Excellent pharmacy for learning on HIV download Drugs

1. PHM-2221
THERAPEUCS FOR HIV
INFECTION
Mrs N. Mwila Bpharm, MSc

3. HIV INFECTION
Two types HIV virus exist: type 1 and type 2
HIV- 1 : the most common and is pandemic and aggressive
 95% of people living with HIV around the world have HIV – 1 of which
2/3 are in Sub-Saharan Africa (SSA)
HIV type 2; is less pathogenic and confined mainly to west Africa
HIV causes acquired immunodeficiency syndrome(AIDS).
 Clinical manifestations of AIDS result from consequences of a critically
impaired immune system (CD4 cell destruction).
 90% of deaths are due to opportunistic infections associated suppression
of the immunity (e.g. PJP,CMV,TB)

6. HIV CHARACTERISTICS
HIV is a Retrovirus: an Enveloped, single stranded RNA virus;
 Uses RNA as it’s genetic material
 Has enzymes and a lipid bilayer membrane surrounding the capsid
 Has surface glycoprotein molecules (gp120,) with strong affinity for
CD4 receptor protein on particular immune cells e.g. T –helper cells
(Lymphocytes),Monocytes and Macrophages express CD4 receptors.
 Replicate using Reverse Transcriptase - enzyme that convert
RNA genome into DNA, which then integrates into host chromosomal DNA
via Integrase enzyme the activities of Protease enzyme

7. HIV CHARACTERISTICS CONT…
 Reverse transcriptase enzyme converts viral RNA to viral
DNA
Integrase enzyme: facilitates the integration of viral DNA
into the host DNA
HIV Gag Polyproteins: interact with host cells proteins, they
are responsible for processing and assembly of non-infectious immature viral
particles
Protease enzymes: responsible for facilitating the
maturation of the viral particles

8. PATHOGENESIS
 The pathogenesis Involve a struggle between HIV replication and
immune responses of the patient,
 Immunosuppression is due to several factors:
1. Increased viral replication that result in Increased viral load
2. The HIV viral burden directly and indirectly contribute to the following:
 Defective innate immune signaling pathways (e.g. cell surface
signaling molecules are compromised function abnormally
 Mediates CD4 + T-cell destruction: gradual loss of peripheral CD4+ cells
and depletion of T- lymphocytes at mucosal sites leading to progressive
immune deficiency and AIDS

10. STRUCTURE OF THE HIV VIRUS

12. LIFE CYCLE OF HIV
1. Attachment of virus to receptors on host cell surface;
2. Entry of virus through host cell membrane;
3. Uncoating of viral nucleic acid;
4. Replication; Synthesis of early regulatory proteins, (e.g. nucleic
acid polymerases); Synthesis of new viral RNA or DNA; Synthesis
of late, structural proteins;
5. Assembly & Maturation of viral particles;
6. Release from host cell

13. LIFE CYCLE OF HIV CONT…
1. After penetration, the virus sheds its outer coat, releases its genetic material (RNA)
2. Viral RNA is converted to viral DNA by the Reverse transcriptase enzymes
using Nucleosides (building blocks) .
3. Viral DNA is integrated into the host genome(DNA) by the Enzyme Integrase.
 Viral DNA undergoes transcription and translation, producing new viral proteins.
4. New virus particles are assembled and bud out of the host cell facilitated by
Gag viral proteins (group-specific antigen: polyproteins make up the inner
core structure proteins before the outer envelope)
5. Maturation of new virus particles into infectious virions require the action of
Protease Enzyme.
 Protease cleaves the precursor proteins(nucleosides) into functional polypeptides.

16. DRUG
TARGETS SITES

18. CHEMOKINE RECEPTORS

19. HIV Tropism: HIV Host Cell Targets Receptors

20. HIV TRANSMISSION

22. UNAIDS Targets by 2030 aim:
 95% living with HIV to know their status
 95% who know their status to be on treatment
 95% of those on treatment to be virally suppressed
WHO test and treat policy:
 Providing ART irrespective/ regardless of CD4, VL levels or HIV clinical staging

23. PATHWAYS OF VIRAL TRANSMISSION
 The transmission of viruses can occur through two
pathways
1. Horizontal transmission
 Viruses are transmitted among individuals
2. Vertical transmission
 Transmission occurs from mother to child (offspring)

