Pathogenesis, clinical course, and recent issues in HIV-1-infected Japanese hemophiliacs: a three-decade follow-up.

Nearly 30% of Japanese hemophiliacs were infected with HIV-1 in the early 1980s. They have unique characteristics compared to HIV-1-infected individuals through other routes, including date of infection of 1986 or earlier, mean age of nearly 50 years, and common co-infection with hepatitis C, but rarely with other sexually transmitted diseases. Antiretroviral therapy (ART) was introduced in Japan in 1997. The clinical courses before and after 1997 were quite different. Careful analysis of the pre-1997 clinical data allowed expansion of our knowledge about the natural course and pathogenesis of the disease. Switching to the second receptor agents proved critical in subsequent disease progression. HIV-1 continued to escape immune pressure, pushing disease progression faster. In contrast, ART was effective enough to overcome the natural course. Prognosis improved dramatically and cause of death changed from AIDS-related opportunistic infections and malignancies before 1997, to hepatitis C virus-related cirrhosis and hepatocellular carcinoma (HCC) around 2010, and again to non-AIDS defining malignancies recently. In most cases, hepatitis C was cured with direct acting antiviral therapy. However, HCV progressed to cirrhosis in some cases and risk of HCC is still high among these patients. Together with improvement in anticoagulants and aging of the patients, risk of myocardial infarction has increased recently. In addition, the numbers of patients with life-style related co-morbidities, such as diabetes mellitus, hypertension, and chronic kidney disease have been also increasing. Finally, stigma is still an important barrier to a better life in HIV-1-positive individuals.

Clinical Improvement by Switching to an Integrase Strand Transfer Inhibitor in Hemophiliac Patients with HIV: The Japan Cohort Study of HIV Patients Infected through Blood Products.

OBJECTIVE: This study aimed to determine improvement in HIV RNA levels and the CD4 cell count by switching to an antiretroviral regimen with an integrase strand transfer inhibitor (INSTI) in patients with HIV. METHOD: This study was conducted on Japanese patients with HIV who were infected by blood products in the 1980s. Data were collected between 2007 and 2014. Data of 564 male hemophiliac patients with HIV from the Japan Cohort Study of HIV Patients Infected through Blood Products were available. Changes in antiretroviral regimen use, HIV RNA levels, and the CD4 cell count between 2007 and 2014 were examined. RESULTS: From 2007 to 2014, the proportion of use of a regimen with an INSTI increased from 0.0% to 41.0%. For patients with HIV who used a regimen, including an INSTI, the proportion of HIV RNA levels <50 copies/mL significantly increased from 58.3% in 2007 to 90.6% in 2014. Additionally, the median CD4 cell count significantly increased from 380/µL to 438/µL. CONCLUSION: There is a large effect of switching to an antiretroviral regimen with an INSTI for Japanese patients with HIV who are infected by blood products. This suggests that performing this switch in clinical practice will lead to favorable effects.

What Triggers a Diagnosis of HIV Infection in the Tokyo Metropolitan Area? Implications for Preventing the Spread of HIV Infection in Japan.

BACKGROUND: Japan has not succeeded in reducing the annual number of new HIV-infected patients, although the prevalence of HIV infection is low (0.02%). METHODS: A single-center observational study was conducted at the largest HIV clinic in Tokyo, which treats 15% of the total patients in Japan, to determine the reasons for having diagnostic tests in newly infected individuals. HIV-infected patients who visited our clinic for the first time between 2011 and 2014 were analyzed. RESULTS: The 598 study patients comprised one-third of the total reported number of new patients in Tokyo during the study period. 76% were Japanese MSM. The reasons for being tested which led to the diagnosis was voluntary testing in 32%, existing diseases in 53% (AIDS-defining diseases in 22%, sexually transmitted infections (STI) in 8%, diseases other than AIDS or STIs in 23%) and routine pre-surgery or on admission screening in 15%. 52% and 74% of the study patients and patients presented with AIDS, respectively, had never been tested. The median CD4 count in patients with history of previous testing (315/µL) was significantly higher than that of patients who had never been tested (203/µL, p<0.001). CONCLUSIONS: Only 32% of the newly HIV diagnosed patients were diagnosed because of voluntary testing, and 53% were diagnosed due to presence of other diseases. These results remain unchanged from our previous report 10 years earlier (2000-2004) on newly diagnosed patients at the same clinic. HIV testing has not been widely used by newly diagnosed patients in the Tokyo metropolitan area.

