GUIDANCE MATERIAL TO SUPPORT THE PROPOSED CHANGES 

TO THE MEDICAL PROVISIONS CONTAINED IN 

ANNEX 1 — PERSONNEL LICENSING 

(Details of the proposed changes to the medical Standards and Recommended Practices 

contained in Annex 1 – Personnel Licensing can be found in 

ICAO State letter AN 5/22-08/33, dated 5 May 2008) 

March 2008 

TABLE OF CONTENTS 

Page 

1. Content of regulatory medical examinations ................................................................................. 1

2. Treatment of depression................................................................................................................. 9 

3. Reporting of medical conditions.................................................................................................... 15 

4. Human immunodeficiency virus.................................................................................................... 17 

5. Insulin-treated diabetes .................................................................................................................. 35 

CONTENT OF REGULATORY MEDICAL EXAMINATIONS 

1. Background 

Class 1 applicants are required to have an annual medical assessment from the time they commence flying 

until they reach 60 years of age, when the frequency becomes 6-monthly. The exception to this is for the 

passenger-carrying single pilot operator, who requires a medical assessment every six months after age 

40 years. The medical assessment varies little during a pilot’s career, although after the initial 

electrocardiogram (ECG) at the first Class 1 examination the frequency for ECGs increases with 

increasing age, initially as a Recommendation (two-yearly from age 30-50 years) and then as a Standard 

(annually from age 50 years). ICAO therefore recognizes the increase in cardiovascular risk with 

increasing age, which is an observation in all Contracting States. There are, however, differences between 

States regarding the rate of increase in risk with increasing age. 

In most Western States, the annual cardiovascular mortality for males reaches around 1 per cent per 

annum at age 70 years, which is about 100 times greater than at age 30. Further, the risk of developing 

other physical diseases such as cancer, diabetes and epilepsy is very low in young adults, but increases 

with increasing age. On the other hand, mental health illness and behavioural problems, including those 

related to drug and alcohol use, do not demonstrate such a steep gradient, and in the general population 

these categories are usually more frequent than physical disease in younger age groups. It therefore seems 

appropriate to consider the likely prevalence of different diseases in the pilot population when considering 

the type of routine periodic examination they should undergo. 

The annual Class 1 medical examination is unlikely to reveal any significant physical problem in pilots 

under age 40 years. Some items of the physical assessment could therefore be omitted in alternate years 

without detriment to flight safety. This would permit additional time to be used to focus on mental health 

aspects, and on preventative aspects of health. It is widely accepted that illness in later life, both physical 

and mental, can be prevented or delayed by lifestyle interventions and treatment, if necessary, at an early 

stage, and professional pilots represent a group of motivated individuals who have a keen interest in 

health maintenance. Such a change of emphasis in the younger pilot should encourage health and, 

therefore, flight safety benefits later on in a pilot’s career. 

The proposed ICAO Standards and Recommended Practices (SARPs) for a Class 1 assessment are being 

adjusted to permit a licensing authority, in alternate years, to omit certain items from the physical 

examination in applicants under 40 years of age, thereby enabling a medical examiner to spend more time 

discussing medical issues, from an educational viewpoint, with an applicant in this age group. However, a 

licensing authority may wish, for example, to undertake some assessment of the vision every year in order 

to ascertain those applicants who would benefit from correcting lenses, or a change in prescription, since 

refractive error can change over time in the younger age group. 

It is felt that an examination of, for example, the heart and lungs, and checking the blood pressure and 

urine in all pilots under 40 years, on an annual basis, is unnecessary – a two yearly examination should be 

adequate. This does not preclude the licensing authority from requiring more frequent checks in those 

who are known to have an increased risk. If the content of the physical examination is reduced in alternate 

years, this releases some time for discussing aspects of health that may, in the longer term (with a 

timescale greater than that of the validity of the medical assessment/certificate) improve the pilot’s health, 

and as a consequence, improve flight safety. 
- 6 - 

Two aspects are particularly worthy of consideration. The first concerns the preservation of physical 

health. The factors for this are well known. Aspects of diet, exercise, smoking, body weight, etc. and their 

effect on health are familiar to all medical examiners and these can be discussed with the individual 

applicant in light of the particular circumstances of the individual, such as family history of illness, body 

weight, exercise habits, etc. Licensing authorities are encouraged to provide guidance to designated 

medical examiners regarding these aspects of health maintenance. 

The second aspect concerns mental health and use of psychoactive substances. Guidance on this area is 

not so readily available, and at the request of ICAO a small group of experts has reviewed the evidence of 

benefit in discussing certain topics with applicants, by means of asking specific questions. This review 

has demonstrated from general population studies that some mental illnesses and misuse of psychoactive 

substances can be prevented by early intervention, before the situation has deteriorated to an extent where 

the health, or medical fitness for flying of a licence holder, has been adversely affected. A separate 

section on this topic with draft guidance material has been provided below. 

Historically, the focus of the periodic medical examination has been to detect medical conditions, almost 

exclusively physical medical conditions, that may pose a threat to flight safety during the forthcoming 

period of validity of the medical assessment/certificate. The medical examiner’s primary role has 

therefore been to detect significant conditions that may cause incapacitation in the relatively short term. 

The role of the medical examiner as educator has not played a formal part in the process, although many 

examiners take on this task as a natural part of the role of any doctor. Whilst the role of the medical 

examiner in determining the physical fitness of the pilot will continue, because of the low level of 

physical pathology encountered in the lower age group, an opportunity to improve the health of the 

applicant, as well as improve flight safety, presents itself. One view is that this is not the role of the 

regulatory medical examiner, but in reality the examiner is in an excellent position to provide this service 

to flight safety and to the applicant (who, experience has shown, is unlikely to seek such advice 

elsewhere). 

By reducing the emphasis on the physical examination in those Class 1 applicants less than 40 years of 

age, time is made available to focus on the non-physical aspects of health, in a non-threatening manner, 

and at no additional cost to the applicant. 

2. Development of questions for use by medical examiners 

As there is evidence that several fatal aviation accidents have been caused by psychiatric disorders or use 

of psychoactive substances, it is reasonable that as part of the periodic aviation medical examination there 

should be questions that pertain to these issues. Little guidance has been provided concerning how such 

aspects could be addressed in the periodic medical examination, although experienced medical examiners 

have often informally and spontaneously included it in assessment of the applicant. Further, the number 

of non-physical conditions that can affect the health of pilots and which can lead to long term unfitness in 

those of middle age appears to be increasing. The conditions addressed by the proposed questions that 

medical examiners could use have been shown to be amenable to preventive action, before they develop 

into significant health problems, and before there is an impact on the pilot’s medical status for flying. 

There are various questionnaires available for assessing mental health and behavioural aspects of an 

individual’s health, having a variety of lengths and complexity. However, the main purpose of 

recommending the questions below is intended to be educational, with the questions serving to promote 

discussion between the medical examiner and the pilot. To encourage dialogue, it is recommended that no 
- 7 - 

written record of the conversation is retained concerning these questions and that this should be made 

clear to the pilot at the outset, thus increasing the likelihood of developing a frank exchange. Further, it is 

to be expected that only rarely will any formal action need to be considered by the medical examiner to 

protect flight safety in the light of response to these questions. 

The questions suggested address those conditions that are most common in the age range of professional 

pilots and those which are most likely to affect performance on the flight deck. Statistics show that the 

main psychiatric conditions that meet these criteria are mood disorders and certain anxiety disorders, 

especially panic episodes. Additionally, in many Contracting States, excessive alcohol intake and use of 

illicit drugs in the general population is occurring with increasing frequency and pilots are not immune 

from these social pressures. Questions have been developed to address these issues as well. 

 

In developing the questions, a review of the literature was undertaken by specialists in the field with the 

aim of choosing simple questions that can be completed quite quickly. The majority of pilots will answer 

all questions in the negative, and it is unnecessary to request pilots without any relevant problems to 

undertake a prolonged screening questionnaire. Those who answer positively, or with uncertainty can be 

engaged with further dialogue by the medical examiner. The main aim is to encourage the pilot to 

consider his lifestyle and improve, where necessary, his or her likelihood of maintaining good mental 

health, including the avoidance of problems linked to the use of psychoactive substances, during his/her 

career. Occasionally, the medical examiner may find conditions that are amenable to medical support or 

even treatment, and the goal is to detect these at an early stage, before they become significant problems 

and before they impact on the pilot’s medical fitness and on flight safety. 

 

Not all medical departments will find the questions relevant to their particular pilot population. Therefore, 

the questions may not represent the best questions for all States, but they offer guidance, a starting point, 

for States that wish to develop such an approach. 

3. Recommended questions concerning mental health and use of psychoactive substances 

Questions for Depression: 

 

1) During the past three months, have you often been bothered by feeling down, depressed or 

hopeless? 

 

2) During the past three months, have you often been bothered by having little interest or pleasure in 

doing things? 

 

3) During the past three months, have you been bothered by having problems falling asleep, staying 

asleep, or sleeping too much, that is unrelated to sleep disruption from night flying or 

transmeridian operations? 

 

4) In the past three months, has there been a marked elevation in your mood lasting for more than 

one week? 

 
- 8 - 

Questions for anxiety/panic attack: 

 

1) In the past three months, have you had an episode of feeling sudden anxiety, fearfulness, or 

uneasiness? 

 

2) In the past three months, did you experience sensations of shortness of breath, palpitations (racing 

heart beat) or shaking while at rest without reasonable cause? 

 

3) In the past year have you needed to seek urgent medical advice because of anxiety? 

 

Questions concerning alcohol use: 

 

1) Have you ever felt that you should cut down on your drinking? 

 

2) Have people annoyed you by criticizing your drinking? 

 

3) Have you ever felt guilty about your drinking? 

 

4) Have you ever needed a drink first thing in the morning? 

 

5) How many alcoholic drinks would you have in a typical week? 

 

6) How many alcoholic drinks would you have on a typical day when you are drinking? 

 

Questions concerning drug use: 

 

1) Have you used drugs other than those required for medical reasons? 

 

2) Which non-prescription drugs have you used? When did you last use this drug(s)? 

References for those who wish to consider the literature themselves are as follows: 

1) Alcohol Alert NIAAA Apr 2002 http://pubs.niaaa.nih.gov/publications/aa56.htm 

2) Screening for Alcohol Problems in Primary Care: Fiellen, Reid, et al, Arch Intern Med Vol. 160 

July 2000. 

3) Case-finding Instruments for Depression. two questions as good as many. Whooley, Avins et al J 

Gen Intern Med. 1997; 12: 439-445. 

4) Using five questions to screen for five common mental disorders in primary care. A.J. MeansChristensen et al; General Hospital Psychiatry 28 (2006) 108-118. 

5) Counselling Resource Welcome to the Drug Abuse Screening Test (DAST). 

http://counsellingresource.com/quizzes/drug-abuse/index.html. 

6) Manual on prevention of problematic use of substances in the aviation workplace, 

Document 9654; International Civil Aviation Organization, Montreal, Canada, 1995

— — — — — — — — 
TREATMENT OF DEPRESSION 

1. Introduction 

A new Recommendation and a Note is proposed concerning licence holders who have depression and are 

in need of treatment with antidepressants: 

6.3.2.2.1 (and 6.4.2.2.1, 6.5.2.2.1) Recommendation.— An applicant with depression, 

being treated with antidepressant medication, should be assessed as unfit unless the medical 

assessor, having access to the details of the case concerned, considers the applicant’s condition 

as unlikely to interfere with the safe exercise of the applicant’s licence and rating privileges. 

