Sex: Male
Education:
- Doctor of Medicine, University of the Philippines Manila
Field of Specialization:
Molecular Biology
Biotechnology
Researches:
Article title: Depression, Nutrition, and Adherence to Antiretroviral Therapy in Men Who Have Sex With Men in Manila, Philippines
Authors: Hend Elsayed, Cara O’Connor , Katerina Leyritana, Edsel Salvana and Sharon E. Cox
Publication title: Frontiers in Public Health 9, September 2021
Abstract:
Introduction: Depression is the most frequently observed psychiatric disorder among HIV patients. The effect of depression on adherence among men who have sex with men (MSM) HIV patients has not been well studied in the Philippines. Depression is commonly undiagnosed and consequently untreated, which leads to a negative influence on antiretroviral therapy (ART) adherence. Other risk factors such as HIV-related stigma, self-body image satisfaction, and nutritional status are recognized as potential barriers to access HIV prevention and treatment services issues and poor adherence. Methods: Hospital anxiety and depression scale (HADS) was used to screen depressive symptoms during scheduled clinic visits. ART adherence was self-reported using a visual analog scale questionnaire covering the last 30 days. Structured questionnaires were used for measuring risk factors and socio-demographic data. Anthropometry was conducted and body composition was assessed using bioelectrical impedance analysis. Results: One-hundred and ninety-three participants were recruited from the SHIP clinic between 7th March and 30th September 2018, of whom, 42 (21.8%) screened positive for depression (HADS score ≥ 8) and 24 (12.4%) were non-adherent to ART (<95% of medication taken as prescribed). The most common reported reason for non-adherence was simply forgotten (18 out of 42, 42.9%). Increasing depressive symptoms were associated with non-adherence [crude odds ratio (OR) = 1.13; 95% CI: 1.02–1.26]. Social family support (SFS) and body image (BI) scores were also associated with non-adherence, but were not statistically significant in multivariable models. Factors significantly associated with depressive symptoms (but not non-adherence) included the following: using intravenous drugs, being in a relationship, anxiety, self-esteem, and stigma scores. Conclusions: Increased depression symptoms, low social family support, and body image dissatisfaction may be interconnected risk factors for ART non-adherence among Filipino MSM HIV patients. Comprehensive mental health services beyond regular post-HIV testing counseling may increase adherence to ART and improve HIV treatment outcomes. Further prospective studies are needed to address the causal/reverse causal pathway between depression and non-adherence.
Full text link https://tinyurl.com/5cvfn54w
Article title: Target product profile for a dengue pre-vaccination screening test
Authors: Noah Fongwen,Annelise Wilder-Smith,Duane J. Gubler,Eng Eong Ooi,Edsel Maurice T. Salvana, et al.
Publication title: PLoS Neglected Tropical Diseases 15(7):e0009557, July 2021
Abstract:
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.
Full text available upon request to the author
Article title: Detection and Genome Sequencing of SARS-CoV-2 Variants Belonging to the B.1.1.7 Lineage in the Philippines
Authors: Francis A. Tablizo, Cynthia P. Saloma, Marc Jerrone R. Castro, Kenneth M. Kim, Maria Sofia L. Yangzon, et al.
Publication title: Microbiology Resource Announcements 10(18), May 2021
Abstract:
We report the sequencing and detection of 36 severe acute respiratorysyndrome coronavirus 2 (SARS-CoV-2) samples containing lineage-defining mutationsspecific to viruses belonging to the B.1.1.7 lineage in the Philippines
Full text link https://tinyurl.com/s5sj4zwy
Article title: Risk factors affecting adherence to antiretroviral therapy among HIV patients in Manila, Philippines: a baseline cross-sectional analysis of the Philippines Connect for Life Study
Authors: Cara O’Connor, Katerina Leyritana, Kris Calica, Randeep Gill, Aoife M. Doyle , James J. Lewis and Edsel Maurice Salvaña
Publication title: Sexual Health 18(1), March 2021
Abstract:
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.
