ANTIVIRAL DRUGS.pptx

Anti viral drugs in Pharmacology

1. Antiviral drugs PRIYANKA NAMDEO ASSISTANT PROFESSOR DEPARTMENT OF PHARMACOLOGY

2. Virus-Introduction Viruses are obligate intracellular parasites Their replication depends primarily on synthetic processes of the host cell Effective antiviral agents inhibit virus-specific replicative events or preferentially inhibit virus-directed rather than host cell-directed nucleic acid or protein synthesis

3. Viral replication and sites of antiviral drug action

4. Classification of Antiviral Drugs CLASSES DRUGS 1. Anti-Herpes virus Idoxuridine, Trifluridine Acyclovir, Valacyclovir, Famciclovir Ganciclovir, Valganciclovir Cidofovir Foscarnet Fomivirsen 2. Anti-influenza virus Amantadine, Rimantadine Oseltamivir, Zanamivir 3. Anti-Hepatitis virus/Nonselective antiviral drugs a. Primarily for Hepatitis B Lamivudine, Adefovir dipivoxil, Tenofovir b. Primarily for Hepatitis C Ribavirin, Interferon α

5. CLASSES DRUGS 4. Anti-retrovirus a. Nucleoside reverse transcriptase inhibitors (NRTIs) Zidovudine (AZT), Didanosine, Stavudine Lamivudine, Abacavir, Emtricitabine Tenofovir (Nt RTI) b. Nonnucleoside reverse transcriptase inhibitors (NNRTIs) Nevirapine, Efavirenz, Delavirdine c. Protease inhibitors Ritonavir, Atazanavir, Indinavir, Nelfinavir Saq u inavi r , Amprenavi r , Lopinavir d. Entry (Fusion) inhibitor Enfuvirtide e. CCR5 receptor inhibitor Maraviroc f. Integrase inhibitor Raltegravir

6. 1. Anti-Herpes Virus Acyclovir Mechanism of action: Acyclovir Herpes virus specific thymidine kinase Acyclovir monophosphate Cellular kinases Acyclovir triphosphate Inhibits herpes virus DNA polymerase competitively Gets incorporated in viral DNA and stops lengthening of DNA strand; the terminated DNA inhibits DNA- polymerase irreversibly

7. Acyclov ir Pharmacokinetics: About 20% of an oral dose of acyclovir is absorbed Less plasma protein bound Primarily excreted unchanged in urine both by glomerular filtration and tubular secretion It accumulates in patients with renal failure Its plasma half life is 2-3 hours

8. Acyclovir Uses: Genital Herpes simplex Primary disease Recurrent disease Mucocutaneo u s H. simp l ex • H. simplex encephalitis (type-1 virus) H. simplex keratitis Herpes zoster Chickenpox Adverse effects: Topical: stinging and burning sensation after each application Oral: Headache, nausea, malaise and some CNS effects Intravenous: Rashes, sweating, emesis, and fall in BP(in few) Dose dependent decrease in GFR (in renal failure)

9. Valacyclovir An ester prodrug of acyclovir Improved oral bioavailability due to active transport by peptide transporters in the intestine Drug of choice in herpes zoster High-dose can cause gastrointestinal problems and thrombotic thrombocytopenia purpura in patients with AIDS An ester prodrug of penciclovir Used as an alternative to acyclovir for genital or orolabial herpes and herpes zoster Side effects are headache, nausea, loose motions, itching, rashes and mental confusion

10. Ganciclovir An analogue of acyclovir Active against all herpes viruses- H. simplex , H. zoster, EBV and CMV Its active metabolite attains higher concentration inside CMV cells (plasma t 1/2 >24 hrs) Adverse effects: Systemic toxicity is high ( bone marrow toxicity, rash, fever, vomiting, neuropsychiatric disturbances) Note: Used only for prophylaxis and treatment of severe CMV infections in immunocompromised patients

11. Cidofovir Mechanism of action: It inhibits viral DNA synthesis. Its phosphorylation is not dependent on viral enzymes (viral phosphokinase) and is converted to the active diphosphate by cellular enzymes. Cidofovir diphosphate does not preferentially accumulate in virus infected cells, but remains intracellularly for long periods to inhibit viral DNA polymerase Pharmacokinetics: Available in intravenous, intravitreal (injection into the eye's vitreous humor between the lens and the retina), and topical administration

