Epidemiological and molecular characterization of HBV and HCV infections in HIV-1-infected inmate population in Italy: a 2017-2019 multicenter cross-sectional study.

HBV/HCV co-infection is common in HIV-1-infected prisoners. To investigate the characteristics of HIV co-infections, and to evaluate the molecular heterogeneity of HIV, HBV and HCV in prisoners, we carried-out a multicenter cross-sectional study, including 65 HIV-1-infected inmates enrolled in 5 Italian detention centers during the period 2017-2019. HIV-1 subtyping showed that 77.1% of inmates were infected with B subtype and 22.9% with non-B subtypes. Italian nationals were all infected with subtype B (93.1%), except two individuals, one infected with the recombinant form CRF72_BF1, and the other with the HIV-1 sub-subtype A6, both previously not identified in inmates of Italian nationality. Non-Italian nationals were infected with subtype B (52.6%), CRFs (36.8%) and sub-subtypes A1 and A3 (5.2%). HIV variants carrying resistance mutations to NRTI, NNRTI, PI and InSTI were found in 7 inmates, 4 of which were never exposed to the relevant classes of drugs associated with these mutations. HBV and/or HCV co-infections markers were found in 49/65 (75.4%) inmates, while 27/65 (41.5%) showed markers of both HBV and HCV coinfection. Further, Italian nationals showed a significant higher presence of HCV markers as compared to non-Italian nationals (p = 0.0001). Finally, HCV phylogenetic analysis performed in 18 inmates revealed the presence of HCV subtypes 1a, 3a, 4d (66.6%, 16.7% and 16.7%, respectively). Our data suggest the need to monitor HIV, HBV and HCV infections in prisons in order to prevent spreading of these viruses both in jails and in the general population, and to implement effective public health programs that limit the circulation of different genetic forms as well as of viral variants with mutations conferring resistance to treatment.

Fatigue Threshold R-Curves for Dental Lithium Disilicate Glass-Ceramics.

Chemical and mechanical fatigue degradation in ceramic materials is generally inconspicuous yet ubiquitous, to the effect that clinical fractures still consist of the main cause of failure in all-ceramic restorations. Implications of this span wide, from a reduced survival prognosis for the affected teeth, including more frequent and increasingly invasive procedural interventions, to the financial burden borne by individuals and health care systems. To suffice as an effective corrective, restoration lifetimes need only to be extended so to outlive the patient. That opens a box of problems from a materials science standpoint, entailing inherent deficiencies of brittle materials to resist mechanical and environmental challenges. Efforts in developing more damage-tolerant and fatigue-resistant restoratives go thus hand in hand with understanding intrinsic mechanisms of crack growth behavior under conditions that simulate the oral environment. Here we developed experiments using size-relevant sharp precracked specimens with controlled size and geometry (truncated semielliptical crack in the surface-crack-in-biaxial-flexure method) to establish a relationship between crack size and strength. The tangent method was used to construct envelopes for the quasi-static resistance curves (R-curves), which served as template for deriving residual cyclic R-curve analogs. By means of experimentally obtained stress-cycle curves, lifetime and fatigue parameters were employed within a mechanistic framework to reveal constitutive toughening mechanisms during subcritical growth under cyclic loading in a wet environment. Using 3 modern dental lithium disilicate glass-ceramics, we demonstrate the extent of R-curve degradation up to a threshold of 10 million cycles (~30 y in service) and draw parallels between the scope of fatigue degradation and the size of the microstructural units responsible for toughening mechanisms in glass-ceramic materials. Our results indicate that larger microstructural elements endow glass-ceramics with a higher reaching quasi-static R-curve at the onset but degrading more rapidly to comparable levels of lithium disilicates having submicrometric and nanometric crystal phases.

Sliding contact wear and subsurface damage of CAD/CAM materials against zirconia.