27. WHO clinical staging of HIV/AIDS
Primary HIV Infection
•Asymptomatic
•Acute retroviral syndrome (fever, arthralgia, pharyngitis,rash and
lymphadenopathy)
Stage Clinical presentation
1 • Asymptomatic
• Persistent generalized lymphadenopathy

28. Clinical Stage Clinical presentation
2 • Moderate unexplained weight loss
• Recurrent respiratory infections(sinusitis,
tonsillitis, otitis media and pharyngitis)
• Herpes zoster
• Angular cheilitis
• Recurrent oral ulceration
• Papular pruritic eruptions
• Seborrhec dermatitis
• Fungal nail infections
3 • Unexplained severe weight loss( > 10%)
• Unexplained chronic diarrhoea (> 1 month)
• Unexplained persistent fever ( > 1month)
• Persistent oral candidiasis
• Oral hairly leukoplakia
• Pulmonary tuberculosis
• Severe bacterial infections( pneumonia,
empyema, pyomyositis, bone/joint infection,
meningitis)

29. Clinical Stage Clinical presentation
3 • Acute necrotising ulcerative stomatitis,
gingivitis
• unexplained anaemia (Hb < 8g/dL)
• Neutropenia ( < 500cells/µL)
• Chronic thrombocytopenia ( < 50000cells/µL)
4 • HIV wasting syndrome
• Pneumocystis jiroveci pneumonia
• Recurrent severe bacterial pneumonia
• Chronic herpes simplex infection
• Oesophageal/ oropharyngeal candidiasis
• Extra pulmonary tuberculosis
• MAC/MAI
• Progressive multifocal encephalopathy
• Chronic cryptospridiosis
• Chronic isosporiasis
• Disseminated mycosis e.g. histoplasmosis

30. (WHO, 2007)
Clinical stage Clinical presentation
4 • Lymphoma
• cervical carcinoma
• HIVAN
• HIV associated cardiomyopathy

31. INVESTIGATIONS/ MONITORING
Current And Previous Infections
1. Initial diagnosis of HIV infection is by detecting antibodies
(seroconversion) against HIV within 3 – 4 weeks of infection. RDT: Oral
fluid HIV test and standard blood antibody test (followed by a confirmation
test).(Read on ELISA and Western blot tests, the combination tests give 99.9%
positive results)
 However Window Period (WP) is up to 3 months after HIV exposure,
required to exclude infection(time after infection and before seroconversion is
up to 3months).
WP: Absence or undetectable markers of infection, HIV can not be detected
2. CD4 Count
 Measures the number of CD4 – positive T – lymphocytes in a sample of
peripheral blood, normal range is 500 – 1500 cells/mm3
 Immunosuppression can be estimated by monitoring a patient’s CD4 count.
CD4 count is no longer used as a major indicator of when to start ART

32. 3. VIRAL LOAD
 Measures the number of HIV RNA in a sample of peripheral blood.
 Estimates the amount of circulating virus in the blood.
 Correlates with prognosis e.g. high viral load predicts faster disease
progression.
 Reduction in viral load due to ART is associated with clinical benefit.
 Clinical decisions such as when to start or change antiretroviral therapies is
no longer based on viral load.
4. RESISTANCE TESTING
 Genotypic HIV resistance test is recommended soon after diagnosis due to
potential of transmitted (primary) resistance (used for initiating third line ART).

33.  Resistance testing allows selection of appropriate initial therapy.
 Further resistance tests should be performed at any subsequent virological
failure to direct therapy choice(in Zambia done before 3rd line treatment.
5. TROPISM TESTING
 Viruses enter host cells using CCR5 co-receptor, CXCR4 co-receptor or both.
 Viruses which only use one co-receptor are referred to as CCR5 – tropic or
CXCR4 – tropic viruses.
 Viruses which can use both co-receptor types are called dual – tropic viruses.
 Mixed – tropic refers to a mixture of virus populations.
 Tests should be performed in real time as viral tropism changes as the
disease progresses to help select appropriate ARVs.

