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.

Investigating the Moderating Effect of HIV Status Disclosure on the Link Between Discrimination Experience and Psychological Distress Among People Living with HIV in Japan Infected Through Sexual Contact.

BACKGROUND: There is a scarcity of research on the potential impact of disclosing HIV status to friends and family in moderating the adverse effects of discrimination on the mental health of people living with HIV (PLWH). This study assessed the experiences of discrimination and HIV status disclosure among PLWH in Japan, and evaluated their potential associations with psychological distress. METHOD: Data were derived from a nationwide cross-sectional survey of PLWH conducted in Japan between 2019 and 2020. The interaction effects of HIV-related discrimination and HIV status disclosure on the psychological distress were examined using logistic and linear regression analyses. RESULTS: The median age of the 804 respondents was 46 years old. Most respondents were male and 85.4% (687/804) identified as homosexuals or bisexuals. A total of 12.7% (102/804) of the respondents reported that they had recently experienced discrimination because of their HIV status. Experience of HIV-related discrimination was independently associated with high psychological distress (adjusted OR 2.02; 95% CI, 1.15-3.57), and HIV status disclosure to friends partially weakened the association between discrimination and the level of psychological distress (regression coefficient -3.115; p = 0.004). CONCLUSION: While measures that aim to end discrimination remain vital, increasing the opportunities of PLWH to communicate with friends they feel comfortable disclosing their HIV status may also be helpful in protecting their mental health.

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).

BMI as a predictor of high fasting blood glucose among people living with HIV in the Asia-Pacific region.

BACKGROUND: Non-Asian body mass index (BMI) classifications are commonly used as a risk factor for high fasting blood glucose (FBG). We investigated the incidence and factors associated with high FBG among people living with HIV in the Asia-Pacific region, using a World Health Organization BMI classification specific to Asian populations. METHODS: This study included people living with HIV enrolled in a longitudinal cohort study from 2003 to 2019, receiving antiretroviral therapy (ART), and without prior tuberculosis. BMI at ART initiation was categorized using Asian BMI classifications: underweight (<18.5 kg/m2 ), normal (18.5-22.9 kg/m2 ), overweight (23-24.9 kg/m2 ), and obese (≥25 kg/m2 ). High FBG was defined as a single post-ART FBG measurement ≥126 mg/dL. Factors associated with high FBG were analyzed using Cox regression models stratified by site. RESULTS: A total of 3939 people living with HIV (63% male) were included. In total, 50% had a BMI in the normal weight range, 23% were underweight, 13% were overweight, and 14% were obese. Median age at ART initiation was 34 years (interquartile range 29-41). Overall, 8% had a high FBG, with an incidence rate of 1.14 per 100 person-years. Factors associated with an increased hazard of high FBG included being obese (≥25 kg/m2 ) compared with normal weight (hazard ratio [HR] = 1.79; 95% confidence interval [CI] 1.31-2.44; p < 0.001) and older age compared with those aged ≤30 years (31-40 years: HR = 1.47; 95% CI 1.08-2.01; 41-50 years: HR = 2.03; 95% CI 1.42-2.90; ≥51 years: HR = 3.19; 95% CI 2.17-4.69; p < 0.001). CONCLUSION: People living with HIV with BMI >25 kg/m2 were at increased risk of high FBG. This indicates that regular assessments should be performed in those with high BMI, irrespective of the classification used.

Weight changes, metabolic syndrome and all-cause mortality among Asian adults living with HIV.

