Changes in Adherence and Viral Load Suppression Among People with HIV in Manila: Outcomes of the Philippines Connect for Life Study.

The Philippines HIV epidemic is among the fastest growing globally. Infections among men who have sex with men are rising at an alarming rate, necessitating targeted evidence-based interventions to retain people living with HIV in care, support adherence, and reach viral suppression. We conducted a 48-week prospective cohort study of 462 participants in which we provided a mobile health (mHealth) adherence support intervention using the Connect for Life platform. We observed an improvement in adherence, with the proportion of participants taking more than 95% of their antiretroviral therapy (ART) doses increasing from 78.6% at baseline to 90.3% at 48 weeks. Among treatment experienced participants, adherence improved significantly (McNemar's test = 21.88, P < 0.001). Viral load suppression did not change, with 92.6% suppression at baseline and 92.0% at 48 weeks. Illicit drug use was associated with reduced adherence (aOR = 0.56, 95%CI 0.31-1.00, P = 0.05) and being on second-line therapy was associated with poor viral load suppression (aOR = 0.33, 95%CI 0.14-0.78, P = 0.01). Quality of life improved following ART initiation, from a mean of 84.6 points (of a possible 120) at baseline to 91.01 at 48 weeks. Due to technical issues, fidelity to the intended intervention was low, with 22.1% (102/462) of participants receiving any voice calls and most others receiving a scaled-back SMS intervention. The mHealth intervention did not have any observed effect on adherence or on viral load suppression. While evidence of effectiveness of mHealth adherence interventions is mixed, these platforms should continue to be explored as part of differentiated treatment support services.

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.

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.

A descriptive retrospective study on HIV care cascade in a tertiary hospital in the Philippines.

INTRODUCTION: The HIV care cascade is a model used to examine the engagement of people living with HIV (PLHIV) in medical care from the time of diagnosis to sustained viral suppression. This study describes the stages of the cascade from linkage to care, antiretroviral therapy (ART) initiation, retention in care, and virologic suppression- at the University of the Philippines-Philippine General Hospital (UP-PGH) STD/AIDS Guidance and Intervention Prevention (SAGIP) treatment hub in the context of existing cascades with similar demographics. METHODS: We retrospectively reviewed the medical records of patients enrolled at the UP-PGH SAGIP treatment hub from June 2015 to December 2017. Baseline demographic and clinical data were collected, relevant to each stage of the cascade. Descriptive statistics using Microsoft Excel version 16.0 was used to characterize data and cumulative and conditional proportions were reported. RESULTS: Of the 584 patients included in the cohort, majority were male (91.1%), with a median age of 29 years (range, 0.17 to 68 years). Male-to-male sex was the most common mode of transmission (325/584, 55.6%). Among all patients enrolled at the UP PGH SAGIP treatment hub, 99.5% were linked to care, 95.0% initiated ART, 78.8% were retained in care and maintained on ART, 47.9% were tested for HIV viral load, and 45.5% achieved viral suppression. CONCLUSION: A high proportion of patients enrolled at the UP-PGH SAGIP treatment hub are linked to care and initiate ART, exceeding the set goal of 90%, which is higher than reported nationwide. However, there is a substantial decrease in the number of patients who are subsequently retained in care, tested for HIV viral load, and achieve viral suppression. Gaps in the cascade related to healthcare delivery need to be investigated further and addressed by future studies. We recommend implementation of a community-based, patient-centered approach in order to reach the goals of the HIV cascade, with particular focus on young, MSM-PLHIV.

Interactive Mobile Phone HIV Adherence Support for Men Who Have Sex With Men in the Philippines Connect for Life Study: Mixed Methods Approach to Intervention Development and Pilot Testing.

BACKGROUND: The HIV epidemic in the Philippines is one of the fastest growing epidemics globally, and infections among men who have sex with men are rising at an alarming rate. The World Health Organization recommends the use of mobile health (mHealth) technologies to engage patients in care and ensure high levels of adherence to antiretroviral therapy (ART). Existing mHealth interventions can be adapted and tailored to the context and population served. OBJECTIVE: This study aims to create a locally tailored intervention using a mobile phone platform to support treatment adherence for HIV patients on ART in the Philippines. METHODS: A mixed methods approach guided by the Behavior Change Wheel framework was used to adapt an existing mHealth adherence support platform for the local setting and target population. A literature review, retrospective clinical record review, and focus group discussions with patients were conducted to understand the drivers of ART adherence and tailor the intervention accordingly. The resulting intervention was pilot-tested for 8 weeks, followed by focus group discussions with patients who received the intervention to assess the acceptability of the design. RESULTS: Key issues contributing to nonadherence included side effects, lack of behavioral skills for pill taking, social support, mental health, and substance use. Patients identified mHealth as an acceptable mode of intervention delivery and wanted mHealth services to be highly personalizable. The study team, clinicians, and software developers integrated these findings into the intervention, which included a menu of services as follows: pill reminders, health tips, adherence feedback, appointment reminders, and symptom reporting. During the pilot phase, technical issues in the interactive voice response system (IVRS) were identified and addressed. Patients who participated in the pilot phase expressed a preference for SMS text messaging over the IVRS. Patients responded positively to the appointment reminders and health tips, whereas patient feedback on daily and weekly pill reminders and adherence feedback was mixed. CONCLUSIONS: The mobile phone-based SMS text messaging and IVRS intervention was acceptable to men who have sex with men in Manila, the Philippines, and qualitative analysis suggested that the intervention helped promote ART adherence and appointment attendance.