12. Cidofovir Uses: CMV-induced retinitis in patients with AIDS Adverse effects: Dose related kidney damage Neutropenia, metabolic acidosis, uveitis and ocular hypotony also occur Note: Probenecid must be coadministered with cidofovir to reduce the risk of nephrotoxicity, but probenecid itself causes rash, headache, fever, and nausea Contraindications: Patients with preexisting renal impairment Patients taking concurrent nephrotoxic drugs, including NSAIDS

13. Foscarnet It is not a purine or pyrimidine analog; phosphonoformate pyrophosphate derivative and does not require activation by viral (or human) kinases CMV retinitis in immunocompromised hosts Acyclovir-resistant HSV and herpes zoster infections Mechanism of action: It reversibly inhibits viral DNA and RNA polymerases, thereby interfering with viral DNA and RNA synthesis

14. Foscarnet Pharmacokine t i c s: Poorly absorbed orally; intravenously Must also be given frequently to avoid relapse when plasma levels fall It is dispersed throughout the body; >10% enters the bone matrix Excreted into the urine Adverse effects: Nephrotoxicity, anemia, nausea, and fever Hypocalcemia and hypomagnesemia Hypokalemia, hypo- and hyperphosphatemia Seizures and arrhythmias

15. 2. Anti-influenza virus Amantadine Its antiviral activity is strain specific = inhibits replication of influenza A virus but not influenza B Mechanism of action: It acts at uncoating as well as viral assembly in viral replication Blocks the viral membrane matrix protein, M2, which functions as a channel for hydrogen ion This channel is required for the fusion of the viral membrane with the cell membrane that ultimately forms the endosome (during internalization of the virus by endocytosis)

16. Amantadine Pharmacokinetics: Well absorbed orally and excreted unchanged in urine over 2-3 days Adverse effects: Nausea, anorexia, insomnia, dizziness, nightmares, lack of mental concentration Hallucinations (rarely) Ankle edema (local vasoconstriction)

17. Amantadine Uses: Prophylaxis of influenza A2 during an epidemic or seasonal influenza (~ 2 months) Treatment of influenzal (A2) illness Reduction in fever, congestion, cough and quicker recovery Parkinsonism Contraindications: Epilepsy and other CNS disease; gastric ulcer, pregnancy

18. Rimantadine Methyl derivative of amantadine More potent, longer acting (t½ 30 hours) and better tolerated Side effects is lower Oral bioavailability is higher and it is largely metabolized by hydroxylation followed by glucuronide conjugation Metabolites are excreted in urine

19. Oseltamivir Influenza A (amantadine sensitive as well as resistant), H5N1 ( bird flu ), nH1N1 ( swine flu ) strains and influenza B An ester prodrug; rapidly and nearly completely hydrolysed during absorption in intestine and by liver to the active form oseltamivir carboxylate ( an oral bioavailability of ~ 80%) Active metabolite is excreted unchanged by the kidney t½ of 6–10 hours

20. Oseltamivir Mechanism of action: Neuraminidase enzyme Release of progeny virions from the infected cell Spread of the virus in the body Uses: Prophylaxis and treatment of influenza A, swine flu, bird flu and influenza B Oseltamivir

21. Oseltamivir Side effects: Nausea and abdominal pain (gastric irritation) Headache, weakness, sadness, diarrhoea, cough, and insomnia Skin reactions Influenza A (including amantadine-resistant, nH1N1, H5N1 strains) and influenza B virus neuraminidase inhibitor Low oral bioavailability; t½ of 2–5 hours Containdication: Asthmatics ( bronchospasms)

22. 3. Anti-Hepatitis Virus/ Nonselective Antiviral Drugs Hepatitis A, B, C, D, and E viruses replicate in and destruct hepatocytes Hepatitis B and C are the most common causes of chronic hepatitis, cirrhosis, and hepatocellular carcinoma Hepatitis B virus (HBV) is a DNA virus, can integrate into host chromosomal DNA to establish permanent infection Hepatitis C virus (HCV) is a RNA virus

23. Lamivudi ne An inhibitor of both hepatitis B virus (HBV) DNA polymerase and human immunodeficiency virus (HIV) reverse transcriptase First line drug for chronic hepatitis B Chronic treatment decreased plasma HBV DNA levels, improved biochemical markers, and reduced hepatic inflammation Mechanism of action: It must be phosphorylated by host cellular enzymes to the triphosphate (active) form This compound competitively inhibits HBV DNA polymerase at concentrations that have negligible effects on host DNA polymerase