OBJECTIVES: We investigated weight changes following antiretroviral therapy (ART) initiation, the development of metabolic syndrome (MetS) and its association with all-cause mortality among Asian adults living with HIV. METHODS: Participants enrolled in a regional Asian HIV-infected cohort with weight and height measurements at ART initiation were eligible for inclusion in the analysis. Factors associated with weight changes and incident MetS (according to the International Diabetic Federation (IDF) definition) were analysed using linear mixed models and Cox regression, respectively. Competing-risk regression models were used to investigate the association of MetS with all-cause mortality. RESULTS: Among 4931 people living with HIV (PLWH), 66% were male. At ART initiation, the median age was 34 [interquartile range (IQR) 29-41] years, and the median (IQR) weight and body mass index (BMI) were 55 (48-63) kg and 20.5 (18.4-22.9) kg/m2 , respectively. At 1, 2 and 3 years of ART, overall mean (± standard deviation) weight gain was 2.2 (±5.3), 3.0 (±6.2) and 3.7 (±6.5) kg, respectively. Participants with baseline CD4 count ≤ 200 cells/µL [weight difference (diff) = 2.2 kg; 95% confidence interval (CI) 1.9-2.5 kg] and baseline HIV RNA ≥ 100 000 HIV-1 RNA copies/mL (diff = 0.6 kg; 95% CI 0.2-1.0 kg), and those starting with integrase strand transfer inhibitor (INSTI)-based ART (diff = 2.1 kg; 95% CI 0.7-3.5 kg vs. nonnucleoside reverse transcriptase inhibitors) had greater weight gain. After exclusion of those with abnormal baseline levels of MetS components, 295/3503 had incident MetS [1.18 (95% CI 1.05-1.32)/100 person-years (PY)]. The mortality rate was 0.7 (95% CI 0.6-0.8)/100 PY. MetS was not significantly associated with all-cause mortality in the adjusted model (P = 0.236). CONCLUSIONS: Weight gain after ART initiation was significantly higher among those initiating ART with lower CD4 count, higher HIV RNA and an INSTI-based regimen after controlling for baseline BMI. Greater efforts to identify and manage MetS among PLWH are needed.

Factors associated with high alanine aminotransferase (ALT) and cirrhosis in people living with HIV on combination antiretroviral treatment (cART) in the Asia-Pacific.

Liver disease is a growing burden among people living with HIV (PLHIV) in resource-limited settings. As an indicator of liver disease, risk factors of high alanine aminotransferase (ALT) and cirrhosis were assessed among PLHIV in the TREAT Asia HIV Observational Database (TAHOD). Patients on combination antiretroviral therapy (cART) with a pre-cART ALT measurement and at least one follow-up ALT measurement were included. Factors associated with high ALT (ALT levels > 5 times its upper limit of normal) were analyzed using repeated measure logistic regression over a 10-year follow-up period. Liver cirrhosis was defined as having an AST to Platelet Ratio Index score > 1.5, fibrosis-4 score > 3.25, or a clinical diagnosis of cirrhosis. Cox regression analysis stratified by site was used to analyze factors associated with cirrhosis among those in follow-up after 2015. Of 5182 patients, 101 patients (1.9%) had high ALT levels with hepatitis C virus (HCV) antibody positive (odds ratio [OR]: 4.98, 95% confidence interval [CI]: 2.82-8.77, p < 0.001) and ever high alcohol consumption (OR: 2.33, 95% CI: 1.00-5.46, p = 0.050) as likely factors. Among 6318 PLHIV in the liver cirrhosis analysis, 151 (2%) developed cirrhosis (incidence rate = 0.82 per 100 person-years). Those HCV-antibody positive (hazard ratio [HR]: 5.54, 95% CI: 3.75-8.18, p < 0.001) and had high alcohol consumption (HR: 2.06, 95% CI: 1.23-3.45, p = 0.006) were associated with liver cirrhosis. HCV-antibody positive and high alcohol consumption are factors associated with high ALT. With raised ALT levels as a known factor associated with liver cirrhosis, greater efforts are required in managing ALT levels and reducing the risk of developing liver cirrhosis among those positive for HCV-antibody and those who consume alcohol.

Evaluation of SARS-CoV-2 Antibodies and the Impact of COVID-19 on the HIV Care Continuum, Economic Security, Risky Health Behaviors, and Mental Health Among HIV-Infected Individuals in Vietnam.

Coronavirus disease 2019 (COVID-19) and associated social responses may uniquely affect people living with HIV (PLHIV). SARS-CoV-2 antibody testing and a cross-sectional survey on COVID-19's socio-behavioral impacts were conducted among a large PLHIV cohort in Hanoi, Vietnam. We examined anonymous antibody test results for 1243 PLHIV (99.8%) from whom plasma was obtained and completed surveys were collected in June/July 2020, just after the end of the first COVID-19 outbreak and nationwide lockdown. Three participants (0.2%) tested positive for anti-SARS-CoV-2 IgG antibodies. HIV treatment was generally maintained without antiretroviral therapy interruption, but COVID-19 had substantial impacts on economic security and risky health behaviors among PLHIV, which may have amplified psychological stress. These findings highlight the need for continuous monitoring of COVID-19's impacts on PLHIV and for efforts to mitigate these impacts.