High prevalence of illicit drug use in men who have sex with men with HIV-1 infection in Japan.

OBJECTIVE: To examine the prevalence of illicit drug use among men who have sex with men (MSM) with HIV-1 infection in Japan, where the life-time prevalence of illicit drug use in the general population is only 2.9%. DESIGN: A single-center cross-sectional study at a large HIV clinic in Tokyo, which treats approximately 15% of HIV-1 infected patients in Japan. METHODS: The prevalence of illicit drug use and the association of characteristics and social demographics of the patients with illicit drug use were examined. Patients who visited the clinic for the first time from 2005 to 2010 were enrolled. Relevant variables were collected using a structured interview and from the medical records. Multivariate logistic regression analyses were applied to estimate the odds of association of MSM over non-MSM HIV-infected patients with illicit drug use. RESULTS: 1,196 patients were enrolled. They were mostly Japanese men of relatively young age. Illicit drug use (including injection drugs) was reported by 35% of the patients (by 40% of MSM), and 4% were IDU while 5% were on methamphetamine. 2% of the population was arrested due to illicit drugs. MSM was significantly associated with illicit drug use (adjusted OR = 4.60; 95% CI, 2.88-7.36; p<0.01). Subgroup analysis of the patients stratified by three age groups (≤ 30, 31 to 40, and >40) showed that the odds of association of MSM with illicit drug use was the strongest in the youngest age group (≤ 30 years: adjusted OR = 7.56; 95% CI, 2.86-20.0; p<0.01), followed by the oldest (>40 years: adjusted OR = 6.15; 95% CI, 2.40-15.8; p<0.01), and the weakest in the group aged 31 to 40 (adjusted OR = 3.39; 95% CI, 1.73-6.63; p<0.01). CONCLUSIONS: The prevalence of illicit drug use is high among MSM patients with HIV-1 infection in Japan. Effective intervention for illicit drug use in this population is warranted.

Illicit drug use is a significant risk factor for loss to follow up in patients with HIV-1 infection at a large urban HIV clinic in Tokyo.

BACKGROUND: Loss to follow up (LTFU) is an important prognostic factor in patients with HIV-1 infection. The impact of illicit drug use on LTFU of patients with HIV-1 infection is unknown in Japan. METHODS: A single center observational study was conducted to elucidate the impact of illicit drug use on LTFU at a large HIV clinic in Tokyo. LTFU was defined as those who discontinued their visits to the clinic for at least 12 months and were not known to be under the care of other facilities or have died within 12 months of their last visit. Patients who first visited the clinic between January 2005 and August 2010 were enrolled. Information on illicit drug use was collected in a structured interview and medical charts. Comparison of the effects of illicit drug use and no use on LTFU was conducted by uni- and multi-variate Cox hazards models as the primary exposure. RESULTS: The study subjects were 1,208 patients, mostly Japanese men, of relatively young age, and infected through homosexual contact. A total of 111 patients (9.2%) were LTFU (incidence: 24.9 per 1,000 person-years). Among illicit drug users and non users, 55 (13.3%) and 56 (7.1%) patients, respectively, were LTFU, with incidence of 35.7 and 19.2 per 1,000 person-years, respectively. Uni- and multi-variate analyses showed that illicit drug use was a significant risk for LTFU (HR=1.860; 95% CI, 1.282-2.699; p=0.001) (adjusted HR=1.544; 95% CI, 1.028-2.318; p=0.036). Multivariate analysis also identified young age, high CD4 count, no antiretroviral therapy, and no health insurance as risk factors for LTFU. CONCLUSIONS: The incidence of LTFU among illicit drug users was almost twice higher than that among non users. Effective intervention for illicit drug use in this population is warranted to ensure proper treatment and prevent the spread of HIV.

Process and contents of telephone consultations between registered nurses and clients with HIV/AIDS in Japan.

Antiviral therapy is essential for HIV/AIDS patients, but many variables impede patients' adherence to therapy. To facilitate adherence, trained registered nurses in Japan provided consultation by phone at the AIDS Clinical Center. This study describes the process and content of this intervention and explores the predictors for length of time of phone consultations. The study was completed over 1 month using a time study, checklist, and medical record inquiry. A total of 175 consultations were described. Mean time was 4.8 +/- 3.8 min, and longer for patients with complications or comorbidity. Although the contents of conversations differed according to the phase of highly active antiretroviral therapy, major identified themes included need for medical consultation, symptom control, provision of information, and active listening. The results are useful for those trying to find ways to use telephone consultation effectively to reinforce adherence.