34. ANTIRETRAVIRAL DRUGS

37. GOALS OF THERAPY
 1. Restore or preserve immunologic function (prevent deterioration of
immune function by restoring or preserving CD4 cells)
 2. Improve quality of life (prolong life)
 3. Suppress and maintain VL to undetectable level (<50 or 20 c/mL)
 4. Prevention of transmission of the virus
 5. Treat or prevent opportunistic infections (e.g. INH, Co-trimoxazole)
 6. Reduce morbidity and mortality
 7. Relieve symptoms

38. THE FOUR PILLARS OF HIV)
 They represent the cornerstones of comprehensive
PMTCT/e-MTCT service delivery
 They are central to the global plan (UNAIDs) and renewed
momentum around preventing and eliminating-Mother To
Child Transmission of HIV which is based on the four pillars
1. Primary prevention of HIV infection among women of reproductive age
2. Prevention of unintended pregnancies among women living with HIV
3. Prevention of HIV transmission from women living with HIV to her infant
during pregnancy ,breastfeeding
4. Treatment ,care and support to women living with HIV , their children and
families

39. GENERAL PRINCIPLES OF ANTIRETROVIRAL
THERAPY
 ART involve Highly active antiretroviral therapy (HAART), effective infection
prophylaxis , treatment and nutritional therapy with proven clinical benefit
1. Management of HIV/AIDS involve multiple antiretroviral (ARV) drugs that act on
different stages of HIV life cycle in an attempt to control HIV infection
 HAART regimen should at least include a minimum of three or more
ARV drugs of which at least two are from different classes of ART
 HAART combination is expected to reduce plasma virus levels to undetectable
 Should be selected on basis of treatment history, resistance tests and
should be prescribed to increase efficacy and reduce adverse effects and
development of drug-resistant virus.

40. GENERAL PRINCIPLES OF ANTIRETROVIRAL
THERAPY CONT…..
2. A regimen should contain at least one drug that penetrates the CNS and
confers protection against HIV – related encephalopathy/ dementia.
3. Treatment strategies should be adopted that sequence drug combinations,
taking potential cross-resistance and future therapy options into consideration.
4. Regimen adopted for a patient should be tailored to suit daily lifestyle (high
level of adherence is required)

41. ANTIRETROVIRAL THERAPY
 ART is currently one of the fastest evolving areas of medicine.
 Specific details of treatment will continue to change as new drugs
emerge.

42. HAART-cART
 HIV treatment comprise of Highly Active Antiretroviral Therapy (HAART)
involving combination of multiple anti-retroviral drugs to achieve
maximum viral load suppression to undetectable levels
 Treatment involve Combination Antiretroviral Therapy (cART) with at
least 3 drugs is done for Synergism to decrease development of drug
resistance.
 cART is an important step toward achieving the goal of universal access
to ARV drugs, treating and preventing HIV, and ultimately ending the HIV
epidemic by 2030 (UNAIDS)

43. CLASSES OF ANTIRETROVIRAL
DRUGS

44. CLASSES OF ANTIRETROVIRAL DRUGS:
1. Nucleoside or Nucleotide analogue reverse
transcriptase inhibitors (NRTIs)
2. Non – Nucleoside reverse transcriptase
inhibitors (NNRTIs)
3. Protease inhibitors (PIs)
4. Integrase inhibitors (INSTIs)
5. Fusion inhibitors
6. Attachment inhibitors
7. Chemokine receptor antagonist two types:
 CCR5 receptor antagonist
 CXCR4 receptor antagonist
1. Three Main
Enzymatic
Targets:
 Reverse Transcriptase,
 Protease,
 Integrase
2. Receptor
Targets:
ENTRY INHIBITORS
 Attachment inhibitors
 CCR5/CXCR4 antagonists
 Fusion inhibitors

45. MECHANISM OF ACTION OF ARV DRUGS

46. EXAMPLES: ANTIRETROVIRAL DRUGS
NRTIs
• Abacavir (ABC)
• Emtricitabine (FTC)
• Lamivudine (3TC)
• Tenofovir (TDF)
• Tenofovir (TAF)
• Zidovudine (AZT)
• Stavudine (d4T)
• Didanosine (ddi)
NNRTIs
• Efavirenz (EFV)
• Nevirapine (NVP)
• Etravirine (ETR)
• Rilpivirin (RPV)
• Delavirdine (DLV)
PIs
• Atazanavir (ATV/R)
• Darunavir
• Lopinavir (LPV/R)
• Ritonavir (R)
• Saquinavir
• Tipranavir
• Fosamprenavir
• Indinavir
• Nelfinavir
Fusion Inhibitors
• Enfuvirtide
CCR5 Antagonist
• Maraviroc
CXCR4 Antagonist
• Plerixafor (AMD3100)
Integrase Inhibitors
(INSTIs)
• Raltegravir
• Dolutegravir
• Cabotegravir (for PrEP)
• Elvitegravir