Effects of National Adoption of Treat-All Guidelines on Pre-Antiretroviral Therapy (ART) CD4 Testing and Viral Load Monitoring After ART initiation: A Regression Discontinuity Analysis.

BACKGROUND: The World Health Organization's Treat-All guidance recommends CD4 testing before initiating antiretroviral therapy (ART), and routine viral load (VL) monitoring (over CD4 monitoring) for patients on ART. METHODS: We used regression discontinuity analyses to estimate changes in CD4 testing and VL monitoring among 547 837 ART-naive patients enrolling in human immunodeficiency virus (HIV) care during 2006-2018 at 225 clinics in 26 countries where Treat-All policies were adopted. We examined CD4 testing within 12 months before and VL monitoring 6 months after ART initiation among adults (≥20 years), adolescents (10-19 years), and children (0-9 years) in low/lower-middle-income countries (L/LMICs) and high/upper-middle-income countries (H/UMICs). RESULTS: Treat-All adoption led to an immediate decrease in pre-ART CD4 testing among adults in L/LMICs, from 57.0% to 48.1% (-8.9 percentage points [pp]; 95% CI: -11.0, -6.8), and a small increase in H/UMICs, from 90.1% to 91.7% (+1.6pp; 95% CI: 0.2, 3.0), with no changes among adolescents or children; decreases in pre-ART CD4 testing accelerated after Treat-All adoption in L/LMICs. In L/LMICs, VL monitoring after ART initiation was low among all patients in L/LMICs before Treat-All; while there was no immediate change at Treat-All adoption, VL monitoring trends significantly increased afterwards. VL monitoring increased among adults immediately after Treat-All adoption, from 58.2% to 61.1% (+2.9pp; 95% CI: 0.5, 5.4), with no significant changes among adolescents/children. CONCLUSIONS: While on-ART VL monitoring has improved in L/LMICs, Treat-All adoption has accelerated and disparately worsened suboptimal pre-ART CD4 monitoring, which may compromise care outcomes for individuals with advanced HIV.

Factors associated with high-risk behaviors of people newly diagnosed with HIV/AIDS: results from a cross-sectional study in Vietnam.

Towards the elimination of this global epidemic, understanding the high-risk behaviors of people newly diagnosed with HIV/AIDS (PNDWH) is essential. This study aimed to describe the general characteristics and high-risk behaviors of PNDWH and identify associated factors for adopting high-risk behaviors. A cross-sectional survey was conducted in Vietnam to explore the high-risk behaviors of 506 PNDWH. Associated factors were identified using multivariable logistic regressions. 83.2% of participants had sex without using a condom, and 27.9% had more than two sex partners. Among injected drug users, 44% had shared needles with an average number of 2.1 shared partners. Male, Kinh ethnicity (Vietnamese), high income, and high educational level were risk factors for high-risk behaviors. Our findings revealed the first time a comprehensive picture of PNDWH and emphasized the high prevalence of STIs, including untreated STIs and the long delay since the early HIV diagnosis. Also, our model found much higher risk behaviors among participants who were non-adherent to ART and those currently enrolled in ART. By better managing newly-diagnosed cases, better integrating STI management services and prevention consultants, as well as improving ART adherence programs, Vietnam can make better progress towards the complete control of HIV for its most vulnerable populations.

The patient voice: a survey of worries and anxieties during health system transition in HIV services in Vietnam.