Full text available upon request to the author
Article title: Intracranial mass lesions in HIV patients in the Philippines: A retrospective cohort study
Authors: Abdelsimar T.OmarII, Marisse J. Nepomuceno, Edsel Maurice T. Salvana, Annabell E. Chua
Publication title: World Neurosurgery 145, October 2020
Abstract:
Background Central nervous system involvement is commonly seen in persons living with HIV infection (PLHIV), with up to 2 – 10% presenting as intracranial mass lesions. The management of these lesions depends largely on their etiology and their relative frequency in the local population. Materials and Methods We performed a retrospective chart review of HIV patients with evidence of intracranial mass lesion/s on cranial MRI or CT scan who were seen at our institution from 2007 – 2018. Data on demographics, clinical features, etiology, surgical management and outcomes were collected. Results The prevalence of intracranial mass lesions in our cohort was 2.2% (45/2,032). 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 toxoplasma 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. Conclusion The prevalence of intracranial mass lesions in Filipino PLHIV is 2.2%. The most common etiology was toxoplasma encephalitis (51%) and tuberculosis (24%). This is substantially different from that reported in the literature, and should be considered in formulating guidelines for our local population.
Full text available upon request to the author
Article title: Benefits and Risks of Prolonged Cotrimoxazole Prophylaxis among People Living with HIV in Immune Reconstitution Phase: A Retrospective Cohort Study
Authors: Christian N. Francisco, Marissa M. Alejandria, Edsel Maurice T. Salvaña
Publication title: Acta medica Philippina 54(3), June 2020
Abstract:
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 (p<0.001), specifically minor cutaneous reactions (p<0.001) and immunologic failures (p<0.001), compared to the non-CP group. There were no statistically significant differences in the frequency of hospitalization, PJP (Pneumocystis jirovecii pneumonia), non-PJP, other respiratory illnesses, diarrhea, toxoplasmosis, tuberculosis, stage 3/4 events and mortality, between the prolonged CP and non-CP groups. Conclusion. We did not observe any additional benefit in giving prolonged CP among PLHIV with CD4 count >200 cells/mm3. More adverse effects were also seen in the CP group.
Full text available upon request to the author
Article title: Assessment of a multiplex PCR and Nanopore-based method for dengue virus sequencing in Indonesia
Authors: Samuel C. B. Stubbs, Barbara A. Blacklaws, Benediktus Yohan, Frilasita A. Yudhaputri, Rahma F. Hayati, et al.
Publication title: Virology Journal 17(1), February 2020
Abstract:
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 ([Formula: see text] = 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 ([Formula: see text] = 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.
Full text link https://tinyurl.com/dr45zf2f
Article title: High rates of tenofovir failure in a CRF01_AE-predominant HIV epidemic in the Philippines
Authors: Edsel Maurice T. Salvana, Genesis May J. Samonte, Elizabeth Telan, Lalaine Arcangel, Noel S. Palaypayon, et al.
Publication title: International journal of infectious diseases: IJID: official publication of the International Society for Infectious Diseases 95, February 2020
Abstract:
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 to 7.52 p<0.001). Higher rates of NRTI, NNRTI, K65R tenofovir resistance, and multi-class resistance were found compared to those reported in literature. Conclusions: HIV treatment failure at one year of treatment in the Philippines is 10.3%. We found unusually high tenofovir and multiclass resistance, and optimal ARV regimens may need to be reevaluated for CRF01_AE-predominant epidemics.
Full text link https://tinyurl.com/yv46ct8a
Article title: Prevalence of Urethral, Rectal, and Pharyngeal Gonorrhea and Chlamydia among Newly Diagnosed Filipino HIV Patients
Authors: Kingbherly L Li, MD, Jose Carlo B. Valencia, MD, Florida F Taladtad, MD, Mary Grace T Hernaez, RMT, Vivienne V Luzentales, RMT, et al.
Publication title: Open Forum Infectious Diseases 6(Supplement_2):S195-S195, October 2019
Abstract:
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.
Full text link https://tinyurl.com/hrhmkxy4
Article title: Transmitted and Acquired NNRTI Resistance in the Philippines: Are Newer Generation NNRTIs a Viable Option?
