Pharmacogenetics-based population pharmacokinetic analysis for dose optimization of ritonavir-boosted atazanavir in Thai adult HIV-infected patients.

BACKGROUND: This population pharmacokinetic-pharmacogenetic study aimed to investigate the optimal dose of RTV-boosted ATV (ATV/RTV) for Thai adult HIV-infected patients. METHODS: A total of 1460 concentrations of ATV and RTV from 544 patients receiving an ATV/RTV-based regimen were analyzed. The CYP3A5 6986 A > G, ABCB1 3435 C > T, ABCB1 2677 G > T, SLCO1B1 521 T > C, and NR1I2 63396 C > T were genotyped. A population pharmacokinetic model was performed using a nonlinear mixed-effect model (NONMEM®). Monte Carlo simulations were conducted to compare the percentages of patients achieving the therapeutic range of ATV through concentrations (Ctrough). RESULTS: The apparent oral clearance of ATV (CL/FATV) without RTV was 7.69 L/h with interindividual variability (IIV) of 28.7%. Patients with CYP3A5 6986 GG had a 7.1% lower CL/FATV than those with AA or AG genotype. The CL/FATV decreased by 10.8% for females compared with males. Simulation results showed higher percentages (~70%) of patient receiving doses of 200/100 or 200/50 mg achieved the target ATV Ctrough, while more patients (~40%) receiving a standard dose (300/100 mg) had ATV Ctrough above this target. CONCLUSIONS: Both CYP3A5 6986 A > G and female decreased CL/FATV in Thai HIV-infected patients. Simulations supported that the reduced dose of ATV/RTV was sufficient to achieve the target concentration for Thai population.

Infectious causes of acute meningitis among Thai adults in a university hospital.

INTRODUCTION: Knowing the epidemiology of acute meningitis may guide physicians to promptly administer appropriate empirical therapy, thereby minimizing morbidity and mortality. We aimed to determine the etiology, clinical manifestations, cerebrospinal fluid (CSF) findings, and outcomes of patients with acute meningitis. METHODS: We conducted a retrospective cohort study among a total 89 adult (age ≥15 years) patients with acute meningitis. RESULTS: Among them, 48 (53.9%) patients were men; the median age (interquartile range; IQR) was 49 (32.1-63.8) years. The most common coexisting conditions were HIV infection (30%), prednisolone therapy (16.9%), and diabetes mellitus (15.7%). Common clinical presentations were fever (74%), headache (70.8%), and confusion (31.5%). Causes of acute meningitis were Cryptococcus neoformans (37%), bacteria (31.5%), Mycobacterium tuberculosis (27%), and viruses (4.5%). In multivariate logistic regression, predicting factors of acute bacterial meningitis were higher white blood cells (WBCs) in a complete blood count [odds ratio (OR) 1.01 per increase of 100 cells/mm3; 95% confidence interval (CI) 1.00-1.02, p = 0.031], no HIV infection (OR 0.08; 95% CI 0.01-0.72, p = 0.023), and higher serum sodium (OR 1.13; 95% CI 1.01-0.23, p = 0.029). Overall, the median (IQR) duration of hospitalization was 23 (11-29) days. A total 26 (29%) patients had complications, such as septic shock, hydrocephalus, seizure, and brain edema. The in-hospital mortality rate was 7.9%. CONCLUSIONS: In this setting, the most common cause of acute meningitis in adults was cryptococcosis followed by tuberculosis. Awareness of local epidemiology and patients' risk factors are important to initiate appropriate antimicrobial therapy.

Influence of CYP3A5 and SLCO1B1 polymorphisms on atazanavir/r concentrations in Thai HIV-infected patients.

Aim: To evaluate the influence of genetic polymorphisms on plasma trough concentrations of atazanavir (ATV) and ritonavir (RTV). Patients & methods: The concentration-to-dose ratios were compared between different genotype groups of CYP3A5, ABCB1, SLCO1B1 and NR1I2 in 490 patients. Multiple regression analysis was used to examine the association between genetic and clinical factors and log-transformed concentration-to-dose ratio of ATV and RTV. Results: Higher concentrations of ATV and RTV were significantly associated with CYP3A5 6986 GG and SLCO1B1 521 TC or CC. Female patients had significantly higher ATV plasma concentration than male patients. Conclusion: Genetic polymorphisms and gender are factors affecting the variability of ATV and RTV concentrations in the Thai population. Thus, genetic testing is worth considering when atazanavir + low dose ritonavir is prescribed.