47. ART Drug Regimens (HAART)
Synergistic combination of multiple agents acting on multiple sites of
virus cycle;
1. Usually 2 NRTIs
with any of :
 A PI
 A NNRTI
 An Integrase
inhibitor
 An Entry
inhibitor
2. FIXED-DOSE COMBINATIONS
•Tenofovir/emtricitabine/efavirenz 600mg(Atripla®)
•Tenofovir/Lamivudine/efavirenz 400mg (Avonza®) ENCORE-1
•Tenofovir/Emtricitabine(Truvada®) -PrEP
•Tenofovir/ Lamivudine (Tenolam®)-PrEP
•Zidovudine/ lamivudine (Zidolam®, combivir®)
•Zidovudine/lamivudine/abacavir
•Abacavir/lamivudine
•Lopinavir/ritonavir LPV/r (Aluvia / Kaletra®)
•Stavudine/lamivudine/nevirapine 30/40(Triomune)
•Atazanazvir/ ritonavir(ATV/r)

48. 1. NRTIs
1. Nucleoside Or Nucleotide Reverse Transcriptase inhibitors( NRTIs)
Mechanism Of Action
 Inhibit reverse transcriptase enzyme acting as a false substrate /
building blocks of DNA.

49. Common Adverse Effects of NRTIs
Zidovudine (AZT)
• Mitochondrial toxicity; anemia, fatigue;
bone marrow suppression; dyslipidemia;
insulin resistance,N/V/D
Hypersensitivity reaction
Abacavir (ABC)
• N/V/D, perioral paresthesias,
hypersensitivity; cardiotoxicity
(increased risk of MI) lactic
acidosis;
Tenofovir (TDF)
•Renal impairment, glucosuria,
asthenia (generally well-tolerated)
Lamivudine (3TC)
• Neuropathy; anorexia; N/V/D,
malaise; lactic acidosis (generally
well-tolerated)
• Emitricitabine(FTC) :
Headache(most common),
nausea, diarrhoea, dizziness,
lactic acidosis

50. 2. NNRTIs
2. Non - Nucleoside Reverse Transcriptase Inhibitors( NNRTIs)
Mechanism of action
 NNRTIs inhibit the reverse transcriptase enzyme by binding to its active site.
 It Bind directly to HIV Reverse Transcriptase preventing conversion of viral
RNA to viral DNA

51. NNTRIs CONT…
 Resistance to NNRTIs occurs rapidly
 Cross resistance between NVP and EFV is high (reason for TLD
declaration as preferred first line to preserve future treatment options of
NNRTIs from cross resistance e.g. Etravirine used as 3rd line NNRTIs).
 Etravirine has a different resistance profile( used as an alternative first –
line NNRTI) but commonly used as third line
 NNRTIs have much longer plasma half – lives than PIs and NRTIs

52. Common Adverse Effects of
NNRTIs
Adverse Effects worst during
first 1 to 2 weeks of therapy
Efavirenz
• CNS effects (insomnia, nightmares,
psychosis, hallucinations, etc);
maculopapular rash; N/V/D; elevated
LFTs
ETV
 Rash,
 nausea,
 Diarrhea, abdominal pain
 Headache, pyrexia, fatigue
Nevirapine
•Hepatitis; Severe skin rash (SJS);
GIT intolerance; ulcerative
stomatitis; Peripheral neuropathy;
Myalgia
Delavirdine
•Postural hypotension; CNS effects
(nightmares, hallucinations,
disorientation, depression, etc); GIT
effects; sexual dysfunction; anemia;
bilirubinemia, etc
RPV – Headache, depression,
insomnia, rash, raised LFTs,
lipodystrophy
Less CNS disturbances than
efavirenz and non – teratogenic.

