A study for precision diagnosing and treatment strategies in difficult-to-treat AIDS cases and HIV-infected patients with highly fatal or highly disabling opportunistic infections

Abstract

Background: Toxoplasma encephalitis (TE) is one of the main opportunistic infections in acquired immunodeficiency syndrome (AIDS) patients, and represents a social burden due to its high prevalence and morbidity. Concomitant antiretroviral therapy (ART), together with effective anti- toxoplasma combination therapy, is an effective strategy to treat AIDS-associated TE (AIDS/TE) patients. However, the timing for the initiation of ART after diagnosis of TE remains controversial. We therefore designed the present study to determine the optimal timing for ART initiation in AIDS/TE patients. Methods/Design: This trial is a 17-center, randomized, prospective clinical study with 2 parallel arms. A total of 200 participants will be randomized at a 1:1 ratio into the 2 arms: the early ART initiation (≤14 days after TE diagnosis) arm and the deferred ART (>14 days after TE diagnosis) arm. The primary outcome will be the difference of mortality between the 2 arms at 48 weeks. The secondary outcomes will be the differences between the 2 arms in the changes of CD4+ counts from baseline to week 48, the rate of virologic suppression (HIV ribonucleic acid <50 copies/mL) from baseline to week 48, the incidence of TE-associated immune reconstitution inflammatory syndrome during the study period, and the incidence of adverse effects during the study period. Discussion: This present trial aims to evaluate the optimal timing for ART initiation in AIDS/TE patients, and will provide strong evidence for AIDS/TE treatment should it be successful. Trial registration: This trial was registered as one of the 12 trials under the name of a general project at the chictr.gov ( http://www.chictr.org.cn/showproj.aspx?proj=35362 ) on February 1, 2019, and the registration number of the general project is ChiCTR1900021195.

Brain opportunistic infections and tumors in people living with HIV — still a challenge in efficient antiretroviral therapy era

“…Patients with TBM and cryptococcal meningitis had short survival and high mortality rates. The intermittent availability of serum cryptococcal antigen (CrAG) tests, first-line fungicidal (amphotericin-based) regimens for cryptococcal meningitis, rapid diagnosis tests (Xpert MTB), and drugs to treat XDR TB may have resulted in increased morbidity and mortality (Hanif et al 2022 ; Okurut et al 2020 ; Zeng et al 2020 ).…”

Early Antiretroviral Therapy in AIDS Patients Presenting With Toxoplasma gondii Encephalitis Is Associated With More Sequelae but Not Increased Mortality

“…Further studies under controlled conditions to generate evidence are needed to corroborate these findings. Future research also needs to address the chronic complications of those who manage to survive ANI secondary to HIV/AIDS and OIs and provide insights into cognitive and physical disabilities and rehabilitation (53).…”

Cerebral toxoplasmosis in HIV-infected patients: a review

“…In a phase IV, multicenter, prospective, randomized open-label clinical trial, Schafer et al found similar safety between immediate (within 7 days) and deferred (after completing OI-therapy) for starting antiretroviral therapy in cerebral toxoplasmosis patients (3–6 weeks) [ 54 ]. A randomized controlled trial is ongoing to evaluate the optimal timing for HAART in PLWH with cerebral toxoplasmosis ChiCTR1900021195 [ 55 ]. Wang et al reported that most HAART compounds had no significant interaction with sulfadiazine and pyrimethamine [ 56 ].…”