Immediate versus deferred antiretroviral therapy in HIV-infected patients presenting with acute AIDS-defining events (toxoplasmosis, Pneumocystis jirovecii-pneumonia): a prospective, randomized, open-label multicenter study (IDEAL-study)

Abstract

BackgroundTo evaluate clinical outcomes after either immediate or deferred initiation of antiretroviral therapy in HIV-1-infected patients, presenting late with pneumocystis pneumonia (PCP) or toxoplasma encephalitis (TE).MethodsPhase IV, multicenter, prospective, randomized open-label clinical trial. Patients were randomized into an immediate therapy arm (starting antiretroviral therapy (ART) within 7 days after initiation of OI treatment) versus a deferred arm (starting ART after completing the OI-therapy). All patients were followed for 24 weeks. The rates of clinical progression (death, new or relapsing opportunistic infections (OI) and other grade 4 clinical endpoints) were compared, using a combined primary endpoint. Secondary endpoints were hospitalization rates after completion of OI treatment, incidence of immune reconstitution inflammatory syndrome (IRIS), virologic and immunological outcome, adherence to proteinase-inhibitor based antiretroviral therapy (ART) protocol and quality of life.Results61 patients (11 patients suffering TE, 50 with PCP) were enrolled. No differences between the two therapy groups in all examined primary and secondary endpoints could be identified: immunological and virologic outcome was similar in both groups, there was no significant difference in the incidence of IRIS (11 and 10 cases), furthermore 9 events (combined endpoint of death, new/relapsing OI and grade 4 events) occurred in each group.ConclusionsIn summary, this study supports the notion that immediate initiation of ART with a ritonavir-boosted proteinase-inhibitor and two nucleoside reverse transcriptase inhibitors is safe and has no negative effects on incidence of disease progression or IRIS, nor on immunological and virologic outcomes or on quality of life.

Timing of antiretroviral therapy for HIV-infected patients with moderate-to-severe Pneumocystis pneumonia: study protocol for a multi-center prospective randomized controlled trial

“…However, a recent study investigating the timing of initiation in HIV-patients with acute AIDS-defining events, enrolling 50 patients with PCP, found that there were no significant differences in safety, efficacy and quality of life between the immediate ART initiation group (initiation within 7 days of PCP diagnosis and treatment) and the deferred initiation group (after the treatment for PCP was over) [7].…”

“…In the study, results from both overall analysis of all OIs, and subgroup analysis of PCP were consistent [8]. However, in a recent study investigated the timing of initiation of proteinase-inhibitor ART in HIV-patients with acute AIDS-defining events, enrolling a total of 61 subjects {11 patients with toxoplasmosis (TE) and 50 patients with PCP}, researchers found that there were no significant immunological or virological differences between the immediate ART initiation group and the deferred initiation group [7]. From the results of the above studies, it is obvious that the timing for ART initiation in HIV-infected persons with PCP remains controversial, and warrants further investigation.…”

“…30%, and may be even higher if diagnosis is delayed [4][5][6]. Although efforts for the early diagnosis and treatment of PCP have been made, the proportion of HIV patients with advanced PCP has not decreased in many high-burden countries [7].…”

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

“…Despite the success of ART in treating AIDS patients, initiating ART too early should be cautious in patients with OIs including those with TE, due to the concerns of immune reconstitution inflammatory syndrome (IRIS), drug-drug interactions and drug toxicities. [ 7 ] The development of IRIS may have significant negative implications for TE patients, for example, as the emergence of IRIS may result in rehospitalization, changes to therapy, or even deaths. [ 8 ] There are very limited data in the literature at present regarding the timing of ART when TE is present in ART-naive patients.…”

Establishment of Novel High-Standard Chemiluminescent Assay for NTPase in Two Protozoans and Its High-Throughput Screening

“…Toxoplasma gondii is a major type of parasites and an obligatory single-cell parasitic eukaryote [1] causing serious health issues in human beings [2] and many warm-blooded animals [1]. The infection leads to Toxoplasmosis, which is particularly acute in AIDS patients [3], organ transplant recipients [4] and pregnant women [5]. Neospora caninum was recently discovered to be another type of protozoa belonging to phylum Apicomplexa [6].…”