Note 1.— Guidance on assessment of applicants treated with antidepressant medication is 

contained in the Manual of Civil Aviation Medicine (Doc 8984).

2. Background 

The use of antidepressant medication in aircrew and air traffic controllers (ATC) has traditionally been 

disqualifying for medical certification due to the underlying medical condition and the potential safety 

relevant side-effects of the available medications to treat it (1, 2). In the United States, in accordance with 

Federal Aviation Administration (FAA) rules, antidepressant usage must have ceased for at least 

three months (3), while in Europe the Joint Aviation Authorities’ policy is that no certification can be 

considered whilst using psychoactive medication(4,5). 

Depression is a common worldwide disorder in the adult population, although reported prevalence varies 

quite widely (6). In the United States the lifetime prevalence of major depressive disorder was found to be 

16.2 per cent, which would involve almost 34 million US adults, and for a twelve-month period the figure 

was 6.6 per cent (7).Whilst there is no evidence that selective serotonin reuptake inhibitors (SSRI) 

medications are more efficacious than older antidepressant medications, this new generation of 

antidepressants is better tolerated by patients and has an improved side effect profile (8, 9, 10). 

Many patients require long term treatment with antidepressants to reduce the risk of recurrence. One 

systematic review (11) found that continuing antidepressant medication treatment after recovery 

dramatically reduced the proportion of patients who relapsed over one to three years, compared with 

placebo. The average rate of relapse on placebo was 41 per cent, compared with 18 per cent on active 

treatment.

There is emerging evidence in the literature that suggests that policies which disqualify pilots from flying 

whilst on antidepressant medications may lead to pilots flying when depressed and untreated, or flying on 

antidepressant medication but not reporting it to the regulatory authority (12, 13, 14). An Aerospace Medical 

Association position paper (12) stated that, according to the Aviation Medicine Advisory Service database 

of pilots’ telephone inquiries, approximately 15 per cent of pilots who had been advised by their 

physicians to take antidepressant medications showed an intention to take the medications and continue 

flying without informing the Federal Aviation Administration. 

Canfield et al. (13) reported on post-mortem toxicological evaluations performed on 4 143 pilots. 

Psychotropic medications were found in 223 pilots but only fourteen of these pilots had reported a 
- 10 - 

psychological condition to the FAA and only one of the fourteen pilots had reported the psychotropic 

medication. 

In Australia in 1987, the Civil Aviation Safety Authority (CASA) began allowing aviation personnel who 

had been depressed to operate once they had been effectively treated and had become stable with the use 

of antidepressant medications. The policy had become somewhat liberal with the allowance of use of 

most medication groups including monoamine oxidase inhibitors (MAOI) and tricyclic antidepressants 

(TCA). There were no reported adverse outcomes related to this policy but in 2003 a more restrictive 

approach was introduced with increased surveillance and limitation to specific medications (17). A study 

published in August 2007 looking at safety outcomes such as accidents and incidents in 481 certificate 

holders over a ten year period found no evidence of adverse outcomes related to allowing pilots to fly on 

antidepressant medication provided specific criteria were met (14). 

In Canada, pilots on maintenance therapy are allowed to fly “with or as co-pilots” under an aeromedically 

supervised treatment protocol in which pilots are followed prospectively (18). 

The AsMA position paper (12) points out that several factors must be considered in relation to safety 

should certificate holders be allowed to operate whilst using antidepressant medications. Firstly, it is 

important to establish the diagnosis. SSRIs are used to treat not just depression, but some other 

aeromedically significant illnesses such as obsessive compulsive disorder and panic disorder. Second, 

patients generally have their adverse reactions to SSRIs early in treatment; these side effects usually 

diminish as the patient becomes physiologically accustomed to the medication. Third, the newer SSRIs 

have fewer side effects than the older antidepressants because the pharmaceutical industry is designing 

them to act only on receptors in specific areas of the brain. 

Some of these medications are sedating and some are not, thus offering a therapeutic choice in treating 

depressed patients who show psychomotor agitation or retardation. Fewer side effects generally result in 

improved aeromedical safety. However, successful treatment of depression is a dynamic and complex 

process involving more than just writing a prescription and the SSRIs can have some aeromedically 

significant side effects and withdrawal effects that are of little importance in ordinary clinical practice (12). 

 

Finally, an important aspect to consider is that a diagnosis of depression often carries with it significant 

social stigma and in many societies it is common that symptoms of depression are not discussed openly 

with either colleagues or the medical profession. Aeromedical policies that place an absolute prohibition 

on operating after a diagnosis of depression may also make it less likely that an aviator or air traffic 

controller will seek treatment or declare their illness to the licensing authority. 

3. Draft guidance 

3.1 The assessment of pilot and ATC applicants with depression

Depressive mood disorders (ICD-10: Depressive episode; DSM-IV-TR: Major Depressive Disorder) are 

common disorders which present with depressed mood, reduced energy, impaired concentration and 

memory, loss of interest in surroundings, slowed cerebration, difficulty in making decisions, alteration of 

appetite and sleep, guilt feelings, and low self esteem. Suicide is common; the incidence varies with 

cultural background, but may approach 20 per cent per depressive episode. 

The illness is usually of insidious onset and persists for many months when not treated adequately. 

Depression may be accompanied by a number of somatic symptoms. There may be diurnal variation in 
- 11 - 

the symptoms, and many persons with depression may have some good days in between. It is not unusual 

for sufferers to try to modify their symptoms (especially the dysphoria and insomnia) by the use of 

alcohol and prescribed medications or illicit drugs.

Depression leads to subtle (and sometimes overt) incapacitation, mainly due to the decreased ability to 

concentrate, as well as to distractibility and indecision, which are frequent features of the illness. It is 

these symptoms, along with the risk of suicide, which make a depressed individual unsuitable to work in 

the aviation environment. Because the symptoms wax and wane during a depressive episode, there may 

be days when the individual is relatively well and may appear to be fit to fly. However, impaired 

concentration and lack of cognitive agility are always more or less present and may interfere with the 

ability to integrate the multiple sensory inputs required to make decisions in an emergency. 

Depression is by nature a recurrent disorder and although single episodes do occur, the history of a 

depressive episode should alert the medical examiner to ask specific questions to ensure that the applicant 

does not currently have the illness. Those persons who have had one serious depressive episode have 

approximately a 50 per cent risk of experiencing a second episode. Because depressive mood disorders 

are recurring disorders, it is imperative that the “recovered” patient be monitored closely for signs of 

recurrence for a period of time following recovery. There is evidence that recurrence is most likely to 

happen during the first two years. An educative approach may help the individual recognize the earliest 

signs and thus facilitate early intervention. 

Historically, pilots have not been allowed to return to flying unless they have ceased taking medication 

for at least some months after having returned to their euthymic state of health. In recent years, the use of 

SSRIs has become widespread in the general population and there is reason to believe that such treatment 

may be compatible with flying duties in carefully selected and monitored cases. This may be in a situation 

of an initial successful response to treatment of acute depressive episode, or where treatment is aimed at 

the prevention of recurrences. 

It should be noted that even with good responses, there may be the potential for impairment of cognition 

and decision making ability from either an incomplete response to treatment or from safety relevant side 

effects of medications. From the patient’s perspective, the pronouncement of “being well” may refer only 

to relative improvement in comparison with the untreated state. Applicants therefore need to be carefully 

assessed for the presence of any residual symptoms and any performance relevant side effects of the 

medication. 

3.2 The assessment of pilot and air traffic controller applicants treated with antidepressants

States may, on a case-by-case basis certificate applicants who are prescribed (and are taking) an approved 

SSRI antidepressant medication for an established diagnosis of depression which is in remission. 

Conditions necessary for air safety may be imposed on the certificate as appropriate, for example "holder 

to fly as or with co-pilot", thus limiting operations to multi-crew aircraft. Pilots and ATCs taking other 

types of anti-depressants will not usually be considered for certification. 

States’ certification of pilots and ATCs taking medications accepted by the Licensing Authority should be 

conditional on the following: 

a) The applicant should be under the care of a medical practitioner experienced in the management 

of depression 
- 12 - 

b) The applicant should: 

1) be stable on an established and appropriate dose of medication for at least four weeks 

before returning to flying/ATC duties and exhibiting: 

i) minimal acceptable side-effects 

ii) no medication interactions or allergic response 

2) be subject to regular clinical review by the medical practitioner with progress reports 

provided to the medical department of the Licensing Authority. The applicant may be 

involved in other concurrent treatment (e.g. psychotherapy). 

3) have an absence of other significant psychiatric co-morbidities 

4) require no other psychoactive medications 

c) Symptoms of depression being well controlled, without evidence of psychomotor retardation 

d) An absence of suicidal ideation or intent 

e) No history of psychotic symptoms 

f) An absence of features of arousal (e.g. irritability or anger) 

g) The presence of a normal sleep pattern 

h) Resolution of any significant precipitating factors of the depression 

Ongoing cognitive-behavioural, rational-emotive or similar therapy is desirable, but not necessarily 

required for certification. 

Pilots or ATCs authorized to fly or perform duties when taking SSRIs or related antidepressant 

medications must cease exercising the privileges of their licences if their antidepressant medication is 

altered or if the dose changed. Their supervising medical practitioner may return them to duty when they 

are assessed as stable and without unacceptable side effects. 

Pilots and ATCs whose medication is being reduced with a view to cessation should stop exercising the 

privileges of their licences for the entire period during which they are weaned off medication, plus an 

additional period of two weeks. Their supervising medical practitioner may return them to duty when they 

are assessed as stable and without unacceptable side effects or evidence of withdrawal syndrome. 

The use of objective assessment tools in the monitoring of these certificate holders is encouraged. The 

Hamilton ratings scale is one such tool and formal neuropsychological testing is another option. 

Simulator or other functional based testing can also be utilized to assess performance. States should 

provide guidance on preferred medications with lower side effect profiles such as sertraline, citalopram, 

and escitalopram. 

Outcome criteria/data on the cohort returned to work should be established prospectively and captured for 

review of the programme. 
- 13 - 

4. References

1. International Civil Aviation Organization. International standards and recommended practices. 

Personnel licensing. Chapter 6. Medical provisions for licensing. Montreal: ICAO; 2005. 

2. Manual of Civil Aviation Medicine (Doc 8984-AN/895), Second Edition, 1985. ICAO 

publication. 

3. Federal Aviation Authority Guide for Aviation Medical Examiners. Accessed 18 December 2005 

http://www.faa.gov/about/office_org/headquarters_offices/avs/offices/aam/ame/guide/media/

amd47psych.pdf

4. Joint Aviation Authorities’ Policy. JAR-FCL 3 Appendix 10, paragraph 2. 

5. Joint Aviation Authorities (Europe) Manual of Civil Aviation Medicine. Accessed 18 December 

2005 http://www.jaa.nl/licensing/manual/11%20-%20Psychiatry.pdf 

6. Prevalence, Severity, and Unmet Need for Treatment of Mental Disorders in the World Health 

Organization World Mental Health Surveys. The WHO World Mental Health Survey 

Consortium JAMA. 2004; 291:2581-2590. 

7. Ronald C. Kessler; Patricia Berglund; Olga Demler; Robert Jin; Doreen Koretz; Kathleen R. 

Merikangas; A. John Rush; Ellen E. Walters; Philip S. Wang The Epidemiology of Major 

Depressive Disorder: Results From the National Comorbidity Survey Replication (NCS-R) 

JAMA 2003 289: 3095-3105 

8. Westenberg HG, Sandner C. Tolerability and safety of fluvoxamine and other antidepressants. Int 

J Clin Pract. 2006 Apr;60(4):482-91. 

http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=16620364

9. Arroll B, MacGillivray S, Ogston S, et al. Efficacy and tolerability of tricyclic antidepressants 

and SSRIs compared with placebo for treatment of depression in primary care: a 

metaanalysis. Ann Fam Med. 2005;3(5):449– 456.

