Treatment training for advocates: Answers to questions in Sections 1-7 www.i-Base.org.uk
HIV i-Base 1 June 2005
Answers to questions from Sections 1-7 of Treatment training for advocates.
This manual is available online in English and Russian from:
HIV i-Base
http://www.i-Base.info
Section 1
1. AIDS stands for:
- Acquired
- Immune
- Deficiency
- Syndrome
2. A CD4 cell is a white blood cell (lymphocyte) that signals CD8 cells to destroy a virus.
HIV uses CD4 cells as factories to reproduce in.
3. A CD8 cell is a white blood cell (lymphocyte) that kills cells that are infected with
viruses (i.e. HIV).
4. The ‘normal’ range for CD4 count in an HIV-negative adult is between 600 and 1600
5. CD4 cell is also called a helper cell, a CD4+ T-lymphocyte, CD4+ T-cell, and
sometimes just T4 cell); CD8 is also called a killer cell
6. CD4% is the percentage of total lymphocytes that are CD4 cells. It is used as a more
stable indication of whether there has been a change in the immune system. Children
are monitored using CD4%.
7. Cellular immune responses are based on CD4 and CD8 responses. Humoral immune
responses are based on antibodies.
8. A surrogate marker is an indirect measure for something else that cannot be easily
measured directly (i.e. the CD4 count is a measure for the disease progression).
9. US and UK treatment guidelines recommend routine CD4 and viral load monitoring
every three months, whether on treatment or not on treatment. These tests should also
be done before any treatment change, and 2-4 weeks after any treatment change. i.e.
4 weeks after starting treatment. Is any one test result produces an unexpectedly high
or low results, it should be repeated. In some countries with limited access to these
tests, they are performed less frequently – perhaps every 6 months.
10. Some guidelines (WHO, UK) would recommend starting treatment before the CD4
count has fallen below 200, while others (US) would recommend before 350.
11. A few weeks after the infection, the CD4 count usually falls, then the immune system
fights back and the count goes back again but not to the levels that it was before HIV
infection. From then on the CD4 count goes down gradually and it takes from 2 to 10
years usually to drop down to 200.
12. Please see graph on page 15.
13. The following OIs become more common below these CD4 levels:
CD4<300 - diarrhoea from microsporidia and cryptosporidia
- skin problems-candida (thrush), dry skin, etc.
<200 - PCP (pneumonia) and chest infection
- toxoplasmosis-a parasitic infection that commonly causes brain
lesions
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<100 - MAI/MAC-bacterial infection similar to TB
- Cryptococcus infection-fungal infection that can cause meningitis in the
brain and PCP-like symptoms in the lungs
<50 - CMV (cytomegalovirus)-a viral infection that can cause permanent
vision loss or blindness
14. Children have much higher CD4 counts than adults. Babies have higher CD4 counts
than children. Over time and as the people age their CD4 count drops gradually.
15. An antigen is the term for infectious material produced by a virus or bacteria.
16. Antibodies are cells in the immune system that recognise antigens.
Section 2
1. HIV is a virus. HIV stands for Human Immunodeficiency Virus.
2. Only 2% of HIV or HIV-infected CD4 cells are in blood.
3. HIV and HIV-infected CD4 cells are mostly in the lymph system and lymph nodes.
4. Blood is the most accessible compartment for regular monitoring.
5. A sanctuary site is the term for a compartment of the body that has barriers that limit
both HIV and HIV drugs from moving freely. The main compartments are the genital
tract, the cerebral spinal fluid and the brain.
6. Viral load levels can be different to blood in each compartment. For example someone
can have undetectable viral load in blood but detectable viral load in semen.
Resistance can also develop independently in different sites.
7. Four main causes of illness include
- Bacteria
- Fungi
- Viruses
- Parasites/protozoa
8. During the first few days and weeks after the infection, the viral load (VL) goes very
high, very quickly. Its levels can reach over 1,000,000 copies. Then, during the
seroconversion, the immune system starts producing antibodies in order to fight back.
As a result the viral load goes down (sometimes to below 50 copies). During the
chronic infection the viral load progressively and consistently goes up to the point when
the person starts ARV therapy. After that, with proper treatment regimen the VL
becomes ‘undetectable’ (below 50 copies).
9. Please see the graph on page 26.
10. The viral load test was developed as a research tool during the 1990s. The first test in
1995 could only measure down to 10’000 copies/mL. By 1996-7 the tests were able to
measure down to 400-500 copies/mL. Since 1998 the most routinely used test
measure down to 50 copies/mL, although some tests are even more sensitive and can
measure down to 5 copies/mL.