Authors: Nina Theresa Dungca, MSc, Brian Schwem, PhD, Geraldine Arevalo, BS, Christian Francisco, MD, Christine Penalosa-Ramos, MD, et al.
Publication title: Open Forum Infectious Diseases 6(Supplement_2):S870-S870, October 2019
Abstract:
Background Doravirine, rilpivirine, and etravirine are newer generation non-nucleoside reverse transcriptase inhibitors (NNRTI) that are intended to be more durable alternatives to efavirenz and nevirapine. We examined transmitted drug resistance (TDR) and acquired drug resistance (ADR) to NNRTIs from recent local TDR and ADR data to determine whether these can be useful as first-line or second-line antiretroviral (ARV) agents. Methods We reanalyzed Sanger-Based sequences (SBS) from an ADR surveillance study; and SBS and near-whole-genome next-generation sequences (NGS) from a TDR surveillance study using the Stanford HIV Drug Resistance Database. Results ADR: Out of 513 Filipino PLHIV from an ADR surveillance study on one year of ARV treatment, 53 (10.3%) failed (HIV VL >1,000 copies/mL). Among these, 48 had clinically significant mutations. Table 1 shows NNRTI ADR frequencies. There was no significant ADR difference between first-generation and newer generation NNRTIs. TDR: 298 treatment-naïve Filipino PLHIV underwent baselines sequencing. All 298 had SBS. 266 had successful NGS. Table 1 shows SBS and NGS TDR NNRTI resistance at a 5% minor variant cutoff. There was no significant TDR difference between first-generation and newer generation NNRTIs. Conclusion ADR and TDR rates to the newer NNRTIs are similar to first-generation NNRTIs. High TDR to doravirine on NGS is concerning, but its clinical significance is unclear. Etravirine had the lowest TDR and ADR and may be the most useful new-generation NNRTI. However, integrase strand transfer inhibitor-based regimens will likely be more durable. Disclosures All authors: No reported disclosures.
Full text link https://tinyurl.com/5shsnkkv
Article title: Residual lamivudine-resistant hepatitis B virus detected on next-generation sequencing of treatment-experienced HIV patients failing antiretrovirals
Authors: Brian Schwem, PhD, Christian Francisco, MD, Nina Theresa Dungca, MSc, Geraldine Arevalo, BS; Patrick Ching, MD, et al.
Publication title: Open Forum Infectious Diseases 6(Supplement_2):S189, October 2019
Abstract:
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.
Full text link https://tinyurl.com/2djk6k6z
Article title: Multidrug-resistant tuberculosis (MDR-TB) and multidrug-resistant HIV (MDR-HIV) syndemic: Challenges in resource limited setting
Authors: Christian Francisco, Mary Ann Lansang, Edsel Maurice Salvana and Katerina Leyritana
Publication title: BMJ Case Reports 12(8):e230628, August 2019
Abstract:
Tuberculosis (TB) is common among persons living with HIV. This public health concern is aggravated by infection with multidrug-resistant organisms and adverse effects of polypharmacy. There are few published cases of multidrug-resistant tuberculosis (MDR-TB) in multidrug-resistant HIV (MDR-HIV) infected patients. We report a case of a 29-year-old Filipino man with HIV on zidovudine (AZT)-containing antiretroviral therapy (ART) but was eventually shifted to tenofovir due to anaemia. He presented with left flank tenderness, which was found to be due to an MDR-TB psoas abscess, and for which second-line anti-TB treatment was started. HIV genotyping showed MDR-HIV infection susceptible only to AZT, protease inhibitors and integrase inhibitors. Subsequently, he developed neck abscess that grew Mycobacterium avium complex and was treated with ethambutol and azithromycin. ART regimen was revised to AZT plus lamivudine and lopinavir/ritonavir. Erythropoietin was administered for recurrent AZT-induced anaemia. Both abscesses resolved and no recurrence of anaemia was noted.
Full text link https://tinyurl.com/593ntcfu
Article title: Emergence of a B/F1 HIV Recombinant in the Philippines: A Potentially New Circulating Recombinant Form
Authors: Brian Schwem, PhD, Nina Dungca, MS, Geraldine Arevalo, BS, Christian Francisco, MD, FPCP, Christine Penalosa, MD, et al.