10. Cipriani A, Geddes JR, Furukawa TA, Barbui, C. Metareview on short-term effectiveness and 

safety of antidepressants for depression: an evidence-based approach to inform clinical 

practice. Can J Psychiatry. 2007 Sep;52(9):553-62

11. Geddes JR, Carney SM, Davies C, et al. Relapse prevention with antidepressant drug treatment in 

depressive disorders: a systematic review. Lancet. 2003;361(9358):653–661.

12. Jones DR, Ireland RR. Aeromedical regulation of aviators using selective serotonin reuptake 

inhibitors for depressive disorders. Aviat Space Environ Med 2004; 75:461–70. 

13. Canfield DV, Salazar GJ, Lewis RJ, Whinnery JE. Pilot medical history and medications 

found in post mortem specimens from aviation accidents. Aviat Space Environ Med. 2006 

Nov;77(11):1171-3. 

14. Ross J, Griffiths K, Dear K, Emonson D, Lambeth L. Antidepressant use and safety in civil 

aviation: a case-control study of 10 years of Australian data. Aviat Space Environ Med. 2007 

Aug;78(8):749-55. 

15. Hudson DE Jr. SSRI use in professional aircrew. [abstract]. Aviat Space Environ Med 2002; 

73:244–5. 

16. Hudson DE Jr. SSRI use in professional aircrew. Panel presentation. Aerospace Medical 

Association annual meeting. 9 May 2002, Montreal, Canada. 
- 14 - 

17. Civil Aviation Safety Authority (CASA) (2003). Use of antidepressant medication by depressed 

pilots and air traffic controllers. Designated Aviation Medical Examiners handbook. 

Australia: Civil Aviation Safety Authority. 

18. Lange M. Maintenance SRI use in professional pilots: the Canadian experience [Abstract]. Aviat 

Space Environ Med 2002; 73:244.

19. Ahmet Sen, Ahmet Akin Gülhane Dennis V. Canfield Arvind K. Chaturvedi. Selective Serotonin 

Reuptake Inhibitors:Medical History of Fatally Injured Aviation Accident Pilots 

DOT/FAA/AM-07/19 Office of Aerospace Medicine 

— — — — — — — — 
REPORTING OF MEDICAL CONDITIONS 

In previous editions of Annex 1, it was a Recommendation that licence holders should inform the 

Licensing Authority of pregnancy, decrease in medical fitness for more than 20 days, or the continued use 

of prescribed medication. However, experience has shown that Licensing Authorities have interpreted 

this in different ways and, following discussion with States it has been revised to the following: 

1.2.6.1.1 Recommendation.— States should ensure that licence holders are aware of 

physical and mental conditions and treatments that are relevant to flight safety. They should 

provide guidance concerning those circumstances when medically related information should be 

forwarded to the Licensing Authority

It is clearly important that licence holders are aware of those medical conditions that are relevant to flight 

safety, so that, when they have developed a medical condition, they know when to seek medical help, and 

when to cease flying. For example, cardiac disease is an important flight safety risk for all Licensing 

Authorities, although the degree of risk is likely to vary from State to State, depending on the prevalence 

of such disease in different States. States should inform applicants of this potential risk to their medical 

fitness and to their health and Licensing Authorities may wish to place more or less emphasis on this 

aspect of fitness for holders of licences issued by their State. The same principle applies to certain 

infections, depending on the prevalence of such infections in different parts of the world. 

States can provide information concerning relevant physical and mental conditions in many ways. 

Examples include: internet website; information circular; medical examiner briefing. The most effective 

way(s) is likely to differ from State to State. A medical examiner briefing may be effective and for Class 

1 applicants under 40 years of age it is suggested that this could be formally included in the preventative 

and educative part of the medical assessment, as discussed in other parts of the proposed amendment to 

Annex 1. 

For many conditions, modern medical practice has changed the length of time required in hospital, and 

some conditions that, in the past, involved a lengthy hospital stay, can now be dealt with very quickly, 

even as an outpatient. One State lists the following conditions (which are not exhaustive) as requiring 

advice from a designated medical examiner before a return to operations can be considered: 

a) any surgical operation 

b) any medical investigation with abnormal results 

c) any regular use of medication 

d) any loss of consciousness 

e) kidney stone treatment by lithotripsy 

f) coronary angiography 

g) transient ischaemic attack 

h) abnormal heart rhythms including atrial fibrillation/flutter 

In many instances of ill-health, a medical practitioner without any training in aviation medicine may be 

unable to provide appropriate advice to a licence holder regarding fitness to fly. Any licence holder 

should be aware of the action to take in the event of suffering a common cold, without having to seek 

advice from a designated medical examiner unless there are complicating factors, but for more serious 

conditions advice concerning fitness to operate should be readily available from those with specialist 

knowledge, e.g. a designated medical examiner or the Licensing Authority headquarters. If a “temporarily 

unfit” assessment is made, the method for regaining fitness should be clear and, when fitness is regained, 

return to operations should not be unduly delayed. If a licence holder is affected by the circumstances 
- 16 - 

such as those listed above, it is considered that they should be aware of the need to seek aviation medicine 

advice before exercising licence privileges. 

— — — — — — — — 
HUMAN IMMUNODEFICIENCY VIRUS (HIV) 

SUGGESTED PROTOCOL FOR ASSESSMENT OF HIV DISEASE 

1. Following an initial diagnosis of HIV seropositivity

 

Assess temporarily unfit, pending submission of reports. 

a) HIV Specialist Review 

• History of infection 

• Current and previous symptoms 

• Stability of condition 

• History of opportunistic infections or associated illnesses 

• History of CD4+ T cell counts 

• History of Viral Load measurements 

• Medication history (including ‘over the counter’ medications and alternative medicines) 

• Report concerning side effects of medications 

• Laboratory testing to include: 

– Hepatitis B & C, Cytomegalovirus, toxoplasma, tuberculosis. 

– Full Blood Count, urea, creatinine and electrolytes, liver function tests, fasting 

glucose, lipids. 

b) Neurology Review – can be undertaken by HIV specialist, or neurologist 

Assessment for neurological sequelae. Include assessment of primitive reflexes (because of 

their association with cognitive decline) 

c) Neuropsychological Review 

• Baseline neuropsychological assessment. 

• Tests should include timed psychomotor tasks and memory tasks requiring attention, 

learning, active monitoring and retrieval of information. 

d) Psychiatry Review 

Assessment for psychiatric sequelae related to HIV seropositivity and antiretroviral treatment. 

e) Cardiology Review (only if indicated) 

Cardiological review is recommended if the following exist: 

• Lipodystrophy or metabolic syndrome (dyslipidaemia — raised total cholesterol, low 

high density lipoprotein cholesterol and raised triglycerides or insulin resistance with 

hyperglycaemia); 
- 18 - 

• Cardiac risk factors are present, including: 

– hypertension, evidence of left ventricular hypertrophy, smoking, raised lipids, 

diabetes, age over 40 years. 

2. Aeromedical Certificatory Assessment

On receipt of satisfactory reports, applicants who are asymptomatic, stable, without significant 

opportunistic infection may be considered for certification, if their CD4* count is above the minima stated 

below. Once diagnosed HIV positive, solo operation as a pilot should not be accepted for Class 1 or Class 

2 applicants. 

a) Table 1 — Applicants not established on combined antiretroviral therapy (cART) 

Age (yr) Minimum CD4+ count

20 – 39 350 

40 – 59 400 

60 + 500 

Applicants over 40 years of age with CD4+ counts below these levels but above 350/mm3

may be considered for certification on an individual basis. 

b) Table 2 Applicants established on combined antiretroviral therapy (cART) 

CD4 Count > 350 = 0 201 − 350 = +0.62 51 − 200 = +1.46 ≤50 = +2.44 

BMI ≤ 18 = +0.80 18.1 − 25 = 0 > 25 = −0.29 

Viral Load < 500 = 0 ≥ 500 = +0.18 

CD4 slope (3 month) < −25/mm3 = +0.49 −25 to +25/mm3 = 0 > 25/mm3 = +0.18 

Anaemia No = 0 

Hb > 14.0g/dl male 

Hb > 12.0g/dl female 

Mild = +0.68 

Hb 8.01 − 14.0g/dl male 

Hb 8.01 − 12.0g/dl female 

Severe = +1.02 

Hb ≤ 8.0g/dl 

ART experience prior to 

cART 

Yes = 0 No = −0.39 

Taking antiretrovirals Yes = 0 No = +1.24 

Age Age × 0.027 

Infected with HIV Via intravenous drug use = +0.25 Via any other route = 0 

Prior diagnosis of AIDS 

at starting cART 

No = 0 Yes = +0.19 

Score % Risk of clinical progression in following twelve months

<1.5 0.5 

1.5 – 2.99 1.4 

3.0 – 4.49 6.25 

≥4.5 >20 

Table 2 enables a risk assessment to be undertaken. The figures are summated to reach a 

score that allows a prediction of risk of progression during the next 12 months. 
- 19 - 

Notes: 

Acceptable medications include: abacavir, didanosine, emtricitabine, lamivudine, tenofovir, zidovudine, 

atazanavir, fosamprenavir, lopinavir/ ritonavir, nelfinavir, saquinavir, nevirapine and efavirenz 

Unacceptable medications include enfuvirtide, zalcitabine, indinavir and stavudine. 

Recently available medication, e.g. tipranavir, darunavir, raltegravir and maraviroc, may be acceptable on 

an individual basis. Particular attention needs to be given to the toxicity and side-effect profile of such 

medications. 

A “temporary unfit” assessment should be made when initiating, modifying or discontinuing ART. When 

stable, recertification after 3 months of monitoring may be permitted providing that there has been an 

acceptable serological response, no ongoing side-effects and FBC, LFTs, lipids and fasting glucose are 

acceptable. 

Those commencing or modifying efavirenz treatment require a psychiatric and neurological examination 

at initial certification or within 6 months after initiating therapy. 

Reviews should take account of any over the counter medications and alternative therapies being taken 

3. Follow-up

Regular follow-up is required, to include: 

• 3 monthly CD4*

 and viral load measurements 

• 6 monthly neurology assessment (by HIV specialist or neurologist including consideration of 

the need for psychiatric evaluation) 

• if taking ART: 6-monthly LFTs, FBC, lipids and fasting glucose. 

• Annual cognitive function assessment 

– Evidence of having passed a Licence Proficiency Check (LPC) or the report from a 

medical flight test (MFT) with a Flight Instructor Examiner (FIE) may be considered in 

lieu of this where disease stability and the risk of disease progression is acceptable. 

Impaired performance will require further neuropsychological assessment to be compared 

with baseline testing and any deficits will require that the pilot is declared temporarily 

unfit. Neuropsychological assessment should be undertaken if there are any clinical 

concerns about cognitive impairment. 

Further co-infection testing should be undertaken where clinically indicated and those with new 

positive tests must be deferred for further assessment. 

If an applicant develops new symptoms and/or fails to achieve the nominal levels listed above*

 he 

must be declared temporarily unfit and referred to the Licensing Authority. 

