed treatment algorithm and in 108 age-, sex-, and comorbidities-matched patients on other therapeutic schedules (ClinicalTrials.gov: NCT04854824). The primary outcome was COVID-19-related hospitalization. Analyses were by intention-to-treat. Results: One (0.9%) patient in the "recommended" cohort and 12 (11.1%) in the "control" cohort were admitted to hospital (P = 0.0136). The proposed algorithm reduced the cumulative length of hospital stays by 85% (from 141 to 19 days) as well as related costs (from €60.316 to €9.058). Only 9.8 patients needed to be treated with the recommended algorithm to prevent one hospitalization event. The rate of resolution of major symptoms was numerically-but not significantly-higher in the "recommended" than in the "control" cohort (97.2 vs. 93.5%, respectively; P = 0.322). Other symptoms lingered in a smaller proportion of patients in the "recommended" than in the "control" cohort (20.4 vs. 63.9%, respectively; P < 0.001), and for a shorter period. Conclusion: The adoption of the proposed outpatient treatment algorithm during the early, mild phase of COVID-19 reduced the incidence of subsequent hospitalization and related costs.

Increasing clinical virulence in two decades of the Italian HIV epidemic.

The recent origin and great evolutionary potential of HIV imply that the virulence of the virus might still be changing, which could greatly affect the future of the pandemic. However, previous studies of time trends of HIV virulence have yielded conflicting results. Here we used an established methodology to assess time trends in the severity (virulence) of untreated HIV infections in a large Italian cohort. We characterized clinical virulence by the decline slope of the CD4 count (n = 1423 patients) and the viral setpoint (n = 785 patients) in untreated patients with sufficient data points. We used linear regression models to detect correlations between the date of diagnosis (ranging 1984-2006) and the virulence markers, controlling for gender, exposure category, age, and CD4 count at entry. The decline slope of the CD4 count and the viral setpoint displayed highly significant correlation with the date of diagnosis pointing in the direction of increasing virulence. A detailed analysis of riskgroups revealed that the epidemics of intravenous drug users started with an apparently less virulent virus, but experienced the strongest trend towards steeper CD4 decline among the major exposure categories. While our study did not allow us to exclude the effect of potential time trends in host factors, our findings are consistent with the hypothesis of increasing HIV virulence. Importantly, the use of an established methodology allowed for a comparison with earlier results, which confirmed that genuine differences exist in the time trends of HIV virulence between different epidemics. We thus conclude that there is not a single global trend of HIV virulence, and results obtained in one epidemic cannot be extrapolated to others. Comparison of discordant patterns between riskgroups and epidemics hints at a converging trend, which might indicate that an optimal level of virulence might exist for the virus.

A simple, home-therapy algorithm to prevent hospitalisation for COVID-19 patients: A retrospective observational matched-cohort study.

BACKGROUND: Effective home treatment algorithms implemented based on a pathophysiologic and pharmacologic rationale to accelerate recovery and prevent hospitalisation of patients with early coronavirus disease 2019 (COVID-19) would have major implications for patients and health system. METHODS: This academic, matched-cohort study compared outcomes of 90 consecutive consenting patients with mild COVID-19 treated at home by their family physicians between October 2020 and January 2021 in Northern and Central Italy, according to the proposed recommendation algorithm, with outcomes for 90 age-, sex-, and comorbidities-matched patients who received other therapeutic regimens. Primary outcome was time to resolution of major symptoms. Secondary outcomes included prevention of hospitalisation. Analyses were by intention-to-treat. FINDINGS: All patients achieved complete remission. The median [IQR] time to resolution of major symptoms was 18 [14-23] days in the 'recommended schedule' cohort and 14 [7-30] days in the matched 'control' cohort (p = 0·033). Other symptoms persisted in a lower percentage of patients in the 'recommended' than in the 'control' cohort (23·3% versus 73·3%, respectively, p<0·0001) and for a shorter period (p = 0·0107). Two patients in the 'recommended' cohort were hospitalised compared to 13 (14·4%) controls (p = 0·0103). The prevention algorithm reduced the days and cumulative costs of hospitalisation by >90%. INTERPRETATION: Implementation of an early home treatment algorithm failed to accelerate recovery from major symptoms of COVID-19, but reduced the risk of hospitalisation and related treatment costs. Given the study design, additional research would be required to consolidate the proposed treatment recommendations. FUNDING: Fondazione Cav.Lav. Carlo Pesenti.

