Efficacy and safety of abacavir/lamivudine plus rilpivirine as a first-line regimen in treatment-naïve HIV-1 infected adults.

BACKGROUND: The anti-retroviral combination of abacavir/lamivudine plus rilpivirine (ABC/3TC/RPV) is not recommended by international guidelines as the first-line regimen. However, it is potent, well-tolerated, and affordable, especially in resource-limited settings. This study evaluates the efficacy and safety of ABC/3TC/RPV as an initial regimen for treatment-naïve HIV-1 infected patients. METHODS: A retrospective study was conducted in the largest HIV care centre in Singapore, with data collected June 2011 to September 2017. All treatment-naïve HIV-1 infected adults prescribed ABC/3TC as part of their initial anti-retroviral therapy regimen were included. The third drug was a non-nucleoside reverse-transcriptase inhibitor (NNRTI) such as RPV or efavirenz (EFV), or boosted protease-inhibitor (PI). Patients were followed up for 48 weeks. The primary end-point was the percentage of patients achieving virologic suppression, analysed using on-treatment analysis. Secondary outcomes included CD4-count change, treatment discontinuation and treatment-related adverse events. RESULTS: 170 patients were included in the study, 66 patients in the RPV group, 104 patients in the comparator group (EFV or boosted PI). 96% (n = 24) in the RPV group and 87% (n = 26) in the comparator group achieved viral suppression at 48 weeks (p = 0.28). Median (interquartile range) time to viral suppression was similar: 17 (14-24) weeks in the RPV group, and 21 (13-26) weeks in the comparator group. There were no statistically significant differences in the CD4 count between the two groups. 14% (n = 9) of patients on RPV discontinued treatment before 48 weeks, compared to 30% (n = 31) from the comparator group (p = 0.053). Of these, 23 discontinuations were due to drug adverse effects, and only 1 attributed to RPV (p < 0.01). One patient in each group had virologic failure. CONCLUSION: RPV is effective, safe and considerably more tolerable than compared to NNRTI or boosted PI in ABC/3TC-containing regimens for treatment-naïve patients. It offers an affordable and attractive option, especially in resource-limited settings.

Syphilis Masquerading As Mass Lesions: The Utility of Modern-Day Imaging and Molecular Sequencing in Clinical Diagnosis.

Syphilis has been known to present in a myriad of symptoms throughout the ages, and until this day, the diagnosis remains elusive to the modern physician. We present 2 unusual cases of syphilis that posed diagnostic challenges even in the current era of new and advancing diagnostic tests.

Reducing hypersensitivity reactions with HLA-B*5701 genotyping before abacavir prescription: clinically useful but is it cost-effective in Singapore?

AIM: Abacavir (ABC) is one of the more affordable antiretroviral drugs used for controlling HIV. Although with similar efficacy to current first-line drugs, its limited usage in Singapore can be attributed to its possible side effect of adverse hypersensitivity reactions (HSRs). HLA-B*5701 genotyping is a clinically relevant procedure for avoiding abacavir-induced HSRs. As patients who do not carry the risk allele are unlikely to develop HSRs, a simple rule can be developed to allow abacavir prescription for patients who are B*5701 negative. Here, we carry out a cost-effectiveness analysis of HLA-B*5701 genotyping before abacavir prescription in the context of the Singapore healthcare system, which caters predominantly to Han Chinese, Southeast-asian Malays, and South-asian Indians. In addition, we aim to identify the most cost-effective treatment regimen for HIV patients. METHODS: A decision tree model was developed in TreeAge. The model considers medical treatment and genotyping costs, genotyping test characteristics, the prevalence of the risk allele, reduction in the quality of life, and increased expenditure due to side effects and other factors, evaluating independently over early-stage and late-stage HIV patients segmented by drug contraindications. RESULTS: The study indicates that genotyping is not cost-effective for any ethnicity irrespective of the disease stage, except for Indian patients with early-stage HIV who are contraindicated to tenofovir. CONCLUSION: Abacavir (as first-line) without genotyping is the cheapest and most cost-effective treatment for all ethnicities except for early-stage Indian HIV patients contraindicated to tenofovir. The HLA-B*5701 frequency, the mortality rate from abacavir-induced HSRs, and genotyping costs are among the major factors influencing the cost-effectiveness.

Nonsurgical management of mitral valve endocarditis due to Cardiobacterium valvarum in a patient with a ventricular septal defect.

