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Background: The Philippines has the fastest growing HIV epidemic in the Asia-Pacific. This increase was accompanied by a shift in the predominant HIV subtype from B to CRF01_AE. Increasing evidence points to a difference in treatment responses between subtypes. We examined treatment failure and acquired drug resistance (ADR) in people living with HIV (PLHIVs) after one year on antiretrovirals (ARVs). Methods: PLHIV maintained on ARVs for one year were recruited. Treatment failure was defined as a viral load of ≥1000 copies/mL. Sanger sequencing for genotyping and drug resistance mutation (DRM) detection was performed on patients failing treatment. Results: 513 PLHIV were enrolled. The most common antiretroviral regimens were TDF+3TC + EFV (269) and AZT+3TC + EFV (155). 53 (10.3%) subjects failed treatment. Among these, 48 (90.6%) had DRMs, 84.9% were subtype CRF01_AE. Tenofovir-based regimens performed worse than zidovudine-based regimens (OR 3.28, 95% CI 1.58–7.52 p

With increasing geographic spread, frequency, and magnitude of outbreaks, dengue continues to pose a major public health threat worldwide. Dengvaxia, a dengue live-attenuated tetravalent vaccine, was licensed in 2015, but post hoc analyses of long-term data showed serostatus-dependent vaccine performance with an excess risk of hospitalized and severe dengue in seronegative vaccine recipients. The World Health Organization (WHO) recommended that only persons with evidence of past dengue infection should receive the vaccine. A test for pre-vaccination screening for dengue serostatus is needed. To develop the target product profile (TPP) for a dengue pre-vaccination screening test, face-to-face consultative meetings were organized with follow-up regional consultations. A technical working group was formed to develop consensus on a reference test against which candidate pre-vaccination screening tests could be compared. The group also reviewed current diagnostic landscape and the need to accelerate the evaluation, regulatory approval, and policy development of tests that can identify seropositive individuals and maximize public health impact of vaccination while avoiding the risk of hospitalization in dengue-naive individuals. Pre-vaccination screening strategies will benefit from rapid diagnostic tests (RDTs) that are affordable, sensitive, and specific and can be used at the point of care (POC). The TPP described the minimum and ideal characteristics of a dengue pre-vaccination screening RDT with an emphasis on high specificity. The group also made suggestions for accelerating access to these RDTs through streamlining regulatory approval and policy development. Risk and benefit based on what can be achieved with RDTs meeting minimal and optimal characteristics in the TPP across a range of seroprevalences were defined. The final choice of RDTs in each country will depend on the performance of the RDT, dengue seroprevalence in the target population, tolerance of risk, and cost-effectiveness., Author summary This paper describes the consensus on the minimum and ideal performance and operational characteristics of rapid tests that would be used for dengue pre-vaccination screening. This profile will incentivize industry to develop better pre-vaccination screening tests. The choice of which test to use depends on the seroprevalence of the population targeted for vaccination and the optimal balance between benefit and risks. The group also made suggestions for accelerating access to these pre-vaccination screening tests through streamlining regulatory approval and policy development.

Background The Philippines HIV epidemic is one of the fastest growing, globally. Infections among men who have sex with men (MSM) are rising at an alarming rate, necessitating targeted evidence-based interventions to reach epidemic control. Treatment as prevention is a key strategy to end AIDS, making it a priority to explore novel approaches to retain people living with HIV (PLHIV) in care, support adherence, and reach viral suppression. Methods: This cross-sectional analysis describes HIV-related risk behaviours and adherence to antiretroviral therapy (ART) in a population of HIV-positive patients at a clinic in Metro Manila, Philippines participating in the Philippines Connect for LifeTM cohort study. Results: Among 426 HIV-positive adults taking ART, 79% reported ≥95% adherence over the prior 30 days. Longer time on treatment was associated with reduced adherence to ART (adjusted odds ratio (AOR) = 0.87 per year, P = 0.027). Being in a serodiscordant relationship, in which the subject’s primary partner was HIV negative, increased adherence (AOR = 3.19, P = 0.006). Inconsistent condom use (AOR = 0.50, P = 0.103) and injection drug use (AOR = 0.54, P = 0.090) are potentially associated with reduced adherence to ART. Patients used drugs and alcohol at significantly higher rates than the general population.? Conclusions: The study found that patients in this setting require intervention to address treatment fatigue. Interventions to improve social support of PLHIV, as well as harm-reduction approaches for drug and alcohol use, could improve adherence in this population, strengthening the test-and-treat strategy to control the epidemic.

