2. Overview
PEP
How to monitor after diagnosis ?
When to start ART?
What to start?
How to monitor after starting ART?
When to refer?
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3. Mayur
Mr Mayur, 24 yr old, IT
guy called at 10 am on
Sunday morning.
H/O Unprotected
exposure (condom
slipped) night before.
Wants to know if he is
HIV infected- TODAY.
What to do?
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4. “Window Period” Following HIV Infection
Acute HIV
syndrome
Primary
HIV
infection
Antibod
Asymptomatic
Viremia
------------------------------------ PCR
P24 a.g
ELISA
a
0
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b
2
3 4
(Weeks since infection)
Years
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Source: S Conway and J.G Bartlett, 2003
6
5. Diagnosis in the window period
After 12 weeks-antibody tests
Elisa/Rapid
At approx 4 weeks- HIV Duo
At approx 2 weeks- HIV RNA
HIV DNA
P24 Ag test
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6. HIV DNA or RNA
HIV DNA or RNA tests are NOT recommended for
diagnosis in adults
False positive results in almost 20% of patients
Costs around Rs 4000.
The patients have to be subjected to antibody testing
for confirmation after 6 TO 12 weeks.
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7. What to do?
Take history: was the risk significant?
Explain about window period
Any symptoms or signs of STD-Treat
Test for baseline HIV status, Hbs Ag, ? Anti HCV
Start PEP for HIV if indicated
Start Heb B vaccine course, if not vaccinated or HbS
Ag neg.
Risk reduction counseling
If woman( Mayuri), Emergency contraception
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9. Drugs for Post exposure prophylaxis
Basic regimen:
1. Tenofovir 300+ Emtricitabine 200mg OD OR
2. AZT 300 mg + Lamivudine 150 mg BD
Expanded regimen:
1. Above plus Atazanavir 300 + Ritonavir 100 mg OD
2. Lopinavir 400mg +Ritonavir 100 mg BD
All for 4 weeks
Test after 6 weeks and 3 months for HIV and Hep B
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10. After 3 months……..
Mayur ‘s HIV test is Negative
Risk reduction counseling .
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11. After 3 months……..
Mayur ‘s HIV test is Positive (……..May be because
I didn’t take his call on Sunday )
Now what?
1. Disclose Mayur that he is HIV positive?
2. Do Western Blot test
3. Do HIV DNA/ RNA test?
4. Repeat Elisa test?
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12. Mayur has confirmed HIV test
Now what?
Don’t know how to break the news, so keep silent
Refer to HIV specialist
Manage further
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14. Then one fine day Mayur comes
with …….
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15. Initial evaluation: history
Fever, night sweats, weight loss, cough (any duration):
TB
Past H/o OI’s: herpes zoster, chronic diarrhoea
ARV use in past
Co-morbidities: DM, HTN, CKD, Jaundice
Smoking, alcohol
High risk behaviour
Ask if he has any sexual partner, marital status , children
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17. Initial evaluation: Laboratory workup
CBC with differential
Urinanalysis, creatinine
Blood sugar
Liver enzymes (optional)
Chest Xray/USG abdomen (before starting ART)
VDRL, TPHA
HbsAg, anti-HCV
CD4 Count
Cervical PAP smear in Mayuri
CD4 to be taken after treating Herpes Zoster
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18. Tests NOT recommended routinely
Plasma viral load
ARV resistance testing
Fasting lipids
CMV, Toxo serology
sCRAG (in pts with CD4<200)
TB ELISA
Tuberculin testing
IGRA assays( TB Gold, Quantiferon)
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19. Rule out TB
Need to screen all HIV patients for TB
Thorough history and physical to identify “TB suspects”
CXR and sputum AFB for all “TB suspects”
Need to screen all TB patients for HIV
Active promotion and routine offering of VCT
19
20. Mayur LOOKS very gloomy- as he he has given up on
his life
He has been keeping well for last 5 -6 years. No OI or
co –morbidity.
But he has taken to smoking and alcohol
No abnormal findings on physical examination
He has never married (He feels he won’t live long
anyway).
He has a girlfriend, whom he has not disclosed his
status.
All reports are normal.
CD4 count 325 cells/ml
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21. What to do next?
1. Start ART?
2. Wait till CD4 falls upto 250 and start
Septran
3. Start ayurvedic treatment or Amway
products?
