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.

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.

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.

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.

The Philippine HIV/AIDS epidemic: A call to arms

The incidence of HIV/AIDS in the Philippines has been rising to unprecedented levels and we are in the midst of a full-blown epidemic. In 2009, a record number of new cases were diagnosed, with the highest number of new cases ever reported in a month (126) occurring last December. While effective treatment exists for persons living with HIV/AIDS, the number of trained healthcare personnel who are competent to care for these patients is in very short supply. HIV/AIDS treatment is tremendously complex, and requires specialized training in order to maximize the benefit derived from medications. Moreover, antiretroviral drugs are prohibitively expensive, and the potential loss of external funding from the Global Fund which currently supports antiretroviral treatment will be catastrophic. Prevention and awareness campaigns remain by far potentially the most effective means of controlling HIV/AIDS in the Philippines. Clinical capacity building through training of physicians is already in effect, but may need to be ramped up further in the face of accelerating case numbers. In addition, international research collaboration for access to state of the art therapies and approaches will play an important role if we hope to reverse the epidemic. Finally, novel policies including opt-out testing, aggressive case finding, and test and treat strategies need to be explored in order to effectively combat this threat.

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.

Schistosomiasis in travelers and immigrants.

Schistosomiasis is caused by trematode parasites of one of five species, Schistosoma mansoni, Schistosoma haematobium, Schistosoma japonicum, Schistosoma intercalatum, or Schistosoma mekongi, acquired via skin contact with fresh water containing infectious larval cercariae. Between 1 and 8 weeks after exposure, acute schistosomiasis presents as dermatitis, fever, fatigue, or eosinophilia. If untreated, long-term infection may cause anemia or undernutrition and may progress to liver fibrosis, portal hypertension, or hydronephrosis. Schistosomiasis represents a threat to residents and visitors in all endemic areas of Africa, Asia, and South America. Travelers should be made aware of infection risk if they become exposed to untreated fresh water. New immigrants and those returning to high-risk areas to visit friends and family should be screened for signs and symptoms of acute and chronic schistosomiasis. Physicians caring for travelers and immigrants must be familiar with the signs and symptoms of schistosomiasis and must be able to diagnose and treat it correctly.

Mycobacterium other than tuberculosis (MOTT) infection: an emerging disease in infliximab-treated patients.

OBJECTIVES: Infliximab has revolutionized treatment of rheumatologic diseases and inflammatory bowel disease. However, it increases the risk of tuberculosis. Less is known about the development of Mycobacterium other than tuberculosis (MOTT) infection. We review the literature on non-tuberculous mycobacterial infections in infliximab-treated patients and report the first case of disseminated Mycobacterium avium complex in an infliximab-treated patient complicated by immune reconstitution inflammatory syndrome. METHODS AND RESULTS: MEDLINE search with the keywords mycobacteria and infliximab revealed four cases of MOTT in patients treated with infliximab: fatal Mycobacterium peregrinum pneumonia in a patient with polymyositis and dermatomyositis; a patient with rheumatoid arthritis with skin and soft tissue infection with Mycobacterium abscessus; Mycobacterium fortuitum in a patient with rheumatoid arthritis; and a case of pulmonary MAC without dissemination. Review of US data from 1998 to 2002 published by Wallis et al. revealed that out of more than 233,000 patients treated with infliximab, 30 developed unspecified mycobacterial species infection. No further data was available regarding these cases. CONCLUSION: MOTT infection is a rare but emerging complication of infliximab therapy. MOTT cases tend to progress rapidly in infliximab-treated patients and withdrawal of infliximab therapy can result in immune reconstitution.

Lactobacillus endocarditis: case report and review of cases reported since 1992.

Lactobacillus is a rare cause of endocarditis with only 78 reported cases in the literature. We report a case of Lactobacillus endocarditis and review reported adult cases since the introduction of the Duke's criteria for endocarditis. An analysis is presented with a focus on outcomes. Mortality from reported cases of Lactobacillus endocarditis was found to have substantially improved since 1992. Surgical rates for persistent disease remain the same. Possible reasons for this improvement include better antibiotics, earlier recognition of cases, and more aggressive treatment regimens.