Objective: The rapid rise of multi-protease inhibitor (PI)-resistant HIV variants urges the development of new classes of PIs which are potent against existing resistant HIV variants and do not allow or delay the emergence of resistance. We generated UIC-94017/TMC114, a novel non-peptidic PI containing 3 (R), 3a (S), 6a (R)-bis-tetrahydrofuranyl urethane (bis-THF) and a sulfonamide isostere, which exerted potent activity against a wide spectrum of HIV including multi-drug-resistant HIV variants (HIV^MDR).
Materials and Methods: The inhibitor was synthesized in a convergent manner by coupling optically active P2-bis-THF ligand and (R)-(hydroxyethylamino) sulfonamide isostere. Antiviral activity of the compound against various HIV^MDR was determined using MTT assay employing MT-2 cells and p24 assay using PHA-stimulated PBM and MT-4 cells. PIresistant HIV variants were selected in vitro by propagating HIV in the presence of increasing concentrations of each of existing PIs including saquinavir, indinavir, nelfinavir, ritonavir, and amprenavir.
Results: UIC-94017/TMC114 was identified to be extremely potent against various laboratory HIV strains and primary clinical isolates (IC₅₀:-0.003μM) with minimal cytotoxicity (CC₅₀: 74μ/M) when tested in CD4⁺ MT-2 cells. TMC114, at relatively low concentrations (IC₅₀: 0.003-0.029μM), blocked the infection and replication of each of HIV-1^NL4-3 variants exposed to and selected by up to 5/μM of saquinavir, indinavir, nelfinavir, or ritonavir. TMC114 was also potent (IC₅₀ values ranging 0.003 to 0.004μM) against multi-PI-resistant clinical HIV-1 variants, isolated from patients who had no response to any existing antiviral regimens after having received a variety of antiviral agents. Structural analysis revealed that the close contact of TMC114 with the main chains of the protease active site amino acids (Asp29 and Asp30) differed from that of other PIs and was thought to be important for its potency and activity against a wide spectrum of HIV^MDR
Conclusion: These data warrant UIC-94017/TMC114 being further developed as a potential therapeutic agent for treatment of infection with primary HIV and HIV^MDR.

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Background: The HIV-positive ratio in donated blood in Japan is much higher than in other industrialized countries, though the HIV infection rate among the general population is the lowest. This study aims to explore effective measures to prevent HIV contamination of donated blood by examining measures taken in other counties to ensure the safety of donated blood.
Materials & Methods: Measures used to prevent HIV contamination of donated blood in Belgium, Switzerland, the UK, Sweden and Canada were investigated by referring to published information, sending questionnaires, site visits and interviews with staff in blood centers.
Results: Commonly used methods in the investigated countries are as follows: Education prior to donation and confirmation of comprehension by candidate donors, identification by ID and data management of donors, completion of questionnaires and signatures by donors, accountable interviews by trained personnel and the opportunity to withdraw donated blood after donation. Some blood centers request candidates to name prior contacts before their first donation for education and/or blood tests.
Detailed descriptions of activities which raise risks of HIV infection and carefulinterviews with first applicants would raise donors' awareness of their suitability for blooddonation. Furthermore, HIV testing is offered in medical facilities in communities and expenses are covered by medical insurance. In contrast to Japan, all countries inform candidatedonors of positive HIV test results, followed by HIV counseling and referral to HIV/AIDS specialists.
Conclusions: Possible measures to prevent HIV contamination of donated blood in Japan include the following: effective education of candidate donors about HIV/AIDS and confirmation of their comprehension initially, followed by checks on donors' identity, building the skills of interviewers and ensuring accountability, and also ensuring easy access to HIV testing at medical facilities.

