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cases. This syndrome is associated with aeromedical risk factors, such as hypertriglyceridaemia,
hypercholesterolaemia, insulin resistance, and Type 2 diabetes mellitus. Possible cognitive effects
of HAART, relevant for flight safety, may be assessed with validated neuropsychological test
ICAO Preliminary Unedited Version — November 2009 III-13-11
batteries or a functional evaluation, e.g. simulator check. A 1997 study showed no impairment of
cognitive processes in patients treated with the NRTIs didanosine or zidovudine (monotherapy).
Regular follow up is required to monitor treatment efficacy, ART adherence, toxic side effects of
medication or evidence of resistance.
j) Other issues
Magnetic Resonance Imaging (MRI) can detect white matter abnormalities, high signal
abnormalities in gray matter structures, and/or cerebral atrophy of HIV encephalopathy.
However, such changes are relatively non-specific and the differentiation of different causes for
the abnormalities is difficult with conventional MRI. Significant improvements may come as
functional imaging methods, such as perfusion imaging, magnetic resonance spectroscopy (MRS)
and brain mapping with functional MRI become more widespread in clinical practice.
Cerebrospinal Fluid (CSF) - Abnormalities of the cerebrospinal fluid (CSF) in HIV-associated
dementia are generally non-specific, with mild elevations in protein and pleocytosis. It appears
that HIV RNA levels in CSF correlate with the presence of cognitive impairment, although the
precise relationship of HIV-1 RNA values in CSF and the risk of development or progression of
neurological disease has not yet been determined. Even in patients with neurological disease, CSF
RNA levels are relatively low. The false-negative rate of CSF RNA values is high, and minor
neurological dysfunction is often not associated with high CSF HIV RNA levels. CNS syphilis
screening should be routinely performed with any CSF sample.
Risk of progression
In HIV-seropositive persons, the average latency period to developing AIDS is 10 years and without any
therapy, survival of about 12 years can be expected. Treatment significantly extends survival and near
normal life expectancy may even be possible with relatively non-toxic and highly effective combination
ART.
During the latency period most HIV infected persons are asymptomatic and those engaged in aviation
duties would be able to continue their careers for several years (if the HIV diagnosis is made early after
infection) until therapy is started and for many years once HAART has been successfully commenced.
However, some patients may present relatively late in the course of their infection and there is
inter-individual variability in the rate of progression to symptomatic disease and then AIDS as well as in
the occurrence of adverse effects of HAART.
As symptomatic HIV-related disease including (subtle) cognitive impairment, AIDS-defining illnesses
and several adverse effects of HAART are incompatible with aviation duties, prediction and early
detection of cognitive involvement and/or AIDS-related symptoms and long-term monitoring for the
adverse effects of treatment are essential for the aeromedical assessment of a HIV-seropositive applicant.
In the absence of HIV-related symptoms (including cognitive decline), aeromedical considerations could
be aided by risk assessment methods that use CD4+ T cell counts, viral load, and age.
Several large study groups have published data that can be used in the assessment of the risk of disease
progression for those who are treatment naïve and those who commenced therapy.
ICAO Preliminary Unedited Version — November 2009 III-13-12
The Concerted Action on Sero-Conversion to AIDS and Death in Europe collaboration (CASCADE) have
produced a Poisson regression model based on data of 5126 person-years of 3226 asymptomatic
seropositive subjects who either had no treatment or monotherapy, to predict the 6-month risk of
developing AIDS. This can be modified to give a 12-month risk (see Table 3).
For the assessment of individual cases, adverse trends in CD4+ and viral load levels and the applicant’s
age should be taken into account.
For those who have already commenced HAART, data from EuroSIDA or the Antiretroviral Therapy
(ART) Cohort Collaboration can provide a basis for estimating the risk of disease progression. The former
reports on the risk of clinical progression (diagnosis of a new AIDS defining illnesses or death). The
scoring system is shown in Table 4. The ART Cohort Collaboration found that six months after starting
ART, the current CD4 count and viral load, but not the baseline values, are strongly associated with
subsequent disease progression. The data presented by the collaboration is limited by its broad categories
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Manual of Civil Aviation Medicine 2(97)