24. Adefovir dipivoxil Mechanism of action: It is phosphorylated to adefovir diphosphate incorporated into viral DNA termination of further DNA synthesis prevents viral replication Both decreased viral load and improved liver function Indicated in chronic hepatitis B, also in lamivudine- resistant cases and in concurrent HIV infection Its plasma t½ is 7 hours; intracellular t½ of the diphosphate is upto 18 hours

25. Adefovir dipivoxil Adverse effects: Sore throat, headache, weakness, abdominal pain and flu syndrome Nephrotoxicity ( higher doses and in those with preexisting renal insufficiency ) Lactic acidosis ( patients receiving anti-HIV drugs )

26. Ribavirin Broad-spectrum antiviral activity Influenza A and B, respiratory syncytial virus (in children only) and many other DNA and double stranded RNA viruses Oral ribavirin is commonly used in chronic hepatitis C Mechanism of action: Its mono- and triphosphate derivatives generated intracellularly inhibit GTP and viral RNA synthesis

27. Ribavirin Oral bioavailability ~50% Partly metabolized and eliminated Accumulates in the body on daily dosing and persists months after discontinuation Long term t½ is > 10 days Adverse effects: Anaemia, bone marrow depression hemolysis; CNS and GI disturbances Teratogenic Aerosol can cause bronchospasm and irritation of mucosae

28. Interferon Cytokines produced by host cells in response to viral infections and other inducers Three types of human IFNs (α, β and γ) are known to have antiviral activity Mechanism of action: Induction of host cell enzymes that inhibit viral RNA translation degradation of viral mRNA and tRNA Interferon receptors are JAK-STAT tyrosine protein kinase receptors which on activation phosphorylate cellular proteins These then migrate to the nucleus and induce transcription of ‘ interferon-induced- proteins ’ which exert antiviral effects

29. Interferon Uses: Chronic hepatitis B Chronic hepatitis C AIDS-related Kaposi’s sarcoma Condyloma acuminata H. simplex , H. zoster and CMV

30. Interferon Pharmacokinetics: Not active orally; administered intralesionally, subcutaneously, or intravenously High cellular uptake and metabolism by the liver and kidney; less plasma level Negligible renal elimination occurs

31. Interferon Adverse effects: Flu-like symptoms: fatigue, aches and pains, malaise, fever, dizziness, anorexia, nausea, taste and visual disturbances develop few hours after each injection, but become milder later Neurotoxicity: numbness, neuropathy, altered behaviour, mental depression, tremor, sleepiness, rarely convulsions Myelosuppression: dose dependent neutropenia, thrombocytopenia Thyroid dysfunction (hypo as well as hyper) Hypotension, transient arrhythmias, alopecia and liver dysfunction.

32. Interferon Drug interaction: It interferes with hepatic drug metabolism Toxic accumulations of theophylline It may also potentiate the myelosuppression caused by other bone marrow depressing agents ( zidovudine )

33. ANTI-RETROVIRUS DRUGS Aim of anti-HIV therapy is to cause maximal suppression of viral replication for the maximal period of time that is possible ARV drugs are always used in combination of at least 3 drugs and regimens have to be changed over time due to development of resistance Life long therapy is required

34. ANTI-RETROVIRUS DRUGS Established targets for anti-HIV attack: Chemokine coreceptor (CCR5) on host cells which provide anchorage for the surface proteins of the virus Fusion of viral envelope with plasma membrane of CD4 cells through which HIV- RNA enters the cell HIV reverse transcriptase : Which transcripts HIV-RNA into proviral DNA HI V - integras e : V iral en z yme which integrates the proviral DNA into host DNA HIV protease : Which cleaves the large virus directed polyprotein into functional viral proteins

35. Nucleoside reverse transcriptase inhibitors (N R TI s ) Zidovudine: is a thymidine analogue (azido- thymidine, AZT), the prototype NRTI after phosphorylation in the host cell—zidovudine triphosphate selectively inhibits viral reverse transcriptase in preference to cellular DNA polymerase Single-stranded viral RNA Virus directed reverse transcriptase (inhibited by zidovudine triphosphate) Double-stranded proviral DNA