Cardiovascular disease incidence projections in the TREAT Asia HIV Observational Database (TAHOD).

BACKGROUND: We aimed to project the 10-year future incidence of cardiovascular disease (CVD) and model several intervention scenarios based on a multi-site Asian HIV-positive cohort. METHODS: Analyses were based on patients recruited to the TREAT Asia HIV Observational Database (TAHOD), consisting of 21 sites in 12 countries. Patients on triple antiretroviral therapy (ART) were included if they were alive, without previous CVD, and had data on CVD risk factors. Annual new CVD events for 2019-2028 were estimated with the D:A:D equation, accounting for age- and sex-adjusted mortality. Modelled intervention scenarios were treatment of high total cholesterol, low high-density lipoprotein cholesterol (HDL) or high blood pressure, abacavir or lopinavir substitution, and smoking cessation. RESULTS: Of 3,703 included patients, 69% were male, median age was 46 (IQR 40-53) years and median time since ART initiation was 9.8 years (IQR 7.5-14.1). Cohort incidence rates of CVD were projected to increase from 730 per 100,000 person-years (pys) in 2019 to 1,432 per 100,000 pys in 2028. In the modelled intervention scenarios, most events can be avoided by smoking cessation, abacavir substitution, lopinavir substitution, decreasing total cholesterol, treating high blood pressure and increasing HDL. CONCLUSIONS: Our projections suggest a doubling of CVD incidence rates in Asian HIV-positive adults in our cohort. An increase in CVD can be expected in any ageing population, however, according to our models, this can be close to averted by interventions. Thus, there is an urgent need for risk screening and integration of HIV and CVD programmes to reduce the future CVD burden.

The influence of age-associated comorbidities on responses to combination antiretroviral therapy in older people living with HIV.

INTRODUCTION: Multiple comorbidities among HIV-positive individuals may increase the potential for polypharmacy causing drug-to-drug interactions and older individuals with comorbidities, particularly those with cognitive impairment, may have difficulty in adhering to complex medications. However, the effects of age-associated comorbidities on the treatment outcomes of combination antiretroviral therapy (cART) are not well known. In this study, we investigated the effects of age-associated comorbidities on therapeutic outcomes of cART in HIV-positive adults in Asian countries. METHODS: Patients enrolled in the TREAT Asia HIV Observational Database cohort and on cART for more than six months were analysed. Comorbidities included hypertension, diabetes, dyslipidaemia and impaired renal function. Treatment outcomes of patients ≥50 years of age with comorbidities were compared with those <50 years and those ≥50 years without comorbidities. We analysed 5411 patients with virological failure and 5621 with immunologic failure. Our failure outcomes were defined to be in-line with the World Health Organization 2016 guidelines. Cox regression analysis was used to analyse time to first virological and immunological failure. RESULTS: The incidence of virologic failure was 7.72/100 person-years. Virological failure was less likely in patients with better adherence and higher CD4 count at cART initiation. Those acquiring HIV through intravenous drug use were more likely to have virological failure compared to those infected through heterosexual contact. On univariate analysis, patients aged <50 years without comorbidities were more likely to experience virological failure than those aged ≥50 years with comorbidities (hazard ratio 1.75, 95% confidence interval (CI) 1.31 to 2.33, p < 0.001). However, the multivariate model showed that age-related comorbidities were not significant factors for virological failure (hazard ratio 1.31, 95% CI 0.98 to 1.74, p = 0.07). There were 391 immunological failures, with an incidence of 2.75/100 person-years. On multivariate analysis, those aged <50 years without comorbidities (p = 0.025) and age <50 years with comorbidities (p = 0.001) were less likely to develop immunological failure compared to those aged ≥50 years with comorbidities. CONCLUSIONS: In our Asia regional cohort, age-associated comorbidities did not affect virologic outcomes of cART. Among those with comorbidities, patients <50 years old showed a better CD4 response.

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.

Epidemiology and outcomes of dengue in kidney transplant recipients: A 20-year retrospective analysis and comparative literature review.

