Impact of HIV status on prognosis of malignancies among people living with HIV in Japan.

BACKGROUND: Antiretroviral therapy has reduced the incidence and mortality of AIDS-defining malignancies (ADM); however, non-AIDS-defining malignancies (NADM) are a major cause of death among people living with HIV (PLWH) today. Though current guidelines suggest that PLWH should receive the same treatment as the general population, there are limited studies focused on how HIV status affects the prognosis of cancers. The present study aimed to investigate the characteristics and prognosis of malignant diseases among PLWH in Japan. METHODS: Patients with HIV diagnosed with malignant diseases at our institution between 2011 and 2021 were retrospectively reviewed. RESULTS: There were 205 patients who were diagnosed with malignancies. Of these, 87 (42.4%) were diagnosed with ADM and 118 (57.6%) were diagnosed with NADM. Among 69 patients who received chemotherapy for ADM, 24 (34.8%) developed AIDS-defining opportunistic infections during treatment. In contrast, only one (1.8%) of the 56 patients administered chemotherapy for NADM developed AIDS-defining opportunistic infections. Complications of opportunistic infections at diagnosis of malignancies, low CD4+ T-cell count, positive HIV RNA, and nonadministration of antiretroviral therapy were associated with 5-year overall survival among patients with malignant lymphomas. However, the variables associated with HIV did not affect NADM prognosis. CONCLUSIONS: In this analysis, HIV status had a small impact on the prognosis of malignant diseases in PLWH. Few patients with NADM developed AIDS-defining opportunistic infections after receiving chemotherapy.

Twelve-month effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide in people with HIV: Real-world insights from BICSTaR cohorts.

BACKGROUND: Real-world evidence is an essential component of evidence-based medicine. The aim of the BICSTaR (BICtegravir Single Tablet Regimen) study is to assess effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in antiretroviral treatment-naïve (TN) and treatment-experienced (TE) people with HIV. METHODS: BICSTaR is a prospective, observational cohort study. Participants (≥18 years) are being followed for 24 months. A pooled analysis is presented at 12 months, with the primary endpoint of effectiveness (HIV-1 RNA <50 copies/mL) and secondary endpoints of safety and tolerability (as per protocol). An exploration of patient-reported outcome measures using standardized questionnaires is included. RESULTS: Between June 2018 and May 2021, 1552 people with HIV were enrolled across 12 countries. The analysed population comprised 1509 individuals (279 TN, 1230 TE); most were white (76%), male (84%) and had one or more comorbid conditions (68%). Median age was 47 years. After 12 months of B/F/TAF treatment, HIV-1 RNA was <50 copies/mL in 94% (221/236) of TN participants and 97% (977/1008) of TE participants. Median CD4 cell count increased by 214 cells/µL (p < 0.001) in TN participants and 13 cells/µL (p = 0.014) in TE participants; median CD4/CD8 ratios increased by 0.30 and 0.03, respectively (both p < 0.001). Persistence was high at 12 months (TN, 97%; TE, 95%). No resistance to B/F/TAF emerged. Study drug-related adverse events occurred in 13% of participants through 12 months, leading to B/F/TAF discontinuation in 6%. CONCLUSIONS: The findings of this study provide robust real-world evidence to support the broad use of B/F/TAF in both TN and TE people with HIV.

Local radiotherapy for chemotherapy-refractory Kaposi's sarcoma in an HIV-infected patient: A case report and literature review.

Human immunodeficiency virus-associated Kaposi's sarcoma (HIV-KS) is a well-documented vascular tumor with a pathogenesis involving human herpesvirus-8 (HHV-8) infection. While antiretroviral therapy (ART) and chemotherapy are effective for treating most KS cases, some become refractory. In this report, we present a case of a 58-year-old man with refractory HIV-KS treated with ART and chemotherapy. Chemotherapy was eventually discontinued due to an adverse reaction, and the patient presented with painful plantar lesions that impaired ambulation. With the exclusion of visceral metastases, localized radiotherapy was administered, which resulted in significant cosmetic and functional improvements. The patient regained ambulation and lived independently, receiving additional radiotherapy as needed. This case underscores the potential use of radiotherapy for the treatment of ART-resistant KS, particularly when the patient is unresponsive to conventional chemotherapy. It also highlights the need for future research in this area.

