Updated PPTCT guidelines of NACO are new for OBG practitioners. Pharmacotherapy can be explained in a less complex manner to meet a busy practitioner's need.

1. A
R
T
1
Moderated by Dr.Padmaja Udaykumar
Presented by Dr. Kamal Sundar

2. A NTI
R ETROVIRAL
T HERAPY
(Reloaded with
relevance to
Updated PPTCT
guidelines)
2

3. A R T
• combination of at least 3 ARVs, with representation
from at least 2 classes of ARVs.
• end points of maximal and durable viral
suppression  prevent the emergence of drug
resistant mutants.
• immune system improves  survival and quality of life
improves.
3

4. Months
No therapy Mono-therapy
Dual-therapy
Triple therapy
Triple therapy
4

5. Sketch
Life of HIV
Highly Active ART
Drugs in updated PPTCT
5

6. RNA
DNA
6

7. Invasion by Retro Viral Villain..
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8. Viral RNA
DNA
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9. 9

10. 10

11. 11

12. 12

13. 13

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15. 15

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19. 19

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22. 22

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31. 31

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55. 55

56. 56

57. 1010 virions bud/day
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58. Typical untreated coarse
58

59. Save Our Soul
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60. 60

61. 61

62. Anatomy of HAART
62

63. Arsenal of
Backbone NRTIs of HAART
NNRTI
Boosted Protease
Inhibitors
NRTI NtRTI
Zidovudine (AZT)
Lamivudine (3TC)
Abacavir (ABC)
Stavudine (d4T)
Tenofovir (TDF) Efavirenz (EFV)
Nevirapine(NVP)
Lopinavir (LPV) +
Ritonavir (RTV)
Atazanavir (ATV) +
Ritonavir (RTV)
8
63

64. 64

65. 65

66. Order of ARV under our radar…
NRTI
• Lamivudine (deoxycytidine analogue)
• Tenofovir
(deoxyadenosine monophosphate analogue)
NNRTI
• Nevirapine
• Efavirenz
HIV-PI
• Ritonavir
• Lopinavir
66

67. 67

68. 68

69. 69

70. False Nucleoside (nitro base + false sugar)
Intracellular Phosphorylation
False Nucleotide (false nucleoside + phosphate)
70

71. Lamivudine (3TC) / 2'3'-dideoxy-3'-thiacytidine
• Deoxycytidine analog
71

72. • oral BA > 80% & not food-dependent
• serum half-life is 2.5 hours, whereas the intracellular half-
life of the triphosphorylated compound is 11–14 hours
• eliminated unchanged in the urine.
72

73. • Water-soluble prodrug of active tenofovir.
• Deoxyadenosine monophosphate analog
Tenofovir disoproxil fumarate (TDF)
73

74. • oral BA in fasting 25% and increases to 39% after a high-fat
meal.
• prolonged serum (12–17 hours) & intracellular half-lives
allow once-daily dosing
• elimination by kidneys.
74

75. ADR
• Nausea, diarrhea, vomiting, flatulence, headache
• proximal renal tubulopathy causes excessive renal
phosphate and calcium losses
Monitoring required
• Bone mineral density and renal function test.
75

76. 76

77. Fingers (Blue)
Palm (Pink)
Thumb (Green)  Ribonuclease
Red  Active site of Polymerase
Yellow  Non NRTI binding pocket
p 66 domain
77

78. Non NRTI
• Binding site of NNRTIs is near to but distinct from that of
NRTIs
• NNRTI neither compete with nucleotide triphosphates
nor require phosphorylation to be active
• allosteric inhibition of RNA- and DNA-dependent DNA
polymerase of HIV-1.
78

79. Nevirapine
• Oral BA is > 90% & not food-dependent
• highly lipophilic
• serum half-life is 25–30 hours
• extensively metabolized by the CYP3A isoform to
hydroxylated metabolites and then excreted in urine.
79

80. 80

81. • Single dose (200 mg) is effective in prevention of
transmission of HIV from mother to newborn when
administered to mother at the onset of labor
• Resistance has been documented after this single dose.
• mutation of RT coding genes leads to amino acid changes in
RT that reduces binding affinity of NNRTI to RT
• RT activity and DNA polymerisation resumes.
81

