Brief Report: Malignancies in Adults Living With HIV in Asia.

BACKGROUND: Hematological malignancies have continued to be highly prevalent among people living with HIV (PLHIV). This study assessed the occurrence of, risk factors for, and outcomes of hematological and nonhematological malignancies in PLHIV in Asia. METHODS: Incidence of malignancy after cohort enrollment was evaluated. Factors associated with development of hematological and nonhematological malignancy were analyzed using competing risk regression and survival time using Kaplan-Meier. RESULTS: Of 7455 patients, 107 patients (1%) developed a malignancy: 34 (0.5%) hematological [0.08 per 100 person-years (/100PY)] and 73 (1%) nonhematological (0.17/100PY). Of the hematological malignancies, non-Hodgkin lymphoma was predominant (n = 26, 76%): immunoblastic (n = 6, 18%), Burkitt (n = 5, 15%), diffuse large B-cell (n = 5, 15%), and unspecified (n = 10, 30%). Others include central nervous system lymphoma (n = 7, 21%) and myelodysplastic syndrome (n = 1, 3%). Nonhematological malignancies were mostly Kaposi sarcoma (n = 12, 16%) and cervical cancer (n = 10, 14%). Risk factors for hematological malignancy included age >50 vs. ≤30 years [subhazard ratio (SHR) = 6.48, 95% confidence interval (CI): 1.79 to 23.43] and being from a high-income vs. a lower-middle-income country (SHR = 3.97, 95% CI: 1.45 to 10.84). Risk was reduced with CD4 351-500 cells/µL (SHR = 0.20, 95% CI: 0.05 to 0.74) and CD4 >500 cells/µL (SHR = 0.14, 95% CI: 0.04 to 0.78), compared to CD4 ≤200 cells/µL. Similar risk factors were seen for nonhematological malignancy, with prior AIDS diagnosis showing a weak association. Patients diagnosed with a hematological malignancy had shorter survival time compared to patients diagnosed with a nonhematological malignancy. CONCLUSIONS: Nonhematological malignancies were common but non-Hodgkin lymphoma was more predominant in our cohort. PLHIV from high-income countries were more likely to be diagnosed, indicating a potential underdiagnosis of cancer in low-income settings.

Changes in renal function with long-term exposure to antiretroviral therapy in HIV-infected adults in Asia.

PURPOSE: Renal disease is common among people living with human immunodeficiency virus (HIV). However, there is limited information on the incidence and risk factors associated with renal dysfunction among this population in Asia. METHODS: We used data from the TREAT Asia HIV Observational Database. Patients were included if they started antiretroviral therapy during or after 2003, had a serum creatinine measurement at antiretroviral therapy initiation (baseline), and had at least 2 follow-up creatinine measurements taken ≥3 months apart. Patients with a baseline estimated glomerular filtration rate (eGFR) ≤60 mL/min/1.73 m2 were excluded. Chronic kidney disease was defined as 2 consecutive eGFR values ≤60 mL/min/1.73 m2 taken ≥3 months apart. Generalized estimating equations were used to identify factors associated with eGFR change. Competing risk regression adjusted for study site, age and sex, and cumulative incidence plots were used to evaluate factors associated with chronic kidney disease (CKD). RESULTS: Of 2547 patients eligible for this analysis, tenofovir was being used by 703 (27.6%) at baseline. Tenofovir use, high baseline eGFR, advanced HIV disease stage, and low nadir CD4 were associated with a decrease in eGFR during follow-up. Chronic kidney disease occurred at a rate of 3.4 per 1000 patient/years. Factors associated with CKD were tenofovir use, old age, low baseline eGFR, low nadir CD4, and protease inhibitor use. CONCLUSIONS: There is an urgent need to enhance renal monitoring and management capacity among at-risk groups in Asia and improve access to less nephrotoxic antiretrovirals.

Optimal timing for elective total hip replacement in HIV-positive patients.