Combination of Amoxicillin 3000 mg and Probenecid Versus 1500 mg Amoxicillin Monotherapy for Treating Syphilis in Patients With Human Immunodeficiency Virus: An Open-Label, Randomized, Controlled, Non-Inferiority Trial.

BACKGROUND: Amoxicillin plus probenecid is an alternative to intramuscular benzathine penicillin G for treating syphilis in the United Kingdom. Low-dose amoxicillin is an alternative treatment option used in Japan. METHODS: We conducted an open-label, randomized, controlled, non-inferiority trial between 31 August 2018, and 3 February 2022, to compare 1500 mg low-dose amoxicillin monotherapy with the combination of 3000 mg amoxicillin and probenecid (non-inferiority margin 10%). Patients with human immunodeficiency virus (HIV) infection and syphilis were eligible. The primary outcome was the cumulative serological cure rate within 12 months post-treatment, measured using the manual rapid plasma reagin card test. Secondary outcomes included safety assessment. RESULTS: A total of 112 participants were randomized into 2 groups. Serological cure rates within 12 months were 90.6% and 94.4% with the low-dose amoxicillin and combination regimens, respectively. Serological cure rates for early syphilis within 12 months were 93.5% and 97.9% with the low-dose amoxicillin and combination regimens, respectively. Non-inferiority of low-dose amoxicillin compared with amoxicillin plus probenecid overall and for early syphilis was not confirmed. No significant side effects were detected. CONCLUSIONS: This is the first randomized controlled trial to demonstrate a high efficacy of amoxicillin-based regimens for treating syphilis in patients with HIV infection, and the non-inferiority of low-dose amoxicillin compared with amoxicillin plus probenecid was not seen. Therefore, amoxicillin monotherapy could be a good alternative to intramuscular benzathine penicillin G with fewer side effects. However, further studies comparing with benzathine penicillin G in different populations and with larger sample sizes are needed. TRIALS REGISTRATION: (UMIN000033986).

Evaluation of cytokine levels in response to mitogen among HIV-1-infected blood cells and their relationships to the number of T cells.

BACKGROUND: Human immunodeficiency virus-1 (HIV-1) infection causes loss and anergy of CD4+ and CD8+ T cells, leading to opportunistic infections, including tuberculosis (TB). QuantiFERON®-TB (QFT) is used as a diagnostic tool to detect TB, but it exhibits limited accuracy among subjects with low CD4+ T cell numbers, including HIV-1-infected individuals. The present study aimed to determine the effect of HIV-1 infection and patients' blood T cell numbers on cytokine production in response to mitogen (Mit) stimulation. METHODS: The number of CD4+ and CD8+ T cells in HIV-1-infected individuals was quantified. Levels of various cytokines in Mit-stimulated and un-stimulated (Nil) supernatants of QFT gold "in tube" were assessed using a MAGPIX System. The correlation between cytokine levels and CD4+/CD8+ T cell counts in response to Mit was analyzed. The cytokine levels were compared between HIV-1-infected and healthy subjects. RESULTS: HIV-1-infected individuals (110) and control subjects (27) were enrolled. Interferon (IFN)-γ, interleukin-1 receptor antagonist (IL-1RA), IL-6, IL-8, and regulated on activation, normal T cell expressed and secreted (RANTES) values in Mit-Nil tubes showed a significant correlation with CD4+ T cell counts, while IFN-γ, IL-6, and IFN-γ-induced protein 10 (IP-10) values in Mit-Nil tubes had significant correlation with CD8+ T cell counts. IL-1RA, IL-8, IP-10, platelet-derived growth factor (PDGF)-BB, and RANTES levels in Nil tubes were significantly higher in the HIV-1-infected group. IFN-γ, IL-2, IL-5, IL-6, IP-10, and macrophage inflammatory protein-1ß values in Mit-Nil tubes were significantly higher, and PDGF-BB and RANTES levels were significantly lower in the HIV-1-infected group. CONCLUSION: The functions of HIV-1-infected T cells and uninfected T cells, such as spontaneous and responsive cytokine production in response to Mit, were different. Our findings may be useful for developing new clinical tools for patients with low T cell counts. Additionally, the study provides new insights into the pathogenesis of HIV-1 infection.