Alkhurma hemorrhagic fever in travelers returning from Egypt, 2010.

Two travelers returning to Italy from southern Egypt were hospitalized with a fever of unknown origin. Test results showed infection with Alkhurma virus. The geographic distribution of this virus could be broader than previously thought.

Peginterferon alfa-2a and ribavirin for 16 or 24 weeks in HCV genotype 2 or 3.

BACKGROUND: Patients infected with hepatitis C virus (HCV) genotype 2 or 3 have sustained virologic response rates of approximately 80% after receiving treatment with peginterferon and ribavirin for 24 weeks. We conducted a large, randomized, multinational, noninferiority trial to determine whether similar efficacy could be achieved with only 16 weeks of treatment with peginterferon alfa-2a and ribavirin. METHODS: We randomly assigned 1469 patients with HCV genotype 2 or 3 to receive 180 mug of peginterferon alfa-2a weekly, plus 800 mg of ribavirin daily, for either 16 or 24 weeks. A sustained virologic response was defined as an undetectable serum HCV RNA level (<50 IU per milliliter) 24 weeks after the end of treatment. RESULTS: The study failed to demonstrate that the 16-week regimen was noninferior to the 24-week regimen. The sustained virologic response rate was significantly lower in patients treated for 16 weeks than in patients treated for 24 weeks (62% vs. 70%; odds ratio for 16 weeks vs. 24 weeks, 0.67; 95% confidence interval, 0.54 to 0.84; P<0.001). In addition, the rate of relapse (a detectable HCV RNA level during follow-up in patients who had undetectable HCV RNA at the end of treatment) was significantly greater in the 16-week group (31%, vs. 18% in the 24-week group; P<0.001). The sustained virologic response rates in patients with a pretreatment serum HCV RNA level of 400,000 IU per milliliter or less was 82% with the 16-week regimen and 81% with the 24-week regimen. Among patients with a rapid virologic response (an undetectable HCV RNA level by week 4), sustained virologic response rates were 79% in the 16-week group and 85% in the 24-week group (P=0.02). CONCLUSIONS: Treatment with peginterferon and ribavirin for 16 weeks in patients infected with HCV genotype 2 or 3 results in a lower overall sustained virologic response rate than treatment with the standard 24-week regimen. (ClinicalTrials.gov number, NCT00077636 [ClinicalTrials.gov].).

Health care-associated native valve endocarditis: importance of non-nosocomial acquisition.

BACKGROUND: The clinical profile and outcome of nosocomial and non-nosocomial health care-associated native valve endocarditis are not well defined. OBJECTIVE: To compare the characteristics and outcomes of community-associated and nosocomial and non-nosocomial health care-associated native valve endocarditis. DESIGN: Prospective cohort study. SETTING: 61 hospitals in 28 countries. PATIENTS: Patients with definite native valve endocarditis and no history of injection drug use who were enrolled in the ICE-PCS (International Collaboration on Endocarditis Prospective Cohort Study) from June 2000 to August 2005. MEASUREMENTS: Clinical and echocardiographic findings, microbiology, complications, and mortality. RESULTS: Health care-associated native valve endocarditis was present in 557 (34%) of 1622 patients (303 with nosocomial infection [54%] and 254 with non-nosocomial infection [46%]). Staphylococcus aureus was the most common cause of health care-associated infection (nosocomial, 47%; non-nosocomial, 42%; P = 0.30); a high proportion of patients had methicillin-resistant S. aureus (nosocomial, 57%; non-nosocomial, 41%; P = 0.014). Fewer patients with health care-associated native valve endocarditis had cardiac surgery (41% vs. 51% of community-associated cases; P < 0.001), but more of the former patients died (25% vs. 13%; P < 0.001). Multivariable analysis confirmed greater mortality associated with health care-associated native valve endocarditis (incidence risk ratio, 1.28 [95% CI, 1.02 to 1.59]). LIMITATIONS: Patients were treated at hospitals with cardiac surgery programs. The results may not be generalizable to patients receiving care in other types of facilities or to those with prosthetic valves or past injection drug use. CONCLUSION: More than one third of cases of native valve endocarditis in non-injection drug users involve contact with health care, and non-nosocomial infection is common, especially in the United States. Clinicians should recognize that outpatients with extensive out-of-hospital health care contacts who develop endocarditis have clinical characteristics and outcomes similar to those of patients with nosocomial infection. PRIMARY FUNDING SOURCE: None.