INTRODUCTION: Evidence about the optimal timing for total hip replacement (THR) in HIV-positive patients is scant. HYPOTHESIS: Preoperative criteria: cluster of differentiation 4 (CD4) counts>200cells/mm3 and an undetectable HIV virus load before THR, improve infection rates, aseptic loosenings, and functional outcomes. MATERIALS AND METHODS: We recruited 16 HIV-positive patients who had undergone 25 THRs between 2003 and 2015. None had hemophilia, and none were intravenous drug users (IVDUs). RESULTS: Their mean age was 41.2 years (range: 24-60); minimum follow-up was 12 months (mean: 64.6); mean duration of prophylactic antibiotics was 2.9 days (range: 1-5); and mean hospital length of stay was 6.0 days (range: 4-11). No patients were treated with subsequent oral antibiotics. The mean preoperative CD4 count was 464.1±237.0 (range: 235-904)cells/mm3. There were no early superficial surgical site infections, late periprosthetic joint infections, or aseptic loosenings. Post-surgery Harris Hip score was significantly (p<0.001) better. DISCUSSION: A preoperative CD4 count>200cell/mm3 and an undetectable HIV virus load might indicate optimal timing for elective THRs in HIV-positive patients without hemophilia and not IVDUs. LEVEL OF EVIDENCE: IV, retrospective or historical series.

Cardiovascular Disease and Cardiovascular Disease Risk in HIV-Positive Populations in the Asian Region.

INTRODUCTION: Cardiovascular diseases (CVD) are becoming more prevalent in HIV-infected populations as they age largely due to improved treatment outcomes. Assessment of CVD risk and CVD risk factors in HIV-positive populations has focused on high income settings, while there are limited studies evaluating CVD in HIV-positive populations in the Asian region. MATERIALS AND METHODS: We provided an overview of the prevalence and incidence of CVD and its risk factors in adult HIV-positive populations, and of the strategies currently in place for CVD management in the Asian region. RESULTS: Studies from the Asian region showed that CVD and CVD risk factors, such as dyslipidaemia, elevated blood glucose, obesity and smoking, are highly prevalent in HIV-positive populations. A number of studies suggested that HIV infection and antiretroviral therapy may contribute to increased CVD risk. National HIV treatment guidelines provide some directions regarding CVD risk prevention and management in the HIV-infected population, however, they are limited in number and scope. CONCLUSION: Development and consolidation of guidelines for integrated CVD and HIV care are essential to control the burden of CVD in HIV-positive populations. To inform guidelines, policies and practice in the Asian region, research should focus on exploring appropriate CVD risk screening strategies and estimating current and future CVD mortality and morbidity rates.

Impact of the 1997 revised Centers for Disease Control criteria on case rates of legionellosis in Taiwan: review of 38 cases at a teaching hospital, 1998-2002.

In 1997, the United States Centers for Disease Control and Prevention (CDC) published revised case definitions for legionellosis which eliminated the previously used category of "probable case" based on a single indirect fluorescence antibody (IFA) titer. This study evaluated the influence of revision on the case rates of legionellosis in Taiwan. From 1988 to 2002, 4615 patients with pneumonia were tested for legionellosis in our hospital. The testing methods included IFA assay for serum specimens and direct fluorescence antibody (DFA) assay for sputum specimens. Using the revised criteria, Legionnaires' disease (LD) was diagnosed by DFA in 27 cases and by IFA in 11 cases. The most common underlying conditions were cigarette smoking (44.7%), chronic obstructive pulmonary disease (28.9%) and corticosteroid use (26.3%). The clinical features were nonspecific, including fever (73.7%), dyspnea (63.2%), cough (63.2%) and leukocytosis (63.2%). The overall mortality rate was 18.4%, and the directly LD-attributable mortality rate was 10.5%. Nasogastric tube insertion, endotracheal intubation, congestive heart failure before the onset of LD, inappropriate antimicrobial therapy, respiratory failure and absence of fever during the LD course were significantly associated with LD-attributable mortality. Older age (>70 years) was not associated with higher mortality (p=0.053). Using the revised diagnostic criteria in our series, the positive rate of case identification by IFA was 0.26%, while use of the previous case definitions resulted in a positive rate of 7.6% (including probable and definitive cases). Recognition that the original CDC criteria of IFA titer >1:256 or elevation of IFA titer <4-fold in paired sera could not adequately define an LD etiology has led to a dramatic lowering of case rates among studies after the criteria revision in Taiwan and elsewhere. Assays that are faster, more sensitive and less technician dependent are needed to diagnosis this disease.