Fatty liver on computed tomography scan on admission is a risk factor for severe coronavirus disease.

OBJECTIVES: To alleviate the overflow of coronavirus disease 2019 (COVID-19) patients in hospitals, less invasive and simple criteria are required to triage the patients. We evaluated the relationship between COVID-19 severity and fatty liver on plain computed tomography (CT) scan performed on admission. METHODS: In this retrospective cohort study, we considered all COVID-19 patients at a large tertiary care hospital between January 31 and August 31, 2020. COVID-19 severity was categorized into severe (moderate and severe) and non-severe (asymptomatic and mild) groups, based on the Japanese National COVID-19 guidelines. Fatty liver was detected on plain CT scan. Multivariate logistic regression analysis was performed to evaluate factors associated with severe COVID-19. RESULTS: Of 222 patients (median age: 52 years), 3.2%, 58.1%, 20.7%, and 18.0% presented with asymptomatic, mild, moderate, and severe COVID-19, respectively. Although 59.9% had no fatty liver on plain CT, mild, moderate, and severe fatty liver occurred in 13.1%, 18.9%, and 8.1%, respectively. Age and presence of fatty liver were significantly associated with severe COVID-19. CONCLUSION: Our study showed that fatty liver on plain CT scan on admission can become a risk factor for severe COVID-19. This finding may help clinicians to easily triage COVID-19 patients.

Does the SARS-CoV-2 rapid antigen test result correlate with the viral culture result?

Rapid antigen tests (RATs) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have advantages over viral culture in terms of cost and rapidity of testing, but they have low sensitivity. In addition, RATs tend to be negative from approximately 11 days after symptom onset. To determine whether the antigen-negative state indicates a lack of infectiousness, we assessed the association between viral culture and RAT results. Viral culture, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and rapid antigen testing were performed on stored nasopharyngeal samples with threshold cycle values < 30, based on previous RT-qPCR testing. SARS-CoV-2 was isolated by viral culture from nine samples (45%) and one sample (17%) with positive and negative RAT results, respectively. The RAT and viral culture results were both associated with the viral load level and their cutoffs were similar, but the associations were not statistically significant. RAT might be a useful indicator of infectiousness, which can be helpful to control infection. However, further studies with larger sample size are warranted to confirm this observation.

Clinical and radiological findings of silent hypoxia among COVID-19 patients.

The aim of this study was to describe the clinical and radiological findings of COVID-19 patients with "silent hypoxia," who had no dyspnea on admission even though their oximetry saturation was less than 94%. This retrospective cohort study included all COVID-19 patients (n = 270) at a large tertiary care hospital between January 31 and August 31, 2020. Clinical and radiological characteristics of patients who met our criteria of "silent hypoxia", which included those who reported no dyspnea even though oximetry saturation was <94%, were extracted. Eight patients (3.0%) met the criteria for "silent hypoxia." The median age was 61 years (interquartile range [IQR]: 48.8-72.3), and five (62.5%) were men. All patients had consolidation on CT and showed a moderate to high COVID-19 CT severity score (median: 13.5, IQR: 10.8-15.3). The median FIO2 of the maximum oxygen required was 55 (IQR: 28-70)%. Two patients (25.0%) were intubated, and one patient (12.5%) underwent extracorporeal membrane oxygenation. Some COVID-19 patients with "silent hypoxia" may develop severe disease. Close and accurate monitoring of patients using arterial blood gas and pulse oximetry is necessary, regardless of their symptoms.

IL-1RA in the supernatant of QuantiFERON-TB Gold In-Tube and QuantiFERON-TB Gold Plus is useful for discriminating active tuberculosis from latent infection.

