The current study was conducted primarily with the

The current study was conducted primarily with the A32 antibody, together with a small number of sera from HIV-infected individuals. ADCC AZD-9291 are among the first elicited following infection, as the gp120–CD4 interaction leads to exposure of cluster A epitopes. Not all such CD4-induced epitopes elicit equivalent ADCC activities, due to subtle differences in antibody-epitope recognition and/or Fc differences (). Moreover, antibodies targeting other Env sites, including some with neutralizing activity such as 2G12 and b12, also mediate ADCC. The relative abundance of all these antibodies in the human sera tested was not determined. Further, the degree of gp120 shedding and levels of CD4 and Env present on the cells tested compared to uncultured, primary HIV-infected cells was not reported. It will be critical to confirm the observations made with studies using the SHIV model. Similarly, the effects of CD4 mimetic administration must be determined. It is an obvious therapeutic candidate, however, the possibility that it might facilitate greater CD4-independent infection must be considered.
By controlling human immunodeficiency virus (HIV) replication and allowing recovery of immune system function, combination antiretroviral therapy (cART) has revolutionised the outlook for people-living-with-HIV (PLWH) to that of a chronic but manageable medical condition. Despite this success, other medical problems, such as hypertension and cardiovascular disease, are reported to occur more frequently and at a younger age in PLWH compared to matched control populations (). Another medical problem with a high prevalence and high morbidity is cognitive impairment (). For many co-morbidities, surrogate markers aid diagnosis and assist in the clinical staging of a disease state. For cognitive impairment however, disease markers to date have either been unreliable or impractical to measure. For instance, clinical assessments such as formal neuropsychological testing are time consuming to perform and prone to many confounding issues such as illicit drug and alcohol use, the presence of depression and anxiety, and day to day variability in a patient\'s performance. Novel cerebral imaging techniques show promise in the diagnosis and assessment of HIV-associated cognitive impairment (). However, many of these novel imaging techniques are not widely available and may only be accessible as part of a research study, rather than in general clinical care. And lastly, although cerebrospinal fluid (CSF) markers, such as neurofilament light protein (NFL) concentration, show promise, collection of CSF is problematic. Lumbar puncture, whilst generally safe, is an invasive and resource expensive procedure which does not lend itself particularly well to repeated measure (). In this issue of , report on the measurement of plasma NFL concentrations, using a new ultrasensitive single molecule assay, and its correlations with CSF NFL concentrations in several cohorts of PLWH. Groups assessed included individuals with primary HIV-infection, neuroasymptomatic PLWH not on cART with different ranges of CD4+ lymphocyte counts (above 350cells/uL, 200–349cells/uL, 50–199cells/uL and below 50cells/uL), individuals with overt HIV-associated dementia and subjects on cART with plasma HIV RNA <50copies/mL for greater than one year. Furthermore an HIV-uninfected control group was included in their analysis. As expected, CSF concentration of NFL was dependent on the cohorts studied with the highest concentrations observed in those with HIV-associated dementia and higher concentrations in PLWH with untreated HIV-disease and low CD4+ lymphocyte counts. Of importance, in all groups studied, a strong correlation between plasma NFL and CSF NFL was reported. The values of NFL plasma concentrations were 1–2 log lower than in the CSF. However, by developing and utilising this new ultrasensitive plasma NFL assay, concentrations as low as a mean of 9.3nmol/L were measured in the HIV-uninfected control group and every subject had a detectable and quantifiable concentration. This impressive dynamic range highlights the potential sensitivity of this biomarker to detect subtle axonal injury in a variety of patient groups.