Acquired Immunodeficiency Syndrome: Oka S

Abe Y, Oka S. · AIDS Clinical Center, International Medical Center of Japan. · Nippon Rinsho. · Pubmed #17491429 No free full text.

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Oka S. · No affiliation provided · Nippon Naika Gakkai Zasshi. · Pubmed #17100274 No free full text.

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Honda M, Oka S. · International Medical Center of Japan, Tokyo, Japan. · Int J Hematol. · Pubmed #16867897 No free full text.

Abstract: Antiretroviral treatments with highly active antiretroviral therapy (HAART) have shown remarkable progress in the past decade and resulted in impressive improvements in life expectancy and quality of life for patients infected with human immunodeficiency virus 1 (HIV-1). Despite the clinical benefits, the management of HIV infection faces many problems. Although HAART is able to suppress the viral load in the plasma, it is unable to eradicate it, and once HAART is initiated, treatment needs to be continued over a lifetime. The side effects of long-term HAART, such as lipodystrophy, lactic acidosis, insulin resistance, and hyperlipidemia, are negative impacts for patients who receive HAART. In addition, patients need to demonstrate high adherence to the therapy to achieve viral suppression and prevent the development of a drug-resistant virus. This review discusses currently recommended antiretroviral treatment strategies, the difficulties with antiretroviral treatments, and current issues regarding HIV management.

Onda J, Oka S. · International Medical Center of Japan, AIDS Clinical Center. · Nippon Rinsho. · Pubmed #16615560 No free full text.

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Oka S. · AIDS Clinical Center, International Medical Center of Japan. · Nippon Rinsho. · Pubmed #12722228 No free full text.

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Teruya K, Oka S. · International Medical Center of Japan, AIDS Clinical Center. · Nippon Rinsho. · Pubmed #11968780 No free full text.

Abstract: Introduction of HAART (highly active antiretroviral therapy) has resulted in dramatic reductions in AIDS-related opportunistic complications and death. We have faced, however, severe complications due to HAART such as lactic acidosis and lipodystrophy syndrome. Regimens currently employed in the treatment may be complex, require multiple drugs to take, difficult to tolerate owing to adverse effects, and decrease level of quality of life in some patients. Decisions about when and with what to initiate HAART must take into account the risk-benefit ratio associated with the therapy. In this article, issues that must be considered in determining timing of initiation and choice of anti-retroviral drugs are discussed.

Murakoshi H, Kitano M, Akahoshi T, Kawashima Y, Dohki S, Oka S, Takiguchi M. · Division of Viral Immunology, Center for AIDS Research, Kumamoto University, Kumamoto, Japan. · Hum Immunol. · Pubmed #19167445 No free full text.

Abstract: HLA-B*4801 is frequently found in Asian populations but rarely in Caucasian or African populations. Although HLA-B*4801-restricted human immunodeficiency virus-1 (HIV-1) epitopes would be useful for acquired immune deficiency syndrome (AIDS) vaccine development in Asia, they have not been reported so far. In the present study, we sought to identify HLA-B*4801-restricted HIV-1 epitopes by using 17-mer overlapping peptides derived from HIV-1 Gag, Pol, and Nef as well as 8- to 11-mer truncated peptides, and thereby identified two HLA-B*4801-restricted Gag epitopes. These epitope-specific CD8(+) T cells strongly responded to HIV-1-infected cells expressing HLA-B*4801, confirming that these Gag epitopes were endogenously presented by HLA-B*4801. These epitope-specific CD8(+) T cells were elicited in five of the seven tested chronically HIV-1-infected individuals with HLA-B*4801, suggesting them to be immunodominant epitopes. These epitopes will be useful for the studies of AIDS immunopathogenesis and the development of an HIV-1 vaccine in Asia.

Kawashima Y, Satoh M, Oka S, Shirasaka T, Takiguchi M. · Division of Viral Immunology, Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan. · Biochem Biophys Res Commun. · Pubmed #18035044 No free full text.