INTRODUCTION: The new-generation QuantiFERON (QFT)-TB Gold Plus (QFT-Plus) is expected to be useful because it includes a new peptide that is supposed to induce a CD8+ T cell response. There is a need for a new marker with sensitivity higher than that of the conventional IFN-γ release assays owing to false-negative results in the latter. This study aimed to compare cytokines in QFT-plus and QuantiFERON-Gold In-Tube (QFT-GIT) supernatants to discriminate between active tuberculosis and latent tuberculosis infection (LTBI). METHODS: A cross-sectional study was conducted at Tokyo National Hospital, wherein 21 LTBI patients and age and sex-matched active TB patients were randomly selected. The levels of various cytokines were measured and compared using the MAGPIX System, and receiver operating characteristic (ROC) curves were generated. RESULTS: IL-1RA, IFN-γ, CXCL10/IP-10, and CCL4/MIP-1ß levels were higher in the active TB group than in the LTBI group in QFT-GIT antigen (GIT Ag) tubes. In QFT-plus tubes, IL-1RA was higher in TB1 and TB2 tubes, while CCL2/MCP-1 was higher only in TB2 tubes. In Nil tubes, CCL5/RANTES, TNF-α, PDGF-BB, and IL-2 levels were significantly higher in the active TB group. IL-1RA in GIT Ag tubes showed the highest area under the curve of 0.8367. The sensitivity and specificity of IL-1RA were 66.7% (95% confidence interval [CI]: 43.0-85.4) and 90.5% (95% CI: 69.6-98.8), respectively, which were the highest among the cytokines. CONCLUSIONS: IL-1RA level in the QFT-GIT supernatant can be a good marker for discriminating active TB from LTBI.

Human immunodeficiency virus-associated vacuolar encephalomyelopathy with granulomatous-lymphocytic interstitial lung disease improved after antiretroviral therapy: a case report.

BACKGROUND: Vacuolar encephalomyelopathy, a disregarded diagnosis lately, was a major neurological disease in the terminal stages of human immunodeficiency virus (HIV)-1 infection in the pre-antiretroviral therapy (ART) era. Granulomatous-lymphocytic interstitial lung disease (GLILD) was classically identified as a non-infectious complication of common variable immunodeficiency; however, it is now being recognized in other immunodeficiency disorders. Here, we report the first case of GLILD accompanied by vacuolar encephalomyelopathy in a newly diagnosed HIV-infected man. CASE PRESENTATION: A 40-year-old Japanese man presented with chronic dry cough and progressing paraplegia. Radiological examination revealed diffuse pulmonary abnormalities in bilateral lungs, focal demyelinating lesions of the spinal cord, and white matter lesions in the brain. He was diagnosed with GLILD based on marked lymphocytosis detecting in bronchoalveolar lavage, and transbronchial-biopsy proven T-cellular interstitial lung disease with granulomas. Microbiological examinations did not reveal an etiologic agent. The patient was also diagnosed with HIV-associated vacuolar encephalomyelopathy on the basis of an elevated HIV viral load in cerebrospinal fluid. After initiating ART, the brain lesions and paraplegia improved significantly, and interstitial abnormalities of the lungs and cough disappeared. CONCLUSION: This report highlights that even in the post-ART era in developed countries with advanced healthcare services, HIV-associated vacuolar encephalomyelopathy should be considered in the differential diagnosis of a progressive neurological disorder during the first visit. Furthermore, GLILD may represent an HIV-associated pulmonary manifestation that can be treated by ART.

Safety and efficacy of reduced-dose pentamidine as second-line treatment for HIV-related pneumocystis pneumonia.