11. i) PCR (Polymerase Chain Reaction) – the most widely used test
ii) bDNA (branched DNA)
iii) NASBA (Nucleic Acid Sequence Based Amplification)
12. All tests have an approximately 3-fold margin of error (i.e. a test result of 30’000 means
that the real number could potentially be anywhere between 10,000 and 90,000)
13. Firstly, the viral load test shows whether the drugs work in a combination are initially
working. You need to see a minimum –1log reduction in the first month and aim to be
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<50 by 3-6 months. In someone who is on treatment with an undetectable viral load,
continued monitoring confirms that the drugs are still working.
14. If the levels are very high (>100,000), then this might be seen as a reason to start
treatment at a higher CD4 count than 200, even though the VL is not as important at
predicting the risk of opportunistic infections as the CD4 count.
15. HIV makes mistakes when replicating. Those mistakes are called mutations. When on
treatment, some mutations will not be affected by the drugs. If these mutations
develop, they will continue to reproduce. The ‘selective pressure’ from the drugs will
force the resistant virus to eventually become the major type of HIV in the individual.
He/she then becomes is said to be resistant to those drugs and cross=resistant to
similar drugs that have the same resistance pathway.
Section 3
1. ARV stands for ‘Antiretroviral’
2. A minimum of three drugs, but can be more
3. i) NRTI-Nucleoside Reverse transcriptase Inhibitors (‘nucleosides’ or ‘nukes’)
ii) NNRTI-Non-Nucleoside Reverse Transcriptase Inhibitors
iii) PI-Protease Inhibitors
iv) EI-Entry Inhibitors
4. Entry inhibitors
5. In June 2005 22 including co-formulated drugs (ie AZT+3TC; tenofovir+FTC etc)
6. In June 2005 there were four combinations recommended by the WHO for first-line
treatment
7. 3TC + d4T + nevirapine
3TC + d4T + efavirenz
3TC + AZT + nevirapine
3TC + AZT + efavirenz
8. – If the person is not ready or does not want to start treatment – delaying
treatment may give more time for them to become more psychologically prepared so
that they adhere to treatment better when they do start
- If the person has an opportunistic infection like TB where starting two different
treatments at the same time will increase side effects. With TB someone with a CD4
count <100 will delay ARVs for 1-2 weeks, and someone with a CD4 count 100-200 will
delay ARVs until after the first 2-months of TB treatment
- If they do not fulfil the guidelines recommended for starting treatment i.e. if their
CD4 count is still much higher than 200.
9. – How regularly a drug is taken and the time it is taken
- Speed of metabolism – how quickly an individual processes drugs – the are
wide ranges of individual differences in the drugs levels absorbed by different people.
Sometimes this can relate to body weight – i.e. larger people need a larger dose – but
more usually it is because of biological differences – i.e. different people have different
levels of the enzymes that the liver uses to process drugs.
- Diet – many drugs are absorbed more quickly or more slowly depending on
whether they are taken with food or on an empty stomach
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- Drug interaction (including some recreational drugs) – one drug can speed up
the metabolism of another drug (therefore reducing those levels) or can slow down the
metabolism (increasing the drug levels).
- Pre-existing liver damage (or kidney damage for some drugs) - ie someone with
liver damage is likely to process drugs much more slowly.
10. Adherence refers to taking the drugs exactly as they are prescribed-at the right time
and following any special diet restriction.
11. Six things that could help adherence include: (there are many others)
– Keeping a daily chart
- Using a pillbox
- Using a Pill beeper or alarm watch
- Having medications for the side effects
- Asking a friend to remind you
- Keep a small supply of drugs at an easy to reach place
12. Drug resistance refers to changes in the structure of an individuals HIV which means
that the drugs no longer work as well or even at all
13. Clinical failure refers to a when an HIV-positive person feels ill and gets symptoms (i.e.
other illnesses), which means that the drugs are not preventing him/her from getting ill.
14. Virological failure relates to the results of viral load blood tests – i.e. if viral load levels
never reach undetectable, or if they rebound and become detectable again.
15. The consensus from many studies seems to show that getting to <50 copies/mL stops
HIV from developing as a virus. After 5 years on treatment with a viral load <50 copies,
the virus will be the same as at the start of treatment. Viral load above 50 copies/mL
continues to evolve, and allows resistance to develop.
16. Please imagine that you are a counsellor and need to explain to your client what is
adherence, why adherence is important and how to improve adherence.
Section 4
1. Side effects are secondary effects of a drug other than the reason it is prescribed. Side
effects are also called adverse events or drug toxicity.