Efficacy and safety of darunavir-ritonavir compared with that of lopinavir-ritonavir at 48 weeks in treatment-experienced, HIV-infected patients in TITAN: a randomised controlled phase III trial.

BACKGROUND: The protease inhibitor darunavir has been shown to be efficacious in highly treatment-experienced patients with HIV infection, but needs to be assessed in patients with a broader range of treatment experience. We did a randomised, controlled, phase III trial (TITAN) to compare 48-week efficacy and safety of darunavir-ritonavir with that of lopinavir-ritonavir in treatment-experienced, lopinavir-naive patients. METHODS: Patients received optimised background regimen plus non-blinded treatment with darunavir-ritonavir 600/100 mg twice daily or lopinavir-ritonavir 400/100 mg twice daily. The primary endpoint was non-inferiority (95% CI lower limit for the difference in treatment response -12% or greater) for HIV RNA of less than 400 copies per mL in plasma at week 48 (per-protocol analysis). TITAN (TMC114-C214) is registered with ClinicalTrials.gov, number NCT00110877. FINDINGS: Of 595 patients randomised and treated, 187 (31%) were protease inhibitor naive; 476 of 582 (82%) were susceptible to four or more protease inhibitors. At week 48, significantly more darunavir-ritonavir than lopinavir-ritonavir patients had HIV RNA of less than 400 copies per mL (77% [220 of 286] vs 68% [199 of 293]; estimated difference 9%, 95% CI 2-16). Fewer virological failures treated with darunavir-ritonavir than with lopinavir-ritonavir developed primary protease inhibitor mutations (21% [n=6] vs 36% [n=20]) and nucleoside analogue-associated mutations (14% [n=4] vs 27% [n=15]). Safety data were generally similar between the groups; grade 3 or 4 adverse events occurred in 80 (27%) darunavir-ritonavir and 89 (30%) lopinavir-ritonavir patients. INTERPRETATION: In lopinavir-naive, treatment-experienced patients, darunavir-ritonavir was non-inferior to lopinavir-ritonavir treatment in terms of our virological endpoint, and should therefore be considered as a treatment option for this population.

Predictors of clinical progression among HIV-1-positive patients starting HAART with CD4+ T-cell counts > or =200 cells/mm3.

BACKGROUND: Baseline and follow-up predictors of new AIDS-defining events (ADE) or death among patients who started HAART with CD4+ T-cell counts > or =200 cells/mm3 have rarely been assessed simultaneously. METHODS: A prospective observational cohort study (1996-2002) is reported. HIV-infected patients initiating HAART with a CD4+ T-cell count > or =200 cells/mm3 were studied. Baseline and time-varying factors were tested for the prediction of new ADE/death using Cox regression models. RESULTS: A total of 896 subjects were studied over a median of 5.1 years. The incidence of a new ADE was 1.6 (95% confidence interval 1.3-2.1) per 100 person-years. Among baseline factors, higher CD4+ T-cell counts before HAART were associated with lower risk of ADE/death, but not after adjustment for time-varying factors. On a multivariable analysis including both baseline and time-varying covariates, longer delay from HIV diagnosis to HAART was an independent predictor of ADE/death (per year, hazard ratio [HR] 1.06; P = 0.025) and was independent of CD4+ T-cell count before treatment. Longer time spent with HIV RNA <400 copies/ml (per month, HR 0.96; P = 0.003) and higher latest CD4+ T-cell count (per log2 cells/mm3, HR 0.65; P < 0.001) were found to be protective. CONCLUSIONS: Patients with higher CD4+ T-cell counts before HAART initiation had a better prognosis. However, except for the delay in starting HAART, viroimmunological evolution outweighed the effect of baseline factors. Moreover, suppressing HIV replication for as long as possible could improve the clinical outcome. Prospective randomized clinical trials to assess the optimal timing of HAART initiation are both feasible and urgently needed.

