Pharmacology PPT

1. HIV TREATMENT
GUIDELINES
DR CHINTAN

2. Introduction
• Treatment of HIV infection and its complications is
complex, prolonged
• Needs expertise, strong motivation and commitment of
the patient, resources and is expensive
• ‘highly active antiretroviral therapy’ (HAART) with
combination of 3 or more drugs whenever indicated
• Monotherapy is contraindicated.

3. Contd.
• None of the currently available regimens can
eradicate HIV from the body of the patient
• Goal of therapy is:
• Inhibit viral replication
• Prevent complication
• Prevent transmission to other person
• Decrease resistance
• Prolong survival

4. Initiating antiretroviral therapy
(a) All symptomatic HIV disease patients.
(b) Asymptomatic patients when the CD4 cell
count falls to 350/μl or less.
(c) All HIV patients coinfected with HBV/HCV
requiring treatment.
(d) All pregnant HIV positive women.
(e) All patients with HIV-nephropathy

5. Therapeutic regimens
• All regimens should have 2 NRTI+1NNRTI.
• Include lamivudine in all regimens.
• The other NRTI can be zidovudine or stavudine.
• Choose one NNRTI from nevirapine or efavirenz.

6. contd
• Choose efavirenz in patients with hepatic dysfunction
and in those concurrently receiving rifampin
• Do not use efavirenz in pregnant women or in those
likely to get pregnant

7. First line Regimen
Preferred regimen
1. Lamivudine + Zidovudine + Nevirapine
Alternative regimens
1. Lamivudine + Zidovudine + Efavirenz
2. Lamivudine + Stavudine+ Efavirenz
3. Lamivudine + Stavudine + Nevirapine
Other options
1. Lamivudine + Tenofovir+ Nevirapine
2. Lamivudine + Tenofovir+ Efavirenz
3. Lamivudine+ Zidovudine + Tenofovir

8. Contd.
• Stavudine is substituted for zidovudine if patient is
anaemic
• Tenofovir is included when there is toxicity or other
Contraindication to both zidovudine and stavudine
• 3NRTI regimen is only for patients unable to tolerate
both nevirapine and efavirenz.

9. Contd.
• The PI containing regimens (2 NRTI + PI or NRTI + NNRTI +
PI) are reserved for advanced cases who have failed
earlier regimens.
• Low dose ritonavir boosted PIs are preferred over higher
dose single PI due to lower pill burden and better
tolerability
• If drug toxicity develops, either the entire should be
interrupted or the offending drug should be changed. No
dose reduction should be tried.

10. Contd.
• Treatment is life-long
• Institution of HAART in patients with latent or
partially treated opportunistic infection may produce
‘immune reconstitution syndrome’
• Pregnancy in women does not contraindicate ART.
• zidovudine, lamivudine, nevirapine, nelfinavir

11. Contd.
• Durability of the regimens depends mainly on adherence
of the patient to it.
• Compliance is a major determinant of outcome.
• Multiple antiretroviral, Anti-P. jiroveci, antitoxoplasma,
anti-CMV/herpes virus, antitubercular, antifungal or
other drugs may have to be used in a patient

12. Contd.
• Combination should be avoided
Combination Reason
Zidovudine + stavudine Pharmacodynamic
antagonism
Stavudine + didanosine: Increased toxicity
(neuropathy, lactic
acidosis
Lamivudine + didanosine Clinically not additive

13. Changing a failing regimen
• Plasma HIV-RNA count is not rendered undetectable (<50
copies/μl) within 6 months therapy
• Repeated detection of virus in plasma after initial
suppression to undetectable levels
• Clinical deterioration
• Fall in CD4 cell count
• Serious opportunistic infection

14. Contd.
• Failure is due to development of resistance to one or
more components of the regimen
• failed regimen should be changed entirely

15. List of second line regimens
(in order of preference)
NRTI PI
Standard regimens
Tenofovir + Abacavir Lopinavir
Atazanavir
Saquinavir Low ritonavir
Indinavir
Nelfinavir
Didanosine + Abacavir
Tenofovir + Zidovudine
Special circumstances
1Didanosine + Zidovudine
2. Didanosine + Lamivudine

16. Prophylaxis of HIV infection
Post-exposure prophylaxis (PEP)
• Indication:
Health care workers and others who get
accidentally exposed to:
– the risk of HIV infection by needle stick
– or other sharp injury

