Transcript 1640ad2b-b9b2-49cb-91b1

HIV and AIDS
Diagnosis & Treatment
Dr. Waseem Hamoudi, M.D
Internal Medicine
Gastroenterology & Hepatology
Acquired Immune Deficiency
Syndrome - AIDS• AIDS is caused by the human immunodeficiency virus
(HIV).
• The primary mechanism is to infect a particular subset of
T lymphocyte called CD4 cells.
• Over the time HIV decreases the number of CD4 cells.
• As a person’s CD4 count drops, they become at
increasing risk of developing opportunistic infections.
• HIV, by itself, does not harm the patient.
• HIV harms by destroying cell-mediated immunity
• The infections that develop are what harm patients.
Etiology
• Intravenous drug use is one of the most
common risk for the development of HIV.
• Homosexuality is also a common risk factor.
• There is often a 10 year lag between contracting
HIV infection and developing the first symptoms.
• This is because CD4 cells drop at a ate of 50100/year without therapy.
• It would take 5-10 years to drop from a normal
level of around 700 to a CD4 count of 200.
Diagnosis
•
•
•
Detection of IgG antibodies to envelope
of HIV by ELISA (anti HIV Ab).
HIV RNA by PCR (quantative).
Isolation of virus in special cultures.
Clinical features of HIV infection
• In the United States, the definition of
AIDS means individuals with CD4 counts
below 200 and clinical pictures.
• European definition means only clinical
features.
There are multiple systems
involved in this syndrome
•
1.
2.
•
1.
2.
•
1.
Neurological disease:
AIDS dementia complex.
Distal sensory polyneuropathy.
Eye disease:
Cytomegalovirus retinitis.
Anterior uveitis.
Muco-membranous manifestations:
Skin: Pruritis, papular eruption and eosinophilic
folliculitis.
2. Mouth: aphtous ulceration.
•
•
•
Hematological complications: Anemia,
neutropenia and thrombocytopenia.
Gastrointestinal manifestations:
weight loss, diarrhea (HIV enteropathy).
Kidney complications: HIV associated
nephropathy.
•
Respiratory complications: repeated upper
and lower respiratory infections.
• Cardiological complications: cardiomiopathy
and congestive cardiac failure.
• Cancers:
1. Kaposi sarcoma: skin cancer.
2. Lymphoma: cancer in the lymphoid system.
3. Squamous cell carcinoma: of the anus and
cervix.
Kaposi Sarcoma –foot, perianal.
Early symptoms
• Many people will not have any symptoms when they first
become infected with HIV. They may, however, have a
flu-like illness within a month or two after exposure to the
virus. This illness may include
• Fever
• Headache
• Tiredness
• Enlarged lymph nodes (glands of the immune system
easily felt in the neck and groin)
• These symptoms usually disappear within a week to a
month and are often mistaken for those of another viral
infection. During this period, people are very infectious,
and HIV is present in large quantities in genital fluids.
Later symptoms
• The immune system becomes more debilitated, a variety of
complications start to take over. For many people, the first signs of
infection are large lymph nodes, or swollen glands that may be
enlarged for more than 3 months. Other symptoms often
experienced months to years before the onset of AIDS include
• Lack of energy
• Weight loss
• Frequent fevers and sweats
• Persistent or frequent yeast infections (oral or vaginal)
• Persistent skin rashes or flaky skin
• Pelvic inflammatory disease in women that does not respond to
treatment
• Short-term memory loss
The 4 stages of AIDS clinical
manifestations
1.
2.
3.
4.
Antibody negative asymptomatic carrier state:
immediately after infection.
Primary HIV infection: within 2-4 weeks, after
infection, this may be associated with fever, malaise,
rash, arthralgia, lymphadenopathy and these remains
from 1 to 3 months.
Antibody positive asymptomatic carriers:
seropositive stage with low CD4 but with no
symptoms.
AIDS related complex: chronic symptoms and signs
manifested by HIV persons; generalized
lymphadenopathy, weight loss, fatigue, chronic
diarrhea, anemia, leucopenia, thrombopenia, candida
and opportunistic infections and cancers.
Oral Hairy leucoplakia -EBV-
Oral and genital Herpes
HIV patients
Herpes Zoster in HIV patient
Wasting in AIDS patient
Opportunistic infections in AIDS
•
•
•
1.
2.
3.
