Factors Associated with All-Cause 30-Day Mortality in Indonesian Inpatient COVID-19 Patients at Cipto Mangunkusumo National General Hospital.

Introduction: Indonesia, as a developing country, has limited data on the factors associated with 30-day mortality in COVID-19 patients in Indonesia. As a matter of fact, study analyzing factors associated with 30-day mortality of COVID-19 infection in Indonesia has never been conducted. This study aims to fill this gap in the literature by conducting a large-scale analysis of factors associated with 30-day mortality in COVID-19 patients in Indonesia. Method: This study employed a single-center retrospective cohort observational design, and was conducted at Cipto Mangunkusumo National General Hospital between the years 2022 and 2023. Sampling was conducted using the consecutive sampling method. The study included patients aged 18 years and above who had been confirmed to have COVID-19 infection. Survival analysis was conducted using Kaplan-Meier and multivariate Cox regression analysis. Result: Our study included a total of 644 patients, with 120 patients (18.6%) expiring within 30 days. In the multivariate analysis using the backward Wald method, severe COVID-19 (HR: 7.024; 95% CI: 3.971-12.744; p value: <0.0001), moderate COVID-19 infection (HR: 1.660; 95% CI: 1.048-2.629; p value: 0.031), liver cirrhosis (HR: 3.422; 95% CI: 1.208-9.691; p value: 0.021), female sex (HR: 1.738; 95% CI: 1.187-2.545; p value: 0.004), old age (HR: 2.139; 95% CI: 1.279-3.577; p value: 0.004), high leukocyte (HR: 11.502; 95% CI: 1.523-86.874; p value: 0.018), high NLR (HR: 1.720; 95% CI: 1.049-2.819; p value: 0.032), high CRP (HR: 1.906; 95% CI: 1.092-3.329; p value: 0.023), high procalcitonin (HR: 3.281; 95% CI: 1.780-6.049; p value: 0.001), and high creatinine (HR: 1.863; 95% CI: 1.240-2.800; p value: 0.003) were associated with 30-day mortality from COVID-19 infection. Subgroup analysis excluding cancer patients showed that age, D-Dimer, CRP, and PCT were associated with 30-day mortality in COVID-19 patients, while steroid therapy is protective. Conclusions: This study finds that COVID-19 severity, liver cirrhosis, sex, age, leukocyte, NLR, CRP, creatinine, and procalcitonin were associated with COVID-19 mortality within 30 days. These findings underscore the multifactorial nature of COVID-19 infection mortality. It is important, therefore, that patients which exhibit these factors should be treated more aggressively to prevent mortality.

Clinical presentation, management, and outcome of suspected central nervous system infections in Indonesia: a prospective cohort study.

BACKGROUND: Little is known about the etiology, clinical presentation, management, and outcome of central nervous system (CNS) infections in Indonesia, a country with a high burden of infectious diseases and a rising prevalence of HIV. METHODS: We included adult patients with suspected CNS infections at two referral hospitals in a prospective cohort between April 2019 and December 2021. Clinical, laboratory, and radiological assessments were standardized. We recorded initial and final diagnoses, treatments, and outcomes during 6 months of follow-up. RESULTS: Of 1051 patients screened, 793 were diagnosed with a CNS infection. Patients (median age 33 years, 62% male, 38% HIV-infected) presented a median of 14 days (IQR 7-30) after symptom onset, often with altered consciousness (63%), motor deficits (73%), and seizures (21%). Among HIV-uninfected patients, CNS tuberculosis (TB) was most common (60%), while viral (8%) and bacterial (4%) disease were uncommon. Among HIV-infected patients, cerebral toxoplasmosis (41%) was most common, followed by CNS TB (19%), neurosyphilis (15%), and cryptococcal meningitis (10%). A microbiologically confirmed diagnosis was achieved in 25% of cases, and initial diagnoses were revised in 46% of cases. In-hospital mortality was 30%, and at six months, 45% of patients had died, and 12% suffered from severe disability. Six-month mortality was associated with older age, HIV, and severe clinical, radiological and CSF markers at presentation. CONCLUSION: CNS infections in Indonesia are characterized by late presentation, severe disease, frequent HIV coinfection, low microbiological confirmation and high mortality. These findings highlight the need for earlier disease recognition, faster and more accurate diagnosis, and optimized treatment, coupled with wider efforts to improve the uptake of HIV services.

Incidence and Clearance of Anal Human Papillomavirus Infection in 16 164 Individuals, According to Human Immunodeficiency Virus Status, Sex, and Male Sexuality: An International Pooled Analysis of 34 Longitudinal Studies.