53. 3.PROTEASE INHIBITORS (PIs)
MECHANISM OF ACTION
PIs bind to the active site of the HIV – protease enzyme that processes viral
proteins into functional conformations , preventing the maturation of newly
produced virions so that they remain non – infectious viral particles
Atazanavir (ATV/r) Indinavir (IDV)
Lopinavir ((LPV/r, Kaletra®) Nelfinavir (NFV)
Ritonavir (RTV)
Darunavir (DRV)
 Ritonavir does not add to antiviral activity it is a
pharmacokinetic enhancer

54. Common Adverse
Effects of PIs
• Metabolic Disorders
• Hepatotoxicity
• Hyperglycemia, Insulin resistance
• Lipid abnormalities (increased TG and LDL
levels)less effect compared to D4T
• Fat redistribution & lipodystrophy
• Elevated lactate levels
• Bone Disorders
• GIT Intolerance(LPV/R chronic diarrhea
• Elevated ALT

55. 4. Integrase Inhibitors
• Bind to an integrase enzyme essential to the replication of HIV; Inhibits
strand transfer - final step of provirus integration, thereby interfering with
the integration of reverse-transcribed HIV DNA into the chromosomes of
host cells.
• Was initially used in patients with resistant virus
• The current preferred first – line regimen or where tolerability with initial
regimens is an issue.
- Raltegravir (RAL) 3rd line
-Elvitegravir (requires boosting with cobicistat)
-Dolutegravir (part of the current preferred 1st line
TLD)
Adverse Effects:
• Insomnia Nausea, Headache, Diarrhea, etc,Nausea and headache,
dizziness, vertigo, abdominal pain, flatulence, constipation, pruritus,

56. ENTRY INHIBITORS
 There are currently two types of entry inhibitors
(fusion inhibitors and CCR5 inhibitors) that are
commonly used

57. 5. FUSION INHIBITORS
Mechanism of action
• Bind to the viral envelope glycoprotein inhibiting conformational changes
required for fusion of viral and cellular membranes
• Block the structural rearrangement of HIV – 1 gp41 thus stop the fusion of the viral
cell membrane with the target cell membrane, preventing viral RNA from entering the
cell.
Enfuvirtide (T – 20, Fuzeon®)
• Given by SC injection and largely used in heavily treatment experienced patients.
Adverse Effects:
 Main side effect is injection site reaction.
 N/D, fatigue, Insomnia, headache, lymphadenopathy, eosinophilia,
hypersensitivity reactions

58. 6. CCR5 receptor antagonists
.Selectively bind to the human chemokine receptors CCR5, preventing CCR5 – tropic HIV – 1 from
entering cells.
• CCR5 antagonists alter conformational state of the CCR5 receptor
• Maraviroc (MVC, Celsentri®) is indicated for use in patients with only CCR5 – tropic virus, which
is determined by tropism just prior to commencing treatment.
• Usually used in patients with resistance to one or more other antiretroviral classes.
Maraviroc
Adverse Effects:
 Upper RTIs, Cough, Hepatotoxicity, Musculoskeletal symptoms, Rash, etc
 Nausea most common, Vomiting, abdominal pain, constipation, bloating, Dizziness,
paraesthesia, somnolence, rash, insomnia, raised LFTs

59. COMMON ADVERSE EFFECTS
ARV
drug
Common associated toxicity ARV substitute
TDF Renal toxicity (renal tubular dysfunction) ABC or TAF
ABC Hypersensitivity reaction/ Lactic acidosis
TDF (if normal creatinine
clearance)
AZT (if child 3 months to
<10 years old)
ATV-R Hyperbilirubinaemia, icterus* LPV-r
EFV Severe or persistent CNS side effects ATV-r or LPV-r or DTG
NVP/
EFV
Rash, Steven Johnson Syndrome, hepatitis LPV-r or ATV-r
LPV-R Persistent diarrhoea, hyperlipidaemia ATV-r or DTG or If in
Children RAL

60. COMMON SIDE EFFECTS
drug Common associated toxicity ARV substitute
Severe anaemia or neutropenia, severe
gastrointestinal intolerance, lactic
acidosis
TDF or ABC (if on 1st line cART reg
rule out
failure before substitution)
d4T (if on 2nd line cART regimen fo
anaemia)
Lactic acidosis, lipodystrophy, peripheral
neuropathy
TDF or ABC (rule out failure before
substitution; if
failure suspected, switch to 2nd lin
Insomnia, anxiety, depression and
hypersensitivity reactions
ATV-r or LPV-r or EFV-400
Rash and hypersensitivity reaction ATV-r or LPV-r
Gastrointestinal symptoms, headache Rarely causes significant side toxi
occurs consult expert advice

61. TREATMENT
GUIDLINES

62. When To Start Therapy
 Under new WHO guidelines: Test and Treat policy.
 Test & Treat policy: providing ART irrespective/ regardless of CD4, VL
levels or WHO HIV clinical staging
 The assessment through WHO Staging guides the evaluation and
management of HIV
 However initiating ART does not require CD4 count/VL according to the
current treatment guidelines.
 Treat irrespective of WHO clinical stage or CD4 count