OBJECTIVE: Most previous work conducted on the wear behavior of dental materials has focused on wear rates and surface damage. There is, however, scarce information regarding the subsurface damage arising from sliding contact fatigue. The aim of this study was to elucidate the wear mechanisms and the subsurface damage generated during sliding contact fatigue in 5 contemporary CAD/CAM materials against a zirconia indenter. METHODS: Forty discs (Ø12mm, 1.55mm thick) were cut out of IPS e.max CAD (e.CAD), Suprinity PC (SUP), Enamic (ENA), Vitablocs Mark II (VMII) and Lava Ultimate (LU) blocks and mirror polished. After cementation onto a dentin-like composite, off-axis mouth-motion cycling was conducted with a spherical zirconia indenter (r=3.18mm) in water (200N load, 2Hz frequency) for 5 different cycling periods (102, 103, 104, 105, 106 cycles, n=8). Analysis of the wear scars was conducted using light-microscopy, scanning-electron-microscopy and optical profilometry. Subsurface damage was assessed using sagittal and transverse sections of the samples. RESULTS: Fatigue wear mechanisms predominated in glassy materials (e.CAD, SUP, VMII), accompanied by extensive subsurface damage, whereas abrasive wear mechanisms were responsible for the large wear craters in the resin composite (LU) with an absolute absence of subsurface fracture. A combination of both mechanisms was observed in the polymer-infiltrated reinforced-glass (ENA), displaying large wear craters and severe subsurface damage. SIGNIFICANCE: Well-controlled laboratory simulation can identify wear and subsurface damage susceptibility of various classes of restorative materials. Both wear and subsurface fracture are determining factors for the long-term success of restorations.

Fracture Rates and Lifetime Estimations of CAD/CAM All-ceramic Restorations.

The gathering of clinical data on fractures of dental restorations through prospective clinical trials is a labor- and time-consuming enterprise. Here, we propose an unconventional approach for collecting large datasets, from which clinical information on indirect restorations can be retrospectively analyzed. The authors accessed the database of an industry-scale machining center in Germany and obtained information on 34,911 computer-aided design (CAD)/computer-aided manufacturing (CAM) all-ceramic posterior restorations. The fractures of bridges, crowns, onlays, and inlays fabricated from different all-ceramic systems over a period of 3.5 y were reported by dentists and entered in the database. Survival analyses and estimations of future life revealed differences in performance among ZrO2-based restorations and lithium disilicate and leucite-reinforced glass-ceramics.

Debio0932, a second-generation oral heat shock protein (HSP) inhibitor, in patients with advanced cancer-results of a first-in-man dose-escalation study with a fixed-dose extension phase.

BACKGROUND: Objective was to determine maximum tolerated dose (MTD), recommended dose (RD) and schedule, safety, pharmacokinetic (PK) profile, pharmacodynamic (PD) effects, and antitumor activity of Debio0932, a new second-generation oral heat shock protein (HSP) inhibitor. PATIENTS AND METHODS: This was a multicenter, uncontrolled, open-label, nonrandomized, dose-escalation study in adults with treatment-resistant advanced cancer. Groups of three patients received oral Debio0932 either daily or every other day. The starting dose of 50 mg was escalated until the MTD was reached, i.e. dose-limiting toxicity (DLT) occurred in ≥2 patients. Further 9 patients and an extension cohort of 30 patients were treated at the next lower dose (=RD). Adverse events (AEs), tumor response, PK, and HSP70 levels in peripheral blood mononuclear cells were recorded over 30 days. RESULTS: Fifty patients were treated with doses up to 1600 mg, at which level three DLT occurred (febrile neutropenia, diarrhea, asthenia). In total, 39 patients were then treated at the RD of 1000 mg daily. Most common drug-related AEs were asthenia and gastrointestinal events. No ocular toxicities were observed. Debio0932 was rapidly absorbed and metabolized. Plasma steady state was reached within 9 days. Volume of distribution was high and elimination half-life was 9-11 h. Food had no effect on PK. PD showed large interpatient variability, but no dose-effect relationship. Partial tumor response was observed in 2 patients (NSCLC and breast cancer), stable disease (SD) in 12 patients (5 of 8 NSCLC patients). In the extension cohort, 9 patients had SD, and 1 patient a partial metabolic tumor response. CONCLUSION: Debio0932 has limited clinical activity, together with manageable toxicity. Further development as adjunct treatment of NSCLC at daily doses of 1000 mg is warranted. CLINICAL TRIAL: NCT01168752.