The relationship between the initiation of antimicrobial therapy and the incidence of stroke in infective endocarditis: an analysis from the ICE Prospective Cohort Study (ICE-PCS).

BACKGROUND: Embolic events to the central nervous system are a major cause of morbidity and mortality in patients with infective endocarditis (IE). The appropriate role of valvular surgery in reducing such embolic events is unclear. The purpose of this study was to determine the relationship between the initiation of antimicrobial therapy and the temporal incidence of stroke in patients with IE and to determine if this time course differs from that shown for embolic events in previous studies. METHODS: Prospective incidence cohort study involving 61 tertiary referral centers in 28 countries. Case report forms were analyzed from 1437 consecutive patients with left-sided endocarditis admitted directly to participating centers. RESULTS: The crude incidence of stroke in patients receiving appropriate antimicrobial therapy was 4.82/1000 patient days in the first week of therapy and fell to 1.71/1000 patient days in the second week. This rate continued to decline with further therapy. Stroke rates fell similarly regardless of the valve or organism involved. After 1 week of antimicrobial therapy, only 3.1% of the cohort experienced a stroke. CONCLUSIONS: The risk of stroke in IE falls dramatically after the initiation of effective antimicrobial therapy. The falling risk of stroke in patients with IE as a whole precludes stroke prevention as the sole indication for valvular surgery after 1 week of therapy.

Effect of adherence to HAART on virologic outcome and on the selection of resistance-conferring mutations in NNRTI- or PI-treated patients.

BACKGROUND: The effect of adherence on the risk of virologic failure and mutations selection was verified in a prospective study. METHOD: At baseline, all patients had a viral load (VL) <50 copies/mL and completed a self-reported questionnaire. Patients were followed for the subsequent 4 months to document virologic rebound (VL > 50 copies/mL). RESULTS: 1,133 patients completed 2,240 questionnaires/follow-up (non-nucleoside reverse transcriptase inhibitor [NNRTI] = 1,479; single protease inhibitor [PI] = 200; boosted PI = 561). Only the type of treatment and the baseline adherence rate were significantly associated with the virologic endpoint. A viral rebound rate >10% was observed in patients treated with single PI (14.7%) or boosted PI (11.7%) up to an adherence rate of 95%, whereas a similar (17.6%) rebound rate was observed only in NNRTI-treated patients with very low adherence (<55%). After adjustment for other baseline predictors of adherence, patients on NNRTIs showed a higher adherence rate than those on PIs but not higher than those on boosted PIs. The same adherence rate did not have the same result, in terms of virologic rebound, in patients on the same HAART for shorter or longer periods of time. Overall, the risk of virologic rebound for patients with >95% adherence rate was 6.2% in the first 6 months of therapy, lowered to 5.0% in the following 6 months, and was 3.2% thereafter. The risk of selecting for resistance-inducing viral mutation for NNRTI-treated patients was higher (4.9%) at very low adherence rates (<75%); the opposite was true for single PI-treated patients (4.2% for adherence >95%). Boosted PI-treated patients showed an intermediate pattern, even if at a much lower level of risk. CONCLUSION: Low adherence is a major determinant of virologic failure, however different therapies have different adherence cutoffs determining a significant increment of risk.

Resistance costs and future drug options of antiretroviral therapies: analysis of the role of NRTIs, NNRTIs, and PIs in a large clinical cohort.