Publication title: Open Forum Infectious Diseases 5(suppl_1):S390-S391, November 2018
Abstract:
The Philippines has one of the fastest growing HIV epidemics globally. This was accompanied by a switch from subtype B to CRF01_AE. With a large population of returning overseas workers, new subtypes are being introduced regularly. Because diagnosis of HIV in the Philippines is usually late, superinfections can occur and may give rise to new circulating recombinant forms (CRFs). We propose a new CRF from the Philippines. Methods Following institutional board approval, treatment-naive patients from two HIV treatment hubs (San Lazaro Hospital and the Philippine General Hospital) were recruited. Blood samples underwent Sanger sequencing of the PR and RT regions and next-generation sequencing (NGS) of near-full length genomes. Sequences were analyzed for recombination using the online tool jumping profile Hidden Markov Model (http://jphmm.gobics.de/). Results 247 samples underwent Sanger sequencing of the PR and RT regions of the pol gene. Phylogenetic analysis indicated a clustering of four of the samples. Further analysis showed all four samples had the same breakpoints at nucleotides 2875, 2996, and 3001 (HXB2 numbering). All four patients were male, MSM, with a mean age of 28 years old (24–32), and >10 sexual partners. Mean CD4 count was 464 cells/µL and median viral load was 2.67 × 10⁴ copies/mL. Two patients had sex with foreigners. To get a better overall view of subtype composition, we performed NGS using Illumina HiSeq. NGS showed the majority of the genome to be subtype F1 with segments of subtype B inserted in the pol, vpu, and env genes. A blast analysis of the consensus sequence showed 8,932 out of 8,943 nucleotides (99%) matched a 1999 sample from Argentina. Phylogenetic analysis of these samples show clustering of the four B/F1 recombinants with some South American sequences. No drug resistance mutations were identified. Conclusion Mutation and recombination contribute to the extensive genetic diversity of HIV. Understanding this is important in choosing treatment regimens, developing future vaccines, and pursuing epidemiological investigations. The emergence of a new CRF in the Philippines underlies the importance of conducting routine surveillance for new HIV recombinant forms. Figure 1 View largeDownload slide View largeDownload slide New CRF genome showing subtype components. Figure 1 View largeDownload slide View largeDownload slide New CRF genome showing subtype components. Disclosures All authors: No reported disclosures.
Full text link https://tinyurl.com/25ayfa8e
Article title: Detection of HIV Transmitted Drug Resistance by Next-Generation Sequencing in a CRF01_AE Predominant Epidemic
Authors: Edsel Maurice Salvana, MD, DTM&H, FIDSA, Nina Dungca, MS, Geraldine Arevalo, BS, Katerina Leyritana, MD, Christian Francisco, MD, FPCP, et al.
Publication title: Open Forum Infectious Diseases 5(suppl_1):S391-S391, November 2018
Abstract:
The Philippines has the fastest growing HIV epidemic in the Asia-Pacific. Concurrent with this is a subtype shift from B to CRF01_AE. We have previously documented transmitted drug resistance (TDR) locally. However, the lack of drug pressure and the insensitivity of Sanger-based sequencing (SBS) may leave archived drug-resistance mutations (DRMs) undetected. To better detect TDR, we performed next-generation sequencing (NGS) on treatment-naïve patients and compared this with SBS. Methods Following ethics approval, newly-diagnosed adult Filipino HIV patients were recruited from the Philippine General Hospital HIV treatment hub. Demographic data were collected, and blood samples underwent SBS with a WHO-approved protocol. Whole-genome NGS was performed using Illumina HiSeq through a commercial provider (Macrogen, Korea). Genotype and DRMs were analyzed and scored using the Stanford HIV Drug Resistance Database. Results 113 patients were analyzed. Median age was 29 years (range 19–68), mean CD4 count was 147 cells/µL (range 0–556) and median viral load was 2.8 × 106 copies/mL. Genotype distribution was: CRF01_AE (93), B (13), possible CRF01_AE/B recombinants (5), CRF02_AG (1), possible URF (1). TDR prevalence by SBS and NGS at different minority variant cutoffs are shown in Table 1. All DRMs on SBS were found on NGS. Some samples had multiple DRMs. No factors were significantly associated with TDR, genotype, viral load or baseline CD4 count. Conclusion NGS is a more sensitive tool for detecting TDR compared with SBS. Nearly double the DRMs were found at an NGS cutoff of ≥5%, including INSTI DRMs. With increasing HIV drug resistance worldwide, switching to NGS may help decrease rates of initial treatment failure, especially in settings with limited repertoires of ARVs
Full text link https://tinyurl.com/vh8vnuby
Article title: Hypermucoviscous capsular 1 (K1) serotype Klebsiella pneumoniae necrotising fasciitis and metastatic endophthalmitis
Authors: Harold Henrison Chang Chiu, Christian Nadonga Francisco, Racquel Bruno, Manuel Jorge II1 and Edsel Maurice Salvaña
Publication title: BMJ Case Reports 11(1):e226096, November 2018
Abstract:
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.