4. Refer?
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22. Reassurance!! Reassurance!!!!Reassurance !!!!!!!
HIV is a chronic manageable disease like Diabetes,
like Hypertension, like asthma.
One can expect a near NORMAL lifespan with HIV
infected individuals
There is no cure, but with regular medicines one can
lead a normal life
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23. More than just medicines…
Mental health
Diet
Hygiene-water, air
Exercise
Lifestyle
Addictions
Financial security
Disclosure / testing of partner, if indicated
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25. When to start ART?
All Pt with hx of AIDS-defining condition
All patients with CD4 T-cell count of <350 cells/mm3
All Pt that are pregnant, HIV nephropathy, HBV co-
infection when HBV Rx is needed
Recommended for all Pt with 350-500 cells/mm3
Optional for Pt with >500 cells/mm3
DSHS,January 10, 2011
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26. Benefits of ART
The survival after development of advanced HIV
disease increased from 18 months to over 25 years for
those who can access medicines.
Prevention of transmission
Secondary prevention
Post-exposure prophylaxis
Occupational and non-occupational
Mother to child transmission
Pre-exposure prophylaxis
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27. Fusion
RNA
Reverse
transcriptase
ZDV, ddI,
ddC, d4T,
3TC, ABC,
TDF, FTC
DLV, NVP,
EFV, ETV
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Viral protease
ENF
CCR5 antag.
maraviroc
RNA
Proteins
RT
RNA
RNA
RT
DNA
DNA
DNA
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Provirus
Integrase
raltegravir
SQV
RTV
IDV
NFV
fAPV
LPV
ATV
DRV
TPV
30. First line regimens
Preferred
TDF/XTC/EFV or NVP( Trustiva, Effoday, )
Alternative
AZT/3TC/EFV or NVP
No options available
d4T/3TC/EFV or NVP
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31. How to monitor when on ART?
1.
Look for IRIS: Immune reconstitution inflammatory
syndrome
2. Look for adverse effects- clinical and lab
investigations
3. Watch for drug drug interaction
4. Monitor response to ART: CD4 and Viral load
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32. How to monitor when on ART?
IRIS: Immune reconstitution inflammatory
syndrome
Iris is occurrence or manifestations of new OIs
within six weeks to six months after initiating
ART; with increase in CD4 count
Two types: Unmasking and Paradoxical
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33. IRIS
3 weeks after ART
(TDF+3TC+EFV)
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33
35. How to monitor when on ART?
TDF: Renal, bone( Do urine R, S creat)
AZT: Anemia( Hb)
EFV: CNS
Nev: HSR, Hepatitis( LFT if symptomatic)
d4T: Neuropathy, lactic acidosis
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36. Nevirapine (NVP)
Rash
Hepatitis
Risk
is greatest in first 6 weeks of therapy
Could be benign or fatal
Increased risk if started in women with CD4
above 250 and men with CD4 above 400
Not to use in concomitant Anti TB drugs
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38. Efavirenz Toxicity
CNS Changes (excessive sleep or loss of sleep,
delusions, nightmares)
Rash
Hepatotoxicity (
Contraindicated during pregnancy
Teratogenic—Class D?
Useful in TB with HIV
Useful when stsrting ART in higher CD4 count
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39. Long term Toxicity (After few
years)
Bone Marrow Suppression Myalgia
Anemia
Myopathy
Neutropenia
Pigmentation of nail
Peripheral Neuropathy
beds
Lipoatrophy
Lactic acidosis, fatty
Fat accumulation
Osteoporosis
Metabolic syndrome
liver
Pancreatitis
Cardiovascular side effects
Renal dysfunction
Hepatic dysfunction
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42. Side effects/Toxicity of ART
Acute side effects: Rash, headache, nausea, vomiting,
loose motions, jaundice, anemia, excessive sleep or
loss of sleep, delusions, nightmares.