BACKGROUND: Understanding the natural history of anal high-risk human papillomavirus (hrHPV) infection is key for designing anal cancer prevention programs but has not been systematically characterized. METHODS: We reanalyzed data from 34 studies including 16 164 individuals in 6 risk groups defined by human immunodeficiency virus (HIV) status, sex, and male sexuality: men who have sex with men (MSM) and people with HIV (MSMWH), HIV-negative MSM, women with HIV (WWH), HIV-negative women, men who have sex with women (MSW) with HIV (MSWWH), and HIV-negative MSW. We used Markov models to estimate incidence and clearance of 13 hrHPV types and their determinants. RESULTS: Human papillomavirus (HPV) 16 had the highest incidence-clearance ratio of the hrHPV types. MSMWH had the highest hrHPV incidence (eg, 15.5% newly HPV-16 infected within 2 years), followed by HIV-negative MSM (7.5%), WWH (6.6%), HIV-negative women (2.9%), MSWWH (1.7%), and HIV-negative MSW (0.7%). Determinants of HPV-16 incidence included HIV status and number of sexual partners for MSM, women, and MSW, and anal sex behavior for MSM only. HPV-16 clearance was lower for people with HIV (PWH) and lower for prevalent than incident infection. Among MSM, increasing age was associated with lower clearance of prevalent, but not incident, HPV-16 infection. CONCLUSIONS: This robust and unifying analysis of anal hrHPV natural history is essential to designing and predicting the impact of HPV vaccination and HPV-based screening programs on anal cancer prevention, particularly in MSM and PWH. Importantly, it demonstrates the higher carcinogenic potential of longstanding anal prevalent hrHPV infection than more recent incident infection.

Ramadan fasting reduces high-sensitivity C-reactive protein among HIV-infected patients receiving antiretroviral therapy.

Background: Inflammatory conditions and oxidative stress increase in HIV infection, and inflammation increases the risk of cardiovascular disease. Ramadan fasting is known to reduce inflammation and oxidative stress in diabetic patients. This study examined the effects of Ramadan fasting on high-sensitivity C-reactive protein (hs-CRP) levels and total antioxidant status (TAOS) in HIV patients on antiretroviral therapy (ART). Methods: This was a prospective cohort study comparing HIV-infected patients on stable ART who fasted throughout Ramadan to HIV-infected patients who did not fast during Ramadan. Inclusion criteria were men aged 20-40 years, taking first-line ART for at least 6 months, Muslims intent to fast for Ramadan, no current hospitalization because of acute conditions and not being treated for opportunistic infections. Results: After 2 weeks, hs-CRP had decreased significantly in the fasting group (-0.41 mg/L [IQR = -1; 0.10]) compared to the non-fasting group (0.20 mg/L [IQR = -0.30; 1.50]) (p = 0.004). The linear regression analysis has shown that Ramadan fasting contributed to 10.10% of the variance in hs-CRP value (R 2 = 0.101) and decreased its value by 0.317 points (B = -0.317). Changes in TAOS did not significantly different (p = 0.405) between the fasting group (0.05 mmol/L [IQR = -0.03; 0.12]) and the non-fasting group (0.04 mmol/L [IQR = -0.13; 0.36]). In the fasting group, there were significant changes in polyunsaturated fatty acid consumption (p = 0.029), body weight (p = 0.001), cigarette smoking (p = 0.001), and sleeping duration (p = 0.001). Conclusion: Ramadan fasting reduces hs-CRP concentrations among HIV patients on ART.

COVID Arm After Moderna Booster in Healthcare Worker: A Case Report.

SARS CoV-2 virus has infected more than 200 million people worldwide and more than 4.4 million in Indonesia. The vaccination program has become one of the solutions launched by many countries globally, including Indonesia, to reduce the transmission rate of COVID-19. Various vaccination platforms are produced, such as inactivated, viral vector, mRNA, and protein subunit. The vaccination booster program with mRNA platform (Moderna) was launched by the Indonesian government to give better protection for health care workers, particularly from delta variant. In this case report, we discuss one of the typical side effects of Moderna vaccine, which is referred to as the COVID arm.

Epidemiology of anal human papillomavirus infection and high-grade squamous intraepithelial lesions in 29 900 men according to HIV status, sexuality, and age: a collaborative pooled analysis of 64 studies.