Full text link https://tinyurl.com/yfteuha5
Article title: Primary intracranial leiomyosarcoma among patients with AIDS in the era of new chemotherapeutic and biological agents
Authors: Christian N. Francisco, Marissa Alejandria, Edsel Maurice Salvaña, Vida Margarette de Vera Andal
Publication title: BMJ Case Reports 2018(Suppl 5), September 2018
Abstract:
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.
Full text link https://tinyurl.com/mxx687nz
Article title: HIV Transmitted Drug Resistance in the Philippines: The Case for Baseline Genotyping and Drug Resistance Testing
Authors: Edsel Maurice Salvana, MD, DTM&H, FIDSA, Brian Schwem, PhD, Christine Penalosa, MD, Geraldine Arevalo, BS, Nina Dungca, BS, et al.
Publication title: Open Forum Infectious Diseases 4(suppl_1):S423-S423, October 2017
Abstract:
The Philippines has one of the fastest growing HIV epidemics in the world. Parallel to the increase is a shift in HIV subtype from B to CRF01_AE. No transmitted drug resistance (TDR) surveillance has ever been conducted. With the widespread rollout of antiretrovirals and the limited repertoire of 6 drugs (tenofovir, lamivudine, zidovudine, nevirapine, efavirenz, lopinavir/ritonavir) makes TDR monitoring imperative. In addition, a high rate of hepatitis B (HBV) co-infection (17%) in the general population raises the risk of TDR with prior NRTI monotherapy. Methods Following IRB approval, we performed TDR surveillance at the Philippine General Hospital, one of the largest tertiary referral centers in the country. Treatment-naïve patients had their HIV RT and PR genes sequenced using WHO approved-protocols for HIV genotyping. Generated sequences were analyzed using the Stanford Drug Resistance Database. Pertinent demographic and clinical data were collected. The current results represent year 1 of the study. Results 95 treatment naïve patients were analyzed. Median age was 30 years (range 20–68). There were 88 males and 7 females. Median CD4 count was 90 cells/mL (range 0–936) and median viral load was 1792000 copies/mL. 18 patients were co-infected with HBV, but all denied previous HBV treatment. Conclusion The TDR rate for HIV in the Philippines is 6.3%. This is above the threshold for recommending baseline TDR genotyping for all local HIV patients. All HIV with TDR were subtype CRF01_AE, and this may signal a higher risk of TDR as the epidemic shifts further to a non-B subtype. Disclosures E. M. Salvana, Merck: Scientific Advisor and Speaker’s Bureau, Consulting fee and Speaker honorarium
Full text link https://tinyurl.com/3kcaeyb3
Article title: High Tenofovir Failure Rates in an Emerging, Non-B Subtype HIV Epidemic
Authors: Edsel Maurice Salvana, MD, DTM&H, FIDSA, Brian Schwem, PhD, Genesis Samonte, MD, Elizabeth Telan, MD, Rosario Tactacan-Abrenica, MD, et al.