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Objective: The delay between HIV infection and patient awareness and hospital visit among HIV-infected and AIDS patients in Japan was examined.
Material & Methods: A self-administered questionnaire was distributed to HIV-infected and AIDS patients visiting 4 area hospitals specializing in AIDS treatment between November 2002 and April 2003. The questionnaire included dates of HIV infection, awareness of it and hospital visit, and HIV testing before AIDS developed. We then analyzed the data from 170 patients.
Results: The delay from HIV infection until awareness of it was 1-2 years for 21%and more than 3 years for 17% of 66 respondants. The delay from awareness of HIV infection until hospital visit was less than 1 month for 69% and more than 1 year for 2% of 163 patients responding. Before AIDS developed, 76% of the AIDS patients did not undergo HIV testing. The frequent reason for no HIV testing was “I was not afraid of HIV infection.”
Conclusion: These results suggested that the delay from HIV infection until awareness of it was long, but that the delay in visiting a hospital was short. Further researchis important.

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Objective: In Japan, most people who have infection with HIV also have infection with HCV caused by administration of coagulation factor products. Fatal lactic acidosisrarely occurs in patients with HIV/HCV co-infection while using both HAART drugs and rivabirin. We experienced a patient with fatal hepatic failure following lactic acidosis after the use of both HAART drugs and rivabirin. We report this rare case with discussion of the results of postmortem examination.
Case Report: A 35-year-old man infected with HIV and HCV after administration of blood products for hemophilia A was started on anti-retroviral therapy for HIV in 1990. He was treated with d4T+ddI+PI (RTV+LPV) from January 2003 after several changes of anti-retroviral drugs. From September 2003, IFNα and ribavirin were also administered for treatment of HCV hepatitis. Symptoms of lactic acidosis initially appeared in October. Although the above-described medication was stopped and treatment for lactic acidosis, including intravenous administration of sodium bicarbonate, was started immediately, hepatic insufficiency rapidly progressed and he died in November 2003.
Conclusion: In this case, rapidly progressing hepatic insufficiency was induced bylactic acidosis. We concluded that hepatic failure was possibly caused by lactic acidosis, side effects of combined therapy with IFNα and ribavirin, and rapid progression to non-compensative liver cirrhosis from HCV hepatitis.

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Objective: This study sought to determine whether male clinical psychologists (CPs) exhibited clinical bias (CB) against gay men by examining the clinical judgments and attitudes of CPs towards their male clients (CLs) and the attitudes of CPs toward gender roles.
Methods: A questionnaire was given to 200 randomly sampled male CPs. In the questionnaire, CPs read a clinical vignette about a male CL and rated the CL on several clinical dimensions. There were two versions of the questionnaire. In the vignette, the sexual orientation (heterosexual or homosexual) of the client was manipulated. After completing the questionnaire, a separate scale was used to measure how liberated the attitudes of the CPs were towards gender roles.
Results: Seventy-seven (77) completed surveys were returned (the return rate was 38.5%). Most of the CPs' attitudes toward gender roles were liberated. A variance analysis revealed a significant effect only for CL sexual orientation. The effect for CPs'attitudes toward gender roles and the interaction of the two factors were not significant. Regardless of the CPs' attitudes toward gender roles, they showed more negative attitudes toward the homosexual CL.
Conclusion: Contrary to the hypothesis, the results did not confirm CPs' CB related to attitudes toward gender roles. However the results didn't suggest the absence of CB by the CPs. The lack of significant findings might stem from the problem of the scale used, the method of stimuli presentation, and so on. It was concluded that more applicable methodologies need to be developed. Future studies will focus on different methodologies to measure the possibility of CB.

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Objective: The purpose of this study was to investigate demographic and behavioral characteristics of HIV antibody test repeaters at a public health center.
Materials and Methods: From April 2002 through March 2004, after getting informed consents to the purpose and the procedures of the study, anonymous self-administered questionnaires were given to all people who visited a public health center in Kyoto City to have their blood tested for HIV antibody.
Results: During the study period, 242 people visited the center for HIV antibody test and 214 (88.4%) responded to the survey. The number of the initial testers was 154 (72.0%), while repeaters who have had more than two tests were 60 (28.0%) in total. The proportion of male and the mean age of repeaters were significantly greater than initial testers. The proportion of people who reported consistent condom use in repeaters was also significantly greater than in initial testers. Logistic regression analysis demonstrated that age over 30 and consistent condom use were significantly associated with repeaters.
Conclusion: Repeaters were found to be older and having more protected sexual behavior than the initial testers. The meaning and the background of such characteristics of repeaters should be further investigated in order to make the services at the public health center more relevant to the clients.

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