OBJECTIVE: To investigate future drug options (FDOs), resistance cost (RCVF), and virologic response to genotypic-driven rescue highly active antiretroviral therapy (HAART), according to type of therapy. METHOD: This was a retrospective analysis in naïve or antiretroviral-experienced patients. Virologic response was defined as HIV RNA <50 copies. RESULTS: There were 108 patients failing first-line HAART; there were 328 experienced patients. FDOs were reduced in subjects failing a thymidine-analogue (TA) regimen (median 3.65, IQR 1.29 ) compared to patients without TA (median 3.82, IQR 1.12) (p = .011). FDOs after first failure were higher for patients with non-nucleoside reverse transcriptase inhibitor (NNRTI; median 3.82; IQR 1.24) than with protease inhibitor (PI; median 3.64, IQR 1.15) (p = .027). In experienced patients, FDOs were much higher for TA (p = .005). Patients responding to genotypic-modified regimens had higher FDOs (median 3.9 4, IQR 2.53) than patients not responding (median 2.18, IQR 3.65) (p > .0001). Switching from an NNRTI-based HAART to a boosted PI had a higher chance (48.1%) of achieving a full virologic suppression, compared to switching from PI to NNRTI (21.4%, p < .0001). CONCLUSION: FDOs and RCVF are parameters that can quantify the therapeutic choices at virologic failure. Different drugs induce different FDOs and RCVF. In successive-line regimens, the higher antiviral effect and genetic barrier of boosted PIs may overcome the limits of using nucleoside reverse transcriptase backbones, with only partial effectiveness.

Predictors of AIDS-defining events among advanced naïve patients after HAART.

BACKGROUND: Baseline and follow-up predictors of new AIDS-defining events or death (ADE/death) among patients who started HAART late in their disease history have rarely been assessed simultaneously. METHOD: ADE and mortality rates were assessed using Cox regression analyses. Variables were tested for prediction of ADE/death within the first 3 months of therapy and from month 3, thereafter. RESULTS: 751 HIV-infected patients with <200 CD4+/mm(3) before HAART were followed for a median of 49 months. 207 new ADE occurred (7.06 [6.16-8.10] per 100 patient-years). ADE/deaths clustered within the first 3 months of treatment (106/207, 51%). Higher CD4+ T-cell counts during the follow-up (per log(e) cells/mm(3): hazard ratio [HR] 0.51; 0.41-0.64; p < .001) and use of antiretroviral therapy (HR 0.38; 95% CI 0.21-0.69; p = .001) appeared to protect from ADE/death after month 3. Conversely, increasing follow-up with HIV RNA >400 copies/mL correlated with ADE/death (per month: HR 1.09; 95% CI 1.06-1.12; p = .001). Use of boosted protease inhibitors as first-line HAART and HCV-seropositivity were additional risk factors. Baseline CD4+ T-cell count and HIV RNA had a predominant impact in the first 3 months after HAART initiation. CONCLUSION: A careful monitoring of patients with low CD4+ is particularly necessary during the first few months of HAART. Length and extent of viral replication during the follow-up appeared to induce a significantly higher risk of HIV disease progression afterwards, implying that new drugs and new strategies aimed at ensuring long-term suppression of HIV RNA are of outstanding importance.

The effect of HIV-1 resistance mutations after first-line virological failure on the possibility to sequence antiretroviral drugs in second-line regimens.

BACKGROUND: One of the more vigorous debates in the field of highly active antiretroviral therapy (HAART) is how to start it and what the optimal drug sequence is. METHODS: A retrospective cohort analysis was performed. The aim was to evaluate which variables could influence the virological response to second-line genotypic-based HAART in patients with virological documented first-line HAART failure. A positive response was defined as a confirmed HIV RNA level < 50 copies/ml. RESULTS: Two hundred and eight patients were included. Demographic characteristics, risk factors for HIV acquisition, and drugs included in the initial treatment did not significantly influence the considered outcome. According to a multiple logistic model, the presence of thymidine analogue mutations (TAMs) had a negative association with the virological outcome (P = 0.006), whereas the use of a boosted protease inhibitor (PI) in second-line HAART was positively associated with the endpoint (P = 0.001). Patients receiving a genotypic-based second-line HAART containing a boosted PI achieved a viral load < 50 copies/ml in a 74.2% of cases compared with 52.2% of those whose therapy did not contain a boosted PI. This difference was statistically significant (P = 0.002) with an odds ratio (OR) of 2.63 and a 95% confidence interval (CI) ranging from 1.46 to 4.76. This last variable positively influenced the outcome even when the analysis was restricted to patients harbouring a virus presenting TAMs. In this case, second-line HAART was successful in 66.7% of cases with an OR of 3.25 and a 95% CI ranging from 1.28 to 8.25 (P = 0.014). CONCLUSIONS: the wider range of available therapeutic options has made resistance and drug-sequencing considerations a crucial point in selecting first-line HAART. Our data indicate that, by limiting the risk of selecting or accumulating TAMs, it could be possible to save further therapeutic options. In second-line regimens, the higher antiviral effect and genetic barrier of boosted PIs may overcome the limits of the use of NRTI backbones, which retain only a partial effectiveness.