Abstract: It is speculated that HLA-A( *)26-restricted HIV-1-specific CTLs can control HIV-1, since HLA-A( *)26 is associated with a slow progression to AIDS. In three major HLA-A( *)26 subtypes, HLA-A( *)2601-restricted, and HLA-A( *)2603-restricted HIV-1 epitopes have been identified, but HLA-A( *)2602-restricted ones have not. We here identified HLA-A( *)2602-restricted HIV-1 epitopes by using reverse immunogenetics and compared the immunodominance of the epitopes among the three subtypes. Out of 110 HIV-1 peptides carrying HLA-A( *)26 anchor residues, only the Gag169-177 peptide, which had been previously identified as an HLA-A( *)2601- and HLA-A( *)2603-restricted immunodominant epitope, induced Gag169-177-specific CD8(+) T cells from only two of six HLA-A( *)2602(+) HIV-1-infected individuals. No difference in affinity of this epitope peptide was found among these three HLA-A( *)26 subtypes, indicating that Gag169-177 was effectively presented by HLA-A( *)2602 but recognized as a subdominant epitope in HIV-1-infected HLA-A( *)2602(+) individuals. These findings indicate different immunodominance of Gag169-177 epitope among 3 HLA-A( *)26 subtypes.

Katano H, Sato Y, Hoshino S, Tachikawa N, Oka S, Morishita Y, Ishida T, Watanabe T, Rom WN, Mori S, Sata T, Weiden MD, Hoshino Y. · Department of Pathology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku, Tokyo 162-8640, Japan. · Microbes Infect. · Pubmed #18024124 links to  free full text

Abstract: Signal transducer and activator of transcription 3 (STAT3) is a DNA-binding transcription factor activated by multiple cytokines and interferons. High expression of STAT3 has also been implicated in cancer and lymphoma. Here, we show a case of B cell lymphoma in which a defective human immunodeficiency virus 1 (HIV-1) integrated upstream of the first STAT3 coding exon. The lymphoma cells with anaplastic large cell morphology formed multiple nodular lesions in the lung of an acquired immunodeficiency syndrome (AIDS) patient with Kaposi's sarcoma. The provirus had a 5' long terminal repeat (LTR) deletion, but the 3' LTR had stronger promoter activity than the STAT3 promoter in reporter assays. Immunohistochemistry showed increased expression of STAT3 in the nuclei of lymphoma cells. Transfection of STAT3 resulted in transient cell proliferation in primary B cells in vitro. Although this is a very rare case of HIV-1-integrated lymphoma, these data suggest that up-regulation of STAT3 caused by HIV-1 integration resulted in the development of B cell lymphoma in this special case.

Vasilescu A, Terashima Y, Enomoto M, Heath S, Poonpiriya V, Gatanaga H, Do H, Diop G, Hirtzig T, Auewarakul P, Lauhakirti D, Sura T, Charneau P, Marullo S, Therwath A, Oka S, Kanegasaki S, Lathrop M, Matsushima K, Zagury JF, Matsuda F. · Centre National de Génotypage, 91057 Evry, France. · Proc Natl Acad Sci U S A. · Pubmed #17360650 links to  free full text

Abstract: Chemokines and their receptors are key factors in the onset and progression of AIDS. Among them, accumulating evidence strongly indicates the involvement of IL-8 and its receptors, CXCR1 and CXCR2, in AIDS-related conditions. Through extensive investigation of genetic variations of the human CXCR1-CXCR2 locus, we identified a haplotype of the CXCR1 gene (CXCR1-Ha) carrying two nonsynonymous single nucleotide polymorphisms, CXCR1_300 (Met to Arg) in the N terminus extracellular domain and CXCR1_142 (Arg to Cys) in the C terminus intracellular domain. Transfection experiments with CXCR1 cDNAs corresponding to the CXCR1-Ha and the alternative CXCR1-HA haplotype showed reduced expression of CD4 and CXCR4 in CXCR1-Ha cells in human osteosarcoma cells as well as in Jurkat and CEM human T lymphocytes. Furthermore, the efficiency of X4-tropic HIV-1(NL4-3) infection was significantly lower in CXCR1-Ha cells than in CXCR1-HA cells. The results were further confirmed by a series of experiments using six HIV-1 clinical isolates from AIDS patients. A genetic association study was performed by using an HIV-1(+) patient cohort consisting of two subpopulations of AIDS with extreme phenotypes of rapid and slow progression of the disease. The frequency of the CXCR1-Ha allele is markedly less frequent in patients with rapid disease onset than those with slow progression (P = 0.0003). These results provide strong evidence of a protective role of the CXCR1-Ha allele on disease progression in AIDS, probably acting through modulation of CD4 and CXCR4 expression.