2. In some cases they are, but generally there is not a big difference. One of the most
important differences is with nevirapine and liver toxicity. Women should not start
treatment with nevirapine if their CD4 count is over 250, compared to men who should
not start if it their count is over 400.
3. Both of these options are possible but not without a discussion with the doctor. Quality
of life is very important and any drug that causes side effects can usually be changed
to an alternative that may be easier to tolerate.
4. Grade 1-mildest; grade 4-most serious.
5. Lipodystrophy has to do with the way the body processes fats and sugars. Symptoms
of lipodystrophy include lipoatrophy, fat accumulation and increased blood cholesterol
and triglycerides. Lipoatrophy is a state where the person has a reduced subcutaneous
fat on the arm; legs or face.
6. Peripheral neuropathy refers to damage to the nerves in the hands or feet It starts in
the fingers and/or toes but can spread into the arms and legs (‘peripheral to the central
body), usually with tingling, numbness, or increased sensitivity.
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7. d4T, ddI and very rarely 3TC. Hydroxyurea increases the risk of neuropathy with ddrugs.
ddC is now discontinued by had a high incidence of neuropathy.
8. AZT is associated with anaemia,
9. Nevirapine, efavirenz are both associated with liver toxicity
10. Symptoms of liver toxicity include; Feeling sick (nausea) or being sick (vomiting), Poor
appetite, If your eyes or skin looks more yellow, Light coloured stool or dark coloured
urine, Tenderness or swelling in your liver - your liver is just below your stomach.
11. Nevirapine, efavirenz, abacavir, fosamprenavir and T-20 can all be associated with
severe rash
12. A severe rash s defined as if the rash covers more than 10% of the body or if it breaks
the skin. However you would show any rash to a doctor or health advisor as soon as
you notice it, if you have recently started a drug associated with this as a side effect.
13. Two examples of Grade 4 side effects are: Diarrhoea requiring hospitalisation, liver
toxicity with AST or ALT levels above 7.5 ULN. Any side effect that requires
hospitalisation is classified as Grade 4.
14. The risk of lactic acidosis increases when d4T is used with ddI. These two drugs
should not be used together by pregnant women as the risk increases even higher.
15. Efavirenz (Sustiva) causes mood changes and vivid dreams in at least 50% people
when they first start treatment.
Section 5
1. Protozoa are tiny parasites. Giardia, cryptosporidia, and microsporidia.
2. A CD4 count fewer than 300 cellls/mm3 increases the risk of gastric infections.
3. - Drink bottled water sourced from underground sources
- Wash vegetables and salads thoroughly
- Cook meet thoroughly
4. Candida (thrush) is a fungal yeast infection that commonly affects the mouth and
throat, gullet, sinuses, genital organs, and much more rarely the brain.
5. Symptoms of candida include white or red patches (especially in the mouth),
sometimes cracks at the corners of the mouth, headaches and possible vomiting,
difficulty eating, and tast changes.
6. - Ketoconazole
- Itraconazole
- Fluconazole
7. PCP stands for Pneumocystis Carinii Pneumonia
8. Risk for PCP increases when CD4 counts is below 200 cells/mm3
9. Prophylaxis treatment against PCP includes co-trimoxazole or dapsone or aerosolised
pentamidine, etc.
10. First line PCP treatment is co-trimoxazole by continuous drip or injection for 3-4 days
and then switch to tablets.
11. Alternative PCP treatments include trimethoprim plus dapsone, pentamidine,
trimetrexate, atovaquone and clindamycin plus primaquine.
12. TB stands for Tuberculosis – it is a microbacterial infection that commonly affects the
lungs but can also affect many other organs
13. A person with active TB is infectious, while a person with inactive TB is not.
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14. First line TB treatment is a 2-month course of a combination of four antibiotics (I.e.
isoniazid, rifampicin, pyrazinamide and ethambutol), followed by a 4-month course of a
combination of 2 antibiotics (i.e. isoniazid and ethambutol)
15. Any PI or nevirapine.
16. TB prophylaxis is recommended for people who share the same confined living or
working place as someone with active TB.
17. Mycobacterium avium /Mycobacterium intracellulare-bacterial organisms closely
related to mycobacterium tuberculosis.
18. A combination of two or more antibiotics; usually clarithromycin or azithromycin plus
ethambutol.
19. Hepatitis is an infection that causes liver inflammation or damage.
20. Hepatitis C takes approximately 20-25 years to progress to in HIV-negative people but
progresses more quickly in people coinfected with HIV.
21. Drugs that are active against hepatitis B include adefovir, 3TC, tenofovir, FTC and
interferon-alpha. Drugs that are also active against HIV can only be used in a
combination with other HIV drugs. Please refer to current HBV treatment guidelines for
recommendations for treatment in HIV coinfected people, (i.e. www,bhiva.org)
22. When CD4 count drops below 50 cells/mm3 the risk of CMV retinitis increase to 30-
40% over 3 years.