BACKGROUND: Vietnam is shifting toward integrating HIV services into the public health system using social health insurance (SHI), and the HIV service delivery system is becoming decentralized. The study aim was to investigate current SHI coverage and patients' perspectives on this transition. METHODS: A survey of 1348 HIV-positive patients on antiretroviral therapy (aged ≥18 years) was conducted at an HIV outpatient clinic at a central-level hospital in Hanoi, Vietnam, in October and November 2018. Insurance coverage, reasons for not having a SHI card, perceived concerns about receiving HIV services in SHI-registered local health facilities, and willingness to continue regularly visiting the current hospital were self-reported. Logistic regression analyses were performed to analyze factors associated with not having a SHI card and having concerns about receiving HIV services in SHI-registered hospitals/clinics. RESULTS: SHI coverage was 78.0%. The most frequently reported reason for not having a SHI card was that obtaining one was burdensome, followed by lack of information on how to obtain a card, and financial problems. Most patients (86.6%) had concerns about receiving HIV services at SHI-registered local health facilities, and disclosure of HIV status to neighbors and low quality of HIV services were the main concerns reported. Participants aged < 40 years old and unmarried were more likely to report lack of SHI cards, and women and those aged ≥40 years were more likely to have concerns. However, 91.4% of patients showed willingness to continue regular visits to the current hospital. CONCLUSIONS: Although SHI coverage has been rapidly improving among HIV patients, most participants had concerns about the current system transition in Vietnam. In response to their voiced concerns, strengthening the link between higher-level and lower-level facilities may help to ensure good quality HIV services at all levels while mitigating patients' worries and anxieties.

Tenofovir disoproxil fumarate co-administered with lopinavir/ritonavir is strongly associated with tubular damage and chronic kidney disease.

BACKGROUD: With expanding antiretroviral therapy (ART) in a resource-limited setting, the use of second line ART with ritonavir boosted lopinavir (LPV/r) is increasing. However, little is known regarding the renal safety of tenofovir (TDF) co-administered with LPV/r. METHODS: In total 1382 HIV-infected patients were enrolled and data were recorded twice (October 2014 and 2015) in Vietnam. Tubular dysfunction (TD) was defined as urinary beta 2 microglobulin (ß2MG) > 1000 µg/L at both timepoints or increase in ß2MG by > 2000 µg/L. Chronic kidney disease (CKD) was defined as creatinine clearance ≤60 ml/min or urinary protein/creatinine ratio ≥ 0.15 g/gCre at both timepoints. RESULTS: The patients'mean weight and age were 55.9 kg and 38.4 years, respectively, and 41.5% were female. Additionally, 98.2% were on ART, 76.3% were on TDF (mean exposure duration was 35.4 months), and 22.4% had never TDF exposure. TD and CKD were diagnosed in 13% and 8.3% of all patients, respectively. In multivariate analyses, age (OR = 1.057; 95%CI, 1.034-1.081), being female (OR = 0.377; 95%CI, 0.221-0.645), HBsAg positive (OR = 1.812; 95%CI, 1.134-2.894), HCVAb positive (OR = 1.703; 95%CI, 1.100-2.635), TDF exposure (OR = 9.226; 95%CI, 2.847-29.901) and LPV/r exposure (OR = 5.548; 95%CI, 3.313-9.293) were significantly associated with TD. Moreover, age (OR = 1.093; 95%CI, 1.068-1.119), being female (OR = 0.510; 95%CI, 0.295-0.880), weight (OR = 0.909; 95%CI, 0.879-0.939), hypertension (OR = 3.027; 95%CI, 1.714-5.347), TDF exposure (OR = 1.963; 95%CI, 1.027-3.7 53) and LPV/r exposure (OR = 3.122; 95%CI, 1.710-5.699) were significantly associated with CKD. CONCLUSIONS: TDF and LPV/r exposure were strongly associated with TD and CKD, in addition to their known risks. Therefore, attention to renal safety for patients on second line ART is necessary.

Geographic distribution and characteristics of genotype A hepatitis B virus infection in acute and chronic hepatitis B patients in Japan.

BACKGROUND AND AIMS: The prevalence of sexually transmitted acute infections of the genotype A hepatitis B virus (HBV) has been increasing in Japan. Genotype A HBV is associated with an increased risk of HBV progression to chronic infection after acute hepatitis B (AHB) in adults. A nationwide survey was conducted to evaluate the geographic distribution, clinical, and virologic characteristics of genotype A AHB and chronic hepatitis B (CHB) in Japan. METHODS: Five hundred seventy AHB patients were recruited between 2005 and 2010, and 3682 CHB patients were recruited between 2010 and 2011. HBV genotypes were determined for 552 and 3619 AHB and CHB patients, respectively. Clinical characteristics were compared among different genotypes in AHB and CHB patients. Genomic characteristics of HBV genotype A were examined by molecular evolutionary analysis. RESULTS: Hepatitis B virus genotype A was the predominant genotype for AHB between 2005 and 2010. Phylogenetic analysis showed that all strains in the AHB patients with genotype A were classified into subtype Ae. Among CHB patients, the occurrence of genotype A was 4.1%, and genotype A was spreading in young adults. In genotype A CHB patients, early stage liver diseases were predominant, although liver diseases progressed to cirrhosis or hepatocellular carcinoma in some patients. CONCLUSIONS: The distribution of HBV genotypes is quite different between AHB and CHB in Japanese patients. Genotype A infection is spreading in young adults of Japanese CHB patients. Sequences derived from Japanese AHB patients were identical to or closely resembled the sequences derived from other Japanese AHB patients.

