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Wednesday, 19 June 2013

The developing brain and HIV

As I typed my notes into this blog, my interest in the topic renewed.  I realize that I wrote these notes long enough that there should be significant advancement.  However , I decided to post regardless because perhaps it will interest some of you enough to search further at what may have changed.  Feel free to share.  When I first heard of AID's I read as many books as were probably available at the time.  Eventually I would work with patients in my internship who were living and dying with this disease.  There is a social stigma regarding people who suffer from HIV.  This is most unfortunate.  If someone in your family has this disease, please support and love them.  Love goes a long way.
 HIV (human immunodeficiency virus)
Is a Retro Virus. 
Target cells are predominately T cells (one of the immune cells).  It latches on and 
dumps contents (RNA).  Paracitic RNA and enzymes on the cell, using it as a template and making a DNA version.  Goes into the nucleus, another enzyme lets it chop open your DNA.  Chicken Pox is a retro virus.  It can give us shingles, an adult version.  Once in there, destroys cells that would normally protect us. 
Primary target:  CD 4 Thymphocytes
                           Normal T4 count: >1000/mm3 blood
                           AIDS                     <200/mm3


Before 1980 there was no HIV as we know it.
1980’s,  Priority of where it was:  Americas, Africa, Europe, Asia
1997 -  30 million
1999-   40 million
There is a male/female division that is more equal than in the past. 
HIV has grown in Africa the most.  It started to rise in Asia and Africa.
2001 Global Data (World Health Organization)
1.  People living with HIV/AIDS > 40 million
2.  New infections in 2001-  3 million
3.  Aids Death in 2001 – 3 million
Aids death (2001)
-Adults – 2.4 million (1.1 million were women)
 -children under 15 years of age: 580,000
Reported 1981 – 1999, average age mid 30’s.  Incubation time as long as ten years.
Canada Stats
Incidence among young gay men:

1995-99:  0.6%
2000:  3.7%
1995 – 8.5% of new cases = to women
2001- 25% of new cases = women
Drugs:
mutates rapidly and very easily, divides at a very rapid rate and changes.  If mutations there are more problems.  Therefore there is a use of several drugs at the same time so it may stop one but not the other.  If the treatment is for someone who can’t take it as it should be, this is risky.  All HIV drugs at the time I wrote these notes had severe side effects. 
 
Attempt to stop it from getting into cells
Stop it from making DNA (reverse transcriptase) inhibitors and can stop replication.
-prevents HIV-DNA production eg. zidovudine (AZT)
2.  Protease inhibitors
 - Interferes with readout of DNA to make more HIV
What is AIDS?
- Primary HIV infection (immune system cells and possibly CNS cells)
-Opportunistic infections
-PCP (pneumocycstis carinii pneumonia
-oral candidiases
-viral infections (CMV, varicella [chicken pox]
- toxoplasmosis (from kitty litter)
Malignancies (eg. Kaposi’s Sarcoma)
 Veritical Transmission (mother to child)
May cross – prenatal (trans –placental) in late pregnancy antibodies cross; most have severe effects.
                   - during birth process
                  -  through breast feeding
Vertical transmission rats:
  -  25-50 % in developing countries
-    10 – 30 % in industrialized
      8 % with AZT therapy for mom and infant
Tests for HIV
- antibodies (not valid for several months post-natal)
Looking for antibodies. If there antibodies than there has been exposure.
- Immune function tests (eg level of T cells)
-Direct detection of HIV in cultures (best)
Incubation periods for Aids
Adults: median 8 years
Infants: bimodal distribution
   -median 4 months
   - median 6 years
Symptons of aids appear in first few months and it is suspected that infected in the womb
Browers et al Study (1995)
All HIV
- 87 symptomatic untreated children (meaning showing evidence of AIDS when brought into the study)
 Controls
-Omitted tumors, infections
-blind evaluation of scans
-age appropriate tests
Question is are children who show damage to the brain with the disease  going to show it?
Used scans  ( CAT Scan is computer driven, 3 dimensional.  What is denser or thinner?  Calcifications means some cells in brain when dying or damage collect calcium deposits so  it shows up as a marked area in the brain.  Seen in other disorders but it is not common in children.  Scientists performing the scans did so blinded as to avoid bias.
Looking at children at wide range of age and therefore has to have different measures for different children.  What were the results?  Found calcification in pre-birth strictly using correlation data.  Seems to be impairment of behavior and more indicators of infection.
Still consider if groups are well matched.  Evaluating meaning having mom with HIV-behavior in house- some factors may have impact on social.
RESULTS:
-strong correlation between brain and behavioral measures
-vertical group more affected
-brain measures affected:
  Cerebral atrophy
Enlarged ventricles
Calcification of basal ganglia
                      Gay et.al
Seropositive woman is a person who has blood evidence of HIV.  At birth all had mothers with HIV (mom having psychological effects?).  Study was done in Miami, cultural appropriate, language and how conveyed.
1st 24 months Bailey -  hypothesizing that HIV infected children (seroreverted) .  Group of children with HIV performed worse overall on tests (standardized tests).
As got older, got worse  because HIV worsened.
Preventive Drugs
1.  Protocol 076:
   -zydovudine (AZT) orally from week 14
- AZT intravenous during labour
-AZT to infant for six weeks
(trying to prevent vertical transmission here)
2. Neviraprine – once to mothers (labour), once to infants (<72 hrs after birth)
Reduced transmission by 50%

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