OBJECTIVES: Parenteral pentamidine isethionate (PM) 4 mg/kg/day is recommended as an alternative therapeutic regimen after failure of first-line treatment for pneumocystis pneumonia (PCP). However, the dose is often reduced to 3 mg/kg/day in clinical settings because of high rates of adverse events and drug toxicity. Although considered equally efficacious, this lower dose has not been well evaluated. METHODS: This was a single-center, retrospective cohort study that analyzed 75 patients with HIV-PCP who were treated with trimethoprim-sulfamethoxazole, but discontinued treatment because of treatment failure or adverse events; they were then administered 3 mg/kg/day of intravenous PM as a salvage therapy. The primary outcomes were the regimen completion rate with the reduced PM dose. RESULTS AND CONCLUSIONS: In total, 40 (53.3%) of the eligible patients completed PCP therapy with reduced-dose PM salvage treatment. The overall survival rate of PCP was 73 (97.3%). The median duration of second-line PM treatment was 8.0 days (interquartile range: 6.0-10.0). Although, the adverse events with reduced-dose PM were observed in 41 (54.7%), including 35 treatment-limiting adverse events, grade 3 or 4 adverse events occurred in only three patients (thrombocytopenia, one patient; neutropenia, two patients). Life-threating adverse events, such as hypoglycemia and arrhythmia, were not observed with reduced-dose PM. Salvage therapy with reduced-dose PM for patients with HIV-PCP is relatively safe and effective; moreover, life-threating adverse events did not occur. This therapy could be recommended for patients with HIV-PCP who fail to respond to first-line treatment with trimethoprim-sulfamethoxazole.

Combination of Clindamycin and Azithromycin as Alternative Treatment for Toxoplasma gondii Encephalitis.

Current standard therapies for toxoplasmic encephalitis often cause severe adverse events. A 57-year-old HIV-positive man in Japan who had toxoplasmic encephalitis but was intolerant to trimethoprim/sulfamethoxazole, pyrimethamine, sulfadiazine, and atovaquone was successfully treated with the combination of clindamycin and azithromycin. This drug combination can be an alternative treatment for this condition.

Case report: new development of fibrosing interstitial lung disease triggered by HIV-related pneumocystis pneumonia.

BACKGROUND: Fibrosing interstitial lung disease is the poor prognostic non-infectious lung disease by unknown etiology. Here, we present one case developing interstitial pneumonia with fibrosis after treatment of pneumocystis pneumonia (PCP) in newly diagnosed HIV-1 infected case. CASE PRESENTATION: A previously healthy 63-year old male was referred to our institute because of protracted dyspnea on effort in 2 weeks after pneumocystis pneumonia treatment. At referral, arterial blood oxygen pressure was within normal range (93.5 mmHg) at rest, but decreased rapidly 30 s after a slow walk (44.5 mmHg). Respiratory function tests showed severe restrictive ventilator impairment (vital capacity = 36.5%; forced expiratory volume in 1 s = 107.4%). Chest computed tomography showed severe fibrotic changes at bilateral basal parts and diffuse fibrotic changes in which PCP lesions were seen initially in previous images although ß-D glucan was not elevated and P. jirovecii was not detected in saliva at referral. Other etiologies of fibrotic IP including infectious and/or autoimmune diseases were excluded by serology. Fibrotic lesion did not expand thereafter although it had not responded to the high-dose corticosteroid therapy. CONCLUSION: We report the first case of fibrosing interstitial lung disease triggered by HIV-related PCP.

Usefulness of Automated Latex Turbidimetric Rapid Plasma Reagin Test for Diagnosis and Evaluation of Treatment Response in Syphilis in Comparison with Manual Card Test: a Prospective Cohort Study.