End-of-life care for HIV-infected patients with malignancies: A questionnaire-based survey.

BACKGROUND: The number of HIV-infected patients who require palliative or end-of-life care is increasing, and the status of end-of-life care for HIV patients with malignancies is unclear. AIM: This study aimed to evaluate the end-of-life care provided to HIV patients with malignancies in Japan. DESIGN: National cross-sectional questionnaire-based survey. SETTING/PARTICIPANTS: Questionnaires were delivered to the medical staff of 378 regional core hospitals/core hospitals for AIDS and 285 palliative care units in Japan. Data were collected between August and October 2013. RESULTS: Overall, 226 regional core hospitals/core hospitals for AIDS (59.8%) responded. A total of 55 institutions (24.3%) provided end-of-life care to HIV patients with malignancies. Regarding the place of death of the patients, 69.1% died at the institution whereas 18.2% were transferred to palliative care units. The requests of 16 (29.1%) institutions to transfer patients to palliative care units were rejected. Of the 378 palliative care units, 179 (62.8%) responded. While 13 palliative care units (4.6%) provided care to hospitalized HIV patients with malignancies, 20 (11.2%) refused to accept these patients for treatment because of a lack of experience in treating these patients and a lack of knowledge regarding HIV infection. CONCLUSION: Our findings suggest that in Japan, HIV patients with malignancies have difficulties obtaining hospitalization at a palliative care unit, which is likely due to a lack of experience among the professionals in treating such patients as well as a lack of knowledge about HIV.

Risk factors for long-term persistence of serum hepatitis B surface antigen following acute hepatitis B virus infection in Japanese adults.

UNLABELLED: The proportion of patients who progress to chronicity following acute hepatitis B (AHB) varies widely worldwide. Moreover, the association between viral persistence after AHB and hepatitis B virus (HBV) genotypes in adults remains unclear. A nationwide multicenter study was conducted throughout Japan to evaluate the influence of clinical and virological factors on chronic outcomes in patients with AHB. For comparing factors between AHB patients with viral persistence and those with self-limited infection, 212 AHB patients without human immunodeficiency virus (HIV) coinfection were observed in 38 liver centers until serum hepatitis B surface antigen (HBsAg) disappeared or a minimum of 6 months in cases where HBsAg persisted. The time to disappearance of HBsAg was significantly longer for genotype A patients than that of patients infected with non-A genotypes. When chronicity was defined as the persistence of HBsAg positivity for more than 6 or 12 months, the rate of progression to chronicity was higher in patients with genotype A, although many cases caused by genotype A were prolonged cases of AHB, rather than chronic infection. Multivariate logistic regression analysis revealed only genotype A was independently associated with viral persistence following AHB. A higher peak level of HBV DNA and a lower peak of alanine aminotransferase (ALT) levels were characteristics of AHB caused by genotype A. Treatment with nucleotide analogs (NAs) did not prevent progression to chronic infection following AHB overall. Subanalysis suggested early NA initiation may enhance the viral clearance. CONCLUSION: Genotype A was an independent risk factor for progression to chronic infection following AHB. Our data will be useful in elucidating the association between viral persistence after AHB, host genetic factors, and treatment with NAs in future studies.

Clinical significance of high anti-entamoeba histolytica antibody titer in asymptomatic HIV-1-infected individuals.