BACKGROUND: Robust age-specific estimates of anal human papillomavirus (HPV) and high-grade squamous intraepithelial lesions (HSIL) in men can inform anal cancer prevention efforts. We aimed to evaluate the age-specific prevalence of anal HPV, HSIL, and their combination, in men, stratified by HIV status and sexuality. METHODS: We did a systematic review for studies on anal HPV infection in men and a pooled analysis of individual-level data from eligible studies across four groups: HIV-positive men who have sex with men (MSM), HIV-negative MSM, HIV-positive men who have sex with women (MSW), and HIV-negative MSW. Studies were required to inform on type-specific HPV infection (at least HPV16), detected by use of a PCR-based test from anal swabs, HIV status, sexuality (MSM, including those who have sex with men only or also with women, or MSW), and age. Authors of eligible studies with a sample size of 200 participants or more were invited to share deidentified individual-level data on the above four variables. Authors of studies including 40 or more HIV-positive MSW or 40 or more men from Africa (irrespective of HIV status and sexuality) were also invited to share these data. Pooled estimates of anal high-risk HPV (HR-HPV, including HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68), and HSIL or worse (HSIL+), were compared by use of adjusted prevalence ratios (aPRs) from generalised linear models. FINDINGS: The systematic review identified 93 eligible studies, of which 64 contributed data on 29 900 men to the pooled analysis. Among HIV-negative MSW anal HPV16 prevalence was 1·8% (91 of 5190) and HR-HPV prevalence was 6·9% (345 of 5003); among HIV-positive MSW the prevalences were 8·7% (59 of 682) and 26·9% (179 of 666); among HIV-negative MSM they were 13·7% (1455 of 10 617) and 41·2% (3798 of 9215), and among HIV-positive MSM 28·5% (3819 of 13 411) and 74·3% (8765 of 11 803). In HIV-positive MSM, HPV16 prevalence was 5·6% (two of 36) among those age 15-18 years and 28·8% (141 of 490) among those age 23-24 years (ptrend=0·0091); prevalence was 31·7% (1057 of 3337) among those age 25-34 years and 22·8% (451 of 1979) among those age 55 and older (ptrend<0·0001). HPV16 prevalence in HIV-negative MSM was 6·7% (15 of 223) among those age 15-18 and 13·9% (166 of 1192) among those age 23-24 years (ptrend=0·0076); the prevalence plateaued thereafter (ptrend=0·72). Similar age-specific patterns were observed for HR-HPV. No significant differences for HPV16 or HR-HPV were found by age for either HIV-positive or HIV-negative MSW. HSIL+ detection ranged from 7·5% (12 of 160) to 54·5% (61 of 112) in HIV-positive MSM; after adjustment for heterogeneity, HIV was a significant predictor of HSIL+ (aPR 1·54, 95% CI 1·36-1·73), HPV16-positive HSIL+ (1·66, 1·36-2·03), and HSIL+ in HPV16-positive MSM (1·19, 1·04-1·37). Among HPV16-positive MSM, HSIL+ prevalence increased with age. INTERPRETATION: High anal HPV prevalence among young HIV-positive and HIV-negative MSM highlights the benefits of gender-neutral HPV vaccination before sexual activity over catch-up vaccination. HIV-positive MSM are a priority for anal cancer screening research and initiatives targeting HPV16-positive HSIL+. FUNDING: International Agency for Research on Cancer.

Hepatitis C continuum of care: Experience of integrative hepatitis C treatment within a human immunodeficiency virus clinic in Indonesia.