Publication title: Open Forum Infectious Diseases 4(suppl_1):S428-S428, et al.
Abstract:
The WHO-recommended regimen for antiretrovirals (ARVs) is tenofovir (TDF) + lamivudine/emtricitabine (3TC/FTC) + efavirenz (EFV), based on demonstrated superiority of TDF+FTC+EFV over zidovudine (AZT) +FTC+ EFV in clinical trials. However, there are reports of increasing TDF resistance in non-B subtypes. We have previously shown that HIV genotypes in the Philippines have shifted (https://idsa.confex.com/idsa/2014/webprogram/Paper45090.html) from B to CRF01_AE. We compared failure rates for ARVs during an acquired drug-resistance surveillance study. Methods We analyzed ARV data from a study with the Department of Health on treatment failure in Filipinos after one year of treatment. Institutional Board Review approval and informed consent were obtained. Results 513 adult patients from 3 national treatment hubs (Philippine General Hospital, San Lazaro Hospital, Vicente Sotto Memorial Medical Center) were enrolled and analyzed. Treatment failure (viral load>1000 copies/mL) at one year for specific regimens are summarized in Table 1. No baseline genotyping was available. 53 (10.3%) patients failed treatment. Genotypes among these were CRF01_AE (87%), B (11%) and C (2%). TDF-containing regimens had significantly higher failure rates (43/303;14.2%) than AZT-containing regimens (10/209;4.5%) (P < 0.001). Failure rates for NVP-based regimens (13/85;15.3%) vs. EFV-based regimens (40/424; 9.4%) were not significantly different (P = 0.1064). The most durable regimen (with >3 patients) was AZT+3TC+EFV, and the worst regimen was TDF+3TC+NVP (P < 0.001). Failure rates for TDF+3TC+EFV were significantly higher than for AZT+3TC+EFV (P = 0.0029). There was no significant difference in adherence (P = 0.5531). 53% of unsuppressed patients had a TDF-resistance mutation, compared with 8% for AZT (P < 0.001). Conclusion TDF-containing regimens were associated with higher treatment failure rates in our CRF01_AE-predominant HIV epidemic. WHO recommendations for treatment may need be revisited for non-B subtypes. Disclosures E. M. Salvana, Merck: Scientific Advisor and Speaker’s Bureau, Consulting fee and Speaker honorarium
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Article title: The Changing Molecular Epidemiology of HIV in the Philippines
Authors: Edsel Maurice T. Salvañaa, Brian E. Schwema, Patrick R. Chingb, Simon D.W. Frostc, Sharie Keanne C. Ganchuaa, Jill R. Itable, et al.
Publication title: International journal of infectious diseases: IJID: official publication of the International Society for Infectious Diseases 61(C):44-50, August 2017
Abstract:
The Philippines has one of fastest-growing HIV epidemics in the world. Reasons for this remain may include increased testing, increased local transmission, and possibly more aggressive strains of HIV. This study sought to determine whether local molecular subtypes of HIV have changed. Methods: 81 newly-diagnosed, treatment-naive HIV patients were genotyped using protease and reverse transcriptase genes. Demographics and CD4 counts were collected. Findings: The cohort had an average age of 29 years (19-51 years), CD4+ count of 255 cells/mm3 (2-744), and self-reported acquisition time of 2.42 years (0.17-8.17 years). All were male including 79 MSM. Genotype distribution was CRF01_AE (77%), B (22%), and C (1%). Previous data from 1985-2000 showed that most Philippine HIV infections were caused by subtype B (71%, N=100), followed by subtype CRF01_AE (20%). Comparison with our cohort shows a significant shift in subtype (p <0.0001). Comparison between CRF01_AE and B showed a lower CD4+ count (230 versus 350 cells/mm3, p=0.03). Survival data showed highly significant survival associated with ARV treatment (p<0.0001) but no significant difference in mortality or CD4 count increase on ARVs between subtypes. Interpretation: The molecular epidemiology of HIV in the Philippines has changed, with the more aggressive CRF01_AE now being the predominant subtype.
Full text link https://tinyurl.com/5cfneuu8