BACKGROUND: Anti-Entamoeba histolytica antibody (anti- E. histolytica) is widely used in seroprevalence studies though its clinical significance has not been assessed previously. METHODS: Anti-E. histolytica titer was measured at first visit to our clinic (baseline) in 1303 patients infected with human immunodeficiency virus type 1 (HIV-1). The time to diagnosis of invasive amebiasis was assessed by Kaplan-Meier method and risk factors for the development of invasive amebiasis were assessed by Cox proportional-hazards regression analysis. For patients who developed invasive amebiasis, anti-E. histolytica titers at onset were compared with those at baseline and after treatment. RESULTS: The anti-E. histolytica seroprevalence in the study population was 21.3% (277/1303). Eighteen patients developed invasive amebiasis during the treatment-free period among 1207 patients who had no history of previous treatment with nitroimidazole. Patients with high anti-E. histolytica titer at baseline developed invasive amebiasis more frequently than those with low anti-E. histolytica titer. Most cases of invasive amebiasis who had high anti-E. histolytica titer at baseline developed within 1 year. High anti-E. histolytica titer was the only independent predictor of future invasive amebiasis. Anti-E. histolytica titer was elevated at the onset of invasive amebiasis in patients with low anti-E. histolytica titer at baseline. CONCLUSIONS: Asymptomatic HIV-1-infected individuals with high anti-E. histolytica titer are at risk of invasive amebiasis probably due to exacerbation of subclinical amebiasis.

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.

The prevalence of opportunistic infections and malignancies in autopsied patients with human immunodeficiency virus infection in Japan.

BACKGROUND: Opportunistic infections and malignancies such as malignant lymphoma and Kaposi sarcoma are significant complications of human immunodeficiency virus (HIV) infection. However, following the introduction of antiretroviral therapy in Japan in 1997, the incidence of clinical complications has decreased. In the present study, autopsy cases of HIV infection in Japan were retrospectively investigated to reveal the prevalence of opportunistic infections and malignancies. METHODS: A total of 225 autopsy cases of HIV infection identified at 4 Japanese hospitals from 1985-2012 were retrospectively reviewed. Clinical data were collected from patient medical records. RESULTS: Mean CD4 counts of patients were 77.0 cells/µL in patients who received any antiretroviral therapy during their lives (ART (+) patients) and 39.6 cells/µL in naïve patients (ART (-) patients). Cytomegalovirus infection (142 cases, 63.1%) and pneumocystis pneumonia (66 cases, 29.3%) were the most frequent opportunistic infections, and their prevalence was significantly lower in ART (+) patients than ART (-) patients. Non-Hodgkin lymphoma and Kaposi sarcoma were observed in 30.1% and 16.2% of ART (-) patients, and 37.9% and 15.2% of ART (+) patients, respectively. Malignant lymphoma was the most frequent cause of death, followed by cytomegalovirus infection regardless of ART. Non-acquired immunodeficiency syndrome (AIDS)-defining cancers such as liver and lung cancer caused death more frequently in ART (+) patients (9.1%) than in ART (-) patients (1.5%; P = 0.026). CONCLUSIONS: The prevalence of infectious diseases and malignancies were revealed in autopsy cases of HIV infection in Japan. The prevalence of cytomegalovirus infection and pneumocystis pneumonia at autopsy were lower in ART (+) patients than ART (-) patients. Higher prevalence of non-AIDS defining malignancies among ART (+) patients than ART (-) patients suggests that onsets of various opportunistic infections and malignancies should be carefully monitored regardless of whether the patient is receiving ART.

Clinical outcomes of AIDS-related Burkitt lymphoma: a multi-institution retrospective survey in Japan.