Chronic toxicity: Lipodystrophy- i.e change in body
shape with reduces fat on face and extremities and
increased fat deposition on abdomen and nape of
neck. Diabetes, bone loss, increased fats in blood,
tingling numbness in limbs
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43. Test
On starting
ART
2-8 weeks after
starting ART
Every 3 to 6
months
Heamogram
√
√ (If on ZDV)
√
Urine R
√
√ (If on TDF,
esp in DM, HT)
√
BSL -F
√
ALT, AST ,S-bili
√
√
√
S. creatinine
√
√
√
S elec, S Ca, S
Phos, Cr Cl
√
√
√
Lipid profile
√
CD4 count
√
√
√( If very
stable and
high counts)
Viral load
√
√
√( If stable and
adherent)
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Every year
√
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√(If last report √ (If last report
abnormal)
normal)
45. Uses of CD4 Cell Count
Decision to initiate ARV
Guide in initiating OI prophylaxis
Assess progression of disease
Measure response to treatment (prognostication)
Detect immunologic treatment failure
Pneumocystis pneumonia
CD4 <200
TLC <1200
Toxoplasmosis
CD4 <100 and positive Toxoplasma serology
Cryptococcal meningitis
CD4 <100
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46. CD4 COUNT
Normal CD4 count is 800-1050 cells/cu.mm
CD4 decreases at a rate of 40-60 cells per yr in an HIV
infected person.
Diurnal variation.
Treat OI before testing for CD4 count.
Sample :3 ml in EDTA bulb
CD4 count increases > 50 cells/mm3 at 4-8 weeks
after ART and then increases an additional 50 – 100
cells / mm3 per year thereafter.
Change more than 30% is significant.
Ideally CD4 count to be measured every 6 months.
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48. Viral Load test of RNA PCR test
Commercial methods/kits in use:
Amplicor
B-DNA
NASBA
Preferable use the same kit/ method for repeat
testing
Sample :3 ml in EDTA bulb
Viral load should be below detectable level after 6
months of effective ART
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49. Viral Load Monitoring
Where available, PCR or NASBA monitoring provide
valuable information about ART effectiveness
Viral load should be checked:
Every 3-6 months when not on ART
6 months after starting ART
Every 6 -12 months in stable ART patients
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51. Detection of Treatment Failure
Immunological failure: If the CD4 cell count fail to
rise, increase < 25-50 in 1st yr, decline after previous
increase; return to pre-ART baseline.
Viral load testing : Failure to achieve undetectable
viral load within first 4-6 months of ART or rise after
achieving a stable, low level of persistent virus
In cases of 1st line treatment failure, refer to HIV
specialist.
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52. Drugs with Potential to Interact
with
PIs or NNRTIs
Statins (simvistatin &
lovastatin)
Azole antifungals
Anticonvulsants
Anti-TB (Rifampicin)
Warfarin
52
Midazolam, trizolam
Alternative medicine
Clarithromycin
Oral contraceptives
Amitriptyline
54. 3 years after starting ART…..
Mayur has undetectable
viral load, CD4 945
cells/cu mm
No toxicity
Mayur comes with Mayuri,
his girl friend who wants
to marry him , pretty well
knowing his positive
status. She is HIV
negative.
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55. What would you ADVISE?
Its illegal. They cannot marry.
2. She would get infected
3. They won’t have an option of having children
4. They can marry provided they are ready to adopt
safer methods.
1.
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56. HPTN O52: The effectiveness of antiretroviral drugs in
reducing sexual transmission of HIV, by up to 96% in
serodiscordant couples.
Prep trials ((iPrEx study, Partners PrEP, and TDF2, FEMPrEP)
Circumcision : Male circumcision is associated with lower
risk for HIV. May reduce female to male
transmission( 50 to 60 %).
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57. Advise for discordant couple
who want to have a child
If male positive
Undetectable viral load
Sperm washing with IUI
Timed intercourse with Prep
If female positive
Undetectable viral load
IUI or Timed intercourse with Prep
ART at-least from 14th weeks of pregnancy, till she stops
breast feeding her child
ART drugs for newborn for 4 to 6 weeks
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58. Mayur and Mayuri have a cute
little baby girl
To test or not to test?
When to test and which tests to use?
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59. Diagnosis in child born to HIV +ve
mother
After 18 months-
Before 18 months-
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Antibody tests
(Elisa/Rapid/WB)
Antigen test
(HIV DNA PCR)
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60. Advise for PPTCT
ART throughout pregnancy
If viral load undetectable close to labour, no need of
Caesarian section
Breast feeding advisable , but mother should
continue ART
ART drugs for newborn for 4 to 6 weeks
Chances of baby getting infection below 5% .
