Cross-resistance to entry inhibitors and lenacapavir resistance through Week 52 in study CAPELLA.

Background: Lenacapavir (LEN) is a first-in-class inhibitor of human immunodeficiency virus type 1 (HIV-1) capsid function for the treatment of heavily treatment-experienced people with HIV (PWH) harbouring multidrug resistance in combination with an optimized background regimen (OBR). Here, we describe in vitro analysis of the interplay between entry inhibitors (EI; enfuvirtide, fostemsavir, ibalizumab, and maraviroc) susceptibility and LEN susceptibility in samples from 72 participants in the phase 2/3 CAPELLA study, as well as the emergence of resistance in CAPELLA through 52 weeks.

Methods: The phenotypic susceptibility to EIs of screening samples from participants was analysed using entry assays, and susceptibility to LEN was generated.

Rapid HIV-1 genotyping assay for the detection of capsid mutations.

Human immunodeficiency virus (HIV) capsid is one of the most recent viral proteins successfully targeted for the development of antiretrovirals. Lenacapavir is a first in class HIV-1 capsid inhibitor that was recently approved for the treatment of highly treatment-experienced people with HIV in combination with other anti-HIV drugs. Owing to the novelty of the viral target, methods to characterize the potential resistance-associated mutations present in capsid upon treatment failure have not been fully established yet.

Resistance Analyses in Highly Treatment-Experienced People With Human Immunodeficiency Virus (HIV) Treated With the Novel Capsid HIV Inhibitor Lenacapavir.

Background: Lenacapavir (LEN) is a first-in-class inhibitor of human immunodeficiency virus type 1 (HIV-1) capsid function in clinical development for the treatment of heavily treatment-experienced (HTE) people with HIV (PWH) harboring multidrug resistance (MDR) in combination with an optimized background regimen (OBR). Here we describe resistance analyses conducted in the pivotal phase 2/3 CAPELLA study.

Methods: CAPELLA enrolled viremic HTE PWH with resistance to ≥3 of 4 of the main antiretroviral (ARV) classes and resistance to ≥2 ARV drugs per class.

Phenotypic resistance to lenacapavir and monotherapy efficacy in a proof-of-concept clinical study.

Background: Lenacapavir in vitro resistance selections identified seven mutations in HIV-1 capsid protein (CA) associated with reduced susceptibility.

Objectives: To analyse lenacapavir activity against lenacapavir-associated resistance mutations in multiple assays. We also report Day 10 resistance analyses conducted in a Phase 1b study of lenacapavir (Study 4072) in people with HIV (PWH).

Substantial Remission in Subacute Sclerosing Panencephalitis by Following the Ketogenic Diet: A Case Report.

An eight-year-old boy presented with rhythmic myoclonic jerks that stretched back to the age of four years. He was diagnosed as having subacute sclerosing panencephalitis (SSPE). This is a progressive and almost uniformly fatal disease.

Dietary Therapy in Secondary Progressive Multiple Sclerosis: A Case Report.

A 60-year-old man presented with a history of an acute episode of mono-ocular involvement and several acute spinal cord episodes from 1988 to 1991. Multiple MRIs of the spinal cord and brain and cerebrospinal fluid analysis were consistent with a clinical diagnosis of multiple sclerosis (MS). Following this, there was a quiescent period of four to five years, after which he reported progressive weakness and spasticity of lower limbs with urgency and precipitancy of urine.