23. Active CMV retinitis is diagnosed by eye examination, and anyone with a CD4 count
below 50 whether on or off treatment should have monthly eye checks. CMV while in
other organs is usually by biopsy sample. Viral load tests for CMV are generally only
used in research.
24. Toxoplasmosis is transmitted by eating raw or undercooked meat. Exposure to cat
faeces that is over 1 day old also is infectious and is a source of toxoplasmosis.
25. Toxoplasmosis treatment has to continue until CD4 count rises above 200.
26. Main AIDS-defining cancers include NHL (Non-Hodgkin Lymphoma), KS (Kaposi’s
Sarcoma) and cervical cancer.
27. It depends on the cancer. Some improve dramatically and go into remission (ie KS) but
others do not dramatically improve.
28. Liver cancer is associated with hepatitis C.
29. AIDS wasting is symptom of different diseases including HIV infection and OIs that
results in weight loss, principally loss of lean muscle mass.
Section 6
1. Without treatment for either the mother or baby, about 25% babies would be born HIVpositive
2. The mothers viral load at delivery is the most predictive of whether the baby with be
born HIV-positive. The lower the viral load, the lower the risk, and risk becomes less
than 1% when viral load is undetectable.
3. No, the fathers HIV status does not directly affect the status of the baby. An HIVnegative
mother cannot have an HIV-positive baby.
4. Pregnancy may cause a drop in a woman’s CD4 count. This is usually about 50
cells/mm3 but it can vary a lot.
5. There is a risk of resistance from using AZT monotherapy (that is not very high), and
the mother might be strongly advised to have a C-section as a mode of delivery.
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6. Less than 1% babies are born HIV-positive in mothers that use combination ARV
therapy with three or more ARVs.
7. A short course of triple combination therapy after the second trimester at 24 to 28
weeks is recommended for mothers who do not need ARV treatment for their own
health
8. Cons for C-section include:
- More probable complications like infections
- Having a natural birth after a C-section is more complicated and difficult
- Babies delivered by C-section are more likely to receive ventilatory support
Pros for C-section include:
- Reduced risk of HIV transmission when the pregnant woman receives only AZT
9. ARV drugs not recommended in pregnancy are efavirenz-generally in pregnancy and
the caution is strongest during the first trimester (12 weeks); nevirapine is not
recommended for women with a high CD4 count (above 250) because of risk of liver
toxicity; ‘ d‘ drugs together as they can cause fatal side effect in pregnant women
10. ARV drunks can contribute to morning sickness, nausea, anaemia, diabetes, lactic
acidosis.
11. A HIV positive woman who is pregnant should avoid amniocentesis, chorionicvillus
sampling, foetal scalp sampling, cordocentis, percutaneous umbilical cord sampling,
and internal foetal labour monitoring.
12. Acyclovir prophylaxis during labour will reduce the risk of transmitting herpes to the
baby.
13. The day the baby is born, one month after that and three months after that, using HIV
PCR DNA test.
14. HIV-positive mothers should not breastfeed. The risk of transmitting HIV from motherto-
baby can be as high as 28%.
15. The baby should take ARV prophylaxis for four to six weeks after birth.
16. After the birth, the mother has to be especially careful of her own adherence and
health.
Section 7
1. IDUs were frequently excluded form ARV treatment due to the wrong but widespread
belief that they are less likely to be adherent to treatment and less likely to have a good
response to treatment.
2. Excluding IDUs form treatment is not based on scientific evidence. Several studies
showed that drug users could achieve high levels of adherence and benefit from
treatment just like any other group of people with HIV.
3. Access to treatment, access to substitution therapy, OI prophylaxis and treatment,
accessible, non-judgemental healthcare team, needle exchange, adherence support
and counselling, strong link with community based programmes, food programmes and
public transport, outreach strategies.
4. Yes. 2 to 3 fold increase in ecstasy levels because of an interaction with ritonavir.
5. Yes. About 50% decrease in blood levels of heroin because of an interaction with
ritonavir.
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6. Yes. People using methadone and efavirenz will have a reduced dose of methadone
(of up to 60 % in blood concentration) and may need to increase the dose of their
methadone.
7. Yes. AZT concentrations are increased by approximately 2-fold.
8. A dose reduction of 50% of the drug is recommended when used with methadone.
9. Those symptoms that develop within 2-3 days are more likely to be a result of ARV
toxicity, and those that develop after 6 days are more likely to be associated with drug
withdrawal.