Abe Y, Matsubara D, Gatanaga H, Oka S, Kimura S, Sasao Y, Saitoh K, Fujii T, Sato Y, Sata T, Katano H. · AIDS Clinical Center, Tokyo, Japan. · Pathol Int. · Pubmed #16984619 No free full text.

Abstract: The expression of Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8)-encoded proteins is herein demonstrated in Kaposi's sarcoma (KS) and multicentric Castleman's disease (MCD) in a single lymph node derived from a patient with acquired immunodeficiency syndrome. Immunohistochemistry revealed that both lytic and latent KSHV proteins were expressed in cells of the MCD lesion. KSHV-encoded viral interleukin-6 was also detected in follicular dendritic cells of the germinal center. Cytoplasmic localization of open reading frame 59 protein and latency-associated nuclear antigen suggested KSHV activation in the MCD lesion. Moreover, a high copy number of KSHV was detected in the blood. Clinically, pegylated-liposomal doxorubicin induced regression of not only KS, but also lymphadenopathy of the MCD lesion with a decrease in KSHV load and human interleukin-6 in the blood. To the best of the authors' knowledge this is the first case demonstrating differential expression of virus proteins in two KSHV-associated diseases, KS and MCD, in the same section. The case confirms lytic KSHV infection in MCD, and suggests that clinical symptoms of MCD might be closely linked with KSHV activation.

Kawado M, Hashimoto S, Yamaguchi T, Oka S, Yoshizaki K, Kimura S, Fukutake K, Higasa S, Shirasaka T. · Department of Hygiene, Fujita Health University School of Medicine, Aichi, Japan. · J Epidemiol. · Pubmed #16710078 links to  free full text

Abstract: BACKGROUND: It is important to examine progression to acquired immunodeficiency syndrome (AIDS) or death and its predictors among human immunodeficiency virus (HIV) infected persons before and after the introduction of the highly active antiretroviral therapy (HAART) available in Japan since 1997. METHODS: The data used were from a survey of persons with HIV infected through blood coagulation factor products in Japan. Progression to AIDS or death during two periods, between January 1994 and March 1997, and between April 1997 and March 2002, were observed. RESULTS: The AIDS-free proportion after 3 years was 74% among 417 participants for the earlier period and 94% among 605 participants in the later one. The hazard ratio of low CD4 cell count (less than 200 cells/microL) was 50.8 for the earlier period and 4.7 for the later one compared with that of 500 cells/microL or more. After adjustment by plasma HIV RNA levels and use of antiretroviral therapy, the hazard ratios of the low CD4 cell count for the later period were still significant. CONCLUSION: The AIDS-free proportion among people with HIV infected through blood products in Japan largely increased after the introduction of HAART. The CD4 cell count remains an important predictor of future progression, but its importance might be less because of HAART.

Yamanaka H, Teruya K, Tanaka M, Kikuchi Y, Takahashi T, Kimura S, Oka S, Anonymous00375. · AIDS Clinical Center, International Medical Center of Japan, Tokyo, Japan. · J Acquir Immune Defic Syndr. · Pubmed #15905732 No free full text.

Abstract: Influenza vaccine is recommended for HIV-1-infected patients. The present prospective study was conducted to evaluate the clinical efficacy and immunologic responses to the vaccine. From November 1 to December 27, 2002, 262 HIV-1-infected patients received a trivalent influenza subunit vaccine, whereas 66 did not. Influenza illness occurred in 16 vaccinated and 14 nonvaccinated patients (incidence = 6.1% [95% confidence interval (CI): 4%-10%] in vaccinated vs. 21.2% [CI: 13%-35%] in nonvaccinated persons, P < 0.001; relative risk = 0.29 [CI: 0.14-0.55]). Influenza vaccine provided clinically effective protection against influenza illness in HIV-1-infected patients. In baseline antibody-negative patients, anti-H1 and anti-H3 antibody responses to the vaccination were significant in those patients with a CD4 count >200 cells/muL compared with those with a CD4 count <200 cells/muL (P < 0.05). In contrast, in baseline antibody-positive patients, good antibody responses were observed irrespective of CD4 counts, like the healthy controls. Based on these results, annual vaccination is recommended. Specific CD4 responses correlated with HIV-1 viral load (VL), especially in patients treated with highly active antiretroviral therapy (HAART) compared with those without HAART (P < 0.01), although the clinical efficacy did not correlate with HIV-1 VL. HAART may enhance the immunologic efficacy of influenza vaccine.