Dental materials for primary dentition: are they suitable for occlusal restorations? A two-body wear study.

AIM: This was to evaluate the wear resistance of different materials, compomers, resin-modified glass ionomer cements (RMGICs), glass ionomer cements (GICs), used for posterior restorations in primary teeth and to compare the results with the reference material, amalgam. STUDY DESIGN: Eight specimens of each material were subjected to two-body wear test, using a chewing simulator. The wear region of each material was examined under a profilometer, measuring the vertical loss (µm) and the volume loss (mm(3)) of the materials. RESULTS: The results showed significant differences of vertical loss and volume loss of the test materials (p < 0.001). Amalgam had the highest wear resistance. Twinky Star (compomer) had the lowest vertical loss and volume loss. There was no significant difference of vertical loss among compomers, Dyract Extra, Dyract Flow and Dyract Posterior. Riva Self Cure (GIC) had no statistically significant difference compared with the compomers (except Twinky Star). No statistically significant difference was found also between Equia (GIC) and Ketac Moral (GIC) with Dyract Extra (Compomer). RMGICs were found to have the lowest wear resistance. STATISTICS: For the statistical analysis, the PASW 20.0 (SPSS Statistics, IBM, Chicago) package was used. Means and standard deviations were measured with descriptive statistics and analyzed using one-way ANOVA. CONCLUSION: Compomers and some GICs, that have moderate wear resistance, may be sufficient for occlusal restorations in primary dentitions.

Takotsubo cardiomyopathy: real life management in the intensive coronary care unit.

AIM: Takotsubo cardiomyopathy is a cardiac syndrome characterized by reversible left ventricular dysfunction, ischemic changes on electrocardiogram, elevation of cardiac biomarkers, absence of obstructive coronary artery disease in the setting of various stressing conditions. To date, little is known on best clinical management of this syndrome in coronary care units. Whe thus aimed to present our experience in a real life takotsubo population. METHODS: We identified all patients with Takotsubo cardiomyopathy at our center Maria Vittoria Hospital, Turin, between October 2006 and February 2012. Patients where considered to have Takotsubo syndrome if they presented chest pain on admission, new elettrocardiographic changes suggestive of myocardial ischemia, evidence of apical balloning with hyperkinesis of basal segments on echocardiography, rise in troponin I and, after coronary angiography, no coronary artery disease. We adjudicated the following clinical events: death and recurrence of ischemic events; we also made a detailed analysis of the stressing conditions leading to clinical syndrome. RESULTS: A total of 26 patients were included, 4 (15%) males and 22 (85%) females; mean age was 71±13. After more than 1 year median follow-up the incidence of death was 7.7% (2 deaths), with all deaths, due to cardiogenic shock, occurring in the first 10 days of hospitalization; 2 patients (8%) experienced recurrence of ischemic event. Leading cause of Takostubo was major depressive episode (16%), followed by mourning (12%), falling down with difficulties in standing up (12%), vomiting (8%) and pulmonary infection (8%). In the coronary care unit major complications of patients with Takotsubo syndrome were acute hearth failure (62%), cardiogenic shock (27%), sepsis (31%), pulmonary aedema (27%) and anemia (12%). Two patients needed non-invasive ventilation support and one intra-aortic balloon conterpulasation. In addition one patient developed rabdomyolysis and one left heart thrombus. Cornerstone drug therapy was as follows: 96% of patients took aspirin, 58% beta blockers, 54% nitroglicerine, 46% intravenous heparin, 27% dopamine. CONCLUSION: Takotsubo syndrome is an important safety issue occurring predominantly in post-menopausal women undergoing specific stressing condition. Heart failure and cardiogenic shock are the most serious clinical complication and leading cause of death in the short period, good prognosis is seen thereafter.

Factors involved in mechanical fatigue degradation of dental resin composites.

The design of clinical trials allows for limited insights into the fatigue processes occurring in resin composites and the factors involved therein. In vitro studies, in contrast, can fundamentally narrow study interests to focus on particular degradation mechanisms and, to date, represent the major contributors to the state of knowledge on the subject. These studies show that microstructural features are important in determining strength and fracture toughness, whereas fatigue resistance is mainly related to the susceptibility of the matrix and the filler/matrix interface to mechanical and chemical degradation. In this review, we focus on fracture mechanisms occurring during fatigue, on the methods used to assess them, and on additional phenomena involved in the degradation of initial mechanical properties of resin composites.