AIDS FREE GENERATION
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62. Will AIDS really end?
Most unlikely.
No.s will fall for some time
It will restrict itself again among those who practice
risky behaviour, eg People practicing risky behaviour;
Sex workers; MSM
But complacency will bring it back again as our track
record against any STD is poor.
First line- Second line-Third line –Salvage regimen
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Please refer to the Ethiopian DACA for current availability of drugs.
Notes: showing features of ascites, hepaotmegaly, and cervical lymphadenopathy.
Hepatotoxicity
If occurs in first 8 weeks: appears to be a hypersensitivity reaction and may be accompanied by drug rash, eosinophilia, and systemic symptoms.
Some patients have presented with nonspecific symptoms of hepatitis and progressed to hepatic failure.
Some patients on NVP develop hepatotoxicity later in the course of treatment. This form of hepatitis is more benign and similar to hepatitis seen with other anti-HIV drugs.
Most commonly appears on the body and arms
Two forms
Milder form – erythematous, maculopapular rash
continue medication with close observation
antihistamines may be administered
Severe form – with mucous membrane involvement, SJS & TEN
DRESS: Drug rash, eosinophilia, systemic symptoms
D/C if fever, blisters mucous membrane, conjunctivitis, edema, arthalgias
Usually appears within the first month of therapy, although occasionally it may start a few weeks later.
Patients that do experience a rash during the 2-week lead-in should not increase the dose until the rash has resolved (mean duration of rash is 14 days).
If the patient experiences rash and stops nevirapine on their own, provider would not reintroduce nevirapine with the dose escalation until the rash has resolved.
Patients should call their provider or pharmacist or return to clinic if they develop a rash or have any blistering in the mouth, and if they develop fever, arthralgias, or myalgias.
Rash
Usually morbiliform
Symptoms can be treated as needed (e.g., hydrocortisone cream and antihistamines for itching).
If patient develops a more serious rash (blistering of mucous membranes or skin, seen in about 1%-2% of cases; or SJS) EFV should be discontinued.
Median time of onset of the rash is 11 days and the duration is 14 days.
Hepatotoxicity
Rate is less frequent and less severe than seen with NVP.
Increase risk of occurrence if co-infected with HCV or also taking other hepatotoxic medications
Bioavailability (F): 40%-45% with or without food.
CSF Levels: .25%-1.2% of serum levels (these levels are above the IC95 for wild-type HIV)
T1/2: 40-55 hours
Elimination: Metabolized by CYP450 3A4. 14% to 34% excreted in urine as glucuronide metabolites and 16% to 61% in stool. Do not need to adjust dose for renal or hepatic compromis.
Nausea
Most common side effect for AZT
Eating prior to dose helps reduce nausea
Macrocytosis is common and not associated with anemia, see increase in MCV of 25-40 units after 6-24 weeks, serves as crude indicator of adherence.
Characterized by thinning of the buccal fat pad. May result or exacerbate stigma associated with HIV.
Appears to be most common with long-term stavudine use.
Usually not reversible, but changing medications may prevent progression.
This slide puts “CD4 cells” in context of all cellular blood elements.
CD4 cells are identified in the lab by a process called “flow cytometry.”
Accurate and reliable enumeration of CD4 T cell counts is crucial for monitoring the rate of progression to AIDS, both for initiating prophylaxis for opportunistic infections as well as monitoring the impact of antiretroviral therapy (ART).
Methodologies used to determine viral load.
Changes in CD4 count that would be evidence of treatment failure include:
Decline after previous increase; return to pre-ART baseline; failure to rise when ART is started
Changes in viral load that would be evidence of treatment failure include:
Possibilities: failure to achieve 1 log drop in viral load within first 4 weeks treatment; failure to achieve undetectable viral load within first 4-6 months of ART; persistent detectable virus after becoming undetectable; rise after achieving a stable, low level of persistent virus
Resistance testing should be ordered when:
available, a change in ART is being considered, and while patient is still taking the failing regimen
Pharmacists play a critical role in detecting drug interactions, before they happen.
Pharmacists need to ask patients what other medications they are currently taking whenever dispensing a new medication to avoid potential interactions. Be aware that changing or discontinuing medications may result in altered drug levels and potential adverse outcomes.