Song J, Yoshida A, Yamamoto Y, Katano H, Hagihara K, Oka S, Kimura S, Yoshizaki K. · Department of Medical Science I, School of Health and Sport Sciences, Osaka University, Osaka, Japan. · Leuk Lymphoma. · Pubmed #15512828 No free full text.

Abstract: We encountered a case of a rapidly progressive HHV-8-associated solid lymphoma with AIDS-associated Kaposi's sarcoma (KS). HHV-8 DNA load in whole blood cells was analyzed quantitatively by real-time PCR using amplification of the HHV-8-encoded ORF26 gene. Ours is the first observation that the rapid increase in the HHV-8 viral load (from 1.9x10(4) copies/microg to 1.6x10(6) copies/microg in 40 days) in conjunction with low CD4+ cell counts was accompanied by an accelerated clinical disease progression. The results indicate that the quantity of circulating HHV-8 is measurable with real-time PCR and can provide clinically useful information.

Yamamoto Y, Teruya K, Katano H, Niino H, Yasuoka A, Kimura S, Oka S. · AIDS Clinical Center, International Medical Center of Japan, Toyama 1-21-1, Toyama, Shinjuku, Tokyo 162-8655, Japan. · Leuk Lymphoma. · Pubmed #14565671 No free full text.

Abstract: We report a case of rapidly progressive solid lymphoma with anaplastic large cell morphology, followed by systemic Kaposi sarcoma in an adult patient with AIDS. The lymphoma cells expressed human herpesvirus 8 (HHV-8)-encoded latent and lytic proteins and Epstein-Barr virus-encoded small RNA, suggesting that this case could be categorized into HHV-8-associated solid lymphoma, a recently identified disease entity.

Ueda A, Gatanaga H, Kikuchi Y, Hasuo K, Kimura S, Oka S. · AIDS Clinical Center, International Medical Center of Japan, Tokyo, Japan. · Clin Infect Dis. · Pubmed #14521151 No free full text.

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Kikuchi Y, Genka I, Ishizaki A, Sunagawa K, Yasuoka A, Oka S. · AIDS Clinical Center, International Medical Center of Japan, Tokyo. · Clin Infect Dis. · Pubmed #12145735 No free full text.

Abstract: We describe 2 patients with acquired immunodeficiency syndrome who had potentially fatal bradyarrhythmia that occurred shortly after commencement of antiretroviral therapy. Lopinavir-ritonavir was the only drug that both patients were using.

Oka S. · AIDS Clinical Center, International Medical Center of Japan, 1-21-1, Toyama, Shinjuku-ku, Tokyo 162-8655, Japan. · Kekkaku. · Pubmed #11855078 No free full text.

Abstract: HIV infection was first reported in 1981 in USA. It has been 20 years since then. Owing to understandings of pathogenesis of this disease and development of new drugs such as the HIV-specific protease inhibitor (PI), prognosis of disease has been tremendously improved. Especially after 1997 in Japan, the strategy of anti-HIV treatment shifted from two drugs combination to three drugs combination, which is called highly active antiretoviral therapy (HAART). HAART was so effective that prevalence of HIV associated opportunistic infections were decreased dramatically. Mortality among hospitalized HIV-infected patients was decreased from 6.7% in 1996 to 2.6% since then in ACC. However, 80% of patients receiving HAART suffered from side effects and 15% of them had to be changed their treatment due to side effects. Furthermore, an unexpected side effect, namely lipodystrophy syndrome (LDS), was emerged among patients who were receiving HAART more than one year. LDS was first reported as re-distribution of lipid such as central obesity with or without lipo-atrophy from extremities and/or face. Now only cosmetic change, but also it is associated with elevation of lipid and glucose level. Therefore, those patients who have LDS are in face of the risk for the ischemic heart diseases. Our survey indicated that the rate of LDS in Japanese patients were almost same as that of Caucasian patients reported elsewhere. Opportunistic infections associated with HIV infection Treatment for HIV infection consists of two major arms; one is use of anti-HIV drugs to prevent development of AIDS described above and the other is diagnosis, treatment, and prophylaxis of opportunistic infections. There are five very important opportunistic infections; Pneumocystis carinii pneumonia (PCP), cryptococcus meningitis, toxoplasma encephalitis, cytomegalovirus (CMV) infection, and Mycobacterium avium complex (MAC) bacteremia. Because if these five were able to diagnose, a patient can survive under appropriate treatment. On the other hand, if these were not diagnosed, patient must be AIDS death. After introducing HAART, number of CMV retinitis, MAC bacteremia, and AIDS dementia complex were decreasing. However, number of PCP sustained high because PCP is the first indicator disease of AIDS if the patient did not know his HIV status. The first choice of drug is sulfamethoxazole/trimethoprim (ST) for PCP treatment. If the patient were in severe respiratory failure, corticosteroid is used concomitantly. Treatment is usually continued for 3 weeks. We have successfully treated 45 out of 47 cases of PCP for 4 years. However, those patients treated with ST for 3 weeks were limited only 35% because of very high rate of side effects of ST. If the patient was intolerant to ST, treatment was switched to pentamidine. After finishing the treatment, the patient is to be treated with a 5-day course of oral desensitization to ST. More than 80% of patients who were previously intolerant to ST became successfully getting tolerance by this method.

