A Prospective Study of Cytomegalovirus-Specific Cell-Mediated Immune Monitoring and Cytomegalovirus Infection in Patients With Active Systemic Lupus Erythematosus Receiving Immunosuppressants.

BACKGROUND: The effects of cytomegalovirus (CMV)-specific cell-mediated immunity (CMI) on CMV infection in patients with autoimmune diseases receiving immunosuppressants have not been explored. METHODS: Patients with active systemic lupus erythematosus (SLE) were preemptively monitored for clinically significant CMV infection (CsCMVI; defined as plasma CMV DNA loads >3 log10 IU/mL). CMV-specific CMI was assessed using an enzyme-linked immunosorbent assay (QuantiFERON-CMV [QF]) before as well as 1 and 3 months after intense immunosuppressive therapy. RESULTS: The study included 55 patients with active SLE; patients were a mean age (SD) of 34 (13) years and had a median SLE Disease Activity Index 2000 score (SD) of 14 (8), and 93% were female. Most patients had renal involvement (67%), received methylprednisolone (93%), and were CMV-seropositive (95%). Thirteen (23.6%) patients developed CsCMVI. Among patients with active SLE who were QF-negative (QF-) and QF-positive (QF+) before receiving immunosuppressive therapy, 28.6% and 25% developed CsCMVI, respectively (P = .69). However, 1 month postimmunosuppression, more QF- than QF+ patients developed CsCMVI (44.4% vs 11.8%; P = .03; adjusted hazard ratio, 4.97; 95% CI, 1.07-23.10; P = .04). CONCLUSIONS: Patients with active SLE and low CMV-specific T-cell responses could develop CMV infection after receiving immunosuppressants. Further studies should focus on CMV-specific CMI among patients with autoimmune diseases.

A Nationwide Survey of Cytomegalovirus Prevention Strategies in Kidney Transplant Recipients in a Resource-Limited Setting.

OBJECTIVE: Strategies to prevent cytomegalovirus (CMV) infection in resource-limited settings have been under-explored. We investigated CMV prevention strategies utilized among transplant centers in Thailand. METHOD: A questionnaire on CMV prevention strategies for kidney transplant (KT) recipients was developed using a web-based electronic survey website (www.surveymonkey.com). The survey was delivered to 31 transplant centers in Thailand. One infectious disease physician (ID) and 1 nephrologist (NP) from each center were included. RESULTS: There were 43 respondents from 26 of the 31 transplant centers (84%), including 26 (60%) IDs and 17 (40%) NPs. Forty-one 95% (41/43) physicians agreed on the necessity of CMV prevention. Of these, 77% (33/43) physicians implemented prevention strategies for their patients. Interventions included preemptive approaches (48%), prophylaxis (45%), hybrid approaches; surveillance after prophylaxis (3%), and CMV-specific immunity-guided approaches (3%). For CMV-seropositive KT recipients, use of preemptive approaches (84%) exceeded prophylaxis (12%). However, 81% of the former preferred targeted prophylaxis in patients receiving antithymocyte globulin therapy. Sixty-five percent and 93% of physicians started preemptive therapy when plasma CMV DNA loads reached 2000 and 3000 copies/mL (1820 and 2730 IU/mL), respectively. A significantly greater percentage of NPs initiated preemptive therapy at a plasma CMV DNA load of 1820 IU/mL compared with IDs (88% vs 50%; P = .02). The most common barrier to prevention strategy implementation was financial inaccessibility of oral valganciclovir (67%) and quantitative CMV DNA testing (12%). CONCLUSIONS: Most physicians agreed on a need for preemptive approaches, although prophylaxis was targeted in those receiving intense immunosuppression. The financial implication is the main barrier for CMV prevention in Thailand.

The use of pharmacogenetics in clinical practice for the treatment of individuals with HIV infection in Thailand.

OBJECTIVES: The objectives of this study were to describe the use of pharmacogenetics in clinical practice for the treatment of individuals with human immunodeficiency virus (HIV) infection and to determine the treatment outcomes of HIV-infected patients in whom pharmacogenetic testing was performed. METHODS: This study involves a retrospective collection of medical records of HIV-infected patients who attended Ramathibodi Hospital during January 2011 to November 2014 and in whom pharmacogenetic testing was performed. We reviewed patients' characteristics, reasons for pharmacogenomic testing, results of human leukocyte antigen-B* (HLA-B*) 5701, HLA-B*3505, HLA-B*4001, CYP2B6, and antiretroviral drug (ARV) levels, treatment planning after the physicians were informed the results, and outcome after changing the treatment. RESULTS: A total of 103 HIV-infected patients with a median age of 46 (range, 20-85) years were enrolled, and 68.9% of them were male. The reasons for pharmacogenomic testing were having adverse drug reactions besides rash (37.9%), screening before prescribing ARV (36.9%), choice of next ARV (19.4%), and confirmation of the cause of skin rash (5.8%). After the physicians knew the results, they adjusted the treatment plan including changing the regimens, changing the ARV dose for avoiding toxicity, and stopping ARV. Among 45 patients, side effects, such as dizziness from efavirenz or rash from abacavir, were improved in 96.4%. Among 27 patients, abnormal laboratory results, such as renal insufficiency from tenofovir or anemia from zidovudine, were improved and some returned to normal in 59.3%. HIV RNA was undetectable after treatment adjustment in 94.9%. CONCLUSION: The benefits of pharmacogenetic testing are either guiding the initial drug regimen or individualizing regimen, increasing efficacy, and simultaneously avoiding adverse drug reactions. Use of pharmacogenetic testing in HIV-infected Thai adults should be considered.