INTRODUCTION: Direct-acting antiviral drugs (DAAs) have changed the paradigm of hepatitis C therapy for both HCV/HIV co-infected and HCV mono-infected patients. We aimed to describe the HCV continuum of care of HIV-infected patients treated in an HIV clinic after a free DAA program in Indonesia and identify factors correlated with sofosbuvir-daclatasvir (SOF-DCV) treatment failure. METHODS: We did a retrospective cohort study of adult HIV/HCV co-infected patients under routine HIV-care from November 2019 to April 2020 in the HIV integrated clinic of Cipto Mangunkusumo Hospital, Jakarta, Indonesia. We evaluated some factors correlated with sofosbuvir-daclatasvir treatment failure: gender, diabetes mellitus, previous IFN failure, cirrhosis, concomitant ribavirin use, high baseline HCV-RNA, and low CD4 cell count. RESULTS AND DISCUSSION: Overall, 640 anti-HCV positive patients were included in the study. Most of them were male (88.3%) and former intravenous drug users (76.6%) with a mean age of 40.95 (SD 4.60) years old. Numbers and percentages for the stages of the HCV continuum of care were as follows: HCV-RNA tested (411; 64.2%), pre-therapeutic evaluation done (271; 42.3%), HCV treatment initiated (210; 32.8%), HCV treatment completed (207; 32.2%), but only 178 of these patients had follow-up HCV-RNA tests to allow SVR assessment; and finally SVR12 achieved (178; 27.8%). For the 184 who completed SOF-DCV treatment, SVR12 was achieved by 95.7%. In multivariate analysis, diabetes mellitus remained a significant factor correlated with SOF-DCV treatment failure (adjusted RR 17.0, 95%CI: 3.28-88.23, p = 0.001). CONCLUSIONS: This study found that in the HCV continuum of care for HIV/HCV co-infected patients, gaps still exist at all stages. As the most commonly used DAA combination, sofosbuvir daclatasvir treatment proved to be effective and well-tolerated in HIV/HCV co-infected patients. Diabetes mellitus was significant factor correlated with not achieving SVR12 in this population.

Impact of sofosbuvir and daclastavir on health-related quality of life in patients co-infected with hepatitis C and human immunodeficiency virus.

BACKGROUND: We conducted a real-life study of health-related quality of life (HRQoL) transformation before and 12 weeks after sofosbuvir and daclatasvir therapy in HCV/HIV co-infected patients. Factors related to the significant changes of each HRQoL domain/item were also evaluated. METHODS: A prospective study was performed in the HIV integrated clinic at Cipto Mangunkusumo Hospital, Jakarta. HCV/HIV co-infected patients who started sofosbuvir and daclatasvir from government free DAA program in 2017-2019. WHOQoL-HIV BREF and RAND SF-36 questionnaires were recorded at baseline and post-treatment week 12. RESULTS: 145 patients with mean age of 37.8 years (SD = 4.2) were included in the analysis. Most of patients were male (89%), previous IVDU (89%), active smoker (50.4%) and non-cirrhosis (80%). SVR12 was achieved in 95.5% of patients. Sofosbuvir and daclatasvir treatments showed positive impacts on 2 domains and 2 other items of WHOQoL-HIV BREF and 2 domains and 1 item of SF-36. Predicting factors of significant increase in each domain/item were: male and normal body mass index (BMI) for level of independence (RR 4.01,95% CI 1.09-14.74 and 4.80,95% CI 1.79-12.81); higher HCV-RNA for overall perception of QoL (RR 0.42,95% CI 0.18-0.94); non-smoking status for overall perception of health (RR 0.32,95% CI 0.15-0.66); male and fibrosis stage 0-1 for general health (RR 6.21,95% CI 1.69-22.88 and 2.86,95% CI 1.16-7.00); and the use of NNRTI-based ART (RR 5.23, 95% CI 1.16-23.65). Spiritual/personal belief decline was predicted by non-smoking status (RR 0.46, 95% CI 0.23-0.95). Treatment success was not associated with any changes of HR-QoL domain/item. CONCLUSIONS: HCV/HIV co-infected patients were successfully treated with sofosbuvir and daclatasvir and experienced improvement of HRQoL 12 weeks after treatment completion.

Talaromycosis clinically and histopathologically mimicking histoplasmosis in an immunocompromised patient.

Talaromycosis is caused by the dimorphic fungus Talaromyces marneffei (formerly Penicillium marneffei) endemic in South and Southeast Asia. Its clinical similarity with other dimorphic fungal infections (sometimes) make the diagnosis challenging. We report an immunocompromised patient with talaromycosis mimicking histoplamosis. A 26-year-old HIV-positive man had suffered from rashes over the face, trunk, and extremities for three months. His physical examination showed centrally necrotic, ulcerated papules and nodules. A biopsied papule revealed granulomas containing numerous oval, yeast-like cells, some displaying central septation. Saboraud agar culture grew mold with diffuse red pigment consistent with T. marneffei. Careful histopathological examination and microbiological culture are important for the accurate diagnosis of fungal infections.

Incidence, clearance, persistence and factors related with high-risk anal HPV persistence in South-East Asian MSM and transgender women.