82. ADR
• Maculopapular eruption that spares the palms and soles
• women appear to have an increased incidence of rash
• rarely Stevens-Johnson syndrome and Toxic epidermal
necrolysis.
82

83. Efavirenz
• given OD because of its long half-life (40–55 hours)
• moderately absorbed following oral administration (45%)
• taken on an empty stomach
• highly bound to albumin (~ 99%)
83

84. • metabolized by CYP3A4 and CYP2B6 to inactive
hydroxylated metabolites
• remainder is eliminated from bowel as unchanged drug.
84

85. ADR
• CNS symptoms: dizziness, drowsiness, insomnia, and
headache tend to diminish with continued therapy; dosing
at bedtime may also be helpful.
• Psychiatric symptoms: depression, mania, and psychosis
have been observed and may necessitate discontinuation.
85

86. 86
86

87. 87

88. 88

89. Protease Inhibitor
• By preventing post-translational cleavage of the Gag-Pol
polyprotein
• prevent the processing of viral proteins into functional
conformations
• resulting in production of immature, noninfectious viral
particles
• active against both HIV-1 and HIV-2
• do not need intracellular activation.
89

90. Ritonavir
• Ritonavir has BA (~ 75%) & increases with food.
• 98% protein-bound ; serum half-life of 3–5 hours
• metabolized to an active metabolite via the CYP3A and
CYP2D6 isoforms & excreted in feces.
• caution is advised when administering the drug to persons
with impaired hepatic function.
90

91. • Potent inhibitor of CYP3A4, resulting in many potential
drug interactions
• “booster” in low doses (100–200 mg BD) in combination
with other PI agents
• increased blood levels of the latter agents permit lower or
less frequent dosing (or both) with greater tolerability.
91

92. • limited experience with full-dose ritonavir during
pregnancy to date
• low-dose ritonavir as a “booster” has appeared to be well
tolerated in mother and infant.
92

93. Lopinavir
• Lopinavir is currently formulated as FDC with Ritonavir
• reduced pill burden  patient compliance improves
• generally well tolerated.
93

94. • Should be taken with food to enhance bioavailability
• highly protein bound (98–99%); serum half-life is 5–6
hours.
• extensively metabolized by CYP3A (which is inhibited by
ritonavir)
94

95. ADR
• Most common - diarrhea, abdominal pain, nausea,
vomiting, asthenia.
• Common – glucose intolerance, hyperlipidemia.
Monitoring required
• Fasting Lipid profile, glucose monitoring
95

96. • Concomitant use of lopinavir/ritonavir and rifampicin is
contraindicated due to an increased risk for hepatotoxicity.
• no evidence of human teratogenicity of lopinavir/ritonavir
• short-term safety in pregnant women has been
demonstrated for mother and infant.
96

97. 97

98. Bibliography
• Basic & Clinical Pharmacology,11thedition,
Katzung
• Medical Pharmacology, 4thedition,
Dr. Padmaja Udaykumar
• Updated PPTCT guidelines,
NACO, Dec 2013.
98

99. Thank u…
New guidelines
for PPTCT of
HIV
updated.
99

100. 100
Regimen National ART Regimen Preference
Regimen I
Zidovudine +
Lamivudine + Nevirapine
First line regimen for patients with Hb
>9 gm/dl and not on concomitant ATT
Regimen I (a)
Tenofovir +
Lamivudine + Nevirapine
First line regimen for patients with Hb
<9 gm/dl and not on concomitant ATT
Regimen II
Zidovudine +
Lamivudine + Efavirenz
First line regimen for patients with Hb
>9 gm/dl and on concomitant ATT
Regimen II (a)
Tenofovir +
Lamivudine + Efavirenz
•First line regimen for patients
with Hb <9 gm/dl and on
concomitant ATT
•First line regimen for all patients
with Hepatitis B & Hepatitis C
co- infection
•First line regimen for pregnant
women, with no exposure to
sd-NVP in the past
100