Clinical effectiveness of a hydrophobic coating used in conjunction with a one-step self-etch adhesive: an 18-month evaluation.

The purpose of this randomized clinical trial was to evaluate the clinical performance of a one-step self-etch adhesive in noncarious cervical lesions with inclusion of a hydrophobic bonding layer not included in the original bonding system as a test of potentially improved bonding. Patients with noncarious cervical lesions received two or four restorations after being randomly assigned to two adhesive technique protocols (n=32): EB, application of Adper Easy Bond (3M ESPE) following manufacturer's instructions; and EB+B, application of Adper Easy Bond, immediately followed by the application of a hydrophobic resin coat (Scotchbond Multi-Purpose Bonding Agent, 3M ESPE). All restorations were restored with a microhybrid composite (Filtek Z250, 3M ESPE). Clinical effectiveness was recorded in terms of retention, marginal discoloration, marginal integrity, postoperative sensitivity, recurrent caries, periodontal health, and pulpal vitality, according to the modified USPHS criteria, for 18 months. Data were analyzed using chi-square, Fisher exact, and McNemar tests at α=0.05. Two restorations of each group were debonded after six months, leading to an overall clinical success rate of 93.8% for both groups. At the 18-month evaluation period, no new restoration was debonded. However, one restoration of the EB group displayed recurrent caries at the dentin margin, decreasing the overall success rate to 90.6% in comparison to 93.8% of EB+B. The success rate between EB and EB+B was not statistically significant (p=0.5). The application of a hydrophobic resin coat over EB did not increase bonding effectiveness in noncarious cervical lesions after 18 months.

Influence of MHC class I and II haplotypes on the experimental infection of Mauritian cynomolgus macaques with SHIVSF162P4cy.

Mauritian cynomolgus macaques (MCM) are widely used in human immunodeficiency virus research because of their restricted major histocompatibility complex (MHC) diversity which provides the opportunity to address the influence of host factors on vaccine studies. We herein report the impact of MHC haplotype on the outcome of 21 MCM infections with the CCR5-tropic simian/human immunodeficiency virus (SHIV)(SF162P4cy). MCM were susceptible to SHIV(SF162P4cy) infection as shown by viremia and loss of CD4+ T cells. A significant association between haplotype M7 (class IA, IB, II) and persistent viremia was observed in chronic phase, whereas recombinant class IA haplotype was associated with a reduction of viral RNA during acute infection. Class IB M4 haplotype displayed significantly lower acute phase provirus copy numbers. In addition, statistical analysis indicated a detrimental effect of haplotype M4 (class IA, IB) on the course of infection as indicated by lower CD4+ T-cell levels during chronic infection. A decrease in post-acute phase CD4+ T-cell numbers was also observed in haplotype M2 animals. This is the first report that documents the effects of host MHC class I and II molecules on the SHIV(SF162P4cy) infection in MCM, particularly with regard to the association between recombinant class IA, M4, and M7 haplotypes and the dynamic of viral replication and level of CD4+ T cells.

A photoelastic assessment of residual stresses in zirconia-veneer crowns.

Residual stresses within the veneer are linked to the high prevalence of veneer chipping observed in clinical trials of zirconia prostheses. We hypothesized that the thermal mismatch between the zirconia infrastructure and the veneer porcelain, as well as the rate used for cooling zirconia-veneer crowns, would be directly proportional to the magnitude of residual stresses built within the veneer layer. Two porcelains with different coefficients of thermal expansion were used to veneer zirconia copings, to create high or low thermal mismatches. The crowns were cooled according to a fast- or a slow-cooling protocol. The retardation of polarized light waves was used to calculate the residual stress magnitude and distribution across the veneer, according to the photoelasticity principle, in 1.0-mm-thick crown sections. While thermal mismatch was an important factor influencing the maximum stress development in the veneer, cooling rate had a minor role. Curved surfaces were preferential sites for stress concentration regardless of thermal mismatch or cooling rate.