Pneumocystis carinii (CD4<200)
Principle manifestation: Pneumonia: dyspnea on
exertion, dry cough, fever, chest pain.
Principle diagnostic test: Bronchoscopy with
bronchoalveolar lavage for direct identification of the
organism.
Therapy and side effects;
Trimethoprim/sulfamethoxazole (TMP/SMZ) – rash
Pentamidine – Pancreatitis, hyper/hypo glicemia
Steroids if severe pneumonia (when Po2 <70)
•
•
Prophylaxis (in order of preference):
TMP/SMZ orally – this is the most effective.
Dapsone.
Atovaquone.
Aerosolized pentamidine
Prophylaxis of pneumonia may be discontinued
if antiretrovirals raise the CD4 count above 200
for more than 6 months.
Cytomegalovirus (CD4<50)
• Principle manifestations:
- Retinitis: blurry vision, double vision, or any visual
disturbances with low CD4.
- Colitis: diarrhea (<20% of patients).
• Principle diagnostic test:
- Funduscopy for retinitis.
- Colonoscopy with biopsy for diarrhea.
• Therapy and side effects:
- Ganciclovir – neutropenia
- Intravitreal ganciclovir.
- Cidofovir - renal
• Prophylaxis: Oral ganciclovir
Mycobacterium avium complex
(CD4<50)
• Principle manifestation: fevers, bacterimia, wasting,
anemia.
• Principle diagnostic tests:
- Blood culture.
- Culture of bone marrow, liver or other body tissue or
fluid.
• Therapy: Clarithromycin and ethambutol
• Prophylaxis:
- Azithromycin orally once a week.
- Clarithromycin twice a day
• Stop prophylaxis if antiretrovirals raise the CD4 count
above 100 for several months.
Toxoplasmosis (CD4 < 100)
• Principle manifestation: Brain mass lesion; headache,
confusion, seizures and focal neurologic deficits.
• Principle diagnostic tests:
- CT or MRI scan of the head (shows ring – contrastenhancing lesion that shrink after 2 weeks of treatment)
- Rare, brain biopsy.
• Therapy: Pyrimethamine and sulfadiazine.
Clarithromycin if sulfa allergic.
• Prophylaxis:
- TMP/SMZ.
- Dapsone/pyrimethamine.
Cryptococcosis
• Principle manifestation: Meningitis.
• Principle diagnostic tests:
- Lumbar puncture : with initial evaluation by India ink.
- Specific crypococcal antigen testing.
• Therapy: Amphotericin intravenously for 10 – 14 days at
least, followed by fluconazole orally (lifelong).
• Prophylaxis: Fluconazole.
Vaccination: all HIV – positive persons should
receive vaccinations for pneumococcus, influenza
and hepatitis B.
Monitoring the immune System
• CD4 count monitoring and viral load testing can
be compared to the staging of cancer in terms of
assessing prognosis for the patient.
• CD4 cell count: is the most accurate method of
determining what infections or other diseases
the patient is at risk for.
• Without treatment, the CD4 count drops 50-75
cells per year.
• Also CD4 is useful for determining when to start
prophylactic medications, and when to initiate
antiretroviral medications and the adequacy of
response to antiretroviral medications.
CD4 Count
700-1500: Normal
200-500: Oral thrush, Kaposi sarcoma, Tuberculosis,
Zoster, Lymphoma.
100-200:
Pneumocytosis carinii pneumonia, dementia.
< 100:
Toxoplasmosis, Cryptococcus,
Cryptosporidiosis.
< 50:
Cytomegalovirus, Mycobacterium avium
complex, Progressive Multifocal
Leukoencephalopathy (PML)
Viral load monitoring
• This test gives a numerical value to the quantity
of HIV in the blood.
• High viral loads are less desirable.
• High viral loads indicate a greater risk of
complications of the disease and a worse
prognosis.
• High viral load indicates that the level of CD4
cells is going to drop more rapidly.
• Other uses for viral load testing are to determine
when to initiate antiretroviral drugs and the
adequacy of response to antiretroviral drugs.
HIV viral load
< 400:
Lower limit of detection and goal for
therapy ( for sensitive tests <50)
>55.000: Level above which drugs should be
started
750.000: Upper limit of the test.
Antiretroviral therapy
•
•
•
•
•
•
•
•
•
Nucleoside reverse transcriptase inhibitors
Zidovudine (ZDV or AZT)- leucopenia, anemia.