Objectives. To determine the effect of prolonged cotrimoxazole prophylaxis (CP) in reducing hospitalization and opportunistic infection rates among people living with HIV (PLHIV) with CD4 count >200 cells/mm3. Methods. We retrospectively reviewed 349 medical charts of PLHIV with CD4 count (or T-cell count) of >200 cells/mm3 enrolled in an HIV treatment hub in Manila, Philippines, from January 2004 to July 2016. Demographic, clinical characteristics and outcomes were extracted. Descriptive statistics were generated. Chi-square test for two proportions was done to compare the difference in outcomes between the CP and non-CP groups. Results. Of the 349 patients, majority (96.6%) were male with a mean age of 28 years (SD 6.4) and mean CD4 count of 373 cells/mm3 (SD 148). CP was continued in 103 patients (29.5%) with mean duration of 1.7 (SD 1.9) years. The prolonged CP group had more events of adverse drug reactions (p200 cells/mm3. More adverse effects were also seen in the CP group.

Background Central nervous system involvement is commonly seen in patients with human immunodeficiency virus (HIV) infection, with up to 2%–10% of patients presenting with intracranial mass lesions. The management of these lesions depends largely on their etiology and their relative frequency in the local population. Methods We performed a retrospective chart review of patients with HIV and evidence of intracranial mass lesions on cranial magnetic resonance imaging or computed tomography from 2007 to 2018. Demographic data, clinical features, etiology, surgical management, and outcomes were collected. Results The prevalence of intracranial mass lesions in our cohort was 2.2% (45/2032). Patients were predominantly male (98%), with a mean age at diagnosis of 28 years. The most common clinical manifestations were headache (75%), focal weakness (49%), and seizures (32%). The most common diagnoses were toxoplasmic encephalitis (51%) and tuberculosis (24%). Biopsy or excision was performed in 10% of cases, leading to a definitive diagnosis in 60% of these cases. A favorable outcome was observed in 58% of all patients at 46 months median follow-up, with adequate disease-specific treatment. Conclusions The prevalence of intracranial mass lesions in Filipino patients with HIV is 2.2%. The most common etiology was toxoplasmic encephalitis followed by tuberculosis. These findings are substantially different from other findings reported in the literature and should be considered in formulating guidelines for the Filipino population.

Background Dengue virus (DENV) infects hundreds of thousands of people annually in Indonesia. However, DENV sequence data from the country are limited, as samples from outbreaks must be shipped across long-distances to suitably equipped laboratories to be sequenced. This approach is time-consuming, expensive, and frequently results in failure due to low viral load or degradation of the RNA genome. Methods We evaluated a method designed to address this challenge, using the ‘Primal Scheme’ multiplex PCR tiling approach to rapidly generate short, overlapping amplicons covering the complete DENV coding-region, and sequencing the amplicons on the portable Nanopore MinION device. The resulting sequence data was assessed in terms of genome coverage, consensus sequence accuracy and by phylogenetic analysis. Results The multiplex approach proved capable of producing near complete coding-region coverage from all samples tested ($$ \overline{x} $$x¯ = 99.96%, n = 18), 61% of which could not be fully amplified using the current, long-amplicon PCR, approach. Nanopore-generated consensus sequences were found to be between 99.17–99.92% identical to those produced by high-coverage Illumina sequencing. Consensus accuracy could be improved by masking regions below 20X coverage depth (99.69–99.92%). However, coding-region coverage was reduced at this depth ($$ \overline{x} $$x¯ = 93.48%). Nanopore and Illumina consensus sequences generated from the same samples formed monophyletic clades on phylogenetic analysis, and Indonesian consensus sequences accurately clustered by geographical origin. Conclusion The multiplex, short-amplicon approach proved superior for amplifying DENV genomes from clinical samples, particularly when the virus was present at low concentrations. The accuracy of Nanopore-generated consensus sequences from these amplicons was sufficient for identifying the geographic origin of the samples, demonstrating that the approach can be a useful tool for identifying and monitoring DENV clades circulating in low-resource settings across Indonesia. However, the inaccuracies in Nanopore-generated consensus sequences mean that the approach may not be appropriate for higher resolution transmission studies, particularly when more accurate sequencing technologies are available.