Metabolic Profile of People Living with HIV in a Treatment Hub in Manila, Philippines: A Pre- and Post-Antiretroviral Analysis.

Objectives: People living with HIV (PLHIV) are susceptible to develop dyslipidemia and hyperglycemia. This study aims to determine the prevalence of these metabolic derangements among Filipino PLHIV. Methodology: We reviewed 635 medical records in a treatment hub in Manila, Philippines from January 2004 to July 2016. Logistic regression analysis was done to determine factors associated with dyslipidemia and hyperglycemia pre- and post-ART. Results: Among 635 PLHIV, 97.3% were males with mean age of 30 years and median CD4 count of 207 cells/mm3. Pre-ART, prevalence of dyslipidemia was 65.4% and hyperglycemia was 10.4%. Risk factors for dyslipidemia include hyperglycemia (AOR 3.8, p 0.001) and >320 days delay in ART initiation from HIV confirmation (AOR 1.5, p 0.032), while dyslipidemia was associated with hyperglycemia (AOR 3.1, p 0.001). Post-ART, prevalence of dyslipidemia was 48.6% and hyperglycemia was 15.6%. Risk factors for post-ART dyslipidemia include being WHO stage 4 (AOR 2.1, p 0.021), hyperglycemia (AOR 16.1, p<0.001), >36 months ART duration (AOR 8.7, p<0.001) and efavirenz-based ART (AOR 2.8, p<0.001). Low CD4 count post-ART had a negative correlation with dyslipidemia (AOR 0.5, p 0.005). Post-ART hyperglycemia was associated with age >30 years (AOR 2.1, p 0.004), being overweight (AOR 1.8, p 0.023), dyslipidemia (AOR 17.8, p<0.001) and zidovudine-based ART (AOR 1.4, p 0.051). Conclusion: Dyslipidemia and hyperglycemia prevalence was high in Filipino PLHIV. Traditional, HIV and treatment related factors contributed to its development. Intensive monitoring and initiation of appropriate treatment is recommended.

Delivering an mHealth Adherence Support Intervention for Patients With HIV: Mixed Methods Process Evaluation of the Philippines Connect for Life Study.

BACKGROUND: The Philippines HIV epidemic is one of the fastest growing epidemics globally, and infections among men who have sex with men are increasing at an alarming rate. Connect for Life Philippines is a mobile health (mHealth) intervention that supports antiretroviral therapy (ART) adherence in this key population through individualized voice calls and SMS text messages. OBJECTIVE: The objective of this process evaluation is to assess the intervention reach, dose delivered and received, fidelity, and acceptability and to describe contextual factors affecting the implementation of an mHealth adherence support intervention for patients on ART in a clinic in Metro Manila, Philippines. METHODS: A mixed methods process evaluation approach was used in an observational cohort study. Quantitative data sources for the process evaluation were call and SMS text message logs obtained from the mHealth platform and questionnaires collected at 12-, 24-, and 48-week study visits. Qualitative data were collected from process reports and through a series of focus group discussions conducted with a subset of participants during the intervention development phase, after an initial 8-week pilot phase, and at the end of the study. RESULTS: The 462 study participants received 31,095 interactive voice calls and 8234 SMS text messages during the study. Owing to technical issues, intervention fidelity was low, with only 22.1% (102/462) of the participants receiving reminders via voice calls and others (360/462, 77.9%) receiving only SMS text messages during the intervention. After 48 weeks in the study, 63.5% (293/462) of the participants reported that they would be quite likely or very likely to recommend the program to a friend, and 53.8% (249/462) of the participants reported that they benefited quite a bit or very much from the intervention. Participants who were on ART for <6 months at the beginning of the study and those who received the daily or weekly pill reminders were more likely to report that they benefited from the intervention (P=.02 and P=.01, respectively). CONCLUSIONS: The Connect for Life intervention had high participant satisfaction and acceptability, especially among those who received high dose of the intervention. However, poor reliability of local telecommunication networks had a large impact on the intervention's usability, fidelity, and dose received.