                                                           

*

 CD4+ T cell counts are subject to substantial variability due to both biological and laboratory methodologies and 

can vary up to 30 per cent on repeated measures in the absence of a change in clinical status. Therefore it is 

important to monitor trends over time rather than take a decision on one specific determination. Sudden changes in 

the count need to be confirmed by a second determination.
- 20 - 

References: 

1. Table 1 is derived from Phillips A. CASCADE Collaboration. Short-term risk of AIDS according 

to current CD4 cell count and viral load in antiretroviral drug-naive individuals and those treated 

in the monotherapy era. AIDS 2004 Jan 2. 18(1):51-8 and from the WHO guidelines on initiating 

ART. 

2. Table 2 is derived from Mocroft A, Ledergerber B, Zilmer K, Kirk O, Hirschel B, Viard J-P, 

Reiss P, Francioli P, Lazzarin A, Machala L, Phillips A, Lundgren J; for the EuroSIDA study 

group and the Swiss HIV Cohort Study Short-term clinical disease progression in HIV-1-positive 

patients taking combination antiretroviral therapy: the EuroSIDA risk-score. AIDS. 21(14):1867-

1875, September 2007. 
- 21 - 

II. REVISED DRAFT OF CHAPTER ON HIV CONTAINED IN DOC 8984 

(Note.— This is a revised draft of the current chapter on HIV, part of Doc 8984 (Manual of Civil 

Aviation Medicine), that is currently available in draft form on the ICAO public website)

1. Introduction

In the introductory chapters of this manual the basic principles for the assessment of an applicant’s 

medical fitness for aviation duties are outlined. 

In the general medical provisions of Annex 1 the SARPs related to Human Immunodeficiency Virus 

(HIV) are the same for all three classes of medical assessment (medical certification) – commercial pilots, 

private pilots, and air traffic controllers – and state that: 

6.3.2.20.1 Applicants who are seropositive for human immunodeficiency virus (HIV) shall 

be assessed as unfit unless full investigation provides no evidence of HIV-associated disease that 

might give rise to incapacitating symptoms. 

Note 1.— Early diagnosis and active management of HIV disease with antiretroviral therapy 

reduces morbidity and improves prognosis and thus increases the likelihood of a fit assessment. 

The main purpose of the guidance material contained in this section is assist with determining the 

requirements for a full investigation and risk assessment for disease that might lead to incapacitation in 

HIV-seropositive applicants. 

2. Background 

HIV infection is pandemic with cases reported from virtually every country. Untreated the infection 

usually leads to Acquired Immunodeficiency Syndrome (AIDS) with AIDS-defining opportunistic 

infections or associated illnesses. A 2007 report from UNAIDS/WHO estimated that 33.2 million people 

are living with HIV. There were 2.5 million new infections in 2007 with 1.7 million (68 per cent) of these 

occurring in sub-Saharan Africa and important increases in Eastern Europe and Central Asia, where there 

are some indications that infection rates have risen by more than 50 per cent since 2004. In 2006, 

2.1 million people died of AIDS defining illnesses. The prevalence of HIV infection in pilots and air 

traffic controllers is unknown. 

3. Causative agent 

In 1984, the human immunodeficiency virus type 1 (HIV-1) was discovered as the primary causative 

agent. In 1986, a second type of HIV, called HIV-2, was isolated from AIDS patients from West Africa. 

Both HIV-1 and HIV-2 have the same modes of transmission and are associated with similar 

opportunistic infections and AIDS. In persons infected with HIV-2, immunodeficiency seems to develop 

more slowly and to be milder. HIV-2 infection is predominantly found in West Africa and there is less 

known about managing infection and predicting outcomes, than for HIV-1. Care is required therefore, 

with interpreting the information provided in this chapter to determine fitness for certification of persons 

with HIV-2 infection. 
- 22 - 

The etiological agent is a retrovirus and the CD4+ T-lymphocyte is the primary target for HIV infection. 

The CD4+ T-lymphocyte coordinates a number of important immunological functions, and a loss of these 

functions results in progressive impairment of the immune response. Studies of the natural history of HIV 

infection have documented a wide spectrum of disease manifestations, ranging from asymptomatic 

infection to life-threatening conditions characterized by severe immunodeficiency, serious opportunistic 

infections, and cancers. Other studies have shown a strong association between a decrease of the number 

of CD4+ T-lymphocytes and an increase of the risk and severity of opportunistic illnesses. 

4. Transmission 

HIV is transmitted by sexual contact (both homosexual and heterosexual), by blood and blood products, 

and by infected mothers to infants either intrapartum, perinatally, or via breast milk. There is no evidence 

that HIV is transmitted by casual contact or by insects, such as mosquito bites. HIV has been 

demonstrated in seminal fluid, cervical smears, and vaginal fluid. In these it appears to concentrate where 

there are increased numbers of lymphocytes and monocytes in the fluid, as in genital inflammatory 

conditions. There are strong associations of HIV transmission with a history of sexually transmitted 

diseases (STDs) and of HIV transmission with anal intercourse. Although the virus can be identified from 

virtually any body fluid, there is no evidence that transmission can occur via exposure to tears, sweat, and 

urine. There is no convincing evidence that saliva can easily transmit HIV infection, although occasional 

cases have been reported in which the victim was bitten by someone infected with HIV. 

5. Course of HIV infection 

The typical course of the HIV-infection in untreated patients is presented in Figure 1. After entrance of 

the virus in the host system, the CD4+ T cells (and to lesser extent cells of monocyte lineage) are the 

major targets of HIV infection. 

In primary HIV infection, virus replication 

in CD4+ T cells intensifies prior to the 

initiation of an HIV-specific immune 

response, leading to a burst of viraemia and 

to rapid dissemination of virus to other 

lymphoid organs, brain, and other tissues. At 

that stage, 3-6 weeks after primary infection, 

50-70 per cent of the patients experience an 

“acute retroviral syndrome” (acute HIV 

infection). The hallmark of acute infection is 

a high level HIV ribonucleic acid (RNA) or 

viral p24 antigen in conjunction with a 

negative HIV enzyme-linked 

immunosorbent assay (ELISA) test, negative 

or evolving Western blot test, and 

subsequent demonstration of full antibody 

seroconversion. Seroconversion typically occurs within 21-28 days after exposure (range 7 days to 12 

months). The classic presentation of acute retroviral syndrome resembles a mononucleosis-like illness, 

which is often mistaken for malaria in tropical settings. The most common symptoms include fever, 

fatigue, myalgia/arthralgia, pharyngitis, lymphadenopathy, rash, anorexia, non-specific gastrointestinal 

complaints, and sometimes neurological symptoms. Symptoms spontaneously resolve in most patients. 
- 23 - 

There is evidence that the persistence of the acute retroviral syndrome beyond 14 days, as well as a 

shorter incubation than 21 days, are predictors of a more rapid progression to AIDS. Significant viraemia 

persists for several weeks, and subsides after 9-12 weeks to much lower levels, while at the same time the 

level of CD4+ T cells increases after having reached its trough at about 6 weeks after infection (Fig. 1). 

During the period of peak viraemia, it is believed that HIV-specific immune responses begin to drive 

down the viral load until a “set point” between viral replication and immune pressure is reached. This 

occurs within the first 6-12 months following infection, and most HIV-researchers assume that the level 

of this set point is highly prognostic of the patient’s rate of progression to AIDS. 

Once the infection has been established, the virus is never cleared completely from the body. A chronic 

infection develops that persists with varying degrees of virus replication. For adults in developed 

countries, the average time of progression to the clinical signs and symptoms of AIDS is approximately 

10 years in the absence of antiretroviral therapy. Progression is markedly age-related, with older patients 

doing much worse than younger patients. Although the patients are asymptomatic during this period, in 

the majority of untreated cases viral load gradually increases and CD4+ T cells gradually decrease, 

patients become symptomatic and clinically ill finally developing severe opportunistic infections. Some 

(20 per cent) untreated persons develop AIDS defining illnesses within 5 years of infection, whereas 

others (<5 per cent) have sustained long-term (>10 years) asymptomatic HIV infection without decline of 

CD4+ T cell counts to <500/μL. Perhaps 2 per cent of untreated infected persons – often called 

“long-term non-progressors” – seem to be able to contain HIV replication to extremely low levels and 

maintain stable CD4+ T cell counts within normal range for lengthy periods (>12 years). The appearance 

of effective antiretroviral therapy, resulting in near-complete suppression of viral replication, has brought 

long-term delay of progression to AIDS defining illnesses and prevention of related conditions for many 

HIV-seropositive subjects in the developed world. These drugs also appear to significantly reduce the rate 

of sexual and vertical transmission of the virus and are of importance in a population such as aircrew, 

who are highly mobile. 

6. Clinical manifestations of HIV infection 

The latency period (clinical latency period; Fig. 1) is characterized by large inter-individual variability in 

duration. Initial symptoms of HIV-related immunosuppression (Stage 2, mild symptom, in the WHO 

clinical staging classification) include herpes zoster, recurrent UTRIs and seborrhoeic dermatitis. Stage 3 

denotes more advances symptoms and includes persistent oral candidiasis, oral hairy leukoplakia, severe 

weight loss or fever or chronic diarrhoea and severe bacterial infections or pulmonary tuberculosis. 

After a latency period, untreated HIV-positive individuals will develop WHO Stage 4 disease or an AIDS 

defining illnesses, which may be characterized by neuropsychiatric symptoms including dementia, 

cognitive or other psychological changes associated with HIV encephalopathy, opportunistic respiratory 

and central nervous system (CNS) infections, and diseases of the cardiovascular, gastrointestinal, 

hepatobiliary, kidney and genitourinary, and endocrine system. The majority of neurological disorders 

will be HIV-associated dementia complex (HAD). Other neurological involvement includes 

myelopathies, peripheral neuropathies and myopathies, opportunistic infections, primary central nervous 

system lymphoma, and cerebrovascular diseases. Moreover, cognitive and psychiatric symptoms, visual 

changes, headache, seizures, dizziness, involuntary movements, gait disturbances, cranial neuropathies 

and focal deficits can impair safe functioning of HIV-positive personnel engaged in aviation duties. 

Conditions included in the 1993 AIDS surveillance case definition are shown in Table 1. 

Along with the four-level WHO clinical staging system for HIV disease, the Centers for Disease Control 

and Prevention (CDC) in the United States have also devised a classification system for HIV disease 
- 24 - 

progression. This was linked with AIDS case definition (which was as initially intended for 

epidemiological use as a surveillance tool) and allows only for a unidirectional progression through the 

categories from asymptomatic (Category A) to having an AIDS indicator condition (Category C). It is 

recognized now that some people can make a significant recovery from AIDS defining illnesses and so 

the development of these illnesses is not necessarily an indicator of long-term unfitness for aeromedical 

certification. The WHO has recently modified the clinical staging system to recognize that antiretroviral 

therapy will reverse disease progression and that subsequent HIV-related events and clinical staging 

events can be used to guide decision making on when to switch to second-line ART. 