Clinical characteristics and prognostic factors of patients with Stenotrophomonas maltophilia bacteremia.

Stenotrophomonas maltophilia is an important nosocomial pathogen with intrinsic multi-drug resistance. This retrospective study reviewed 84 episodes of S. maltophilia bacteremia over a 4-year period from July 1999 to September 2003. Stenotrophomonas maltophilia bacteremia was hospital-acquired in 64 patients (76%), and developed after prolonged hospitalization in 48 (57%). Seventy patients (83%) had a central venous catheter (CVC), 64 (76%) had prior antibiotic therapy, 55 (65%) had underlying malignancy, and 43 (51%) were receiving immunosuppressive therapy. Twenty seven percent of the episodes of bacteremia had polymicrobial isolates. The overall and bacteremia-related mortality rates were 44% and 33%, respectively. Forty six percent of the bacteremia-related mortality occurred within 3 days after onset of symptoms. The most common sources of bacteremia were respiratory tract (33%) and CVC (31%), while the source of the bacteremia was unknown in 26% of episodes. The most effective antibiotics in vitro were trimethoprim-sulfamethoxazole, ciprofloxacin, chloramphenicol, and ceftazidime; however, a trend of increasing drug resistance in these agents was identified over the study period. On univariate analysis, nosocomial bacteremia, long-lasting neutropnenia (>10 days), bacteremia originating from the respiratory tract, shock, low serum albumin level (<3 g/dL), and thrombocytopenia (platelet count <100,000/mm3) were significantly related to mortality (p<0.05). Among these variables, shock and thrombocytopenia were independent factors associated with mortality. In contrast, patients with CVC-related bacteremia had a lower mortality rate (odds ratio, 0.04; p<0.001). Patients treated with appropriate antibiotics had a lower mortality rate, but this difference was not significant (p=0.477). In S. maltophilia bacteremia, careful evaluation of CVC was important for identifying the source of bacteremia and predicting prognosis. The source of bacteremia and condition of patients at presentation were the major factors influencing prognosis.

Patient data, early SARS epidemic, Taiwan.

Of the first 10 patients in the epidemic of severe acute respiratory syndrome (SARS) in Taiwan, 4 were closely associated with a SARS patient in an airplane. Loose stools or diarrhea, hemophagocytosis syndrome, and high serum levels of interleukin (IL)-6, IL-8, and tumor necrosis factor-a associated with lung lesions were found in all 10 patients.

Hemophagocytic syndrome: an unusual manifestation of acute human immunodeficiency virus infection.

An 18 year-old heterosexual man was hospitalized because of fever, chills, a sore throat, and a dry cough for 8 days. He had had sexual intercourse with a new partner within the 4 months prior to admission. At admission, the patient presented a clinical picture compatible with hemophagocytic syndrome (HPS). The presence of hemophagocytosis was subsequently determined pathologically from bone marrow and lymph node specimens. An exhaustive diagnostic work-up failed to reveal any causative etiology, the symptoms improving after 2 doses of intravenous immunoglobulin (IVIG) infusion, given at a dose of 0.5 mg/kg each, the 2 doses being administered 1 week apart. Three months subsequent to the patient's initial presentation, acute human immunodeficiency virus (HIV) infection was diagnosed, and the patient received highly active antiretrovirus therapy (HAART) from the time of diagnosis. The patient remained well for the following 2 years. HPS in the advanced stages of HIV infection has previously been described, but HPS during seroconversion of an acute form of the infection is rare. We most definitely suggest, however, that acute HIV infection be included in the list of potential causes of HPS. IVIG therapy appears to be an appropriate therapeutic modality, and HAART also is effective, for prevention of recurrence of HPS in a patient with acute HIV infection.