Young age is a key determinant of body weight gain after switching from tenofovir disoproxil fumarate to tenofovir alafenamide in Japanese people living with HIV.

BACKGROUND: Treatment with tenofovir alafenamide fumarate (TAF) is associated with body weight gain. However, little or no information is available on this issue in Asian populations. METHODS: This single-center retrospective study included Japanese people living with HIV (PLWH) who satisfied the following criteria; 1) switching from TDF to TAF after HIV-suppression, 2) follow-up for ≥2 years while on TDF and TAF, and 3) no switching of the third antiretroviral agent. Changes in annual body weight and lipid profiles were compared between the TDF and TAF periods. RESULTS: Of 328 patients, dolutegravir (DTG) was used in 118 PLWH. Overall, no significant difference in weight gain was observed between TDF and TAF (0.76 vs. 0.9 kg/year, p = 0.331). In TAF-period, younger (<50 years of age) group showed significantly greater weight gain than older group (1.03 vs. 0.12 kg/year, p = 0.037). In DTG group, weight gain was larger in TAF-period (0.74 vs. 1.31 kg/year, p = 0.046), especially in younger subgroup (1.43 kg/year) compared with older one (-0.12 kg/year). Multivariate regression analysis showed that TAF was not associated with weight gain (estimates 0.201, p = 0.170) except for DTG group, whereas young age was associated with weight gain in all subjects (estimates -0.033/1 year older, p < 0.001), DTG, RAL, and EFV groups. CONCLUSION: In Japanese PLWH, annual body weight change was comparable in TDF- and TAF-period, while TAF plus DTG correlated with weight gain. Since young age was a key determinant of weight change, careful interpretation is needed for TAF-associated weight gain.

Long-term administration of pegylated liposomal doxorubicin at almost twice the recommended lifetime dose in 10 years without cardiotoxicity in a Japanese patient with HIV-associated Kaposi sarcoma.

We report a Japanese patient with HIV-associated Kaposi sarcoma (KS) who had many cutaneous KS lesions with extensive bilateral groin edema. As the KS was refractory to antiretroviral therapy and pegylated liposomal doxorubicin (PLD), he was administered PLD up to a cumulative dose of 940 mg/m2 in 10 years, which exceeded the recommended lifetime dose (550 mg/m2). However, the patient showed no major adverse events, including cardiotoxicity, and he eventually died of pancreatic cancer.

[Undetectable anti-platelet factor 4/heparin antibodies with IgG-specific chemiluminescent immunoassays in a heparin-induced thrombocytopenia patient].

A 51-year-old man with a 9-month history of narrowing of visual fields and papilledema was admitted to the Department of Neurosurgery. Upon admission, glycerol was intravenously administered and heparin flushes were initiated to maintain intravenous access. Brain MRI revealed right transverse and sigmoid sinus thrombosis on hospital day 2, and the patient was treated with unfractionated heparin. On hospital day 9, the patient had a seizure and impaired mental status. Moreover, on hospital day 10, the platelet count decreased to less than half compared with that documented upon admission. The patient was then switched from heparin to argatroban because thrombosis exacerbation due to heparin-induced thrombocytopenia (HIT) was suspected. Despite negative IgG-specific chemiluminescent immunoassay for anti-platelet factor 4 (PF4) /heparin antibodies, positive functional assay led to the diagnosis of HIT. Warfarin was initiated and the platelet count was restored. Because maintaining the patient's PT-INR within the therapeutic range was difficult probably due to concomitant antimicrobial administration for complicating pneumonia, anticoagulation was switched to rivaroxaban. No bleeding or thrombotic complications developed. Thus, the presentation and clinical course should be considered for an accurate diagnosis of HIT. This is particularly important when the immunological assay is negative for anti-PF4/heparin antibodies. Furthermore, anticoagulation with rivaroxaban can be useful in the management of the subacute phase of HIT.

[Exhaustive analysis of genetic mutations associated with protein S deficiency utilizing next-generation sequencing analysis].