Table 1. — AIDS defining illnesses 

Candidiasis of oesophagus, bronchi, trachea or lungs 

Cervical cancer, invasive 

Coccidioidomycosis, disseminated or extrapulmonary 

Cryptococcosis, extrapulmonary 

Cryptosporidiosis, chronic intestinal (greater than 1 month duration) 

Cytomegalovirus disease (other than liver, spleen or nodes) 

Cytomegalovirus retinitis (with loss of vision) 

Encephalopathy (Dementia), HIV related 

Herpes simplex: chronic ulcer(s) (greater than 1 month duration); or bronchitis, pneumonitis or 

oesophagitis 

Histoplasmosis, disseminated or extrapulmonary 

Isosporiasis, chronic intestinal (greater than 1 month duration) 

Kaposi’s sarcoma 

Lymphoma, Burkitt’s (or equivalent term) 

Lymphoma, immunoblastic (or equivalent term) 

Lymphoma, primary, of brain 

Mycobacterium avium complex or M. kansasii, disseminated or extrapulmonary 

Mycobacterium tuberculosis, any site (pulmonary or extrapulmonary) 

Mycobacterium, other species or unidentified species, disseminated or extrapulmonary 

Pneumocystis carinii pneumonia 

Pneumonia, recurrent 

Progressive multifocal leukoencephalopathy 

Salmonella septicaemia, recurrent 

Toxoplasmosis of brain 

Wasting syndrome due to HIV 

7. Assessment of HIV and disease that might give rise to incapacitating symptoms 

7.1 Current health 

General examination 

Besides specific screening for progression of the disease and CNS involvement (described separately), 

HIV-positive applicants should be thoroughly screened to exclude any disqualifying condition. HIV 

and/or antiretroviral medication may also affect heart, respiratory system, liver, and metabolic functions 

and so the assessment should include haematological, cardiovascular, and pulmonary evaluation, liver and 

kidney function, and metabolic tests. Opportunistic infections generally occur with advanced or severe 

disease and the physician should always pay attention to signs and symptoms of Stage 3 or Stage 4 

disease, such as oral or oesophageal candida, pneumocystis carinii pneumonia, toxoplasmosis, 
- 25 - 

cytomegaly, progressive multifocal leukoencephalopathy, tuberculosis, and fungal infections. This 

especially applies for candida infections, which can be seen early in the course of HIV infection, 

heralding the onset of clinical immunodeficiency. 

The following specific assessments are recommended: 

a) Immunological status 

Two laboratory tests are routinely used as surrogate markers of HIV disease progression to 

determine indications for treatment and to monitor the efficacy of therapy. These are the CD4+ T 

cell count and plasma HIV RNA (or viral load). 

CD4+ T cell count.— The extent of immune system damage is indicated by the CD4+T cell 

count, which is a measure for disease status and can enhance the assessment of the risk of 

developing opportunistic infections and other sequelae of HIV infection when used together with 

viral load determinations. CD4+ T cell counts are subject to substantial variability due to both 

biological and laboratory methodologies and can vary up to 30 per cent on repeated measures in 

the absence of a change in clinical status. Therefore it is important to monitor trends over time 

and to repeat a test to confirm a value rather than take a decision on one specific determination. 

Sudden changes in the count need to be confirmed by a second determination. The number of 

CD4+ cells varies diurnally, being higher in the morning, increasing slightly with smoking and 

decreasing acutely with stress and with intercurrent infection. A significant change between two 

tests (two standard deviations) is defined approximately as more than a 30 per cent change of the 

count. For practical use, a decline in CD4+ T cells by 75/year is considered to indicate a higher 

risk for progression to AIDS, when the reference CD4+ T cell count is <500/μL. A CD4+ T cell 

count of <200/μL is AIDS-defining even in the absence of any signs and symptoms of HIV 

disease. 

Viral load.— The rate of progression of HIV disease is predicted by the magnitude of active HIV 

replication, which is reflected by the viral load. Measurement of the viral load through the use of 

quantitative plasma HIV RNA assays permits assessment of the relative risk of disease 

progression and time to death. However, plasma HIV RNA levels obtained within the first six 

months of HIV infection do not accurately predict disease progression. In contrast, plasma HIV 

RNA levels stabilize after approximately six to nine months of initial HIV infection and the viral 

set point is considered predictive of subsequent disease progression. Immunizations and 

intercurrent infections can lead to transient elevations of plasma HIV RNA levels. Values 

obtained within 4 weeks of such episodes may not accurately reflect the actual plasma HIV RNA 

level. Two specimens should be obtained within one to two weeks of each other and analyzed by 

the same quantitative method (either Branched DNA=bDNA, or Reverse Transcriptase 

Polymerase Chain Reaction=RT-PCR). Plasma HIV RNA assays are also used as the best 

measure of the activity of antiretroviral therapy. A viral load of <5000 copies/ml is considered 

low and provides evidence for non-progression of the disease. The minimal change in viral load 

considered to be statistically significant (2 standard deviations) is a threefold or a 0.5 log 10

copies/ml change. For practical use, an increase by >20,000 copies/year is considered to indicate 

a higher risk of progression to AIDS. 

b) Assessing co-infection 

Hepatitis B and C are frequent co-infections in HIV-infected individuals. They can cause 

progressive liver disease especially in those receiving anti-retroviral therapy. The progression of 

HIV infection appears to be slowed in people co-infected with Hepatitis G virus. Other sexually 
- 26 - 

transmitted diseases such as syphilis should also be considered. Tuberculosis is the most common 

HIV associated opportunistic infection in developing countries, compared to pneumocystis 

pneumonia in industrialised countries. Cytomegalovirus is the most frequent cause of retinitis in 

advanced HIV infection. Other associated co-infections include Epstein-Barr virus, toxoplasma 

gondii (associated with multiple CNS lesions) and JC virus (named after the initials of the patient 

in whom it was first discovered) that cause progressive multifocal leukoencephalopathy, and 

cryptococcal meningitis, particularly in tropical countries. 

c) Neurological assessment 

The spread of HIV-1 into the CNS is known to occur early in the course of the infection. 

However, except for early HIV-associated meningitis (as part of an acute HIV seroconversion 

illness), the majority of nervous system complications of HIV in the CNS take years to appear. 

HIV-related neurological disorders may arise from infection, neoplasm, systemic metabolic 

derangement, antiretroviral therapy, or direct HIV effects on the nervous system. 

Several large-scale studies have shown that HIV-associated cognitive dysfunction is antedated by 

immunological (CD4+ T cell) decline. This finding is important when considering aeromedical 

fitness. 

During neurological examination, specific attention should be paid to extra-pyramidal signs, and 

ocular disorders such as dissociated nystagmus, gaze-evoked nystagmus, impaired saccadic 

function, and smooth pursuit. Testing of primitive reflexes (glabellar, snout, Rossolimo, digital 

signs) should be part of the examination because they are associated with cognitive decline in 

HIV patients without overt neurological disease. 

Most studies demonstrate that the risk of new-onset seizures in asymptomatic individuals is low. 

In the majority of cases, seizures in HIV-positive individuals are caused by disorders that 

generally occur in late stages of HIV-infection, such as encephalopathy, neoplasm, or 

opportunistic infections. 

d) Cognitive function testing 

HIV associated dementia (HAD), also known as AIDS dementia complex and HIV 

encephalopathy is a late complication of HIV disease that occurs in those with very low CD4+ 

cell counts. Fortunately, HAD is very responsive to anti-retroviral therapy and has become 

uncommon in the developed world. In the developing world, more studies are required to enable 

conclusions to be made on HAD. Since the introduction of Highly Active Anti-Retroviral 

Therapy (HAART) in 1996 the incidence of HAD has declined significantly by about 50 per cent 

compared to the early 1990s. Studies conducted in the pre-HAART era found that HAD was 

associated with increasing age, a diagnosis of AIDS and injection drug use. The majority of cases 

have presented with advanced immunosuppression with CD4+ counts <200. However more cases 

are presenting at higher CD4+ counts since the advent of HAART. 

The clinical presentation in adults includes prominent psychomotor slowing, deficits in learning, 

attention/working memory, speeded information processing, mental flexibility, and motor control. 

Neuropsychological testing can demonstrate deficits in these areas. Typically, HAD progresses 

slowly over several months, rather than being sudden in onset, and those affected or their families 

describe a slowing of thought with loss of interest in activities previously enjoyed and a tendency 

to forget details. Less commonly, psychotic behaviour may be quite florid. Diagnosis of HAD can 

be made clinically, but MRI imaging or CT scanning should be considered to exclude 
- 27 - 

opportunistic lesions. The scans may be normal in the presence of HAD but generally cerebral 

atrophy is present. 

e) Mild neurocognitive impairment 

It is difficult to come to a clear conclusion on the absolute risk and significance of mild 

neurocognitive impairment in asymptomatic HIV infected individuals. Whilst some studies 

comparing cognitive function in asymptomatic HIV positive persons and HIV negative persons 

find no difference others have detected a higher frequency of cross-sectional neuropsychological 

test abnormalities than in seronegative controls. However, few have shown that these cognitive 

impairments are progressive, or predictive of later development of dementia. The clinical 

significance of new cognitive symptoms or test impairment in asymptomatic HIV infection is 

uncertain because the reported neuropsychological abnormalities do not necessarily affect every 

day function, may not progress, and in some individuals may improve on retesting. 

Where abnormalities have been detected they relate to timed psychomotor tasks and memory 

tasks, which require attention, learning and active monitoring or retrieval of information. These 

may be assessed using trail making, digit symbol substitution, grooved pegboard and 

computerized reaction time tests. The development of sensitive and reliable neuropsychological 

test batteries now means that evolving neurocognitive impairment may be detected at a relatively 

early stage in individuals at risk of HIV dementia. 

Under ideal circumstances every patient should receive baseline neuropsychological assessment 

when first diagnosed with HIV but there is no perfect approach. Tests vary in their sensitivity and 

specificity, as well as the degree to which they are affected by other general factors such as age, 

education and cultural background, premorbid neurological disease, and alcohol and drug use, 

fatigue and constitutional symptoms, and mood. This is a reason for assessing cognitive ability 

domains utilizing more than one test of each domain. 

Overall neuropsychological assessment may be enhanced by the results of functional assessment 

such as the Proficiency Checks that commercial pilots undertake in a flight simulator. This may 

be particularly useful where cognitive function testing has detected mild impairments of uncertain 

significance or instead of cognitive function testing in asymptomatic individuals who are at low 

risk of disease progression (see Risk of Progression). 

 

f) Simulator checks 

In general, simulator checks test two main abilities, which are: learned skills, e.g. controlling an 

aircraft after engine failure, flying an instrument approach with engine(s) failed, and decision 

making, e.g. choosing an appropriate course of action given more than one alternative, 

determining the cause of a malfunction from a given set of data. Most, if not all, of the identified 

types of neurocognitive deterioration can be identified by a well-designed simulator check.

Controlling a twin-engine aircraft after an engine failure, following take-off and when flying an 

approach and go-around is a demanding psychomotor task and should be part of any routine 

simulator test. Memory tasks are also necessary as a routine, but can be emphasized by the 

airline medical officer in discussion with the training captain. Tasks such as recall of six digits 

when changing frequencies can be required of the affected pilot, delegation to the second pilot 

should not be permitted, and conditional clearances (“after waypoint X, descend to flight level 

120” can test longer term memory. 
- 28 - 

It is vital to involve the operator’s training department when assessing a pilot who is returning to 

line flying after the diagnosis of HIV infection. Good communications should be established and 

the airline’s medical adviser should ensure that he or she is very familiar with the simulator 

environment and with the tasks required of pilots in routine checks. It is only if the medical 

adviser is knowledgeable of simulator tests, and mutual trust is established between the medical 

adviser and training department that the most benefit can be obtained from simulator checks. 

Any performance that is regarded as below average for that individual pilot should be seen as a 

cause for concern, and should require further assessment. 

g) Psychiatric assessment 

Although it is assumed to be uncommon that psychiatric symptoms are the first manifestations of 

CNS involvement, the psychiatric examination should address the potentially serious 

complications of infection with HIV. There is evidence that the average HIV infected person 

experiences at least transient difficulties following notification of HIV seropositivity. A study (in 

the pre-HAART era) among HIV-infected US military personnel in 1993 showed that 17 per cent 

of the subjects had experienced serious suicidal ideation or behaviours since notification of 

seropositivity. Ten percent had a major mood disorder and 5 per cent a psychoactive substance 

disorder. The knowledge of being seropositive per se may be a reason for (temporary) 

disqualification. The examiner should focus on signs of depression, other mood disorders and use 

of psychoactive substance. A similar study of military personnel does not appear to have been 

undertaken since the introduction of HAART, but there is evidence of a lower prevalence of 

mood disorders amongst those attending HIV outpatient clinics compared to the pre-HAART era. 