Dengue virus (DENV) sequencing is a vital tool for surveillance and epidemiology studies. However, the current methods employed for sequencing DENV are expensive, laborious and technically demanding, often due to intra- and inter-serotype variability. Therefore, on-site DENV sequencing is not feasible in many of the areas where DENV is endemic. Surveillance in these areas can only be performed by shipping samples to well-equipped central laboratories for sequencing. However, long periods of inadequate storage and unreliable shipping conditions mean that such samples can arrive degraded, rendering sequence recovery difficult. We therefore aimed to develop an approach that is simple, portable and effective, to be used for on-site DENV sequencing in limited resource settings.To achieve this, we first used the ‘Primal Scheme’ primer design tool to develop a simple and robust protocol for generating multiple short amplicons, covering the complete coding-region of DENV isolates. We then paired this method with the Nanopore MinION, a portable and affordable sequencing device, well-suited to minimal resource settings.The multiplex PCR method produced full-coding-region coverage of all DENV samples tested with no optimisation required, and Nanopore sequencing of the short amplicons generated consensus sequences with high accuracy (99.52 - 99.92 %). Phylogenetic analysis of the consensus sequences generated using the new method showed that they formed monophyletic clusters with those produced by the current, long-amplicon, Illumina method, thus demonstrating that the two approaches are comparable. The multiplex method’s simplicity and portability compared to the current DENV sequencing approach make it well-suited for use in resource-limited, DENV-endemic regions. Deployment of the method in these regions would increase the capacity for DENV surveillance and has the potential to provide vital resolution for future DENV epidemiology studies.

A 48-year-old man presented with a non-healing wound on his left foot after stepping on a nail. He self-medicated with amoxicillin, but the wound progressed prompting consult. On examination, his left foot was diffusely swollen with surrounding erythema, areas of gangrene, foul-smelling purulent discharge and subcutaneous emphysema. He was managed as a case of necrotising fasciitis and underwent emergent amputation. Three days after amputation, he developed a sudden and progressive blurring of vision, swelling and conjunctival erythema, with purulent discharge and the presence of hypopyon on the left eye. He was then managed as a case of endophthalmitis of the left eye and underwent pars plana vitrectomy. All cultures (blood, tissue and vitreous fluid) grew pan-susceptible hypermucoviscous Klebsiella pneumoniae, with positive string tests and confirmed by multilocus gene sequencing and sequence type analysis. He gradually improved with intravenous antibiotics, but only regained light perception in the left eye.

Primary intracranial leiomyosarcoma (PIL) is a rare non-infectious aetiology of focal mass lesions among HIV-infected individuals. With only 16 published cases worldwide, information on its pathophysiology, risk factors, clinical course and management options is limited. We report two cases of PIL in HIV-infected Filipino men who presented with 1–3 months history of persistent headache, progressing in severity. Both had cranial MRI revealing intracranial mass diagnosed as leiomyosarcoma by excision biopsy and immunohistochemical staining. Both patients underwent adjuvant cranial radiotherapy and chemotherapy. Biologics were initiated in one patient. Both patients were alive with evidence of the disease.