Oka S, Yasuoka A. · No affiliation provided · Nippon Naika Gakkai Zasshi. · Pubmed #11681050 No free full text.

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Wakabayashi H, Yano M, Tachikawa N, Oka S, Maeda M, Kido H. · Division of Enzyme Chemistry, Institute for Enzyme Research, The University of Tokushima, Kuramoto-cho 3-18-15, 770-8503, Tokushima, Japan. · Clin Chim Acta. · Pubmed #11580914 No free full text.

Abstract: BACKGROUND: 14-3-3 proteins are major evolutionarily conserved cytosolic proteins that regulate signal transduction, apoptosis and neurotransmitter synthesis. Five homologous 14-3-3 isoforms, beta, gamma, zeta, epsilon and eta, are reported in mammalian neurones. To elucidate the diagnostic value of 14-3-3 in cerebrospinal fluid (CSF), a highly specific antibody against each isoform and studies on the isoform patterns in patients with neuronal destruction are needed. METHODS: In this study, we raised isoform-specific antibodies against 14-3-3 proteins and established a semiquantitative method of identification of each isoform by Western immunoblotting. RESULTS: We found that three isoforms, 14-3-3 epsilon, gamma and zeta, appeared in the CSF of HIV patients with AIDS dementia complex or cytomegalovirus encephalitis, but not in AIDS patients without neurological symptoms or the non-HIV patients examined. The isoform patterns in AIDS patients were different from those reported in Creutzfeldt-Jakob disease and herpes simplex encephalitis, suggesting that the isoform patterns may facilitate the differential diagnosis. A high frequency of 14-3-3 in CSF was observed in seriously ill AIDS patients, particularly those with CD4 levels of less than 20 mm(3). CONCLUSION: These findings suggested that 14-3-3 proteins were released from destroyed neural cells and are useful real-time markers of the rate and amount of neural cell destruction in these patients.

Yamamoto Y, Yasuoka A, Tachikawa N, Teruya K, Genka I, Yamaguchi M, Yasuoka C, Kikuchi Y, Yoneyama A, Oka S. · AIDS Clinical Center, International Medical Center of Japan, Tokyo. · Intern Med. · Pubmed #11393423 links to  free full text

Abstract: The prognosis of Mycobacterium avium complex (MAC) infection has been improved by new macrolides-containing regimens and the use of highly active antiretroviral therapy (HAART) in the treatment of acquired immunodeficiency syndrome (AIDS). We report on two AIDS cases with long lasting bacteremia due to MAC under this regimen. Both patients experienced problems due to side effects from the anti-MAC regimen and from an immune-reconstitution syndrome related to HAART. MAC infection persisted despite treatment, however, no anti-MAC drug-resistant isolates emerged throughout the clinical course in either case. These cases demonstrate that therapy for disseminated MAC infection is sometimes difficult even with HAART and macrolides-containing regimens.