63. TREATMENT GUIDLINES
WHO/ZCGTP-HIV guidelines should be used
Preferred first line
 Tenofovir- Lamivudine-Dolutegravir (TLD)
Tenofovir : (TDF) disoproxil fumerate OR (TAF): Alafenamide)
 Alternative first line-Tenofovir-Lamivudine-Efavirenz 400mg (TLE)
Second Line
 NRTIs /Protease inhibitors e.g. Zidovudine/Lamivudine(AZT/3TC) +
Lopinavir/Ritonavir LVP/r or Atazanavir(ATV/r) or DRV-r. (Also TDF/3TC)
Third Line
 After genotypic resistance test (use of salvage therapy)
 E.g. Raltegravir, Darunavir(DRV/r), Etravirine researved for 3rd line and other
ARVs classes (1st line inclusive) demonstrating to be effective after resistance
test

64. PREFERRED 1st LINE cART
tions Description Preferred 1st line cART Alternative
MTCT
+
d Bearing
regnant
ARV naïve or sure of tail coverage TDF + XTC + DTG TDF + XTC +
Or ABC + 3
TDF + XTC +
Previous sdNVP exposure; or NVP
monotherapy exposure or unsure
of tail coverage
TDF + XTC + DTG
OR
AZT/3TC/LPV/r OR
TDF + XTC + LPV-r
ABC + XTC +
or ABC + XT
weeks) All AZT + 3TC + NVP
Consult or re
opinion
ks to  5
All ABC + 3TC + LPV-r AZT + 3TC +
All TDF + XTC + DTG
TDF + XTC +
TDF or TAF +

65. 1. HIV and TB Co-Infection

66. HIV and TB CONT…
Preferred 1st line cART:
 TDF + XTC + DTG, (increase dose of DTG 50mg twice daily, return to
normal dose when treatment with R is stopped )
Alternative regimen:
 TDF + XTC + EFV 400mg
Or
Use 2nd line cART in TB/HIV treatment as first line:
 TDF + XTC + LPV-r
 (double the dose of LPV-r if on rifampicin regimen) or switch rifampicin to
rifabutin (avoid in pregnancy or breast-feeding mothers)
Alternative Regimen:
 Replace LPV/r with ATV/r in patients with no liver disease
 ABC + 3TC + LPV-r (double dose of LPV/r)

67. IRIS Immune Reconstitution Inflammatory
Syndrome
 An exaggerated inflammatory reaction from a boosted immune system
presenting as unmasking of previously sub-clinical opportunistic infections
OR clinical worsening of pre-existing opportunistic infections OR
development of autoimmune disease.
 Onset: usually within 2-12 weeks after starting ART
 Frequency: 10% among all patients on ART, up to 25% when ART initiated
with CD4 <50 cells/mm3
Risk Factors
 Initiating ART close to diagnosis of an opportunistic infection
 Initiating ART when CD4 is less than 50 cells/mm3
 Rapid initial fall in HIV-1 RNA level in response to ART in patients with low
CD4 counts

68. Post-Exposure Prophylaxis
(PEP)
 PEP Is the use of cART to prevent HIV transmission.
 Non-occupational exposure to HIV in children is mostly due to sexual
abuse.
 In adults, exposure to HIV is mostly associated with occupational injuries
 Risk of acquiring HIV infection after occupational exposure to HIV-infected
blood is low (1:300 after percutaneous exposure and to <1:1000 after
mucocutaneous exposure).
 Start PEP preferably within 2 hours of the exposure.
 If 72 hours have passed since exposure, do not provide PEP because of
lack of effectiveness.
 Do not give PEP without HIV testing or to individuals who are found to be
HIV positive at the initial test.
 If negative, retest at 6 weeks, 3 months and 6 months after exposure

69. Pre-Exposure Prophylaxis
 Oral PrEP is the use of antiretroviral (ARV) drugs before HIV exposure by
people who are not infected with HIV to block the acquisition of HIV
 WHO recommends oral PrEP containing TDF/FTC (TRUVADA) BUT
TDF/XTC is an alternative e.g. Tenolam should be offered as an additional
prevention choice for people at substantial risk of HIV infection as part of
combination HIV prevention approaches
 TDF+XTC should be used for those on PrEP