BACKGROUND: Kidney transplant (KT) recipients in dengue-endemic areas are at risk of exposure. We investigated the epidemiology and outcomes from dengue in KT recipients at our transplant center and conducted a literature review. MATERIALS AND METHODS: We conducted a 20-year retrospective study of KT recipients who were diagnosed with laboratory-confirmed dengue from January 1997 to September 2017 according to the 2009 World Health Organization (WHO) classification. We analyzed clinical characteristics and treatment outcomes. RESULTS: There were 13 (0.7%) dengue cases among 1917 KT recipients with a median age of 39 years (interquartile ranges [IQR], 22-46); 54% were males. Cases occurred with a median onset of 24 months (IQR, 6-122) after KT. Dengue was diagnosed via dengue NS1 antigen (85%), IgM antibodies (38.5%), or RT-PCR (15.4%). Patients were classified as having dengue without warning sign (30.8%), with warning sign (53.8%), or severe dengue (15.4%). All patients resolved without complications, except one had hemophagocytic lymphohistiocytosis. Ten (76.9%) patients experienced eGFR reduction with a median of 13.7 mL/min/1.73 m2 (IQR, 8.3-20.5); eight (80%) had a full allograft function recovery. CONCLUSIONS: Dengue in KT recipients in endemic areas is uncommon. Although a transient decline in allograft function can occur, the overall clinical and allograft outcomes seem to be favorable.

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.

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.

Pituitary tuberculoma: A consideration in the differential diagnosis in a patient manifesting with pituitary apoplexy-like syndrome.

Pituitary tuberculoma is extremely rare, even in endemic regions of tuberculosis and much less frequently as a presentation of pituitary apoplexy. We describe a 25-year-old female presented with sudden onset of headache and vision loss of left eye which mimicking symptoms of pituitary apoplexy. MRI of the pituitary gland showed a rim-enhancing lesion at the intrasellar region extending into the suprasellar area, but absence of posterior bright spot with enhancement of the pituitary stalk. Pituitary hormonal evaluation revealed panhypopituitarism and diabetes insipidus. An urgent transphenoidal surgery of the pituitary gland was undertaken for which the histopathology showed necrotizing granulomatous inflammation with infarcted adjacent pituitary tissue. Despite negative fungal and AFB staining, pituitary tuberculoma was presumptively diagnosed based on imaging, pathology and the high incidence of tuberculosis in the country. After the course of anti-tuberculosis therapy, the clinical findings were dramatically improved, supporting the diagnosis. Pituitary tuberculoma is extremely rare in particular with an apoplexy-like presentation but should be one of the differential diagnosis list of intrasellar lesions in the patient presenting with sudden onset of headache and visual loss. The presence of diabetes insipidus and thickened with enhancement of pituitary stalk on MRI were very helpful in diagnosing pituitary tuberculosis.

Trends in first-line antiretroviral therapy in Asia: results from the TREAT Asia HIV observational database.

BACKGROUND: Antiretroviral therapy (ART) has evolved rapidly since its beginnings. This analysis describes trends in first-line ART use in Asia and their impact on treatment outcomes. METHODS: Patients in the TREAT Asia HIV Observational Database receiving first-line ART for ≥ 6 months were included. Predictors of treatment failure and treatment modification were assessed. RESULTS: Data from 4662 eligible patients was analysed. Patients started ART in 2003-2006 (n = 1419), 2007-2010 (n = 2690) and 2011-2013 (n = 553). During the observation period, tenofovir, zidovudine and abacavir use largely replaced stavudine. Stavudine was prescribed to 5.8% of ART starters in 2012/13. Efavirenz use increased at the expense of nevirapine, although both continue to be used extensively (47.5% and 34.5% of patients in 2012/13, respectively). Protease inhibitor use dropped after 2004. The rate of treatment failure or modification declined over time (22.1 [95%CI 20.7-23.5] events per 100 patient/years in 2003-2006, 15.8 [14.9-16.8] in 2007-2010, and 11.6 [9.4-14.2] in 2011-2013). Adjustment for ART regimen had little impact on the temporal decline in treatment failure rates but substantially attenuated the temporal decline in rates of modification due to adverse event. In the final multivariate model, treatment modification due to adverse event was significantly predicted by earlier period of ART initiation (hazard ratio 0.52 [95%CI 0.33-0.81], p = 0.004 for 2011-2013 versus 2003-2006), older age (1.56 [1.19-2.04], p = 0.001 for ≥ 50 years versus <30 years), female sex (1.29 [1.11-1.50], p = 0.001 versus male), positive hepatitis C status (1.33 [1.06-1.66], p = 0.013 versus negative), and ART regimen (11.36 [6.28-20.54], p<0.001 for stavudine-based regimens versus tenofovir-based). CONCLUSIONS: The observed trends in first-line ART use in Asia reflect changes in drug availability, global treatment recommendations and prescriber preferences over the past decade. These changes have contributed to a declining rate of treatment modification due to adverse event, but not to reductions in treatment failure.