Psychiatric symptoms may also be associated with medication, e.g. Efavirenz and assessment 

should be made after commencing this treatment and before considering a return to certification. 

Consideration should be given to psychiatric assessment, particularly at the first assessment after 

seroconversion, with subsequent review associated with clinical indication and the introduction of 

efavirenz in any HAART regimen. 

h) Cardiological assessment 

Lipodystrophy and a metabolic syndrome may arise as an interaction between HIV disease and/or 

immune recovery and antiretroviral medication. This may manifest as dyslipidaemia with raised 

total cholesterol, low HDL cholesterol and raised triglycerides or insulin resistance with 

hyperglycaemia. Cardiology review may be required in the presence of these or other significant 

cardiac risk factors, e.g. hypertension, smoking, raised lipids, diabetes, age and evidence of left 

ventricular hypertrophy. Some antiretroviral medicines are more likely to cause these side effects 

and expert consultation with a view to changing ART regimen is indicated. 

i) Medication 

The clinical effectiveness and tolerability of antiretroviral therapy has improved markedly over 

the last few years. Most regimens are patient-friendly with low pill burden and few dietary 

restrictions. Since 1996, there have been dramatic falls in the incidence of new AIDS cases and 

AIDS associated deaths in the developed world. Many (highly active) antiretroviral therapy 

regimens (HAART or ART) result in near-complete suppression of HIV-1 replication. For HIV-2 

the picture is not quite so clear, as it is far less prevalent and there is limited clinical experience. 

Both the nucleoside reverse transcriptase inhibitors (NRTI) and protease inhibitors (PI) classes of 

ARV medicines are active but neither efavirenz nor nevirapine as, non-nucleoside reverse 

transcriptase inhibitors (NNRTI) are active against HIV-2. 
- 29 - 

HAART does not cure HIV infection so once started life-long therapy is always necessary. 

Although complete eradication of the infection cannot be achieved, sustained inhibition of viral 

replication results in partial and often substantial reconstitution of the immune system in most 

patients, greatly reducing the risk of clinical disease progression. 

Combination ART usually starts with 2 NRTI together with a NNRTI as the first-line therapy. 

The PI class is usually reserved for second-line therapy. Some drugs are so similar or have 

synergistic toxic effects and so should not be combined. Expert opinion should always be sought. 

Adequate viral suppression for most patients on therapy is defined as a reduction in viral load to 

undetectable levels. There are cases in which adequate viral suppression may not be achieved 

despite appreciable increases in CD4 cell count. Increases in CD4 cell count in people with good 

virological control show an average increase of approximately 100 cells/mm3 per year for 

subsequent few years until a threshold is reached, which in many patients may be within the 

normal range. However, successful outcomes have not been observed across all patients. 

Problems encountered with HAART are drug resistant virus, poor patient adherence, drug-drug 

interactions when treating co-infections like tuberculosis, and drug toxicity. In the beginning of 

the HAART era it was hoped that all HIV-seropositive persons would benefit from antiretroviral 

therapy. Nowadays, clinicians have considerable reservations about treating asymptomatic 

immunocompetent cases, because of the risk of adverse drug effects, the challenge of long-term 

adherence and development of virus resistance. 

In asymptomatic patients with HIV, decisions on when to start treatment are based on an 

assessment of the risk of disease progression over the medium term if treatment is not started (e.g. 

using data from the CASCADE collaboration – see section on “Risk of Progression”) versus the 

potential risks of starting treatment earlier (toxicity and resistance), and in any case always before 

the CD4+ lymphocyte count has fallen to below 200 cells/mm3

. 

In 2004 the Panel on Clinical Practices for Treatment of HIV Infection (convened by the 

Department of Health and Human Services, USA) published revised indications for antiretroviral 

therapy, which are shown in table 2. Similar cut-off values are used in guidelines in other 

industrialized countries. WHO recommendations, adopted by many low and middle-income 

countries are slightly more conservative and the debate about early treatment with HAART vs. 

deferring until lower CD4+ counts are reached goes on. 

When assessing aeromedical certification of persons on HAART, consideration must be given to 

aeromedically relevant adverse effects and clinicians treating aviation personnel should be asked 

to carefully design treatment regimens to minimise these. Drugs that are likely to interfere with 

flight safety should be avoided e.g. indinavir, which causes nephrolithiasis (with radiolucent 

stones), and with others specialist assessment may be required before deciding on certification, 

e.g. efavirenz, which may cause psychiatric symptoms. 
- 30 - 

Table 2.— Indications for antiretroviral therapy 

(Panel on Clinical Practices for Treatment of HIV Infection, 2004, USA) 

1 

Antiretroviral therapy is recommended for all patients with history of an 

AIDS-defining illness or severe symptoms of HIV infection regardless of 

CD4+ T cell count. 

2 Antiretroviral therapy is also recommended for asymptomatic patients with 

< 200 CD4+ T cells/ μL. 

3 Asymptomatic patients with CD4+ T cell counts of 201-350 cell/ μL should 

be offered treatment. 

4 For asymptomatic patients with CD4+ T cell of >350/ μL and plasma HIV 

RNA >100.000 copies/mL most experienced clinicians defer therapy but 

some clinicians may consider initiating treatment. 

5 Therapy should be deferred for patients with CD4+ T cell counts of >350 

cells/ μL and plasma HIV RNA < 100.000 copies/mL. 

 

Only drugs that are licensed by national authorities will be acceptable. During the initiation of 

therapy and when adjustments are made to the regimen used, applicants should be assessed as 

temporarily unfit. Further assessment should then be made for side effects that are likely to be 

disabling after treatment is stable for a period of months, before any decision on certification is 

made. Adverse effects of HAART include GI intolerability, drug hypersensitivity, 

Stevens-Johnston syndrome, cytochrome P450 interactions, CNS effects, myopathy, neuropathy, 

bone marrow depression, nausea, diarrhoea, fatigue, headache, hepatitis, hepatic steatosis, lactic 

acidosis, pancreatitis, dilated cardiomyopathy, renal colic, nephrolithiasis, haematuria, abdominal 

pain, metabolic syndrome and lipodystrophy. There is considerable variability in the occurrence 

of adverse effects between drugs and between individuals. Noteworthy is the occurrence of a 

lipodystrophy syndrome, characterized by a “buffalo hump” fat distribution, in 50 per cent of the 

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 

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, ARV adherence, toxic side effects or 

evidence of drug 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. 
- 31 - 

Cerebrospinal Fluid (CSF) - Abnormalities of the 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. 

7.2 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. 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 on 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. 

The Concerted Action on SeroConversion 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 assessing 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 6 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 

(although recent updates on their original publication have improved this). The CDC category A and B 

(both asymptomatic individuals and those who have had symptoms of conditions attributed to or 

complicated by HIV infection) are included in one group and the age ranges divided into 4 groups. Their 

most recent study reports that the annual risk of developing a new AIDS defining illnesses during the first 

year after commencing HAART is around 1 per cent per annum for those whose 6 month CD4+ count is 

>=350, viral load is <500 and where HIV transmission was not by intravenous drug use, the person meets 
- 32 - 

the criteria for CDC category A or B and aged 16-29yr and gradually decreases over the subsequent four 

years. A calculator can be found on their web site at http://www.art-cohortcollaboration.org/6mhiv_form.html

Table 3.— Risk of developing AIDS in those who have had 

no treatment or monotherapy 

Rate = exp{-3.55 + [-0.21 √(CD4 cell count)] + 0.71 (log viral load) + 0.024(Age)} 

12-month percentage risk of developing AIDS = [1 – exp(-1Rate)] x 100% 

exp = exponential function 

CD4 cell count = count x 106

 cells/l 

log = logarithm 

viral load = copies/ml 

Age = age in years

Example: A 25 year old pilot with CD4+ cell count of 450 and viral load of 5000 will have 

a 12-month risk of developing AIDS of 0.84 per cent. 

Rate = exp {-3.55 + [-0.21 x √450] + [0.71 x log5000]+ [0.024 x 25]} = 0.008 

12-month percentage risk of developing AIDS = [1 – exp(-1 x 0.008 )] x 100% = 0.84% 

A pilot aged 50yr with the same serological measurements would have a 12-month risk of 

developing AIDS of 1.52 per cent.

Derived from Phillips A. CASCADE Collaboration. Short-term risk of AIDS according 

to current CD4 cell count and viral load in antiretroviral drug-naive individuals and 

those treated in the monotherapy era. AIDS 2004 Jan 2. 18(1):51-8.

Table 4.— Risk of Clinical Progression in those being treated 

with combination Anti-Retroviral Therapy (cART)

CD4 Count (/mm3) >350 = 0 201−350 = +0.62 51−200 = +1.46 ≤50 = +2.44 

Body Mass Index ≤18 = +0.80 18.1−25 = 0 >25 = −0.29 

Viral Load 

(copies/ml) 

<500 = 0 ≥500 = +0.18 

CD4 slope (3 

month) 

< −25/mm3 = +0.49 −25 to +25/mm3 = 0 >25/mm3 = +0.18 

Anaemia No = 0 

Hb >14.0g/dl male 

Hb >12.0g/dl female 

Mild = +0.68 

Hb 8.01−14.0g/dl male 

Hb 8.01−12.0g/dl female 

Severe = +1.02 

Hb ≤8.0g/dl 

Retroviral treatment 

prior to cART 

Yes = 0 No = −0.39 
- 33 - 

Currently taking 

antiretrovirals 

Yes = 0 No = +1.24 

Age Age × 0.024 

Total Score % Risk of Clinical Progression in following 12 months (95% CI) 

<1.5 0.50

1.5−2.99 1.40

3.0−4.49 6.25

≥4.5 ≥20.00 

Example: 30yr old who has had no previous anti-retroviral therapy prior to cART, whose current CD4 count is 

400, viral load 50, BMI 22 and no anaemia. Their CD4 slope increased by 15/mm3

 in the last three months and 

they are currently taking cART. Total score is 0.38 and therefore their risk of progression for next 12 months is 

0.66 per cent. 

(Data from Mocroft A, Ledergerber B, Zilmer K, Kirk O, Hirschel B, Viard J-P, Reiss P, Francioli P, Lazzarin A, 

Machala L, Phillips A, Lundgren J; for the EuroSIDA study group and the Swiss HIV Cohort Study Short-term 

clinical disease progression in HIV-1-positive patients taking combination antiretroviral therapy: the 

EuroSIDA risk-score. AIDS. 21(14):1867-1875, September 2007) 

Both these studies indicate that the lowest risk of progression in the most favourable groups is about 

0.7 to 1.0 per cent per annum (but not significantly less than 1 per cent) after commencing HAART. The 

populations used in these studies are predominantly Western European, Israeli and Australian and so 

caution may be required when applying the data to pilots from out with these regions. In addition the 

socioeconomic groups of pilots and air traffic controllers may differ from the study populations. 