The usefulness of an automated latex turbidimetric rapid plasma reagin (RPR) assay, compared to the conventional manual card test (serial 2-fold dilution method), for the diagnosis of syphilis and evaluation of treatment response remains unknown. We conducted (i) a cross-sectional study and (ii) a prospective cohort study to elucidate the correlation between automated and manual tests and whether a 4-fold decrement is a feasible criterion for successful treatment with the automated test, respectively, in HIV-infected patients, from October 2015 to November 2017. Study i included 518 patients. The results showed strong correlation between the two tests (r = 0.931; P < 0.001). With a manual test titer of ≥1:8 plus a positive Treponema pallidum particle agglutination (TPPA) test as the reference standard for diagnosis, the optimal cutoff value for the automated test was 6.0 RPR units (area under the curve [AUC], 0.998), with positive predictive value (PPV) of 92.5% and negative predictive value (NPV) of 99.4%. Study ii enrolled 66 men with syphilis. Their RPR values were followed up until after 12 months of treatment. At 12 months, 77.3% and 78.8% of the patients achieved a 4-fold decrement in RPR titer by the automated and manual test, respectively. The optimal decrement rate in RPR titer by the automated test for a 4-fold decrement by manual card test was 76.54% (AUC, 0.96) (PPV, 96.1%; NPV, 80.0%). The automated RPR test is a good alternative to the manual test for the diagnosis of syphilis and evaluation of treatment response and is more rapid and can handle more specimens than the manual test without interpersonal variation in interpretation.

Increased risk of non-AIDS-defining cancers in Asian HIV-infected patients: a long-term cohort study.

BACKGROUND: Data on the long-term risks of non-AIDS defining cancers (NADCs) are limited, especially in Asians. The incidence of NADCs may correlate with the epidemiological trend of cancers or oncogenic infection in each country, and thus the target cancers would be different between Western and Asian countries. We aimed to elucidate the incidence of NADCs and its predictive factors in Asian HIV-infected patients. METHODS: Subjects were HIV-infected patients (n = 1001) periodically followed-up for 9 years on average. NADCs were diagnosed by histopathology and/ or imaging findings. Standardized incidence ratios (SIR) were calculated as the ratio of the observed to expected number of NADCs for comparison with an age-and sex-matched general population. Cox's proportional hazards model was used to estimate hazard ratios (HR). RESULTS: During the median follow-up of 9 years, the 10-year cumulative incidence of NADCs was 6.4%.At NADC diagnosis, half of patients presented at age 40-59 years and with advanced tumor stage. Compared with the age-and sex-matched general population, HIV-infected patients are at increased risk for liver cancer (SIR, 4.7), colon cancer (SIR, 2.1), and stomach cancer (SIR, 1.8). In multivariate analysis, a predictive model for NADCs was developed that included age group (40-49, 50-59, 60-69, and ≥ 70 years), smoker, HIV infection through blood transmission, and injection drug use (IDU), and HBV co-infection. The c-statistic for the NADCs predictive model was 0.8 (95%CI, 0.8-0.9, P < 0.001). The higher 10-year incidence rate of NADCs was associated with increasing prediction score. CONCLUSIONS: Liver and colon cancer risk was elevated in Asian HIV-infected individuals, similar to in Western populations, whereas stomach cancer risk was characteristically elevated in Asian populations. Half of Asian NADC patients were aged 40-59 years and had advanced-stage disease at diagnosis. Periodic cancer screening may be warranted for high-risk subpopulations with smoking habit, HIV infection through blood transmission or IDU, and HBV co-infection, and screening should be started over 40 years of age.

Time to development of ocular syphilis after syphilis infection.

To provide an estimate of the incubation period of ocular syphilis based on serology using both clinical data and stored serum samples, we retrospectively reviewed patients with HIV-1 infection who presented with ocular syphilis between August 1997 and July 2015 in a tertiary hospital in Japan. The incubation period of ocular syphilis was defined as the time from syphilis infection to the development of ocular symptoms due to ocular syphilis. During the study period, 20 patients were diagnosed with ocular syphilis and 8 patients were enrolled in the present study. All patients were Japanese men who have sex with men with a median age of 46 years (IQR 41.5-53.5). The median CD4 count was 668.5/µL (IQR 567.8-734.3) and 5 of the 8 patients had HIV-1 viral load of less than 50 copies/mL. All study patients presented to our clinic because of the development of ocular symptoms, and they did not have any other symptoms compatible with primary, secondary, or tertiary syphilis. The median time between syphilis infection and development of ocular symptoms was 11 months (IQR 4-19, range 2.5-45). Seven out of eight (87.5%) cases developed ocular syphilis within 2 years of syphilis infection. Ocular syphilis should be suspected even in patients with early syphilis who present with ocular symptoms. Moreover, routine serologic screening for syphilis among patients with HIV-1 infection is critical for prevention of irreversible visual loss in ocular syphilis cases.