Didanosine (DDI)- pancreatitis, neuropathy.
Stavudine (D4T)- peripheral neuropathy.
Lamuvidine (3TC)
Abacavir – rash.
Protease Inhibitors
Nelfinavir-gastrointestinal.
Indinavir- nephrolithiasis, hyperbilirubinemia
Ritonavir- gastrointestinal.
Non-nucleoside reverse transcriptase inhibitors
Efavirenz- neurologic, psychatric
Nucleoside/Nucleotide Reverse
Transcriptase Inhibitors (NRTIs )
Non-nucleoside reverse
transcriptase Inhibitors
Protease Inhibitors (PI)
Entry Inhibitors (and Fusion
Inhibitors)
Integrase Inhibitors
When to start therapy?
• When the CD4 count has dropped or the
viral load has risen.
• Both of these events imply a worse
prognosis.
• Antiretroviral therapy should raise the CD4
count and drop the viral load.
Guidelines for starting:
• CD4 < 350 or
• Viral load (by PCR-RNA) > 55.000
What to start?
• Use two nucleosides combined with protease
inhibitor or
• Use two nucleosides combined with efavirenz
(Sustiva) or
• Use two nucleosides combined with two
protease inhibitors.
There is a general agreement that
AZT/3TC/Nelfinavir is a good starting regimen
D4T (Stavudine) or didanoside can be used in
combination instead of AZT.
What is considered adequate
therapy?
• Any regimen that increases the CD4 count
and drops viral load to undetectable
amounts or close to undetectable amounts
is adequate.
• When starting medication, a drop of at
least 50% of viral load in the first month is
expected to indicate adequate therapy.
Pregnant patients
• Without treatment, approximately 25-39% of
children born to HIV-positive mothers will truly be
HIV positive.
• All children at birth will carry he maternal
antibody to the virus and will be positive by
ELISA testing, but only 25-30% will remain truly
infected.
• Pregnant women with serious disease (low CD4
or high viral load) should be treated fully for their
HIV infection. That is, they should get triple
antiretroviral therapy as you would in a
nonpregnant person.
• C-section is only used routinely in those whose CD4 cont
and viral load are not controlled with medication.
• At least, Zidovudine (AZT) treatment indicated in all
pregnant women.
• AZT alone will decrease the transmission from 25 to 8%.
• AZT should begin in pregnant women at 14 weeks of
pregnancy if the patient is not already on therapy for
their own disease.
• The only adverse side effect is transient anemia.
• The only known teratogen is efavirenz in animal studies.
Post exposure prophylaxis
• All patients with serious exposure to blood
body fluids oh HIV-positive patients should
receive AZT + Lamivudine + nelfinavir or
any other fully suppressive three drug
combination for 4 weeks.
• You can modify the regimen as needed to
ensure compliance.
• Zidovudine (AZT) alone will decrease the
risk of transmission by 80% .
Post exposure prophylaxis (PEP)
•
Risk of contamination 0,1 -0,5%:
1. Skin injury: ex. Needle stick injury
* Deep  infection risk < 0,3%  PEP
* Superficial  infection risk < 0,3%  PEP
2. Mucous membrane/broken skin:
* Large surface I. risk < 0,1%  PEP
* Small surface I. risk < 0,1%  offer the option
3. Unbroken skin I. risk < 0,1%  advice against
PEP = Post Exposure Prophylaxis
What to do ?
• Follow up examination for HIV infection ( at 1, 3, 6,12
months)
• Give PEP for those with infection risk > 0,1% :
IDV =Indinavir or nelfinavir.
3TC = Lamuvidine.
ZDV = Zidovudine.
- Early monotherapy with Zidovudine reduces HIV infection
by 80%.
- Start PEP within 6 hours of suspected exposure, do not
wait results, stop treatment if results are negative.
- Total course should take 4 weeks (28 days).
 Follow up HIV at the start of treatment
and after 1, 3, 6 and 12 months, if results
still negative then no HIV infection has
been taken place.
 After 12 months take another HIV test to
R/O delayed seroconversion.
Thank you
HIV life cycle - Binding
HCV life cycle – reverse
transcriptase-
HCV life cycle –Integration-
HCV life cycle – Transcription-
HCV life cycle –Translation-
HCV life cycle – Viral assembly and
maturation-