70. Stopping PrEP
 PrEP should be discontinued after 4 weeks of elimination of the
exposure ( i.e. 4 weeks from time of last exposure)
 When the situation is likely to be sustained (i.e., partner starts
cART and is virally suppressed and there are no other sexual
partners), however safer sex practices must be re-inforced
 Significant side effects or if the creatinine clearance decreases
to <50mL/min

71. CO-TRIMOXAZOLE FOR PROPHYLAXIS
 Co-trimoxazole is a drug of choice for prophylaxis of opportunistic
infections associated with HIV
 Prevents P. jiroveci pneumonia, toxoplasmosis, cystoisosporiasis,
cryptosporidiosis and other HIV- and non-HIV related diseases and
prolongs survival.
 The reason is that co-trimoxazole is cost effective against a wide range of
organisms (bacteria, fungi and protozoa)
 An alternative to co-trimoxazole in patients allergic to Sulphur drugs
Is Dapson 100mg o.d
 Prevents HIV- and non-HIV related diseases and prolongs survival.

72. CO-TRIMOXAZOLE PROPHYLAXIS
 Co-trimoxazole(Septrin) can be safely taken with cART and/or ATT and in
pregnancy
NOTE:
 HIV-infected pregnant women on co-trimoxazole should not
be given sulfadoxine-pyrimethamine for malaria prophylaxis
in pregnancy because Co-trimoxazole(Septrin) is also effective for
Adult dosage
 Co-trimoxazole 960 mg (2 tab od po also given to pregnant women
 Co-trimoxazole 480mg (1tab)od po for children below 12 years

73. PMTCT/EMTCT
 ART is currently one of the fastest
evolving areas of medicine.
 Specific details of treatment continue to
change as new drugs emerge.
 E.g. TDF & EFV ,TLD were contraindicated in
pregnancy and childbearing age but are are
safe to use

74. EMTCT
 The prongs/pillars of HIV represent the cornerstones of the comprehensive
Elimination of Mother To Child Transmission of HIV (e-MTCT) service delivery
 WHO currently recommend a third option to provide life long ART to all HIV-infected
pregnant women, regardless of CD4 cell count referred to as Option B+
 Options A and B included prophylaxis no treatment for life
 (WHO) PMTCT antiretroviral (ARV) guidelines are for treating pregnant women and
preventing infection in infants
 The current ambitious goals are for eliminating paediatric HIV infection
 The new Global Plan is Towards the Elimination of New HIV Infections among
Children and Keeping their Mothers Alive thru substantial progress in the global
scale-up of PMTCT and ART coverage

75. PMTCT/EMTCT

76. ADVANTAGES OF OPTION “B+”
Option B+ WHO 2013 recommended PMTCT antiretroviral (ARV) programme
options with the following benefits:
 Further simplification of regimen and service delivery
 Harmonization with ART programmes,
 Extended protection against mother-to-child transmission in future
pregnancies,
 A strong and continuing prevention benefit against sexual transmission in
serodiscordant couples and partners
 Avoiding stopping and starting of ARV drugs

77. OPTION B+ ADVANTAGES.
 The Option B+ approach of life long ART for all HIV-infected pregnant women,
regardless of CD4 count, has important advantages over both Options A and B (if
viral suppression is maintained)
 Further simplification of PMTCT programme requirements— no need for CD4 testing
to determine ART eligibility (as required in Option A) or whether ART should be
stopped or continued after the risk of mother-to-child transmission has ceased (as in
Option B) (although CD4 counts or viral load assays are still desirable for
determining baseline immunological status and monitoring response to treatment)
 Provide benefit to the woman’s health of earlier treatment and avoiding the risks of
stopping and starting triple ARVs, especially in settings with high fertility
 A simple message to communities that, once ART is started, it is taken for life.

78. IMPLICATIONS OF OPTION A & B
 Options A and B included prophylaxis no treatment for life
 Exposure to single dose NVP monotherapy a drug with long 1/2 life without
AZT/3TC cover for 7 days risk development of resistance to NNRTIs/cross
resistance therefore such pregnant women required to be initiated on TLD or
second line AZT/3TC/Lpv/r instead of TLE depleting the future treatment
options
 The proposal by some countries to move to the new Option B+ approach of
lifelong ART for PMTCT for all HIV infected pregnant women, rather than
stopping ARVs for women not eligible for treatment, as in both Option A and
Option B risking drug resistance
 Information is subjective considering that the patient provide information on
drug history

79. THE
END
THANK