A phase II, randomised clinical trial to demonstrate the non-inferiority of low-dose MF59-adjuvanted pre-pandemic A/H5N1 influenza vaccine in adult and elderly subjects.

BACKGROUND: Effective planning and preparedness against a possible future A/H5N1 influenza pandemic is a major global challenge. Because dose sparing strategies are required to meet the global demand for vaccine, efforts have focused on the development of adjuvanted vaccine formulations of relatively lower antigen content. AIM: This study aimed to demonstrate the non-inferiority of a low-antigen-dose (3.75 µ) [DOSAGE ERROR CORRECTED] A/H5N1 pre-pandemic vaccine compared with a licensed, higher-dose (7.5 mg) formulation in adult and elderly subjects. Immunogenicity was assessed according to European and U.S. licensure criteria. METHODS: A total of 722 subjects were randomized in equal numbers to receive either the licensed or low-dose formulation. All subjects received two vaccine doses administered three weeks apart. Immunogenicity was assessed three weeks after the administration of each vaccine dose by hemagglutination inhibition (HI), single radial haemolysis (SRH) and microneutralization assays (MN). Local and systemic reactions were assessed over a seven day period post-vaccination. Adverse events were recorded throughout. RESULTS: The low-dose vaccine was demonstrated to be non-inferior to the licensed formulation in terms of antibody titres against the vaccine strain. All three European licensure criteria were met by adult subjects in response to the low-dose vaccine; two criteria were met by the elderly age group. Cross-reactive antibodies were detected against the heterologous A/H5N1 antigen strains A/Indonesia/05/05 and A/turkeyTurkey/01/05. Both vaccines were generally well tolerated by both age groups. CONCLUSION: These data demonstrate that a low antigen dose in combination with MF59 adjuvant is adequate for the routine pre-pandemic immunization of adult and elderly subjects.

Viral outcome of simian-human immunodeficiency virus SHIV-89.6P adapted to cynomolgus monkeys.

Simian-human immunodeficiency virus (SHIV) 89.6P is considered to be one of the most pathogenic chimeric viruses in rhesus macaques. However, when crossing from one to another species of monkeys the pathogenicity of this virus may be affected. By using SHIV-89.6P(cy243), a virus obtained by passaging SHIV-89.6P in cynomolgus macaques, we investigated the dynamics of viral replication and the impact of the inoculum size (from 10 up to 50 monkey infectious dose) on the progression of the infection in 22 cynomolgus macaques. SHIV-89.6P(cy243 )caused massive depletion of CD4+ T-cells within 4 weeks of the inoculum, followed by an irreversible immune deficiency in a high proportion of the infected monkeys. This study demonstrates that SHIV-89.6P(cy243) is pathogenic in cynomolgus macaques and that the dynamics of the viral replication and the rate of clinical progression depend on the size of the inoculum. Our findings provide unique and relevant data, particularly with regard to the value of the in vivo titration used to select the most appropriate infectious dose to study the "virus-host" interplay.

Myopericarditis versus viral or idiopathic acute pericarditis.

OBJECTIVE: To investigate the relative incidence, clinical presentation and prognosis of myopericarditis among patients with idiopathic or viral acute pericarditis. DESIGN: Prospective observational clinical cohort study. SETTING: Two general hospitals from an urban area of 220 000 inhabitants. PATIENTS: 274 consecutive cases of idiopathic or viral acute pericarditis between January 2001 and June 2005. MAIN OUTCOME MEASURES: Relative prevalence of myopericarditis. Clinical features at presentation including echocardiographic data (ejection fraction (EF), wall motion score index (WMSI)) and follow-up data at 12 months including complications, results of echocardiography, electrocardiography and treadmill testing. RESULTS: Myopericarditis was recorded in 40/274 (14.6%) consecutive patients. At presentation, the following clinical features were independently associated with myopericarditis: arrhythmias (odds ratio (OR) = 17.6, 95% confidence interval (CI) 5.7 to 54.1; p<0.001), male gender (OR = 6.4, 95% CI 2.3 to 18.4; p = 0.01), age <40 years (OR = 6.1, 95% CI 2.2 to 16.9; p = 0.01), ST elevation (OR = 5.4, 95% CI 1.4 to 20.5; p = 0.013) and a recent febrile syndrome (OR = 2.8, 95% CI 1.1 to 7.7; p = 0.044). After 12 months' follow-up an increase of EF (basal EF 49.6 (5.1)% vs 12-month EF 59.1 (4.6)%; p<0.001) and decrease of WMSI (basal WMSI 1.19 (0.27) vs 12-month WMSI 1.02 (0.09); p<0.001) were recorded in patients with myopericarditis, with a normalisation of echocardiography, electrocardiography and treadmill testing in 98% of cases. Use of heparin or other anticoagulants (OR = 1.1, 95% CI 0.3 to 3.5; p = 0.918) and myopericarditis (OR = 2.3, 95% CI 0.7 to 7.6; p = 0.187) was not associated with an increased risk of cardiac tamponade or recurrences. CONCLUSIONS: Myopericarditis is relatively common and shows a benign evolution also in spontaneous cases not related to vaccination.