It is recommended that CD4+ T cell count and viral load levels should be determined every three to four 

months and that clinical condition, including general, neurological and, if indicated, psychiatric 

examinations should be assessed every six months. A neuropsychological evaluation may be considered 

every twelve months. Regular assessment of cockpit performance may be considered in lieu of this or to 

enhance assessment in asymptomatic, stable applicants with very low risk of progression. Further 

co-infection testing will be required where clinically indicated and those with new positive tests may 

require specialist evaluation prior to further certificatory assessment. 

Clearly not every individual with HIV infection will be fit for certification. However, some applicants 

may be fit and remain so for a prolonged period and it is to assist in the identification of such individuals 

that the information in this chapter is written. The assessment of HIV-positive applicants requires 

specialist expertise and careful consideration of all the points mentioned in this chapter and applicants 

need to be advised at the outset that continued certification will require ongoing medical scrutiny and 

prolonged follow-up. 

8. Asymptomatic HIV positive cases and travel vaccination 

Vaccinations can temporarily increase the viral load for approximately four weeks. As a rule, 

immune-compromised people should not receive vaccines based on live-attenuated organisms, such as 

measles and yellow fever. However, risk is not increased in true asymptomatic and immuno-competent 

cases, confirmed by a sufficient CD4+ T cell level (> 350/ μL) and these cases will have a normal 

response of the immunological system to these vaccinations. 

— — — — — — — — 

INSULIN-TREATED DIABETES 

GUIDANCE FOR CERTIFICATION OF AIRCREW WITH 

INSULIN TREATED DIABETES MELLITUS 

This guidance should be used in conjunction with the Manual of Civil Aviation Medicine (Doc 8984, 

Chapter 4) and Annex 1 (below) — Risk Analysis and Literature Review. 

1. Introduction

Several Contracting States permit applicants having insulin treated diabetes to exercise the privileges of 

their licence. The purpose of this guidance material is to provide a protocol that will enable other States to 

consider such applicants under the flexibility Standard in Annex 1 — Personnel Licensing, 

paragraph 1.2.4.8. The key areas of concern in certificating aircrew with insulin treated diabetes mellitus 

are hypoglycaemia and the enhanced risks of micro and macrovascular disease. In the paragraphs that 

follow, the focus will be on the risks of hypoglycaemia, but the protocol at the end of the section will 

include an assessment of cardiovascular risk. 

2. Hypoglycaemia 

Achieving and sustaining near normal glycaemia is a central target in the management of patients with 

both Type 1 and Type 2 diabetes mellitus whose microvascular complications are then reduced 1, 2. 

However, the clinical consequence of improving glycaemic control is an increase in the frequency of 

hypoglycaemia 2, 3 which is a concern in the risk assessment of diabetic aircrew. The relative risk of 

severe hypoglycaemia (requiring the assistance of another) is greater for intensively treated (to achieve 

lower HbA1C levels) patients with Type 1 diabetes (about 27 per cent per year according to the Disease 

Control and Complications Trial [DCCT]) 3 than for those with Type 2 (2 per cent per year according to 

the UK Prospective Diabetes Study [UKPDS]) 2 despite similar glycaemic control. 

Several factors may explain why patients with Type 2 diabetes are less prone to severe hypoglycaemia. 

Normally, as plasma glucose concentrations fall, there is a hierarchy of defense responses. The first is an 

increase in the release of counter-regulatory hormones as plasma glucose falls to approximately 

3.8 mmol/L which is designed to prevent glucose concentrations from falling further. The second is an 

awareness of warning symptoms, predominantly autonomic (sweating, hunger, anxiety, tachycardia, etc.), 

which begin as plasma concentration decreases to approximately 3.4 mmol/L. In patients well educated 

in diabetic management, such symptoms will prompt preventative steps, i.e. ingestion of carbohydrate, 

which will prevent neuroglycopaenia, which commences at approximately 3.0 mmol/L. 

In people who have had Type 1 diabetes for over five years, counter-regulatory hormone responses to 

hypoglycaemia are generally impaired. Initially, most patients lose their glucagon response to 

hypoglycaemia, thereby becoming dependent on catecholamine responses to prevent or reverse 

hypoglycaemia. Sometimes even that response becomes impaired and the risk of severe hypoglycaemia 

increases several fold. Additionally, episodes of mild hypoglycaemia, even if symptomless, can further 

impair glucose counter regulation and may reduce ß-adrenergic sensitivity leading to a situation of 

“hypoglycaemic unawareness”. In this situation, patients may not recognize impending hypoglycaemia 

until it is too late to institute preventative measures (Gerich J F) 4. The situation is somewhat different in 

Type 2 diabetes; firstly, although glucagon responses are commonly impaired, catecholamine responses 

are usually normal or increased. Secondly, the patients are insulin resistant and thirdly, they have 

persistent ß-cell function. The ability to modulate insulin secretion can act as a buffer, since endogenous 

insulin secretion will decrease as plasma glucose falls. This opportunity is not available in Type 1 patients 
- 36 - 

whose insulin availability is pre-determined by the amount already injected. Fourthly, most Type 2 

patients are not on intensive insulin regimes so they are less at risk of hypoglycaemic unawareness as a 

result of insulin induced hypoglycaemia. 

This differing rate of hypoglycaemia has been confirmed recently by Heller et. al.(5) who found no 

differences in the rate of severe hypoglycaemia in Type 2 diabetic patients treated with sulfonylureas or 

insulin for less than 2 years (0.1 and 0.2 episodes per subject – year) and this frequency was far less than 

that encountered in Type 1 diabetes (< 5 years 1.1; > 15 years 3.2 episodes per subject – year). 

From a number of studies including Akram et. al.(6), the risk factors for severe hypoglycaemia include 

previous hypoglycaemia, long duration of diabetes and impaired hypoglycaemic awareness. 

3. Protocol

From the literature review, the risk of hypoglycaemia in Type 1 diabetes is outside that which would be 

acceptable in terms of the “1 per cent rule”. States using different risk criteria should make their own 

assessment of risk. 

For aircrew with Type 2 diabetes, whether taking insulin or not, individuals should be at low risk of 

hypoglycaemia. What follows is a cautious protocol that may assist States to determine fitness in 

applicants who present with Type 2 diabetes. It provides guidance and may be adjusted by individual 

States to suit their own requirements. 

4. Initial assessment

• Stimulated C-peptide levels*

 > 25 per cent of normal; 

• No previous hypoglycaemic episodes requiring the intervention of another person; 

• Stable blood glucose control: satisfactory HbA1C ~ 7 – 8 per cent; 

• Adequate self-monitoring with a memory chip glucose meter; 

• No evidence of hypoglycaemic unawareness; 

• Good diabetes education and understanding; 

• Positive attitude to monitoring and self-care. 

 

An annual assessment may include: 

• Review of adequate self-monitoring with a glucose meter; 

• Review of blood glucose control with satisfactory, stable HbA1C; 

• Report from the treating physician to confirm no complications of diabetes, including renal 

and visual complications; 

                                                           

*

 C-peptide is an indicator of beta cell activity. Most Type 1 diabetics are C-peptide negative. 
- 37 - 

• Annual cardiovascular assessment such as a symptom limited exercise ECG and clinical 

review by a cardiologist. 

Follow-up should be agreed jointly between the treating physician and the medical assessor. 

This approach could be extended to encompass pilots and air traffic control officers with Type 2 diabetes 

on sulphonylureas as well as those on insulin. This would avoid any period of unfitness on sulphonylureas 

with the resultant potential degradation in training. 

 

5. References

1. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment 

of diabetes on the development and progression of long-term complications in insulin dependent 

diabetes mellitus. N Engl J Med 1993; 329: 977-86. 

2. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with 

sulphonylureas or insulin compared with conventional treatment and risk of complications in 

patients with type 2 diabetes (UKPDS 33). Lancet 1998; 352: 837-53. 

3. The DCCT Research Group. Hypoglycaemia in the diabetes control and complications trial. 

Diabetes 1997; 46: 271-86. 

4. Gerich J F. Hypoglycaemia and counter regulation in type 2 diabetes. Lancet 2000; 356: 

1946-47. 

5. Heller S. Risk of hypoglycaemia in types 1 and 2 diabetes: effects of treatment modalities and 

their duration. Diabetologia 2007; 50(6): 1140-7. 

6. Akram K, Pedersen-Bjergaard U, Carstensen B et al. Frequency and risk factors of severe 

hypoglycaemia in insulin-treated Type 2 diabetes: a cross-sectional survey. Diabetic Medicine 

2006; 23: 750-6. 

- 39 - 

ANNEX 1 

INSULIN TREATED DIABETIC AIRCREW 

1. Risk analysis and literature review 

Any risk assessment requires a review of the literature looking at the prevalence of hypoglycaemia in 

insulin treated diabetes mellitus and the application of clinical judgement as to whether one can 

extrapolate population data to individual cases. It is proposed to discuss the rate of hypoglycaemia firstly 

in Type 1 diabetes and secondly review the differing rates in Type 2. 

It is very difficult to assess the frequency of hypoglycaemia in insulin treated diabetic populations 

because of the wide variation of severity and outcome. For example, the common occurrence of 

asymptomatic biochemical hypoglycaemia that is only evident if blood glucose is measured frequently 

and the failure to recognize or record many mild episodes including those occurring during sleep. 

However, a critical review of the medical literature on the subject provides some data on which to base a 

risk assessment. Since the publication of the Diabetes Control and Complication Trial {DCCT} (1993) in 

Type 1 diabetes which showed that tight diabetic control could assist in the prevention of complications, 

diabetic physicians have striven to improve overall control. However, this study showed an approximate 

three-fold increase in prevalence of severe hypoglycaemia in the intensively treated group compared to 

that of the conventionally treated (0.54 v 0.17 episodes/patient/year). An analysis of the cumulative 

incidence of successive episodes indicated that intensive treatment was also associated with an increased 

risk of multiple episodes within the same patient (e.g. 22 per cent experienced five or more episodes of 

severe hypoglycaemia within five years of follow-up v 4 per cent in the conventional group). Several 

sub-groups defined by baseline characteristics, including males, adolescents and subjects with no 

C-peptide or with a prior history of hypoglycaemia had a particularly high risk of severe hypoglycaemia 

in both treatment groups. Ward and colleagues (1990) found in an out-patient study of 158 patients in 

Auckland that almost all, 98 per cent, had experienced hypoglycaemic episodes and for 30 per cent these 

were a major problem. These symptoms of hypoglycaemia, which represent a combination of 

neuroglycopaenia and autonomic neural stimulation, would be likely to degrade pilot performance. In 

theory this may be modulated by good hypoglycaemic awareness and adequate early correction. The 

adverse effects of hypoglycaemia on cognitive function, in Type 1 diabetes, have been studied by Holmes 

(1983, 1986), Pramming (1986) and Herold (1985). Cox and colleagues (1993) studied this problem in a 

driving simulator and found that the degradation in performance was not reliably recognized by subjects, 

none of whom had lost hypoglycaemic awareness. In practice, therefore, it would be unacceptable for a 

pilot to experience a hypoglycaemic episode in flight where a lack of hypocglycaemic awareness would 

present a risk to the safety of the flight. 

The risk of severe hypoglycaemia with intensive insulin therapy was further explored in a study by Bott 

and colleagues (1997) in 636 insulin dependent diabetics. The incidences of severe hypoglycaemia 

between participants in the study varied between 0.05 and 0.27 cases per patient per year. In particular, 

the authors sought to find a relationship between a level of haemoglobin A1 which could predict severe 

hypoglycaemia but there was no linear or exponential relationship. 

