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.

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.

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.

Depression, Nutrition, and Adherence to Antiretroviral Therapy in Men Who Have Sex With Men in Manila, Philippines.

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.

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.

HIV care cascade among cisgender men who have sex with men in a key population-led community center in the Philippines.

The HIV epidemic in the Philippines is the fastest growing globally, and disproportionately affects cisgender men who have sex with men (cis-MSM) demanding effective strategies for this key population (KP) group. KP-specific and community-based (CB) interventions have improved the HIV response elsewhere, but these have yet to be evaluated locally. We analyzed the HIV care cascade outcomes in a KP-led, CB HIV test-and-treat center and determined factors that affect these by performing a retrospective study of medical records of 3137 patients diagnosed from January 2016 to March 2019 in LoveYourself in Manila, Philippines. Multivariate logistic regression was performed to determine predictors affecting the likelihood of antiretroviral therapy (ART) initiation and viral load (VL) suppression. As to UNAIDS 90-90-90 targets, LoveYourself had higher rates than national outcomes with 78% initiated ART and 84% achieved VL suppression. Such satisfactory performance is consistent with other studies exploring CB, KP-led approaches among cis-MSM. Patients who presented with WHO Stages 2-4 and those with sexually transmitted infections were less likely to initiate ART. Patients who presented with WHO Stages 2-4 and those whose ART was started late were less likely to be virally suppressed. These findings suggest the need to develop responsive interventions to reach the UNAIDS targets.

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.

Regional Differences in the Prevalence of Major Opportunistic Infections among Antiretroviral-Naïve Human Immunodeficiency Virus Patients in Japan, Northern Thailand, Northern Vietnam, and the Philippines.

To identify regional differences in the distribution of opportunistic infections (OIs) among human immunodeficiency virus (HIV)-infected patients in Asia, the medical records of antiretroviral therapy (ART)-naïve patients who attended the following tertiary hospitals from 2003 to 2011 were reviewed: Nagoya Medical Center (NMC, Nagoya, Japan), Lampang Hospital (LPH, Lampang, northern Thailand), Bach Mai Hospital (BMH, Hanoi, northern Vietnam), and Philippine General Hospital (PGH, Manila, Philippines). Logistic regression analyses were performed to identify associations between country of origin and risk of major OIs. In total, 1,505 patients were included: NMC, N = 365; LPH, N = 442; BMH, N = 384; and PGH, N = 314. The median age was 32 years, and 73.3% of all patients were male. The median CD4 count was 200 cells/µL. Most patients at NMC and PGH were men who have sex with men. Injection drug users were most common at BMH (35.7%). Mycobacterium tuberculosis (TB) was most common at PGH (N = 75) but was rare at NMC (N = 4). Pneumocystis pneumonia (PCP) prevalence was highest at NMC (N = 74) and lowest at BMH (N = 13). Multivariable logistic regression showed increased odds of TB at PGH (adjusted odds ratio [aOR] = 42.2, 95% confidence interval [CI] = 14.6-122.1), BMH (aOR = 12.6, CI = 3.9-40.3), and LPH (aOR = 6.6, CI = 2.1-21.1) but decreased odds of PCP at BMH (aOR = 0.1, CI = 0.04-0.2) and LPH (aOR = 0.2, CI = 0.1-0.4) compared with those at NMC. The cryptococcosis risk was increased at LPH (aOR = 6.2, CI = 0.9-41.0) compared with that at NMC. Cytomegalovirus (CMV) retinitis prevalences were similar in all countries. OI prevalence remained high among ART-naïve patients in our cohort. The risks of TB, PCP, and cryptococcosis, but not CMV retinitis, differed between countries. Improved early HIV detection is warranted.