Locally advanced non-small cell lung cancer: role of induction chemotherapy in resectable N2 disease.

Patients with resectable stage IIIA-N2 non-small cell lung cancer should receive induction chemotherapy before surgery. The aim is to early control systemic disease, eventually cure the mediastinal tumor spread and improve patients' survival. A recent metanalysis of randomized trials with second-generation platinum-based combinations has reinforced the evidence concerning the benefit of induction chemotherapy followed by surgery versus surgery alone in resectable disease. Moreover a large number of phase II trials have explored the activity and feasibility of platinum-based combinations with third-generation drugs in the same setting. Still opened questions to address with current clinical research are the eventual role of radiotherapy as induction treatment, the impact of definite chemoradiation versus induction treatment followed by surgical resection on local control and survival and finally the non-easy choice between neo-adjuvant and adjuvant chemotherapy.

Elevated 8-isoprostane levels in basal cell carcinoma and in UVA irradiated skin.

Isoprostanes are prostaglandin isomers produced from the peroxidation of polyunsaturated fatty acids from the cellular membrane. They have been used as a specific index of cellular lipoperoxidation and as an indirect measure of oxidative stress. However, these molecules also present several biological activities. An oxidative environment measured as the presence of other indirect measurements of reactive oxygen species lipoperoxidation has recently been described in basal cell carcinoma, the most frequent type of non-melanoma skin cancer. This study aims to measure the levels of 8-isoprostaglandin F2alpha, an isoprostane widely studied in other models as a by-product of ROS-induced lipid peroxidation, in basal cell carcinoma and in UVA irradiated healthy skin. We found that 8-iso-PGF2 alpha is present in higher levels in BCC specimens compared to healthy non sun-exposed skin, confirming previous studies on the production of lipoperoxidation in this tumor. Moreover, we demonstrated that topical pre-treatment with a compound containing vitamin E is capable of reducing 8-iso-PGF2 alpha formation in UV irradiated skin suggesting a role for isoprostanes in UV induced inflammation and eventually carcinogenesis and confirming the function of vitamin E as an antioxidant in this model.

Effect of vaccination with recombinant modified vaccinia virus Ankara expressing structural and regulatory genes of SIV(macJ5) on the kinetics of SIV replication in cynomolgus monkeys.

The efficacy of a multicomponent vaccination with modified vaccinia Ankara constructs (rMVA) expressing structural and regulatory genes of simian immunodeficiency virus (SIV(mac251/32H/J5)) was investigated in cynomolgus monkeys, following challenge with a pathogenic SIV. Vaccination with rMVA-J5 performed at week 0, 12, and 24 induced a moderate proliferative response to whole SIV, a detectable humoral response to all but Nef SIV antigens, and failed to induce neutralizing antibodies. Two months after the last boost, the monkeys were challenged intravenously with 50 MID50 of SIV(mac251). All control monkeys, previously inoculated with non-recombinant MVA, were infected by week two and seroconverted by weeks four to eight. In contrast a sharp increase of both humoral and proliferative responses at two weeks post-challenge was observed in vaccinated monkeys compared to control monkeys. Although all vaccinated monkeys were infected, vaccination with rMVA-J5 appeared to partially control viral replication during the acute and late phase of infection as judged by cell- and plasma-associated viral load.