HIV multi-drug resistance at first-line antiretroviral failure and subsequent virological response in Asia.

INTRODUCTION: First-line antiretroviral therapy (ART) failure often results from the development of resistance-associated mutations (RAMs). Three patterns, including thymidine analogue mutations (TAMs), 69 Insertion (69Ins) and the Q151M complex, are associated with resistance to multiple-nucleoside reverse transcriptase inhibitors (NRTIs) and may compromise treatment options for second-line ART. METHODS: We investigated patterns and factors associated with multi-NRTI RAMs at first-line failure in patients from The TREAT Asia Studies to Evaluate Resistance - Monitoring study (TASER-M), and evaluated their impact on virological responses at 12 months after switching to second-line ART. RAMs were compared with the IAS-USA 2013 mutations list. We defined multi-NRTI RAMs as the presence of either Q151M; 69Ins; ≥ 2 TAMs; or M184V+≥ 1 TAM. Virological suppression was defined as viral load (VL) <400 copies/ml at 12 months from switch to second-line. Logistic regression was used to analyze (1) factors associated with multi-NRTI RAMs at first-line failure and (2) factors associated with virological suppression after 12 months on second-line. RESULTS: A total of 105 patients from 10 sites in Thailand, Hong Kong, Indonesia, Malaysia and Philippines were included. There were 97/105 (92%) patients harbouring ≥ 1 RAMs at first-line failure, 39/105 with multi-NRTI RAMs: six with Q151M; 24 with ≥ 2 TAMs; and 32 with M184V+≥ 1 TAM. Factors associated with multi-NRTI RAMs were CD4 ≤ 200 cells/µL at genotyping (OR=4.43, 95% CI [1.59-12.37], p=0.004) and ART duration >2 years (OR=6.25, 95% CI [2.39-16.36], p<0.001). Among 87/105 patients with available VL at 12 months after switch to second-line ART, virological suppression was achieved in 85%. The median genotypic susceptibility score (GSS) for the second-line regimen was 2.00. Patients with ART adherence ≥ 95% were more likely to be virologically suppressed (OR=9.33, 95% CI (2.43-35.81), p=0.001). Measures of patient resistance to second-line ART, including the GSS, were not significantly associated with virological outcome. CONCLUSIONS: Multi-NRTI RAMs at first-line failure were associated with low CD4 level and longer duration of ART. With many patients switching to highly susceptible regimens, good adherence was still crucial in achieving virological response. This emphasizes the importance of continued adherence counselling well into second-line therapy.

Prevalence of positive syphilis serology among HIV-infected patients: role for routine screening in Thailand.

Data regarding syphilis screening in resource-limited settings is limited. We aimed to determine the prevalence and associated factors of positive syphilis serology in HIV-infected adult patients in an outpatient setting in Thailand. A cross sectional study was conducted among 178 HIV-infected patients. Ninety-eight patients (55%) were male; then median (interquartile range; IQR) age was 43 (36-49) years. The majority of the patients (84.3%) had a heterosexual risk. Three patients (1.7%) had a positive rapid plasma reagin (RPR) test (range, 1:2 to 1:16), 9 (5%) patients had a positive Treponema pallidum particle agglutination (TPPA) test, and 3 patients (1.7%) had positive results on both tests. On multivariate logistic regression analysis, a pruritic papular eruption [odds ratio (OR) 5.37; 95% confidence interval (CI): 1.09-26.38; p = 0.038], current CD4 cell count (OR 1.22, per 50 cells/mm3; 95% CI: 1.01-1.46; p = 0.035), and using abacavir in the current regimen (OR 59.19; 95% CI: 2.15-1,628.68; p = 0.016) were associated with positive syphilis serology. In conclusion, the prevalence of positive syphilis serology among Thai HIV-infected patients was low. Routine screening for syphilis in HIV-infected patients who are asymptomatic may need to be re-considered at the national level in this resource-limited setting.

Serum antioxidant levels and nutritional status in early and advanced stage lung cancer patients.