36. ZIDOVUDINE Pharmacokinetics: The oral absorption of AZT is rapid, but bioavailability is ~65% It is quickly cleared by hepatic glucuronidation (t1⁄2 1 hr); 15–20% of the unchanged drug along with the metabolite is excreted in urine Plasma protein binding is 30% and CSF level is ~50% of that in plasma It crosses placenta and is found in milk

37. ZID O VUDINE Adverse effects: Anaemia and neutropenia are the most important and dose-related adverse effects Nausea, anorexia, abdominal pain, headache, insomnia and myalgia are common at the start of therapy, but diminish later Myopathy, pigmentation of nails, lactic acidosis, hepatomegaly, convulsions and encephalopathy are infrequent

38. ZIDOVUDINE Interactions: Paracetamol increases AZT toxicity, probably by competing for glucuronidation Azole antifungals also inhibit AZT metabolism Other nephrotoxic and myelosuppressive drugs and probenecid enhance toxicity Stavudine and zidovudine exhibit mutual antagonism by competing for the same activation pathway

39. ZIDOVUDINE Uses: Zidovudine is used in HIV infected patients only in combination with at least 2 other ARV drugs It is one of the two optional NRTIs used by NACO for its first line triple drug ARV regimen AZT also reduces neurological manifestations of AIDS and new Kaposi’s lesions do not appear AZT, along with two other ARV drugs is the standard choice for post-exposure prophylaxis of HIV, as well as for mother to offspring transmission

40. DIDANOSINE Is a purine nucleoside analogue which after intracellular conversion to didanosine triphosphate competes with ATP for incorporation into viral DNA, inhibits HIV reverse transcriptase and terminates proviral DNA Antiretroviral activity of didanosine is equivalent to AZT Use has declined due to higher toxicity than other NRTIs

41. S T A VUDINE A thymidine analogue By utilizing the same thymidine kinase for activation, AZT antagonises the effect of stavudine and the two should not be used together Should also not be combined with didanosine, because both cause peripheral neuropathy Frequent peripheral neuropathy, lipodystrophy, lactic acidosis, and rarely pancreatitis are the serious adverse effects which have restricted its use

42. LAMIVUDINE Deoxycytidine analogue, is phosphorylated intracellularly and inhibits HIV reverse transcriptase as well as HBV DNA polymerase Its incorporation into DNA results in chain termination Most human DNA polymerases are not affected and systemic toxicity of 3TC is low Oral bioavailability of 3TC is high and plasma t1⁄2 longer (6–8 hours)

43. LAMIVUDINE Used in combination with other anti-HIV drugs, and appears to be as effective as AZT Synergises with most other NRTIs for HIV, and is an essential component of all first line triple drug NACO regimens for AIDS Side effects are few—fatigue, rashes , abdominal pain Pancreatitis and neuropathy are rare Hematological toxicity does not occur

44. ABAC A VIR Guanosine analogue , potent , acts after intracellular conversion to carbovir triphosphate Hypersensitivity reactions such as rashes, fever, abdominal pain, bowel, upset, flu-like respiratory and constitutional symptoms Lypodystrophy is least likely Avoidance of alcohol is advised

45. TENOFOVIR Is the only nucleotide analogue ,relatively newer Due to good tolerability profile, it is included in first line regimens Tenofovir containing regimens have been found at least as effective and less toxic as other first line regimens NACO includes tenofovir in its first line 3 drug regimen as an alternative when either zidovudine or nevirapine/efavirenz cannot be used due to toxicity/contraindication

46. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) Nevirapine (NVP) and Efavirenz (EFV) are nucleoside unrelated compounds which directly inhibit HIV reverse transcriptase without the need for intracellular phosphorylation are more potent than AZT on HIV-1, but do not inhibit HIV-2 they should always be combined with 2 other effective drugs Cross- resistance between NVP and EFV is common

47. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) Nevirapine (NVP) and Efavirenz (EFV) enzyme inducers, and cause autoinduction of their own metabolism Nevirapine is started at a lower dose (200 mg/day); the dose is doubled after 2 weeks when its blood levels go down Rifampin induces NVP metabolism and makes it ineffective, but has little effect on EFV levels Either NVP or EFV is included in the first line triple drug regimen used by NACO