Vaccination with DNA containing tat coding sequences and unmethylated CpG motifs protects cynomolgus monkeys upon infection with simian/human immunodeficiency virus (SHIV89.6P).

Recent evidence suggests that a CD8-mediated cytotoxic T cell response against the Tat protein of human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) controls primary infection after pathogenic virus challenge, and correlates with the status of long-term nonprogressor in humans. Due to the presence of unmethylated CpG sequences, DNA vaccination can boost the innate immunity driving more potent T cell-mediated immune responses. Therefore, cynomolgus monkeys were vaccinated with a tat-expressing vector containing defined unmethylated CpG sequences (pCV-tat). Here it is shown that the intramuscular inoculation of the pCV-tat contained primary infection with the highly pathogenic SHIV89.6P virus preventing the CD4(+) T cell decline in all the vaccinated monkeys. Undetectable virus replication and negative virus isolation correlated in all cases with the presence of anti-Tat CTLs. However, a CD8-mediated non cytolytic antiviral activity was also present in all protected animals. Of note, this activity was absent in the controls but was present in the monkey inoculated with the CpG-rich vector alone that was partially protected against viral challenge (i.e. no virus replication but positive virus isolation). These results suggest that a CTL response against Tat protects against primary infection by blocking virus replication at its early stage, in the absence of sterilizing immunity. Nevertheless, the boost of the innate immunity by CpG sequences can contribute to this protection both by driving more potent CTL responses and by inducing other CD8-mediated antiviral activities. Thus, the CpG-rich tat DNA vaccine may represent a promising candidate for preventive and therapeutic vaccination against AIDS.

Event history calendars and question list surveys: a direct comparison of interviewing methods.

The research reported in this article provides the first direct experimental comparison between Event History Calendar (EHC; N=309; 84.4 percent response rate) and standardized state-of-the-art question list (Q-list; N=307; 84.1 percent response rate) interviewing methodologies. Respondents and 20 interviewers were randomly assigned to EHC and Q-list interviews that were conducted via telephone in the spring of 1998. All interviews asked for retrospective reports on social and economic behaviors that occurred during the calendar years of 1996 and 1997. Using data from the same respondents collected 1 year earlier on events reported during 1996 as a standard of comparison, the quality of retrospective reports on 1996 events from the 1998 administration of EHC and Q-list interviews was assessed. In comparison to the Q-list, the EHC condition led to better-quality retrospective reports on moves, income, weeks unemployed, and weeks missing work resulting from self illness, the illness of another, or missing work for these reasons in combination with other ones. For reports of household members entering the residence, and number of jobs, the EHC led to significantly more overreporting than the Q-list. Contingent on additional research that examines a wider range of reference periods and different modes of interviewing, the EHC may become a viable and potentially superior method to the Q-list in the collection of self-reported retrospective information.

SHIV89.6P pathogenicity in cynomolgus monkeys and control of viral replication and disease onset by human immunodeficiency virus type 1 Tat vaccine.

The Tat protein of human immunodeficiency virus (HIV) is produced very early after infection, plays a key role in the virus life cycle and in acquired immunodeficiency syndrome (AIDS) pathogenesis, is immunogenic and well conserved among all virus clades. Notably, a Tat-specific immune response correlates with non-progression to AIDS. Here, we show that a vaccine based on the Tat protein of HIV blocks primary infection with the simian/human immunodeficiency virus (SHIV)89.6P and prevents the CD4 T cell decline and disease onset in cynomolgus monkeys. No signs of virus replication were found in five out of seven vaccinated macaques for almost 1 year of follow-up. Since the inoculated virus (derived from rhesus or from cynomolgus macaques) is shown to be highly pathogenic in cynomolgus macaques, the results indicate efficacy of Tat vaccination in protection against highly pathogenic virus challenge. Finally, the studies of the Tat-specific immunological responses indicate a correlation of protection with a cytotoxic T cell response. Thus, a Tat-based vaccine is a promising candidate for preventive and therapeutic vaccination in humans.