Cardiobacterium valvarum is a relatively novel agent of infective endocarditis. We describe the first case of infective endocarditis due to this pathogen in the Asian Pacific. This case is unique in its involvement of the mitral valve as well as its clinical resolution exclusively resulting from treatment with antibiotics without resorting to valve replacement/explantation.

Naturally acquired human Plasmodium knowlesi infection, Singapore.

We report a case of naturally acquired Plasmodium knowlesi in Singapore, a malaria-free country. Diagnosis was confirmed by PCR with validated species-specific primers. In industrialized countries, free-ranging primates are a potential source of P. knowlesi human infection. P. knowlesi infection is a differential diagnosis of febrile illness acquired in Singapore.

Healthcare workers and HIV health issues.

Should healthcare workers (HCWs) be routinely tested for HIV? The authors reviewed the literature on the risk and incidence of HIV transmission from HCW to patients and offer recommendations for HIV testing in HCWs in Singapore. Management of HCWs who are tested seropositive for HIV infection is also discussed in this paper.

An Unusual Case of Mycotic Popliteal Aneurysm Presenting as Recurrent Salmonella enteritidis Bacteraemia.

We describe a patient with a Salmonella enteritidis mycotic aneurysm. A 91-year-old man presented with recurrent episodes of S. enteritidis bacteraemia 2 months apart. During the second presentation, he underwent magnetic resonance imaging of the left lower limb that revealed rupture of the popliteal artery with a popliteal fossa collection. This was aspirated and cultures grew S. enteritidis. He underwent endovascular stenting and received a prolonged course of antibiotics. Popliteal artery mycotic aneurysm should be considered as a differential in patients presenting with unilateral painful leg swelling and bacteraemia from microorganisms with a propensity for endovascular infections. LEARNING POINTS: Our case illustrates a rare and unusual entity of ruptured popliteal mycotic aneurysm in an otherwise common scenario of recurrent nontyphoidal salmonellosis.In patients with recurrent Salmonella bacteraemia, clinicians often perform computed tomography scans to look for extraintestinal sites of involvement; however, this frequently misses any peripherally sited aneurysms, which often do not manifest with any early clinical symptoms.

Cluster of Staphylococcus aureus and dengue co-infection in Singapore.

INTRODUCTION: Singapore saw a resurgence of dengue infections in 2005. Concurrent bacterial co-infections in dengue is rare. CLINICAL PICTURE: We report a cluster of serious methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia or severe soft tissue infection in 5 epidemiologically linked construction workers presenting with dengue and non-resolving fever. TREATMENT: Surgical intervention was indicated in 4 of the 5 patients despite appropriate antistaphylococcal therapy. OUTCOME: All but 1 patient were eventually discharged. Clonality and Panton-Valentine leucocidin genes were not demonstrated. Epidemiological investigations suggested that occupational contact dermatitis could have predisposed the patients to this opportunistic co-infection. CONCLUSION: Clinicians need to be vigilant to unusual manifestations of dengue which may signal a concomitant aetiology.

Differences in clinical and psychiatric outcomes between prevalent HIV-1 molecular subtypes in a multiethnic Southeast Asian sample.

OBJECTIVE: In Southeast Asia, subtypes B and CRF01_AE are the prevalent human immunodeficiency virus-1 (HIV-1) subtypes. This study examines the intersubtype differences in clinical indicators and psychiatric symptoms in a multiethnic sample. METHODS: The study site was a national HIV treatment center. Data were extracted from the Molecular Epidemiology Research study and the HIV-Psychiatry Integrated Mental Health Project, and analyzed according to groups defined by viral subtype. RESULTS: Of 177 subjects, 54.8% were infected with subtype CRF01_AE; 42.9% screened positive on the Hospital Anxiety and Depression Scale (HADS). The CRF01_AE group was significantly older (mean 38.29 years vs. 34.62 years, P=.031) and had advanced immunosuppression (CD4 <200) just prior to HADS screening (33.0% vs. 13.5%, P=.003). By multivariate logistic regression, homosexual transmission [odds ratio (OR) 0.388, 95% confidence interval (CI) 0.158-0.951, P=.038], subtype CRF01_AE (OR 2.898, 95% CI 1.199-7.001, P=.018) and positive HADS screening (OR 2.859, 95% CI 1.261-8.484, P=.012) were associated with advanced immunosuppression; and only advanced immunosuppression was associated with screening positive on the HADS (OR 3.270, 95% CI 1.299-8.227, P=.012). CONCLUSION: Subtype CRF01_AE is associated with advanced immunosuppression but not with symptoms of anxiety and depression. The results suggest that psychiatric symptoms are associated with advanced HIV disease regardless of subtype.

