Oral and systemic HPV antibody kinetics post-vaccination among HIV-positive and HIV-negative men

Duration and functional aspects of the oral and systemic antibody responses following HPV vaccination in HIV-negative (HIV^?) and HIV-positive (HIV⁺) men are not well characterized. Oral and systemic HPV-16 and HPV-18-specific antibody levels were evaluated over 18-months of follow-up, in HIV⁺ and HIV^? men. Sera and oral gargles from 147 HIV^? men, ages 27–45 and 75 HIV⁺ men, ages 22–61, who received 3-doses of quadrivalent HPV vaccine were tested for HPV-16 and HPV-18 antibodies at Day 1, Month 7 (1?month post-dose 3), and Month 18 (12?months post-dose 3) and HPV avidity (Day 1, and Month 7) using L1-VLP ELISA.All individuals seroconverted, regardless of HIV-status, following 3-doses of vaccine for HPV-16 and HPV-18. Serum HPV-16 and HPV-18 antibody geometric mean levels were >2-fold lower in HIV⁺ compared to HIV^? men at Month 7 (HPV-16: 808.5 versus 2119.8?EU/mL, and HPV-18: 285.8 versus 611.6?EU/mL, p?<?0.001) but not significantly different at Month 18 (HPV-16: 281.8 versus 359.7?EU/mL, p?=?0.145, and HPV-18: 120.2 versus 93.4?EU/mL, p?=?0.372). Post-vaccination, only oral HPV-16 antibody levels at Month 7 were significantly different between HIV⁺ and HIV^? men (127.7 versus 177.1?EU/mg of IgG, p?=?0.008). Among baseline HPV-seronegative men, circulating levels of HPV-16 and HPV-18 antibodies were up to >3 fold lower in HIV⁺ men, at Months 7 and 18. In contrast, levels of HPV-16 and HPV-18 antibodies after vaccination were not inferior in baseline HPV-seropositive, HIV⁺ men. HPV-16 and HPV-18 avidity was lower among HIV⁺ compared to HIV^? men at Month 7 (HPV-16: 1.95?M versus 2.12?M, p?=?0.027; HPV-18: 1.50?M versus 1.72?M, p?<?0.001).Although differences in peak antibody levels were observed between HIV⁺ and HIV^? men following 3 doses of vaccine, plateau antibody levels were overall comparable, and avidity was relatively high for both groups. These data indicate that the vaccine induced antibody affinity maturation in both HIV⁺ and HIV^? men and will likely result in long-term protective immune responses.     

Phase 2 study of the safety and efficacy of vicriviroc, a CCR5 inhibitor, in HIV-1-Infected, treatment-experienced patients: AIDS clinical trials group 5211

BACKGROUND: Vicriviroc, an investigational CCR5 inhibitor, demonstrated short-term antiretroviral activity in a phase 1 study. METHODS: The present study was a double-blind, randomized phase 2 study of vicriviroc in treatment-experienced, human immunodeficiency virus (HIV)-infected subjects experiencing virologic failure while receiving a ritonavir-containing regimen with an HIV-1 RNA level >or=5000 copies/mL and CCR5-using virus. Vicriviroc at 5, 10, or 15 mg or placebo was added to the failing regimen for 14 days, after which the antiretroviral regimen was optimized. The primary end point was the change in plasma HIV-1 RNA levels at day 14; secondary end points included safety/tolerability and HIV-1 RNA changes at week 24. RESULTS: One hundred eighteen subjects were randomized with a median HIV-1 RNA level of 36,380 (4.56 log(10)) copies/mL and a median CD4 cell count of 146 cells/mm(3). At 14 days and 24 weeks, mean changes in HIV-1 RNA level (log(10) copies/mL) were greater in the vicriviroc groups (-0.87 and -1.51 [5 mg], -1.15 and -1.86 [10 mg], and -0.92 and -1.68 [15 mg]) than in the placebo group (+0.06 and -0.29) (P<.01). Grade 3/4 adverse events were similar across groups. Malignancies occurred in 6 subjects randomized to vicriviroc and in 2 to placebo. CONCLUSIONS: In HIV-1-infected, treatment-experienced patients, vicriviroc demonstrated potent virologic suppression through 24 weeks. The relationship of vicriviroc to malignancy is uncertain. Further development of vicriviroc in treatment-experienced patients is warranted.     

Potential risks and benefits of HIV treatment simplification: a simulation model of a proposed clinical trial.