OBJECTIVE: Malnutrition frequently occurs in lung cancer patients. We aimed to determine nutritional status and antioxidant and mineral levels in Thai patients with lung cancer. METHODS: A prospective study with matched case-control was conducted. Nutritional status was assessed by body mass index (BMI) and subjective global assessment (SGA). Eastern Cooperative Oncology Group (ECOG) performance status was used to assess the performance. The serum antioxidant and mineral levels were determined. RESULTS: Forty-nine patients with a mean age of 58.8 (range, 35-82) who were first diagnosed with lung cancer were enrolled. They were compared with 60 healthy controls, and levels of retinol, α-tocopherol, ß-carotene, lycopene, ß-cryptoxanthin, selenium, and zinc were lower (P < 0.05). However, peroxidase activity was higher (P = 0.002) in patients. Selenium levels were higher in early stage compared to advanced stage patients (P = 0.041). Overweight patients had higher selenium levels (0.04 mg/L) than normal BMI patients (ß = 0.04, P = 0.035). Patients with SGA class C had lower selenium levels (0.03 mg/L) than those with class A (ß = -0.03, P = 0.035). The poorer ECOG performance patients had significantly lower ß-carotene (ß = -0.192, P = 0.003) and selenium (ß = -0.031, P = 0.011) levels compared with those with good ECOG performance status. CONCLUSIONS: Significantly lower levels of antioxidants and selenium were found in lung cancer patients compared to healthy controls. Levels of some antioxidants and minerals differed among categories of BMI, SGA categories, or ECOG performance status. These findings may be helpful for further studies, such as the effect of nutritional supplementation on clinical outcomes.

Late and low compliance with hepatitis B serology screening among HIV-infected patients in a resource-limited setting: an issue to improve HIV care.

Although hepatitis B serology screening has been recommended for HIV care, it has not been routinely performed. We aimed to assess compliance and timing of hepatitis B serology screening among HIV-infected patients in a resource-limited setting. A cross-sectional study was conducted in Thailand. Compliance, timing of hepatitis B serology screening, and factors associated with no HBsAg screening were determined. A total of 416 HIV-infected patients with 61% males were enrolled. Median (range) age at HIV diagnosis was 34 (16-75) years and 92% had heterosexual risk. Proportion of HBsAg screening and prevalence of positive HBsAg were 69.2% and 9.0%, respectively. There was no difference in the proportion of no HBsAg screening during the period 1990-2008 (p = 0.865). Proportion of anti-HBs and anti-HBc screening were 40.9% and 21.2%, respectively. HBsAg was screened before or on the day of anti-HIV testing in 9.1% and before antiretroviral therapy (ART) initiation in 27.2%. By Kaplan-Meier analysis, median time from anti-HIV testing to HBsAg screening was 55.9 (95% confidence interval [CI] 43.9, 68.3) months. By multivariate logistic regression, duration of HIV infection (odds ratio [OR] 1.14; 95% CI 1.07, 1.21), no anti-HBs screening (OR 1.65; 95% CI 1.4-2.63), and no anti-HCV screening (OR 2.60; 95% CI 1.62, 4.17) were associated with no HBsAg screening before ART initiation. In conclusion, compliance with hepatitis B serology screening was relatively low and late. Educational program regarding hepatitis B serology screening, identification of barriers, and interventions to eliminate these barriers in resource-limited settings are crucial to improve HIV care.

Retrospective evaluation of caspofungin therapy in invasive aspergillosis (RECAM-IA).

To evaluate caspofungin in high-risk invasive aspergillosis (IA) patient, a retrospective review of patient characteristics, antifungal therapies and clinical outcomes on hospitalised patients at sites in Russia, Canada, Germany, and Thailand was performed. Fifty-five patients were included, six with proven and 49 with probable aspergillosis; 76.4% had haematological diseases, 80% were on immunosuppressive drugs, 32.7% were neutropenic at caspofungin initiation. Median duration of prior antifungal therapy was 9 days (range 1-232). Reasons for initiating caspofungin included: disease refractory to first-line antifungal (49.1%) and toxicities with prior antifungals (18.2%). Median caspofungin therapy duration was 14 days (range 2-62), with a median of 13 days (range 1-62) as monotherapy. Favourable responses were observed in 45.5% of the patients, complete responses in 40% and partial responses in 5.5%; 74.5% survived 7 days after completion of caspofungin therapy with 69.1% having been successfully discharged from the hospital. Few patients (14.6%) on caspofungin switched because of suspected resistance, lack of response or adverse events. There were no increases in hospital stay as a result of adverse events or drug-drug interactions related to caspofungin; 7.3% of patients had a mean value of 13 (± 14.11) days of increased stay attributable to treatment failure. Caspofungin was well-tolerated. It exhibited effectiveness and high survival in treating severe IA patients.

Cytomegalovirus, adenovirus, and polyomavirus co-infection among pediatric recipients of allogeneic stem cell transplantation: characteristics and outcome.