More recently Egger and colleagues (1997) performed a meta-analysis of 14 trials which contributed to 

16 comparisons of 1028 patients with Type 1 diabetes allocated to intensive insulin treatment and 1039 

allocated to conventional treatment. The authors found a substantial risk of adverse effects associated 

with intensive insulin treatment which included an excess of severe hypoglycaemia confirming that the 
- 40 - 

findings noted in the DCCT (1991) were not exceptional, but commented that multiple daily injection 

schemes may be safer than treatment with insulin pumps. 

Having accepted that there is evidence in the literature that intensive insulin regimens increase the rate of 

hypoglycaemia, it is logical to postulate how one might predict the frequency of such hypoglycaemic 

episodes and perhaps prevent them. 

Cox and colleagues (1994) studied 78 insulin dependent subjects with diabetes mellitus from two 

different sites performing self-monitoring of blood glucose. Over the following six-month period these 

subjects recorded their severe hypoglycaemic episodes (stupor or unconsciousness). There was no 

difference in the number of severe hypoglycaemic episodes between the subjects in good versus poor 

metabolic control. The higher frequency of severe hypoglycaemia during the subsequent six months of 

follow-up was predicted by frequent and extreme low self-monitoring blood glucose readings and the 

variability in the day-to-day readings of the blood glucose. Regression analysis indicated that 44 per cent 

of the variance in severe hypoglycaemic episodes could be accounted for by initial measures of blood 

glucose variance and the extent of low blood glucose readings. Individuals who had lower haemoglobin 

A1 levels were not at a higher risk of severe hypoglycaemic episodes and thus blood glucose variability 

and low blood glucose readings were good predictors of severe hypoglycaemia. 

Casparie (1985) found that one of the causes of hypoglycaemia in a study of 32 severe hypoglycaemic 

episodes in 26 patients (a patient per year incidence of 8 per cent) was often a lack of alertness or 

carelessness in calculating the insulin dose. The author felt that by teaching patients to respond more 

adequately to changing circumstances in daily life and to react to warning signs by appropriate action 

would also reduce the incidence of hypoglycaemia. The difficulty in predicting hypoglycaemic episodes 

in an individual patient was highlighted by Goldgewitch and colleagues (1983) when they found that 

emotional factors were often given as a cause of hypoglycaemia but in 11 per cent of cases there were no 

obvious reasons for the hypoglycaemic attacks in spite of the appropriate management of their diabetic 

control. 

Ter Braak and colleagues (2000) carried out a retrospective study of 195 consecutive cases with Type 1 

diabetes to ascertain frequency of severe hypoglycaemia and found this to be 150 episodes per 100 patient 

years and occurred in 40.5 per cent of the study population. The clinical characteristics which predisposed 

to hypoglycaemic coma were the presence of neuropathy, coincident treatment with beta blocking agents 

and the use of alcohol. These three observations were controlled to adjust for duration of diabetes, which 

is also a significant predictor of hypoglycaemia. 

The data on mild hypoglycaemia are more variable and it is difficult to obtain accurate estimates. 

However, Pramming (1991) studied the frequency of the symptomatic hypoglycaemic episodes in 411 

randomly selected Type 1 diabetic outpatients. From questionnaire analysis the retrospective frequencies 

of mild and severe hypoglycaemia were 1.6 and 0.029 episodes per patient per week. From the patient 

diaries prospective frequencies of mild and severe hypoglycaemic episodes were 1.8 and 0.027 episodes 

per patient per week. Interestingly, symptomatic hypoglycaemia was more frequent on working days than 

during weekends (1.8:1) and more frequent in the morning than during the afternoon, evening and night 

(4.5: 2.2: 1.4:1). Importantly, the symptoms of hypoglycaemia were somewhat non-specific, 

heterogeneous, and weakened with increasing duration of diabetes. These data are congruent with other 

data in the literature suggesting that hypoglycaemic unawareness increases with duration of diabetes and, 

of course, the duration of diabetes is also a predictor of hypoglycaemia. 

The basic pathology in Type I diabetes is islet cell failure and that of Type 2 diabetes is of insulin 

resistance. It is, therefore, inappropriate to transpose hypoglycaemic frequency data from Type 1 

individuals to Type 2. 
- 41 - 

MacLeod and colleagues (1992) studied the frequency of severe hypoglycaemia in 600 randomly selected 

patients with insulin treated diabetes attending a large diabetic outpatient clinic. 175 (29.2 per cent) of 

the 600 patients reported a total 964 episodes of severe hypoglycaemia in the preceding year giving an 

overall frequency of the group of 1.6 episodes per patient per year. Interestingly, the frequency of severe 

hypoglycaemia in Type 1 diabetics was almost double that of Type 2 diabetics being treated with insulin 

(1.7 v 0.73 episodes per patient per year). 

This differing rate of hypoglycaemia has been confirmed recently by Heller et al (2007) who found no 

differences in the rate of severe hypoglycaemia in Type 2 diabetic patients treated with sulfonylureas or 

insulin for less than 2 years (0.1 and 0.2 episodes per subject – year) and this frequency is far less than 

that encountered in Type 1 diabetes (< 5 years 1.1; > 15 years 3.2 episodes per subject – year). 

This finding of a lower average rate of hypoglycaemia in Type 2 diabetes was noted by Wright and 

colleagues (2002) in the United Kingdom Prospective Diabetic Study (UK PDS 57) who found the rate of 

severe hypoglycaemia in Type 2 diabetics treated with insulin alone was 3.2 per cent per annum and 

1.6 per cent per annum in those who were treated with clorpropramide or glycazide with or without 

insulin. Cryer (2002) in a review of the literature also suggested that the risk of serious hypoglycaemia is 

much less in Type 2 diabetes, even in patients treated intensively as judged by HbA1c levels. 

2. Estimation of incapacitation risk 

Using the data from this literature review, the rate of severe hypoglycaemia, i.e. hypoglycaemia requiring 

the help of another in Type 2 diabetes treated with insulin, is of the order of 3 per cent per annum. These 

data, however, do come from hospital populations and the pilot group are highly selected, well motivated 

and meticulous in managing their diabetes. By selecting those with Type 2 diabetes who have a low risk 

of hypoglycaemia the figure may be less. Using this extrapolation one may estimate the rate to be 

between 1 and 2 per cent per annum. 

4. Risk of subtle impairment of performance 

Data to estimate this prevalence are rather difficult to obtain and frequently not robust but from the study 

of Pramming (1991) one may postulate using the work of McLeod (1992) that the rate of mild 

hypoglycaemia may be 50 per cent less in Type 2 diabetics than Type 1, giving a figure of approximately 

0.85 episodes/patient/week. This may be due in part to the preservation of the glucose counter regulation 

mechanism which may protect against progression to severe hypoglycaemia. 

 

5. Selection criteria 

On the basis of the literature review it would be appropriate in the first instance to look at Type 2 diabetes 

which would appear to have a lower prevalence of hypoglycaemia. For Class 1 professional pilots the 

certification category should be limited to a multicrew operation. What follows are the selection criteria 

used by one Contracting State. 

• No hypoglycaemic episodes requiring the intervention of another party during the previous 

five years. In Type 2 diabetes it is reasonable to reduce this period to six months 

• Stability of blood glucose control in the year prior to certification as measured by 

glycosylated haemoglobin which should be less than twice the upper limit of normal for the 

laboratory assay. 90 per cent of blood glucose levels should be greater than 5.5 mmol/L. The 

individual should have good diabetic education and be well motivated to achieve good 
- 42 - 

control. There should be no evidence of hypoglycaemic unawareness and the individual 

should fall into the “low risk group of hypoglycaemia” shown in Table 1. In addition they 

should be regularly monitored by their diabetic specialist to exclude any complications. 

Specifically, with the increased incidence of coronary heart disease in Type 2 diabetics, there 

should be a cardiovascular assessment to include, for example, an annual exercise ECG to 

mitigate against the cardiovascular risk. 

Table 1 

Hypoglycaemia Risk Among 

Insulin users

• Stimulated C-Peptide levels > 25% of normal 

• No previous hypoglycaemic reactions requiring the intervention of another 

person.

• Stable blood glucose control as measured by:

(a) Glycated Hb (Patient /upper lab normal ratio <2.0.

(b) 90% of blood glucose measurements >5.5 mmol.L.

• Adequate self monitoring with a memory chip glucose meter.

• Good diabetes education and understanding.

• No evidence of hypoglycaemia unawareness

• Positive attitude to monitoring and self care.

C-peptide is an indicator of beta cell activity

Most Type 1 diabetics are C-peptide negative

Low Risk

 

6. Risk benefit analysis 

The benefit to aviation of introducing this protocol would be to maintain individuals in the flight deck 

environment who have a wealth of experience as the majority of Type 2 diabetics present with oral 

hypoglycaemic failure between 40 and 50 years. Individuals in this age group have excellent flying 

experience and arguably may be safer than those more junior individuals without such. By selecting 

Type 2 diabetics who are already professional pilots and returning them to the flight deck with a 

multicrew limitation the risk is further reduced due to the incapacitation training that commercial pilots 

are required to undertake when operating on two-pilot flight decks. This risk can be further mitigated by a 

stipulation that the pilot must inform their colleagues on the flight deck of the nature of their multicrew 

endorsement and instruct them in actions should mild or severe hypoglycaemic events occur. In any long 

haul operation there is ample time to check blood sugar levels at regular intervals and the availability of 

carbohydrate is not a problem. In a short haul operation it is unlikely that the blood sugar will change 

dramatically over a one to two hour period but at the midpoint of the flight monitoring should be carried 

out. Using these interventions this approach has potential benefit to the aviation industry. 
- 43 - 

7. Monitoring procedures 

It is essential that individuals who are accepted for this approach use a glucometer which is regularly 

calibrated and has a memory chip. The individual must carry a supply of 10 g portions of readily 

absorbable carbohydrate to cover the duration of the flight. Prior to the flight the blood glucose must be 

greater than 6.0 mmol/L. During the flight the blood glucose should be monitored every 30-60 minutes, 

and if the blood glucose falls below 6.0 mmol/L then a 10 g carbohydrate portion should be ingested. If, 

for operational reasons, the inflight blood glucose measurement cannot be done then 10 g of carbohydrate 

should be ingested. The frequency of monitoring on flights/duty periods over two hours may be reduced 

depending on individual circumstances, in consultation with the diabetologist and aviation medicine 

specialist. 

Blood glucose should be measured approximately 30-45 minutes prior to landing and if the blood glucose 

has fallen below 6.0 mmol/L, 10 g of carbohydrate should be consumed. With modern diabetic 

management involving prandial bolus injections of insulin, it is reasonable on long haul flights to have the 

diabetic pilot inject at appropriate times. In flights over 8 hours it is likely that the aircraft will carry 

“heavy crew” and thus this should not present a significant problem. If, despite this approach, the blood 

glucose exceeds 15 mmol/L then the individual should arrange for medical advice in order that corrective 

therapeutic measures may occur. 

8. End points for terminating 

This approach balances risk and benefit, but should event rates exceed those experienced in the literature 

and stated above, consideration should be given to discontinuing it. Any significant hypoglycaemia, i.e. 

requiring the help of another, which has caused any potential impact on flight safety would again result in 

close scrutiny with a view to terminating this approach. 

The approach is highly specific and an estimate of the numbers likely to be included is difficult. 

However, in the UK approximately 1-2 professional pilots/20,000 per annum show oral hypoglycaemic 

failure and it is likely that similar numbers may occur within the jurisdiction of other Authorities. This is 

similar to the rate experienced by another Contracting State which permits pilots on insulin to fly. 

9. Acknowledgements 

Dr. Hugh O’Neill, Transport Canada 

Dr. Warren Silberman, FAA. 

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