OBJECTIVE: Acquired immunodeficiency syndrome-related non-Hodgkin lymphoma is treated similarly to non-acquired immunodeficiency syndrome lymphoma, but it is not clear whether highly intensive regimens are beneficial for acquired immunodeficiency syndrome-related Burkitt lymphoma. We conducted a multicenter retrospective survey to clarify the clinical outcomes of acquired immunodeficiency syndrome-related Burkitt lymphoma in the combined antiretroviral therapy era in Japan. METHODS: We retrospectively analyzed the outcome of 33 patients with acquired immunodeficiency syndrome-related Burkitt lymphoma, who were diagnosed at five regional hospitals for human immunodeficiency virus/acquired immunodeficiency syndrome in Japan between January 2002 and December 2010. RESULTS: The median follow-up period was 20.0 months (range 0.5-92.7 months). Six (18.2%) patients were treated with cyclophosphamide, vincristine, doxorubicin, high-dose methotrexate, ifosphamide, etoposide and high-dose cytarabine, and 23 (69.7%) patients were treated with hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone, high-dose methotrexate and high-dose cytarabine. The overall response rate for all patients was 78.8%, with a complete response rate of 72.7%. The two-year overall survival rate was 68.1%. There was no significant difference in overall survival between chemotherapeutic regimens with rituximab (n = 20) and without rituximab (n = 13) (P = 0.49). The two-year overall survival rate was 66.7% for patients receiving cyclophosphamide, vincristine, doxorubicin, dexamethasone, etoposide, ifosfamide and cytarabine, and was 72.6% for patients receiving cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate and cytarabine (P = 0.72). There was one treatment-related death. CONCLUSIONS: Highly intensive chemotherapy would bring a high remission rate and prolonged overall survival for patients with acquired immunodeficiency syndrome-related Burkitt lymphoma.

Low body weight and tenofovir use are risk factors for renal dysfunction in Vietnamese HIV-infected patients. A prospective 18-month observation study.

BACKGROUND: The use of tenofovir has been rapidly increasing in Vietnam. Several studies identified low body weight as a risk factor for tenofovir-induced nephrotoxicity. However, little is known about the impact of tenofovir on renal function in HIV-infected Vietnamese with generally low weight. METHODS: An observational single-center cohort of adult HIV-infected patients on antiretroviral therapy at National Hospital of Tropical Diseases, Hanoi. Patients on tenofovir or with creatinine clearance ≤60 ml/min at baseline were excluded. The incidence of renal dysfunction was compared between patients who switched to tenofovir and those who did not. Renal dysfunction was defined as 25% decline of creatinine clearance from baseline. Time to renal dysfunction was analyzed by the Kaplan-Meier method between the two groups. The Cox hazard model was used to determine risk factors for renal dysfunction in uni- and multivariate analyses. RESULTS: Of 556 patients enrolled in this study, 403 were non-tenofovir group while 153 were the tenofovir-switched group. Renal dysfunction occurred at a higher rate in the tenofovir-switched group (92.5 per 1000 person-years) than the non-tenofovir group (47.8 per 1000 person-years)(p = 0.023, Log-rank test). Multivariate analysis confirmed that tenofovir use, low body weight and glucosuria were significant risk factors for renal dysfunction (hazard ratio = 1.980; 95% confidential interval, 1.094-3.582, HR = 1.057; 95%CI, 1.016-1.098, HR = 5.202; 95%CI, 1.245-21.738, respectively). CONCLUSIONS: Tenofovir use, low body weight and glucosuria were significant risk factors for renal dysfunction. We suggest close monitoring of renal function in patients with these risk factors even in resource-limited setting.

Skin rash induced by ritonavir-boosted darunavir is common, but generally tolerable in an observational setting.

Ritonavir-boosted darunavir (DRV/r) is a protease inhibitor widely used in the treatment of HIV-1 infection. However, skin rash is a well-known adverse event of DRV, and limited data are available from observational settings. This observational study examined the characteristics of DRV-induced skin rash in treatment-naïve patients who commenced once-daily DRV/r-containing antiretroviral therapy (ART). Of the 292 study patients, DRV rashes developed in 31 (11%) patients with a median latency of 10 days (developing from 7 to 14 days in 93%) from initiation of ART. DRV skin rash was generally mild, as only one patient (3%) had grade 3 rash whereas 24 (77%) patients had grade 2 and 6 (19%) patients had grade 1. Only two patients (7%) discontinued DRV/r due to skin rash, and the other continued DRV/r and their rashes disappeared completely without any complications. Interestingly, DRV rash occurred more frequently to patients with less advanced HIV-1 infection than those with advanced infection. The incidence of DRV rash was not significantly different between patients with and without history of sulfonamide allergy (p = 0.201). Furthermore, when we exclude patients without history of sulfonamide use and only examine patients with sulfonamide use (n = 145), the result was similar (p = 0.548). In conclusion, DRV rashes were frequently observed but the prognosis was benign. Most patients tolerated DRV rashes with use of oral steroid or antihistamine without discontinuation of DRV. To date, there is no clear clinical evidence to suggest that DRV should be avoided in patients with history of sulfonamide allergy.