Leptospirosis outbreak after a heavy rainfall typhoon in the Philippines: Clinical features, outcome and prognostic factors for mortality

@#<p style="text-align: justify;"><strong>BACKGROUND AND OBJECTIVES:</strong> In September 2009, Metro Manila was hit by a heavy rainfall typhoon Ketsana inundating several cities of Metro Manila causing an outbreak of leptospirosis. We analyzed the prognostic factors associated with mortality among leptospirosis patients admitted after the typhoon at nine tertiary hospitals from September to November 2009.<br /><strong>METHODS:</strong> We reviewed the charts of patients with probable and confirmed leptospirosis. Confirmed leptospirosis was based on any of the following: positive leptospiral culture of blood or urine, single high leptospira microagglutination titer (MAT) of 1:1600 or a fourfold rise in MAT antibody titers or seroconversion. Patients with negative serology or cultures but with history of wading in floodwaters plus any of the following signs and symptons: fever, headache, myalgia, conjunctival suffusion, diarrhea and abdominal pain, jaundice, oliguria and changes in sensorium were considered probable cases. <br /><strong>RESULTS:</strong> We analyzed 332 probable and 259 confirmed leptospirosis patients. Mean age was 37.95± 14.09, mostly males (80.2%). Almost all patients (98%) waded in floodwaters. Majority had moderate to severe form of leptospirosis (83%). Acute renal failure was the most common complication (87.1%). Mortality was 11.3% mostly due to pulmonary hemorrhage. On multivariate analysis of confirmed and probable cases, the factors independently associated with mortality were pulmonary hemorrhage (OR 2.75, 95% CI 1.46 to 5.20), severity of the disease (OR 3.85, 95% CI 1.60 to 9.26), thrombocytopenia (OR 3.16, 95% CI 1.22-8.16), duration of illness before admission (OR 0.88, 95% CI 0.78-0.99) and age (OR 1.03, 95% CI 1.00-1.06).<br /><strong>CONCLUSION:</strong> Pulmonary hemorrhage remains a poor prognostic factor and strong predictor of mortality among patients with severe leptospirosis. Early consult through heightened awareness of the public and prompt recognition of leptospirosis among clinicians can decrease the risk for progression to complications of leptospirosis and mortality. <br /><br /> </p>

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.

Clinical profile of patients diagnosed with leptospirosis after a typhoon: a multicenter study.

This study described the clinical features and complications of leptospirosis among patients seen at nine tertiary hospitals from September 28 to November 30, 2009 after a heavy rainfall typhoon. The clinical findings of the confirmed cases were compared with the previous clinical studies on seasonal leptospirosis in the Philippines. Risk factors for complicated disease were also identified. Confirmed cases were based on any of the following: positive leptospiral cultures of blood or urine, single high leptospira microscopic agglutination test (MAT) titer of 1:1,600, a fourfold rise in MAT, and/or seroconversion. Of 670 patients with possible leptospirosis, 591 were probable by the WHO criteria, 259 (44%) were confirmed. Diagnosis was confirmed by MAT 176 (68%), by culture 57 (22%), and by MAT and culture 26 (10%). The mean age of the confirmed cases was 38.9 years (SD 14.3). The majority were males (82%) and had a history of wading in floodwaters (98%). The majority of the patients presented with nonspecific signs, with fever as the most common (98.5%). Other findings were myalgia (78.1%), malaise (74.9%), conjunctival suffusion (59.3%), oliguria (56.6%), diarrhea (39%), and jaundice (38%). Most of the patients presented with a moderate-to-severe form of leptospirosis (83%). Complications identified were renal failure (82%), pulmonary hemorrhage (8%), meningitis (5%), and myocarditis (4%). Mortality rate was 5%, mostly due to pulmonary hemorrhage. This study emphasizes the importance of public awareness and high index of suspicion among clinicians of leptospirosis during the monsoon months when flooding is common. Early recognition and detection of the disease should decrease morbidity and mortality.

New world cutaneous leishmaniasis in a traveler: The first documented case in the Philippines

We describe New World cutaneous leishmaniasis (Leishmania amazonensis), a disease not endemic in the Philippines, in a 45-year-old man with ulcerating lesions on his hand and leg ater returning from South America. The patient responded to treatment with liposomal amphotericin B. This imported case of leishmaniasis highlights the importance of obtaining a detailed travel history in patients with chronic, non-healing skin lesions which should lead to earlier recognition and treatment.