17. Contd.
AIM
• Suppress local viral replication prior to dissemination
• Not necessary when the contact is only with intact
skin, or with mucous membrane by only a few drops
for short duration

18. Contd.
Basic (2 drug) regimen (for low risk)
Zidovudine 300 mg +
Lamivudine 150 mg
Twice daily
for 4 weeks
Expanded (3 drug) regimen (for high risk)
Zidovudine 300 mg + Twice daily
Lamivudine 150 mg
4 weeks
+
Indinavir 800 mg(Another PI) : Thrice daily

19. Contd.
Low risk
• When the source is HIV positive, but asymptomatic
with low HIV-RNA titer and high CD4 cell count.
• Exposure is through mucous membrane, or
superficial scratch, or through thin and solid needle

20. Contd.
High risk
• When the source is symptomatic AIDS patient with
high HIV-RNA titer or low CD4 count.
• Exposure is through major splash or large area
• Contact of longer duration with mucous membrane

21. Prophylaxis after sexual exposure
• No data to evaluate the value of prophylaxis after
sexual exposure, the same regimen as for needle
stick may be used.

22. Perinatal HIV prophylaxis
• The first line NACO regimen for pregnant
women is:
• Zidovudine + Lamivudine + Nevirapine

23. Contd.
 In HIV-positive women who are not taking ART:
• Zidovudine (300 mg BD) started during 2nd trimester
and continued through delivery to postnatal period
• With treatment of the neonate for 6 weeks
• Has been found to reduce mother-to-child
transmission by 2/3rd.

24. Contd.
• AZT administered during labour and then to the
infant is also substantially protective.
• Breastfeeding by HIV-positive mother is
contraindicated,

25. MCQ
• Ganciclovir is preferred over acyclovir in the
following condition:
• (a) Herpes simplex keratitis
• (b) Herpes zoster
• (c) Chickenpox
• (d) Cytomegalovirus retinitis in AIDS patients

26. • Drug of choice for herpes simplex virus
infection is:
• (a) Acyclovir
• (b) Zidovudine
• (c) Indinavir
• (d) Ribavarin

27. • Drug of choice for chronic hepatitis –B is
• (a) Lamivudine
• (b) IFN-alpha
• (c) Ribavirin
• (d) Zidovudine

28. • Drug of choice for swine flu:
a. Acyclovir
b. Oseltamivir
c. Gancyclovir
d. Interferon alfa

29. • Which of the following is a reverse
transcriptase inhibitor?
• (a) Ritonavir
• (b) Saquanavir
• (c) Amprenavir
• (d) Tenofovir

30. • Pancreatitis is a common complication of
which one of the following
• (a) Zidovudine
• (b) Didanosine
• (c) Zalcitabine
• (d) Stavudine

31. • Which one of the following is not an
antiretroviral drug:
• (a) Saquinavir
• (b) Ganciclovir
• (c) Indinavir
• (d) Atazanavir

32. • Peripheral neuropathy not caused by which
antiretroviral drug?
• (a) Lamivudine
• (b) Didanosine
• (c) Zidovudine
• (d) Zalcitabine

33. • Integrase inhibitor
a. Raltegravir
b. Maraviroc
c. Zidovudine
d. Neverapine

34. • All of the following drugs are protease
inhibitors EXCEPT:
• (a) Nelfinavir
• (b) Saquinavir
• (c) Abacavir
• (d) Ritonavir

35. • Nevirapine is:
• (a) Non-nucleoside reverse transcriptase
inhibitor(NNRTI)
• (b) Nucleoside reverse transcriptase inhibitor
(NRTI)
• (c) Protease inhibitor
• (d) Fusion inhibitor

36. • The basis of combining ritonavir with
lopinavir:
• (a) Pharmaceutical compatibility
• (b) C4P3A4 inhibition by ritonavir
• (c) Long elimination half life of ritonavir
• (d) Ability to counteract side-effects of
lopinavir

37. • Bone marrow depressive drugs in the
treatment of AIDS patient are:
• (a) Didanosine
• (b) Zalcitabine
• (c) Zidovudine
• (d) Cotrimoxazole

38. • Select the drug that is active against both HIV
and hepatitis B virus:
• (a) Lamivudine
• (b) Indinavir
• (c) Didanosine
• (d) Efavirenz

39. 06-08-2021