ADV and PMV infection have increasingly been documented as significant complications following allo-HSCT. Despite increasing recognition, characteristics and outcome of CMV, ADV, and PMV viral co-infection remain obscured. In this study, a retrospective quantitative PCR analysis of ADV, PMV (BKV and JCV) was performed from pediatric patients' stored blood samples previously tested for CMV viremia after allo-HSCT. Clinical and virological characteristics and outcome among patients with and without viral co-infection were analyzed and compared. From 2001 to 2006, 219 blood samples from 69 patients were studied. Viral DNA was present in 119 samples (52.9%).The proportion of viremia was highest for BKV (30.6%), followed by CMV (20.9%), ADV (9.1%), and JCV (0.5%). Viral co-infection occurred in 17 patients (24.6%), with CMV/BKV as the most common type (11.6%), followed by CMV/ADV (4.3%) and ADV/BKV (2.9%). From multivariate analysis, factors associated with viral co-infection were acute GVHD (OR 4.57; 95% CI 1.9-10.96, p = 0.001), level of blood CMV viral load (OR 1.53; 95% CI 1.24-1.89, p < 0.001), and level of blood ADV viral load (OR 1.56; 95% CI 1.05-2.32, p = 0.027). Higher probability of developing viral disease was strongly associated with more types of virus detected in blood (p < 0.001). Significant difference in the causes of death was observed among patients with and without viral co-infection (p = 0.014). Infection (87.5%) was the major cause of death of patients with viral co-infection, whereas relapse of hematologic disease (70%) was the major cause of death of patients with mono-viral infection. Viral co-infection is a common and significant infectious complication in pediatric recipients of allo-HSCT. Blood monitoring of CMV, ADV, and BKV is suggested among pediatric patients who develop GvHD or who have rising of CMV or ADV viremia following allo-HSCT.

Emerging of HIV drug resistance: epidemiology, diagnosis, treatment and prevention.

Antiretroviral therapy for HIV/AIDS patients are used globally including in resource-limited settings. Successful outcomes are not always observed and HIV resistance to antiretroviral agents is a major cause of treatment failure. Both primary and secondary drug resistance have been described and reported worldwide. Primary resistance, which presumably means that individuals are infected with drug-resistant virus and secondary resistance typically, means a result of treatment failure. Pathogenesis of resistance of each antiretroviral drugs class differs and depends on the mechanism of action of the drugs. Three main laboratory investigations for diagnosis of treatment failure and HIV drug resistance are HIV RNA level, CD4 cell count, and HIV resistance testing. Management concepts for patients with HIV drug resistance are discussed. Strategies for prevention of HIV resistance emergence include finding cases with acute HIV infection, early detection of virological failure, and behavioral interventions such as adherence and condom usage.

Long-term efficacy and safety of first-line therapy with once-daily saquinavir/ritonavir.

BACKGROUND: The aim of this study was to assess the long-term efficacy and safety of first-line treatment with once-daily saquinavir/ritonavir plus two nucleoside reverse transcriptase inhibitors (NRTIs). METHODS: A total of 272 antiretroviral-naive patients with a CD4+ T-cell count of 200-350 cells/mm3 were treated with two NRTIs and saquinavir/ritonavir 1,600/100 mg per day for > 24 weeks. Patients were followed up every 12 weeks for CD4+ T-cell counts, HIV RNA levels, clinical and laboratory toxicities. Intention-to-treat analyses were used for the first 24 weeks of treatment and as-treated analysis after week 24. RESULTS: The median baseline CD4+ T-cell count was 269 cells/mm3 and HIV RNA was 4.7 log10 copies/ml. At a median follow-up time of 56 (interquartile range [IQR] 25-113) weeks, 262/272 (96.3%) had HIV RNA < 400 copies/ml, with a median HIV RNA decline of -2.89 (IQR 3.31--2.37) log10 copies/ml (P < 0.001) and a median rise in CD4+ T-cell count of 192 (IQR 117-317) cells (P < 0.001). At weeks 24, 48, 72 and 96, 249/272 (91.5%), 157/164 (95.7%), 113/126 (89.7%) and 84/90 (93.3%) had HIV RNA < 400 copies/ml, respectively; at the same time points, 83.8%, 92.7%, 85.7% and 85.6% had HIV RNA < 50 copies/ml. Drug-related adverse events were reported in 6.30%. Significant rises in total cholesterol, triglyceride, low-density lipoprotein and high-density lipoprotein were seen. CONCLUSION: First-line highly active antiretroviral therapy with once-daily saquinavir/ritonavir plus two NRTIs showed strong antiviral efficacy.