HIV-1 Subtype Shift in the Philippines is Associated With High Transmitted Drug Resistance, High Viral Loads, and Fast Immunologic Decline.

OBJECTIVES: The Philippines has one of the fastest growing HIV epidemics in the world. A subtype shift from B to CRF01_AE may have contributed to the increase in cases. We undertook a genotyping and transmitted drug resistance (TDR) study to determine if the dominant subtype has any advantages in resistance and transmission. METHODS: Filipinos who were treatment-naive who were living with HIV were recruited from two large government treatment hubs from March 2016 to August 2018. HIV-1 viral load, CD4 count, genotyping, and TDR testing were performed. Demographic and clinical data were collected and compared across subtypes. RESULTS: A total of 298 Filipinos living with HIV were recruited. Median CD4 count was 143 cells/µl and HIV viral load was 2,345,431 copies/ml. Sanger-based sequencing showed 230/298 (77.2%) had subtype CRF01_AE, 41 (13.8%) subtype B, and the rest had other subtypes or recombinants. Overall TDR was 11.7%. TDR was associated with lower viral loads and no previous HIV testing. CRF01_AE had a higher likelihood of a viral load >100,000 copies/ml and having a baseline CD4 count <50 cells/mm3. CONCLUSION: TDR in the Philippines is high at 11.7%. CRF01_AE was observed to have a higher baseline viral load and lower CD4 counts compared with other cocirculating subtypes. Further research needs to confirm this observation because it suggests that CRF01_AE may have a survival advantage that led to replacement of subtype B as the dominant subtype. Drug resistance testing is recommended in the Philippines when initiating NNRTI-based antiretroviral therapy but may not be necessary for INSTI-based regimens.

Infectious complications associated with monoclonal antibodies and related small molecules.

Biologics are increasingly becoming part of routine disease management. As more agents are developed, the challenge of keeping track of indications and side effects is growing. While biologics represent a milestone in targeted and specific therapy, they are not without drawbacks, and the judicious use of these "magic bullets" is essential if their full potential is to be realized. Infectious complications in particular are not an uncommon side effect of therapy, whether as a direct consequence of the agent or because of the underlying disease process. With this in mind, we have reviewed and summarized the risks of infection and the infectious disease-related complications for all FDA-approved monoclonal antibodies and some related small molecules, and we discuss the probable mechanisms involved in immunosuppression as well as recommendations for prophylaxis and treatment of specific disease entities.

Intracranial Mass Lesions in Human Immunodeficiency Virus Patients in the Philippines: A Retrospective Cohort Study.

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.

Target product profile for a dengue pre-vaccination screening test.

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.

Detection and Genome Sequencing of SARS-CoV-2 Variants Belonging to the B.1.1.7 Lineage in the Philippines.

We report the sequencing and detection of 36 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) samples containing lineage-defining mutations specific to viruses belonging to the B.1.1.7 lineage in the Philippines.

High rates of tenofovir failure in a CRF01_AE-predominant HIV epidemic in the Philippines.

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 < 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.

Multidrug-resistant tuberculosis (MDR-TB) and multidrug-resistant HIV (MDR-HIV) syndemic: challenges in resource limited setting.

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.

Primary intracranial leiomyosarcoma among patients with AIDS in the era of new chemotherapeutic and biological agents.

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.

Hypermucoviscous capsular 1 (K1) serotype Klebsiella pneumoniae necrotising fasciitis and metastatic endophthalmitis.

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.

The changing molecular epidemiology of HIV in the Philippines.

BACKGROUND: The Philippines has one of the fastest-growing HIV epidemics in the world. Possible reasons for this 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: Viruses from 81 newly diagnosed, treatment-naive HIV patients were genotyped using protease and reverse transcriptase genes. Demographic characteristics and CD4 count data were collected. RESULTS: The cohort had an average age of 29 years (range 19-51 years), CD4+ count of 255 cells/mm3 (range 2-744 cells/mm3), and self-reported acquisition time of 2.42 years (range 0.17-8.17 years). All were male, including 79 men who have sex with men (MSM). The genotype distribution was 77% CRF01_AE, 22% B, and 1% C. 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 the present cohort showed a significant shift in subtype (p<0.0001). Comparison between CRF01_AE and B showed a lower CD4+ count (230 vs. 350 cells/mm3, p=0.03). Survival data showed highly significant survival associated with antiretroviral (ARV) treatment (p<0.0001), but no significant difference in mortality or CD4 count increase on ARVs between subtypes. CONCLUSIONS: The molecular epidemiology of HIV in the Philippines has changed, with the more aggressive CRF01_AE now being the predominant subtype.

Invasive trichosporonosis in an AIDS patient: case report and review of the literature.

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.