BACKGROUND: In recent studies, subjects who had achieved suppression of the human immunodeficiency virus (HIV) RNA level while receiving an initial 3-drug antiretroviral regimen successfully maintained suppression while receiving treatment with a "boosted" protease inhibitor (PI) alone. We projected the long-term outcomes of this treatment simplification strategy to inform the design of a proposed multicenter, randomized clinical trial. METHODS: We used published studies to estimate the efficacy, adverse effects, and cost of a sequence of HIV drug regimens for the simplification strategy, compared with those outcomes for the current standard-of-care (SOC) strategy. Using a published simulation model of HIV disease, we projected life expectancy, discounted quality-adjusted life expectancy (QALE), and discounted lifetime medical costs for each strategy. RESULTS: Subjects who have not developed PI-resistant HIV infection at the time of failure of the simplification regimen have a greater life expectancy (27.9 vs. 27.1 years) and QALE (14.9 vs. 14.7 years), compared with SOC subjects, because they receive an additional line of therapy without negative consequences for future treatment options. The QALE for the simplification strategy remains higher than that for the SOC, unless a large proportion of patients experiencing virologic failure while receiving the simplification regimen develop PI resistance. Depending on the probability of simplification regimen failure, the advantage is maintained even if HIV develops PI resistance in 42%-70% of subjects. Projected lifetime costs are $26,500-$72,400 per person lower for the simplification strategy than for the SOC strategy. CONCLUSIONS: An HIV treatment simplification strategy involving use of a boosted PI alone may lead to longer survival overall at lower cost, compared with the SOC combination therapy, because the simplification strategy potentially adds an additional line of therapy. The risk of emergence of PI resistance during treatment with a simplified regimen is a critical determinant of the viability of this strategy.     

Assessing Human Immunodeficiency Virus Type 1 Tropism: Comparison of Assays Using Replication-Competent Virus versus Plasma-Derived Pseudotyped Virions

Detection of CXCR4-using human immunodeficiency virus by the Trofile assay was compared to that by assays using virus isolates or replication-competent recombinants. Concordance with the Trofile assay was good, but assays using replicating viruses did not increase substantially the ability to detect the presence of CXCR4-using virus.Human immunodeficiency virus type 1 (HIV-1) can be assigned to one of three classes based on its ability to utilize the CCR5 and CXCR4 coreceptors: viruses that use CCR5 but not CXCR4 (R5 virus), those that use CXCR4 but not CCR5 (X4 virus), and those that can use either coreceptor (dualtropic virus). HIV-1 also can be classified according to its ability to replicate and induce syncytia in MT-2 cells (8, 12). The use of CXCR4 is a defining feature of syncytium-inducing (SI) viruses in MT-2 cells; most but not all non-SI (NSI) viruses are R5 (1, 13, 16).Testing to determine coreceptor usage of HIV-1 isolates is essential to identify patients who are suitable candidates for treatment with CCR5 antagonists. The tropism assay (Trofile; Monogram BioSciences, South San Francisco, CA) used in clinical trials of CCR5 antagonists to date is a validated single-cycle assay performed in a Clinical Laboratory Improvement Amendments/College of American Pathologists-certified laboratory; the assay is based on pseudotyped virus and sensitively detects the presence of CXCR4-using virus (14). However, up to 10% of subjects identified as having exclusively R5 virus at screening had evidence of dualtropic or mixed-tropic (D/M) virus at the time treatment with maraviroc or vicriviroc (VCV) was begun (3, 4). To test the hypothesis that the sensitivity of tropism testing could be improved by use of replicating viruses instead of pseudotyped viruses, we compared the results of tropism testing with the Trofile assay to those of assays using replication-competent viruses using clinical samples from AIDS Clinical Trials Group (ACTG) protocol A5211, a phase 2b trial of the investigational CCR5 antagonist VCV (SCH-D; SCH417690; Schering-Plough, Kenilworth, NJ) (4).(This work was presented in part at the 14th Conference on Retroviruses and Opportunistic Infections, Los Angeles, CA, 25-28 February 2007 [5a].)     

Contemporary issues in dental education in Australia

Australia has witnessed a proliferation of dental workforce training opportunities over the last 15 years, including dentists, dental therapists, dental hygienists and prosthetists. The reasons for this have not been examined critically. Universities have welcomed the opportunities to increase the student base but do not seem to have examined the advisability of continued expansion or its impact on the delivery and costs of health services. Nor have they enquired expressly whether they have any responsibility in these matters. Public health benefits should constitute a significant element of curriculum design. There seems to have been a general acceptance of the premise that more is necessarily better. Ironically, these developments have occurred in the face of significant recurrent cost increments and serious academic staff shortages. The schools have responded with alterations to curriculum content. Student cohort composition, course structures, educational focus, postgraduate training and research have been affected. The primary purpose of this review is to highlight the issues which currently drive workforce training and curriculum content and to suggest that some current practices should be re-examined as a starting point for setting defined common objectives within the Australian dental educational spectrum. Salient issues which require examination include course standards and accreditation, workforce mix, dental health demands, public service obligations and staffing profiles.     

Design of the Balance@Work project: systematic development, evaluation and implementation of an occupational health guideline aimed at the prevention of weight gain among employees

Background  

Occupational health professionals may play an important role in preventive health promotion activities for employees. However, due to a lack of knowledge and evidence- and practice based methods and strategies, interventions are hardly being implemented by occupational physicians to date. The aim of the Balance@Work project is to develop, evaluate, and implement an occupational health guideline aimed at the prevention of weight gain among employees.