Protein S (PS) gene (PROS1) is found on chromosome 3 (3q11.1). To date, the reported detection rate of causative gene mutations in patients suspected of PS deficiency is only approximately 50%. To improve the detection rate of causative mutations, an exhaustive analysis of PROS1 was attempted using the next-generation sequencing method (NGS) to analyze the entire nucleotide sequence of PROS1 without analyzing those affected by pseudogenes. A total of 10 different mutations (three males and six females (52.9%) out of 17 patients (3 males and 14 females) with clinical PS deficiency were identified in this study. Remarkable improvements in the detection rate of causative mutations could not be obtained even with NGS analysis. These results suggested that the rate of diagnosis did not improve even after performing an exhaustive genetic analysis in patients clinically diagnosed with low PS antigen level and/or low PS activity. Although no reports were found on the gender gap in the rate of gene diagnosis for PS deficiency, the fluctuation of estrogen levels especially in women might cause a lower rate of diagnosis.

[Syphilis Testing and High Rate of Infection Among HIV-infected Patients].

Background: The incidence of syphilis has globally increased over the last decade, particularly among men who have sex with men coinfected with the human immunodeficiency virus (HIV). HIV infection may make the clinical symptoms and seroreactivity of syphilis atypical, which requires careful consideration in terms of diagnoses and treatments by clinicians. Syphilis is known as a great imitator, and is often difficult to be diagnosed or it can be overlooked if clinicians depend only on its symptoms or signs. It is also highly contagious and could be transmitted without sexual intercourse, and reinfection is common. Guidelines recommend that all HIV-infected persons be provided with STD screening, including syphilis, at least annually. However, to our knowledge, there are no published data on the actual frequency of testing and instances of syphilis among HIV-infected persons in Japan. Materials and Methods: We collected data from HIV infected male patients who had sex with men (MSM) at Tokyo Medical University Hospital from June 2011 to June 2012. Data from the patients, who had been tested with the rapid plasma reagin assay (RPR) at least once during the study period, were retrospectively obtained from clinical records and were analyzed. Results: Among 1000 patients with HIV infection, 935 patients were MSM. 723 patients (77.4%) were tested using the Treponema pallidum latex agglutination test (TPLA) and RPR more than once during the study period. Out of the 723 patients, 443 patients (61.3%) were reactive for TPLA and 238 patients (32.9%) had reactive tests for RPR. All patients who were reactive for RPR were reactive for TPLA. Among the patients who were reactive for RPR, 93 patients (12.9%) were considered newly diagnosed or with a repeat infection. In this cohort, all patients were MSM with a median age of 37 years, and a median CD4+T-lymphocyte cell count of 465/uL. A total of 76 patients had been prescribed antiretroviral therapy, and 61 patients had a documented HIV-1 RNA viral load of <40 copies/mL at their most recent test. Two patients both developed two episodes of syphilis during the study period. Of the 95 episodes, 44% were symptomatic syphilis and the most common symptom among them was a skin rash at the second stage. Nearly half of the patients (47%) were diagnosed at regular screenings. Two thirds (67%) had syphilis infections before the study period, whereas at least 20% of them were newly diagnosed during the study period. Conclusions: A substantial percentage of the participants were newly or recurrently diagnosed with syphilis during the study period. More public health awareness should be encouraged regarding the current epidemic of syphilis among HIV-infected persons in Japan. It is also important for clinicians to provide HIV-infected persons with periodical syphilis screening, regardless of the apparent clinical signs or symptoms to achieve earlier treatment intervention.

Native valve endocarditis caused by Neisseria elongata Subsp. nitroreducens.

Neisseria elongata, a normal resident in the human oral cavity, rarely causes invasive infections. We herein report a case of endocarditis caused by Neisseria elongata subsp. nitroreducens that occurred in a patient without any apparent cardiac complications. The patient received aortic valve replacement following the administration of intravenous beta-lactam for five weeks. To our knowledge, this is the first published case in Japan of N. elongata infection in a patient without a prosthetic device.