Teruya K, Yasuoka A, Yamaguchi M, Yasuoka C, Yamamoto Y, Genka I, Tachikawa N, Kikuchi Y, Oka S. · AIDS Clinical Center, International Medical Center of Japan. · Intern Med. · Pubmed #11310488 links to  free full text

Abstract: OBJECTIVE: To describe the incidence of complications before and during therapy of Pneumocystis carinii pneumonia (PCP) in patients with acquired immunodeficiency syndrome (AIDS). METHODS: A retrospective review of the patient's medical records. PATIENTS: A total of 29 patients with AIDS and PCP who were admitted to the AIDS Clinical Center, International Medical Center of Japan from July 1996 to November 1999. RESULTS: Adverse effects were found in 24 (88.9%) of 27 patients treated with trimethoprim/sulfamethoxazole (T/S), 6 (46.1%) of 13 treated with parenteral pentamidine, and 2 (20%) of 10 treated with inhaled pentamidine. Infectious and/or non-infectious complications were found in 25 (86.2%) of 29 study patients. Regarding infectious complications, 16 (55.2%) were found on admission and 10 cases (34.5%) with infectious complications were identified during admission; including oral candidiasis (37.9% and 17.2%, respectively) and genital herpes (3.4% and 6.9%, respectively). Cytomegalovirus antigenemia was detected in 4 cases (13.8%) on admission and 12 cases (41.4%) during admission. Non-infectious complications affected 11 cases (37.9%) on admission, and 6 cases (20.7%) during admission, the latter included heart failure (10.3%) and pneumothorax (6.9%). PCP was successfully treated in all but one patient who suffered from repeated pneumothorax. CONCLUSION: Treatment of PCP can be problematic and it is important to be aware of the high incidence of various complications that can occur during the treatment of PCP.

Yamaguchi K, Mori A, Oka S, Takeyama M, Okabe N. · No affiliation provided · Nippon Naika Gakkai Zasshi. · Pubmed #11307341 No free full text.

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Shimomura S, Kikuchi Y, Oka S, Ishitoya J. · Department of Otorhinolaryngology, International Medical Center of Japan, 1-21-1 Toyama, Shinjuku-ku, 162-8655, Tokyo, Japan. · Auris Nasus Larynx. · Pubmed #10996492 No free full text.

Abstract: Kaposi's sarcoma (KS) is frequently seen in the head and neck regions of HIV-infected patients. We report two cases of patients with AIDS who consulted the ENT clinic. One patient came to our clinic complaining of abnormal sensations in the pharynx, and dysphasia due to a gross KS in the oropharynx. The excision of the tumor improved the difficulty of swallowing. The other patient complained of masticatory problems and tongue pain due to a bulky KS on the dorsal side of the tongue. We treated the tongue lesion with intralesional chemotherapy. The administration of intralesional vinblastine resulted in a partial response. Unless systemic chemotherapy is effective enough to improve a functional disorder, it is thought that local therapy employing excision or intralesional chemotherapy is one of the common therapeutic option of the otolaryngologist, because this treatment avoids severe side effects caused by systemic chemotherapy or radiotherapy.

Fukutake K, Ueda Y, Tatsunami S, Ajisawa A, Oka S, Takamatsu J, Taki M, Shirahata A. · Department of Clinical Pathology, Tokyo Medical University Hospital. · Rinsho Ketsueki. · Pubmed #10483137 No free full text.

Abstract: Our group conducted a national survey of patients who had died of acquired immunodeficiency syndrome (AIDS) after being infected with human immunodeficiency virus type 1 (HIV-1) by contaminated blood coagulation factor products. A total of 1446 hospitals, clinics, and other health-care institutions throughout Japan were enrolled in the study, which was supported by the Japanese government Ministry of Health and Welfare with a health sciences grant for research on HIV/AIDS. Of the 1434 registered patients who had been infected with HIV-1 by contaminated blood coagulation factor products, 493 (34%) had died as of Oct. 30, 1997. Most were hemophiliacs. The average CD4+ cell count was 25/microliter for the 398 who died of complications from AIDS, compared to an average of 158/microliter for those who died of other causes. Pneumocystis carinii pneumonia, cytomegalovirus infection, and atypical mycobacterial disease were the main causes of death in patients with AIDS. The annual death rate for AIDS patients in Japan dropped dramatically in 1997, 1 year later than a similar trend observed in the United States. The introduction and widespread adoption of new and effective drugs and treatment regimens for HIV-1 and opportunistic infections will be essential life-saving measures.