Severe acute respiratory syndrome and pulmonary tuberculosis.

In Singapore, of 236 patients with probable severe acute respiratory syndrome (SARS), 2 were coinfected with tuberculosis, a phenomenon not previously reported. The patients' tuberculosis episodes only came to light after full recovery from SARS, when they presented with persistent respiratory symptoms and/or worsening chest radiography findings.

Large artery ischaemic stroke in severe acute respiratory syndrome (SARS).

Of the 206 patients who contracted Severe Acute Respiratory Syndrome (SARS) in Singapore five developed large artery cerebral infarctions. Four patients were critically-ill and three died. Intravenous immunoglobulin was given to three patients. An increased incidence of deep venous thrombosis and pulmonary embolism was also observed among the critically-ill patients. We believe our experience warrants an increased vigilance against stroke and other thrombotic complications among critically-ill SARS patients in future outbreaks, especially if treatment such as intravenous immunoglobulin, that increases pro-thrombotic tendency, is contemplated.

Risk factors and time-trends of cytomegalovirus (CMV), syphilis, toxoplasmosis and viral hepatitis infection and seroprevalence in human immunodeficiency virus (HIV) infected patients.

INTRODUCTION: Chronic bacterial, viral and parasitic infections contribute to the morbidity and mortality associated with human immunodeficiency virus (HIV) infection. This study investigated risk factors and time-trends of the seroprevalence of cytomegalovirus (CMV), toxoplasmosis and hepatitis A total antibody; and co-infection with syphilis, hepatitis B and hepatitis C among newly diagnosed HIV individuals in Singapore. MATERIALS AND METHODS: This was a cross-sectional study. A random sample of 50% of HIV infected patients who visited the Communicable Disease Centre (CDC), Singapore for first-time care from January 2006 to December 2011 were analysed. RESULTS: Among the 793 study subjects, 93.4% were male; 77.9% of them were of Chinese ethnicity; mean age at HIV diagnosis was 41.4 years; and the mean baseline CD4+ T-cell count was 222 cells/mm³. The prevalence of sero-reactivity for CMV was 96.8%; hepatitis A: 40.9%; and toxoplasmosis: 23.7%. Co-infection with syphilis was identified in 12.3%; hepatitis B: 8.1%; and hepatitis C: 2%. Among those co-infected with hepatitis C, 73.3% of them were intravenous drug user (IVDU). Syphilis co-infection was significantly more common among men who have sex with men (MSM) (multivariate OR: 2.53, 95% CI, 1.31 to 4.90, P = 0.006). CONCLUSION: This study described the baseline rates of HIV co-infection with syphilis, hepatitis B and C in Singapore, and sero-reactivity to CMV, toxoplasmosis and hepatitis A. The increased rates compared to the general population may have important consequences for disease progression, response to antiretroviral treatment and long-term general health.

Causes of death in hospitalised HIV-infected patients at a National Referral Centre in Singapore: a retrospective review from 2008 to 2010.

INTRODUCTION: Highly active antiretroviral therapy (HAART) has improved outcomes for individuals infected with human immunodeficiency virus (HIV). This study describes the causes of death in hospitalised HIV-positive patients from 2008 to 2010 in Tan Tock Seng Hospital, the national referral centre for HIV management in Singapore. MATERIALS AND METHODS: Data were retrospectively collected from HIV-positive patients who died in Tan Tock Seng Hospital from January 2008 to December 2010. RESULTS: Sixty-seven deaths occurred in the study period. A majority of patients died of non-acquired immune deficiency syndrome (AIDS)-defining illnesses (54.7%). The median CD4 count was 39.5 (range, 20.0 to 97.0), and 7 patients had HIV viral loads of <200 copies/mL. There were 27 deaths due to opportunistic infections, 27 due to non AIDS-defining infections, 4 due to non AIDS-associated malignancies. This study also describes 3 deaths due to cardiovascular events, and 1 due to hepatic failure. Patients who had virologic suppression were more likely to die from non AIDS-defining causes. CONCLUSION: Causes of death in HIV-positive patients have changed in the HAART era. More research is required to further understand and address barriers to testing and treatment to further improve outcomes in HIV/AIDS.