Protease inhibitor-associated bone mineral density loss is related to hypothyroidism and related bone turnover acceleration.

BACKGROUND: Clinical and experiments evidence indicate that protease inhibitors (PI) can cause bone mineral density (BMD) loss. However, the mechanism of such loss remains obscure. METHODS: This single-center, cross-sectional study included 184 HIV-infected patients treated with PI who underwent dual-energy X-ray absorptiometry scan. Serum phosphorus, percentage of tubular reabsorption of phosphate (%TRP), thyroid and parathyroid function (iPTH), vitamin D, osteocalcin (OC), urinary deoxypyridinoline (DPD), and urinary cross-linked N-telopeptide of type I collagen (u-NTx) were measured. RESULTS: The rate of hypothyroidism in PI-users [32/117 (27%)] was double that in non-PI users [8/67 (12%), p = 0.016] and was significantly associated with PI use in multivariate analysis [odds ratio (OR) 11.37, 95% confidence interval (CI) 1.358-95.17, p = 0.025]. Spine BMD was significantly lower in hypothyroid patients than euthyroid, for both total population (-1.37 vs. -1.00, p = 0.041) and PI users (-1.56 vs. -1.13, p = 0.029). Multivariate regression analysis identified inverse correlation between hypothyroidism and spine BMD [estimate -0.437, 95% CI -0.858 to -0.024, p = 0.042]. OC, DPD and u-NTx were significantly higher in PI users than in non-PI users (p = 0.01, 0.05, and 0.01, respectively). CONCLUSIONS: PI use is associated with hypothyroidism as well as bone turnover acceleration, which worsens PI-associated BMD loss. In PI-treated patients, thyroid function tests are warranted to prevent further progression of PI-associated BMD loss.

Prognosis of ocular syphilis in patients infected with HIV in the antiretroviral therapy era.

OBJECTIVE: To describe the clinical course and prognosis of ocular syphilis in patients infected with HIV-1 in the antiretroviral therapy (ART) era. METHODS: We conducted a single-centre retrospective chart review of ocular syphilis in patients infected with HIV-1 diagnosed between August 1997 and July 2015. The prognosis of best-corrected visual acuity (BCVA) was analysed. RESULTS: The study subjects were 30 eyes of 20 men who had sex with men (MSM) (median age, 41). Loss of vision and posterior uveitis were the most common ocular clinical features (43%) and location of inflammation at presentation (50%), respectively. The median baseline BCVA was 0.4 (IQR 0.2-1.2), including three eyes with hand motion. BCVA≤0.4 at diagnosis was significantly associated with posterior uveitis or panuveitis (p=0.044). Seventy-five per cent were treated with intravenous benzylpenicillin and 53% were diagnosed with neurosyphilis. After treatment (median follow-up: 21 months), BCVA improved in 89% of the eyes, including all eyes with hand motion, to a median BCVA of 1.2 (IQR 0.8-1.2). Kaplan-Meier analysis showed that >28 days of ocular symptoms before diagnosis was the only factor associated with poor prognosis of BCVA. Three patients (15%) developed recurrence after treatment. CONCLUSIONS: The prognosis of BCVA in HIV-infected patients with ocular syphilis in the ART era was favourable after proper treatment. Having >28 days of ocular symptoms before diagnosis was associated with poor prognosis. Changes in visual acuity in HIV-infected MSM should prompt an immediate assessment for ocular syphilis as delays in diagnosis and therapy can lead to irreversible visual loss.

High-dose oral amoxicillin plus probenecid is highly effective for syphilis in patients with HIV infection.