OBJECTIVES: Persistent anal high-risk human papillomavirus (HR-HPV) infection is a major risk factor for anal cancer among MSM and transgender women (TGW). We aimed to estimate incidence, clearance, and persistence of anal HR-HPV in HIV-positive and HIV-negative MSM and TGW, and to assess factors for HR-HPV persistence. DESIGN: Prospective cohort study. METHODS: MSM and TGW aged at least 18 years, were enrolled from Indonesia, Malaysia, and Thailand, then followed up 6-monthly for 12 months. Anal swabs were collected at every visit for HR-HPV genotypes to define anal HR-HPV incidence, clearance, and persistence. Logistic regression was used to evaluate factors associated with HR-HPV persistence. RESULTS: Three hundred and twenty-five MSM and TGW were included in this study, of whom 72.3% were HIV-positive. The incidence of anal HR-HPV persistence was higher in HIV-positive than HIV-negative MSM participants (28.4/1000 vs. 13.9/1000 person-months). HIV-positive participants had HR-HPV lower clearance rate than HIV-negative participants (OR 0.3; 95% CI 0.1-0.7). The overall persistence of HR-HPV was 39.9% in HIV-positive and 22.8% HIV-negative participants. HPV-16 was the most persistent HR-HPV in both HIV-positive and HIV-negative participants. HIV infection (aOR 2.87; 95% CI 1.47-5.61), living in Kuala Lumpur (aOR 4.99; 95% CI 2.22-11.19) and Bali (aOR 3.39; 95% CI 1.07-10.75), being employed/freelance (aOR 3.99; 95% CI 1.48-10.77), and not being circumcised (aOR 2.29; 95% CI 1.07-4.88) were independently associated with anal HR-HPV persistence. CONCLUSION: HIV-positive MSM and TGW had higher risk of persistent anal HR-HPV infection. Prevention program should be made available and prioritized for HIV-positive MSM and TGW where resources are limited.

Diagnostic performance of APRI and FIB-4 for confirming cirrhosis in Indonesian HIV/HCV co-infected patients.

BACKGROUND: After successful of antiretroviral therapy, highly effective direct acting antiviral (DAA) make HCV elimination reasonable in HIV/HCV co-infected patients. However, in achieving this target, there are still barriers to start DAA treatment, particularly in the area of liver fibrosis assessment that determine the duration of therapy. We aimed to assess the diagnostic performance of APRI and FIB-4 for diagnosing cirrhosis in HIV/HCV co-infected patients using hepatic transient elastography (TE) as gold standard. METHOD: This is a retrospective study on HIV/HCV co-infected patients who concomitantly performed hepatic TE measurement, APRI, and FIB-4 evaluation before HCV treatment initiation at a tertiary hospital in Jakarta from 2014 to 2019. Sensitivity, specificity and diagnostic accuracy of indirect biomarkers for liver stiffness measurement (LSM) ≥ 12.5 kPa was determined by receiver operator characteristics curves. RESULTS: 223 HIV/HCV co-infected patients on stable antiretroviral therapy were included, of whom 91.5% were male with mean age of 37 (SD 5) years. Only 28.7% of patients were classified as cirrhosis (F4). Using TE as gold standard (≥12.5 kPa), the low threshold of APRI (1) had specificity 95%, sensitivity 48.4%, correctly classified 81.6% of patients, with moderate performance, AUC at 0.72 (95% CI 0.63-0.80). The optimal cut-off of FIB-4 was 1.66 [specificity 92.5%, sensitivity 53.1%, AUC at 0.73 (95% CI 0.65-0.81)] and correctly classified 81.1% of the patients. CONCLUSION: APRI score ≥ 1 and FIB-4 score ≥ 1.66 had moderate performance with high specificity in diagnosing cirrhosis. These biochemical markers could be used while TE is not available.

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.

A novel diagnosis scoring model to predict invasive pulmonary aspergillosis in the intensive care unit.

OBJECTIVES: To improve the quality of invasive pulmonary aspergillosis (IPA) management for intensive care unit (ICU) patients using a practical diagnostic scoring model. METHODS: This nested case-control study aimed to determine the incidence of IPA in 405 ICU patients, between July 2012 and June 2014, at 6 hospitals in Jakarta, Indonesia. Phenotypic identifications and galactomannan (GM) tests of sera and lung excreta were performed in mycology laboratory, Parasitology Department, Faculty of Medicine, Universitas Indonesia in Jakarta, Indonesia. RESULTS: The incidence of IPA in the ICUs was 7.7% (31 of 405 patients). A scoring model used for IPA diagnosis showed 4 variables as the most potential risk factors: lung excreta GM index (score 2), solid organ malignancy (score 2), pulmonary tuberculosis (score 2), and systemic corticosteroids (score 1). Patients were included in a high-risk group if their score was greater than 2, and in a low-risk group if their score was less than 2. CONCLUSION: This study provides a novel diagnosis scoring model to predict IPA in ICU patients. Using this model, a more rapid diagnosis and treatment of IPA may be possible. The application of the diagnosis scoring should be preceded by specified pre-requisites.