Antiretroviral therapy in chronic liver disease: focus on HIV/HCV coinfection--statements of the First Italian Consensus Workshop.

Hepatitis C virus common transmission routes and HCV coinfection is frequent in persons living with HIV. Liver enzyme elevation following the initiation of antiretroviral therapy is frequently seen in HIV-infected patients with chronic liver disease, particularly those with chronic hepatitis C. This complication may lead to treatment discontinuation, complicating HIV therapeutic management. Multiple factors influence the risk of liver toxicity under antiretroviral therapy, including the specific drug in use (e.g. use of full doses of ritonavir), and environmental factors (e.g. alcohol abuse). However a beneficial effect of antiretroviral therapy on liver disease has been supported by some studies. Despite increasing knowledge of HCV/HIV coinfection, there is no clear consensus on how to treat HIV in HCV-coinfected patients An Italian group of experts were invited to discuss in detail the current risks and implications of antiretroviral treatment in HIV-infected persons with chronic hepatitis C, and their main conclusions are summarized in this consensus document.

Similar adherence rates favor different virologic outcomes for patients treated with nonnucleoside analogues or protease inhibitors.

BACKGROUND: This prospective study verified the effect of adherence on the risk of virologic failure. METHODS: At enrollment in the study, a total of 543 patients who were following a steady (duration, >or=6 months) and effective (viral load, <50 human immunodeficiency virus [HIV] RNA copies/mL) regimen of highly active antiretroviral therapy (HAART) completed a self-reported questionnaire derived from the Adult AIDS Clinical Trials Group Adherence Follow-up Questionnaire. Patients were followed up for the subsequent 6 months to document virologic failure, which was defined as 2 consecutive viral load measurements of >500 HIV RNA copies/mL. RESULTS: Only the type of treatment and the adherence rate at baseline were significantly associated with the virologic end point. Among patients who reported an adherence rate of 95%. When analysis was adjusted according to the type of regimen received, patients who were receiving protease inhibitor (PI)-based HAART and who had an adherence rate of up to 85% had a virologic failure rate of >20%, whereas, only for patients who were receiving nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based HAART and who had an adherence rate of 10%. For the comparison of NNRTI-treated patients and PI-treated patients with an adherence rate of 75%-95%, the odds ratio was 0.157 (95% confidence interval, 0.029-0.852). The number of pills and daily doses received correlated with the reported adherence rate. CONCLUSIONS: Patients receiving NNRTIs report a higher rate of adherence than do patients receiving PIs. Adherence is significantly influenced by the number of pills and daily doses received. Low adherence is a major determinant of virologic failure; however, different therapies have different cutoff values for adherence that determine a significant increment of risk.

Quadruple-drug induction HAART in advanced HIV infection.

A randomized controlled study exploring an induction-maintenance strategy was performed with a quadruple-drug regimen: zidovudine/lamivudine/abacavir/nevirapine. The study was prematurely interrupted due to the high proportion of adverse events. The median time on protocol-defined therapy was 110 days; 13/28 (46%) patients interrupted therapy and 2/6 tested patients selected praecox viral mutants. Despite this, we observed a significant (p

Clinical and laboratory features of acute rheumatic fever: a 18-year experience.

We present the retrospective analysis of clinical manifestations and laboratory findings observed in 30 patients (M/F 13/17; age range 9-66 yrs) affected by acute rheumatic fever observed within the Infectious Disease Department along a period of 18 years (1986-2004). Diagnosis of carditis was stated on clinical and echocardiographical bases and occurred in 50% of patients. Such patients presented mild to moderate heart disease (30%) and severe carditis (20%). Therefore, our data stand to confirm that rheumatic cardiac disease could determine permanent and/or severe heart damage. All patients were observed during a 48-month period of follow-up without exitus.