Background Hepatitis B is highly prevalent in the Philippines, with 17% of the population infected. With the fastest-growing HIV epidemic in the Asia-Pacific, 12% of HIV patients are HBsAg reactive. With the use of lamivudine and tenofovir-based antiretrovirals (ARVs), hepatitis B virus (HBV) treatment in co-infected HIV patients is not usually an issue. However, there is a potential to develop HBV resistance when patients are switched off tenofovir when antiretroviral resistance develops. With high rates of acquired K65R tenofovir resistance, the potential for inadvertently causing re-emergence of lamivudine-resistant HBV is present. We report two HIV patients with residual whole-genome HBV with lamivudine and telbivudine resistance mutations. Methods As part of a surveillance study on acquired drug resistance in the Philippines, samples with an HIV viral load >1,000 copies underwent Sanger sequencing of RT and PR for genotyping and HIV drug-resistance testing. Near-whole-genome next-generation sequencing (NGS) for HIV using Illumina HiSeq was also performed on these samples. Results Two patients had coincidental whole-genome amplification of HBV on NGS (Table 1). HBV serology for both showed reactive anti-HBsAg and non-reactive HBsAg and Anti-HBc. The two HBV samples were genotype A and were resistant to lamivudine and telbivudine, with intermediate resistance to entecavir. Conclusion Residual HBV may be present in patients on ARVs. Antibody responses for HBV serology may not be very reliable in highly immunosuppressed patients. The potential of lamivudine-resistant HBV to emerge when HIV patients are shifted off tenofovir due to resistance in patients should be considered when deciding on second-line ARVs. Disclosures All authors: No reported disclosures.

Background The Philippines has the fastest-growing HIV epidemic in the Asia-Pacific. Concurrent sexually-transmitted infections increase the risk of HIV transmission and complications. The prevalence of Neisseria gonorrheae (NG) and Chlamydia trachomatis (CT) infection among Filipino HIV patients is unknown and screening is not universal. A symptom-based approach likely underestimates the prevalence of NG and CT among men who have sex with men (MSM). We determined the rectal, pharyngeal, and urethral prevalence of gonorrhea and chlamydia infection in our patient population using nucleic acid testing (NAT). Methods This is a single-center, prospective cross-sectional study at Philippine General Hospital. Following ethical approval and informed consent, pharyngeal, rectal, and urine samples from newly-diagnosed, treatment-naïve HIV adult patients were tested using the Xpert® CT/NG assay (Cepheid, Sunnydale, CA). Patients with recent (≤21 days) antibiotic use with activity against NG or CT were excluded. Demographic and clinical data were also collected. Results 46 subjects were enrolled. Mean age was 31 years (range 19–49), 83% (38/46) were male, 96% (44/46) were asymptomatic, and 92% (35/38) of the males were MSM. Median CD4 count was 225 cells/μL (range 0–1,335). The overall prevalence of CT/NG was 33% (15/46). Table 1 shows the prevalence of CT and NG by site. Four patients had both genital and rectal CT. More patients had rectal NG/CT compared with urethral and pharyngeal sites. No gonorrhea was found in the urine specimens; no chlamydia was found in the pharynx. Conclusion The prevalence of CT and NG among newly diagnosed Filipino HIV patients at 33% is sufficiently high to warrant routine NAT screening. Urine testing alone will miss a significant number of cases in an MSM-predominant population. We recommend NAT screening of both urethral and rectal sites for newly-diagnosed Filipino HIV patients. Disclosures All authors: No reported disclosures.

Invasive Trichosporon infection is a rare, life-threatening infection in immunocompromised patients. It has been reported as an emerging opportunistic infection in those with acquired immune deficiency syndrome (AIDS). Only 12 cases of invasive trichosporonosis in patients with HIV have been documented, none in Southeast Asia. We report a case of fatal, disseminated trichosporonosis in a Filipino AIDS patient with severe cutaneous and pulmonary involvement. Invasive trichosporonosis should be considered in HIV-positive patients with disseminated fungal infection since this may be refractory to conventional antifungal treatment.