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.

Presentation, etiology, and outcome of brain infections in an Indonesian hospital: A cohort study.

BACKGROUND: Little detailed knowledge is available regarding the etiology and outcome of CNS infection, particularly in HIV-infected individuals, in low-resource settings. METHODS: From January 2015 to April 2016, we prospectively included all adults with suspected CNS infection in a referral hospital in Jakarta, Indonesia. Systematic screening included HIV testing, CSF examination, and neuroimaging. RESULTS: A total of 274 patients with suspected CNS infection (median age 26 years) presented after a median of 14 days with headache (77%), fever (78%), seizures (27%), or loss of consciousness (71%). HIV coinfection was common (54%), mostly newly diagnosed (30%) and advanced (median CD4 cell count 30/µL). Diagnosis was established in 167 participants (65%), including definite tuberculous meningitis (TBM) (n = 44), probable TBM (n = 48), cerebral toxoplasmosis (n = 48), cryptococcal meningitis (n = 14), herpes simplex virus/varicella-zoster virus/cytomegalovirus encephalitis (n = 10), cerebral lymphoma (n = 1), neurosyphilis (n = 1), and mucormycosis (n = 1). In-hospital mortality was 32%; 6-month mortality was 57%. The remaining survivors had either moderate or severe disability (36%) according to Glasgow Outcome Scale. CONCLUSION: In this setting, patients with CNS infections present late with severe disease and often associated with advanced HIV infection. Tuberculosis, toxoplasmosis, and cryptococcosis are common. High mortality and long-term morbidity underline the need for service improvements and further study.

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.

Prevalence of and risk factors for anal high-risk HPV among HIV-negative and HIV-positive MSM and transgender women in three countries at South-East Asia.

This study aimed to assess the prevalence of and associated risk factors for anal high-risk human papillomavirus (hr-HPV) infection among men who have sex with men (MSM) and transgender women (TGW) in Indonesia, Thailand, and Malaysia.This was baseline data from a prospective cohort study with clinic sites in Jakarta and Bali (Indonesia), Bangkok (Thailand), and Kuala Lumpur (Malaysia).MSM and TGW aged 18 years and older from Indonesia, Thailand, and Malaysia were enrolled. Demographic and behavioral characteristics were assessed, and anal samples were collected for HPV genotyping. Multivariate logistic regression models were used to assess risk factors for anal hr-HPV overall and among HIV-positive participants.A total of 392 participants were enrolled, and 48 were TGW. As many as 245 were HIV-positive, and 78.0% of the participants were on combination antiretroviral therapy (cART). Median CD4 count was 439 cells/mm and 68.2% had undetectable HIV-RNA. HIV-positive participants had significantly more hr-HPV compared to HIV-negative participants (76.6% vs 53.5%, P < .001). HPV-16 was the most common high-risk type (20%), whereas HPV-33, -39, and -58 were significantly more common among HIV-positive participants. HIV-positive participant significantly associated with anal hr-HPV infection compared with HIV-negative (OR: 2.87, 95% CI: 1.76-4.70, P ≤ .001), whereas among HIV-positive participants transgender identity had lower prevalence of hr-HPV infection (OR: 0.42, 95% CI: 0.19-0.91, P = .03).High-risk HPV infection was very common among MSM and TGW in South-East Asia. Overall, HIV-infection, regardless of cART use and immune status, significantly increased the risk, while among HIV-positive participants transgender identity seemed to decrease the risk of anal hr-HPV.

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.

Increased proportions of dendritic cells and recovery of IFNγ responses in HIV/HCV co-infected patients receiving ART.

Dendritic cell (DC) numbers and functions can be affected by HIV and HCV disease, but the effects of antiretroviral therapy (ART) on DC and the implications of these changes are unclear. We examined circulating DC in samples from Indonesian patients beginning ART with advanced HIV disease and documented mild/moderate HCV hepatitis. Frequencies of myeloid and plasmacytoid DC increased after 6 months on ART, but frequencies of DC producing IL-12 or IFNα following stimulation with TLR agonists (CL075, CpG) did not change. IFNγ responses to CL075, HCV and other antigens rose over this period. Hence increased IFNγ responses during ART may be associated with increased DC frequencies rather than changes in their functional capacity.