BACKGROUND: Intramuscular benzathine penicillin G (BPG) is widely used for the treatment of syphilis. However, BPG is not available in some countries. This study examined the effectiveness and safety of high-dose oral amoxicillin plus probenecid for the treatment of syphilis in patients with human immunodeficiency virus type 1 (HIV-1). METHODS: This retrospective observational study included 286 HIV-infected male patients with syphilis (median age, 36 years; median CD4 count, 389 cells/µL) who were treated with oral amoxicillin 3 g plus probenecid. Syphilis was diagnosed by both serum rapid plasma reagin (RPR) titers ≥8 and positive Treponema pallidum hemagglutination test. Patients with neurosyphilis diagnosed by cerebrospinal fluid examination were excluded. Successful treatment was defined as a at least 4-fold decrement in RPR titer. RESULTS: The overall treatment efficacy was 95.5% (95% confidence interval [CI], 92.4%-97.7%; 273/286 patients), and efficacy for primary, secondary, early latent, late latent, and unknown duration syphilis was 93.8% (95% CI, 68.1%-99.8%; 15/16), 97.3% (95% CI, 92.9%-99.2%; 142/146), 100% (95% CI, 90.5%-100%; 37/37), 85.7% (95% CI, 58.6%-96.4%; 18/21), and 92.4% (95% CI, 81.9%-97.3%; 61/66), respectively. Treatment duration was mostly 14-16 days (49.7%) or 28-30 days (34.3%), with efficacy of 94.4% (134/142) and 95.9% (94/98), respectively; 96.3% of successfully treated patients achieved a ≥4-fold decrement in RPR titer within 12 months. Adverse events were noted in 28 (9.8%) patients, and 25 of these (89.3%) were successfully treated. Only 6% of patients underwent lumbar puncture. CONCLUSIONS: The combination of oral amoxicillin 3 g plus probenecid was highly effective and tolerable for the treatment of syphilis in patients with HIV-1 infection.

Single-nucleotide polymorphisms in the UDP-glucuronosyltransferase 1A-3' untranslated region are associated with atazanavir-induced nephrolithiasis in patients with HIV-1 infection: a pharmacogenetic study.

OBJECTIVES: Ritonavir-boosted atazanavir (atazanavir/ritonavir) is a widely used antiretroviral drug, though it can potentially cause nephrolithiasis. The aim of this study was to determine the relationship between polymorphisms in genes encoding proteins involved in metabolism and transportation of atazanavir, and atazanavir/ritonavir-induced nephrolithiasis in HIV-1-infected patients treated with atazanavir/ritonavir. METHODS: Nineteen SNPs in the ABCB1, NR1I2, UGT1A1, SLCO1B1 and CYP3A5 genes were examined in case patients with atazanavir/ritonavir-induced nephrolithiasis (n = 31) and controls (n = 47). Case patients were those with a clinical diagnosis of nephrolithiasis while on atazanavir/ritonavir, based on new-onset acute flank pain plus one of the following: (i) new-onset haematuria; (ii) documented presence of stones by either abdominal ultrasonography or CT; or (iii) confirmed stone passage. Control patients were consecutively enrolled among those with >2 years of atazanavir/ritonavir exposure free of nephrolithiasis. Genotyping was performed by allelic discrimination using TaqMan 5'-nuclease assays with standard protocols. Associations between alleles and atazanavir/ritonavir-induced nephrolithiasis were tested by univariate and multivariate logistic regression analyses. RESULTS: Multivariate analysis showed a significant association between atazanavir/ritonavir-induced nephrolithiasis and genotype T/C versus C/C at position c.211 (adjusted OR = 3.7; 95% CI, 1.13-11.9; P = 0.030), genotype G/C versus C/C at 339 (adjusted OR = 5.8; 95% CI, 1.56-21.3; P = 0.009) and genotype G/G or G/C versus C/C at 440 (adjusted OR = 5.8; 95% CI, 1.56-21.3; P = 0.009) of the UGT1A-3' untranslated region (UTR). CONCLUSIONS: This is the first known study to identify the association between SNPs in the UGT1A-3'-UTR and atazanavir-induced nephrolithiasis. Further studies are warranted to confirm this association and to elucidate how these SNPs might influence atazanavir exposure.