48. NEVIRAPINE Rashes are the commonest adverse effect, followed by nausea and headache Occasionally skin reactions are severe NVP is potentially hepatotoxic

49. E F A VIRENZ Side effects are headache, rashes, dizziness, insomnia and a variety of neuropsychiatric symptoms Contraindicated in pregnancy and in women likely to get pregnant, since it is teratogenic Because of its longer plasma t 1⁄2 , occasional missed doses of EFV are less damaging

50. Retroviral protease inhibitors (PIs) Acts at a late step in HIV replication, i.e. maturation of the new virus particles when the RNA genome acquires the core proteins and enzymes Bind to the active site of protease molecule, interfere with its cleaving function, and are more effective viral inhibitors than AZT Because they act at a late step of viral cycle, they are effective in both newly as well as chronically infected cells

51. Retroviral protease inhibitors (PIs) Nelfinavir, lopinavir and ritonavir induce their own meta- bolism metabolism of PIs is induced by rifampin and other enzyme inducers rendering them ineffective patient acceptability and compliance are often low most prominent adverse effects of PIs are gastrointestinal intolerance, asthenia, headache, dizziness, limb and facial tingling, numbness and rashes

52. Retroviral protease inhibitors (PIs) lipodystrophy , dyslipidaemia and insulin resistance are of particular concern Diabetes may be exacerbated Indinavir crystalises in urine and increases risk of urinary calculi

53. Retroviral protease inhibitors (PIs) Atazanavir (ATV) is administered with light meal which improves absorption, while acid suppressant drugs decrease its absorption Bioavailability and efficacy of ATV is improved by combining with RTV Dyslipidaemia and other metabolic complications are minimal with ATV jaundice occurs in some patients without liver damage due to inhibition of hepatic glucuronyl transferase

54. Retroviral protease inhibitors (PIs) Indinavir (IDV) Is to be taken on empty stomach g.i. intolerance is common excess fluids must be consumed to avoid nephrolithiasis Hyperbilirubinaemia occurs less frequently used now Nelfinavir (NFV) Is to be taken with meals Often produces diarrhoea and flatulence; lower clinical efficacy than other PIs

55. Retroviral protease inhibitors (PIs) Ritonavir (RTV) Is potent Drug interactions, nausea, diarrhoea, paresthesias, fatigue and lipid abnormalities are prominent more commonly employed in a low dose Saquinavir (SQV) Two types of formulations (hard gel and soft gel capsules) have been produced tablet load is large and side effects are frequent; photosensitivity can occur

56. Retroviral protease inhibitors (PIs) Lopinavir: Available only in combination with RTV to improve bioavailability, though it is itself a CYP3A4 inhibitor Diarrhoea, abdo- minal pain, nausea and dyslipidaemias are more common Dose needs to be increased by 1/3rd if either NVP or EFV is used concurrently

57. Entry (fusion) Inhibitor-Enfuvirtide HIV derived synthetic peptide binds to HIV 1 envelope transmembrane glycoprotein(gp41) involved in fusion of viral and cellular membranes entry of virus into host cell is blocked Not active against HIV 2 Pharmacokinetics: Administered s.c twice daily Used as add on drug in earlier regimens Adverse reactions: Local nodule/ cyst at injection site

58. CCR5 receptor inhibitor-Maraviroc Targets the host cell chemokine -CCR5 receptor and blocks it attachment and entry of virus is inhibited Has no effect on CXCR4 receptor tropic HIV strains Adverse reactions: impaired immune surveillance Increased risk of infection/malignancy

59. Integrase inhibitor-Raltegravir Inhibits the viral enzyme integrase HIV Integrase nicks the host chromosomal DNA and integrates the proviral DNA with it Active against both HIV 1 and 2 and causes improved CD4 cell count Uses: As a component of initial triple drug regimen along with 2NRTIs Adverse effect: myopathy

60. HIV treatment principles and guidelines Monotherapy is contraindicated HAART: highly active antiretroviral therapy with a combination of 3 or more drugs is indicated Greater the supression of viral replication, lesser is the chance of emergence of drug resistant virus

61. Initiating antiretroviral therapy The US Department of Health and Human Services guidelines (2010) recommend instituting ART to: All symptomatic HIV disease patients. Asymptomatic patients when the CD4 cell count falls to 350/μl or less. All HIV patients coinfected with HBV/HCV requiring treatment All pregnant HIV positive women. All patients with HIV-nephropathy.