Older age at initial presentation to human immunodeficiency virus (HIV) care and treatment at the Communicable Disease Centre (CDC) in Singapore, 2006 to 2011.

INTRODUCTION: The incidence of newly diagnosed older patients diagnosed with human immunodeficiency virus (HIV) has increased worldwide in recent years. In this study, we compared the demographics and clinical presentation of younger and older patients in our HIV sentinel cohort. MATERIALS AND METHODS: Among all HIV patients presenting to the Communicable Disease Centre (CDC), Singapore from 2006 to 2011, 793 were randomly included in our cohort, representing about 50% of the patients seen during that period. We collected demographic, clinical, laboratory, and outcome data from patient records to compare younger (<50 years old) and older (≥50 years old) HIV patients. RESULTS: Older patients comprised 27.1% of our HIV cohort and presented with lower median CD4 T cell counts (65 cells/mm³, interquartile range [IQR]: 27 to 214 cells/mm³) compared to younger patients (250 cells/mm³, IQR: 74 to 400 cells/mm³; P <0.001). The median time from HIV diagnosis to initiation of antiretroviral therapy (ART) differed significantly for both age groups as well (49 days for patients <50 years old, IQR: 18 to 294 days; versus 35 days for patients ≥50 years old, IQR: 14 to 102 days; P = 0.008). More of our younger patients were single (72.2%) or homosexual (44.1%), in contrast to older patients, of whom 48.8% were married and 84.7% were heterosexual. CONCLUSION: Upon comparison of our younger and older patients, we identified distinct differences in risk transmission and clinical presentation. Increased awareness of older patients at risk of HIV may improve time to diagnosis among this age group.

Increased rate of CD4+ T-cell decline and faster time to antiretroviral therapy in HIV-1 subtype CRF01_AE infected seroconverters in Singapore.

BACKGROUND: It remains controversial as to whether HIV-1 subtypes influence disease progression. Singapore offers a unique opportunity to address this issue due to the presence of co-circulating subtypes. We compared subtype CRF01_AE and non-CRF01_AE infected patients, with regards to estimated annual rate of CD4+ T-cell loss and time from estimated data of seroconversion (EDS) to antiretroviral therapy (ART). METHODS: We recruited ART-naive patients with known dates of seroconversion between October 2002 and December 2007 at the Singapore Communicable Disease Centre, the national reference treatment centre. Multilevel mixed-effects models were used to analyse the rate of CD4+ T-cell decline. Time from EDS to ART was analyzed with the Kaplan-Meier survival method and compared with Cox proportional hazards models. RESULTS: 54 patients with previously assigned HIV-1 subtypes (24 CRF01_AE, 17 B, 8 B', 1 CRF33_01B, 3 CRF34_01B and 1 G) were observed for 89 patient-years. Subtype CRF01_AE and non-CRF01_AE infected patients did not differ in age, gender, risk factor, rate of symptomatic seroconversion, baseline CD4+ T-cell count, log(10) viral load or haemoglobin concentration. The estimated annual rate of CD4+ T-cell loss was 58 cells/mm(3)/year (95% CI: 7 to 109; P = 0.027) greater in subtype CRF01_AE infected patients compared to non-CRF01_AE patients, after adjusting for age, baseline CD4+ T-cell count and baseline log(10) viral load. The median time from EDS to ART was 1.8 years faster comparing CRF01_AE to non-CRF01_AE infected patient with a 2.5 times (95% CI: 1.2-5.0; P = 0.013) higher hazard for ART initiation, after controlling for age, baseline CD4+ T-cell count and baseline log(10) viral load. CONCLUSIONS: Infecting subtype significantly impacted the rate of CD4+ T-cell loss and time to treatment in this cohort. Studies to understand the biological basis for this difference could further our understanding of HIV pathogenesis.

Severe varicella infection occurring after herpes zoster reactivation in a patient with AIDS.

Herpes zoster reactivation occurs in patients who had primary varicella infection, afflicting mainly the elderly and the immunocompromised. However, it is rare that varicella infection develop after zoster reactivation. We report on a patient with underlying HIV/AIDS who had two previous episodes of herpes zoster and still developed varicella infection, complicated by pneumonitis and polyradiculitis. We also review the relevant literature.