62. Initiating antiretroviral therapy contd.. In addition to above, the current NACO guidelines give priority in treatment to: All HIV-positive persons in WHO-clinical stage 3 and 4 All persons who tested HIV positive 6–8 years ago Patients with history of pulmonary TB and/ or Herpes zoster HIV infected partners of AIDS patients. All HIV positive children < 15 years of age

63. First line antiretroviral therapy 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 Recommended by National AIDS control Organization

64. First line therapy All regimen should have 2 NRTI+ 1NNRTI and treatment is life long Efavirenz is indicated for patient with hepatic dysfunction and concurrently taking rifampin. It is contraindicated in pregnancy PI containing regimen: 2NRTI+PI or NRTI+NNRTI +PI(low dose ritonavir boosted PIs are used) Development of drug toxicity: no dose reduction Either entire regimen should be interrupted Or the offending drug should be changed

65. First line therapy contd… Institution of HAART with latent or partially treated opportunistic infection causes immune reconstitution syndrome Safe drugs in pregnancy : Zidovudine Lamivudine Nevirapine Nelfinavir Saquinavir

66. Changing a failing regimen An ART regimen is considered to have failed when: Plasma HIV-RNA count is not rendered undectable (<50 copies/μl) with in 6 months therapy Repeated detection of virus in plasma after initial supression to undectable levels despite continuation of drug regimen Clinical deterioration,fall in CD4 cell count,serious opportunistic infection while continuing drug therapy

67. Second line regimen Drugs with known overlapping viral resistance should not be used. Indinavir should not be substituted for nelfinavir or saquinavir Efavirenz should not be replaced by nevirapine Viral resistance testing is recommended for selecting the salvage regimen A boosted PI is nearly always included

68. List of second line regimens (NACO) NRTI component Standard regimen 1. Lopinavir 2. Atazan a vir Tenofovir + Abacavir Didanosine + Abacavir Tenofovir + Zidovudine Tenofovir + Lamivudine 3. Saq u i n avir 4.I nd i nav i r 5.Nelfinavir Special circumstances Didanosine + Zidovudine Didanosine + Lamividine

69. Antiretroviral combination to be avoided 1.Zidovudine + stavudine Pharmacodynamic antagonism Stavudine + didanosine Increased toxicity ( neuropathy, lactic acidosis ) Lamivudine + didanosine Clinically not additive

70. Prophylaxis of HIV infection 1.Post- exposure prophylaxis: Drugs used Comments A .Basic (2 drug) regimen for low risk Both for 4 weeks Zidovudine ( 300mg) + twice daily Lamivudine ( 150 mg) Twice daily B. Expanded ( 3 drugs) regimen for high risk Both for 4 weeks Zidovudine (300 mg )+ lamivudine ( 150 mg ) Twice daily Indinavir( 800 mg) (or another PI) Thrice daily

71. Post exposure prophylaxis(PEP) Aim is to supress local viral replication prior to dissemination to abort infection PEP should be started within 1-2 hours of exposure a) Basic regimen: Asymptomatic HIV +ve source with low HIV-RNA titre and high CD4 cell count Exposure is through mucous membrane, superficial scratch or solid needle b ) Expanded regimen: symptomatic HIV +ve source with high HIV-RNA titre or low CD4 cell count Exposure is through large area contact of longer duration with mucus membrane or large bore hollow needle, deep puncture.

72. Prophylaxis of HIV infection Prophylaxis after sexual intercourse : the same method as for needle stick Perinatal HIV prophylaxis: Vertical transmission: Highest rate of transmission (2/3 rd ) through placenta ,during delivery or breast feeding HIV positive mother (not on ART) : should take 3 drug ART, continue through delivery and into postnatal period. First line NACO regimen for pregnant women: Zidovudine + Lamivudine + Nevirapine Nevirapine : higher risk of hepatotoxicity in women with CD4 cell count > 250 cells /μl Efavirenz is teratogenic particularly in 1 st trimester

73. Perinatal HIV prophylaxis For HIV +ve women not on ART : Zidovudine (300 mg BD) started at 2 nd trimester and continued through delivery to postnatal period with treatment of neonate for 6 month reduce the transmission by 2/3 rd AZT started during labour and then to infant is substantially protective

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