ANTIRETROVIRAL THERAPY
Dr. Samuel Mwaniki
(BPharm., MSc TID, UoN)
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Definition of ART
• Treatment with antiretroviral medicines, against the retrovirus (HIV),
which resides and multiplies within the human body
• HIV; etiological agent of AIDS
• Hallmark of HIV; RNA virus that transcripts DNA from RNA via the
Reverse Transcriptase enzyme
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Classification of Antiretroviral
medicines
• NRTI (Nucleoside Reverse Transcriptase Inhibitors)
• NtRTI (Nucleotide Reverse Transcriptase Inhibitors)
• NNRTI ( Non-Nucleoside Reverse Transcriptase Inhibitors)
• PI (Protease Inhibitors)
• Entry Inhibitors
• Integrase Inhibitors
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NRTIs
• Abacavir (ABC)
• Didanosine (DDI)
• Emtricitabine (FTC)
• Lamivudine (3TC)
• Stavudine (D4T)
• Zidovudine (AZT)
• Tenofovir (TDF) - NtRTI
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NNRTIs
• Efavirenz (EFV)
• Nevirapine (NVP)
• Etravirine
• Rilpivirine
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PIs
• Atazanavir (ATV)
• Durunavir (DRV)
• Fosamprenavir (f-APV)
• Indinavir (IDV)
• Lopinavir (LPV)
• Nelfinavir (NFV)
• Ritonavir (RTV)
• Saquinavir (SQV)
• Tripranvir (TPV)
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Other ARVs
• Entry inhibitors: Enfuvirtide, Maraviroc
• Integrase inhibitors: Raltegravir, Elvitegravir
• Maturation inhibitors: Beviramat
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Uses of ART
• ART (Antiretroviral Therapy)
• PMTCT (Prevention of Mother To Child Transmission)
• PEP (Post Exposure Prophylaxis)
• PrEP (Pre Exposure Prophylaxis)
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ART
• Combines at least 3 ARVs from at least 2 different classes.
• Why combination?
Synergism
Reduced toxicity
Prevent resistance
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ART Combinations
• 2 NRTI + 1 NNRTI
• 1 NRTI + 1 NtRTI + 1 NNRTI
• 2NRTI + boosted PI
• 1 NRTI + 1 NtRTI + boosted PI
• 3 NRTI (One must be Abacavir)
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Goals of ART
• Maximal and durable suppression of viral replication
to prevent development of HIV, drug resistance and
treatment failure
• Restoration/ preservation of immunologic function
• Reduction of HIV-related morbidity and mortality
• Improvement of the patient’s quality of life
• Prevention of onward transmission of HIV infection
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Indications of ART
Indicated in all HIV-positive adults and adolescents with
the following:
WHO clinical stage 1 or 2 and a CD4 count ≤ 350
cells/mm3,
WHO clinical stage 3 or 4 regardless of CD4 count,
HIV and TB co-infection regardless of the CD4 count,
HIV/HBV co-infection with evidence of active liver
disease.
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First line ART regimens
Recommended first-line antiretroviral regimens in
treatment of naive adults and adolescents are:
•TDF + 3TC + EFV or NVP or
•AZT + 3TC + NVP or EFV
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Changing to second line
• Treatment failure
– Clinical
– Immunological
– Virological
• Inability to tolerate a drug because of adverse effects
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Second line ART regimens
Recommended second-line for patients failing first line therapy
First-line Second-line
TDF + 3TC + EFV or NVP AZT + 3TC + LPV/r or ATV/r
AZT + 3TC + EFV or NVP TDF + 3TC + LPV/r or ATV/r
d4T + 3TC + EFV or NVP TDF + 3TC + LPV/r or ATV/r
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MTCT
• MTCT accounts for more than 90% of
pediatric HIV infection.
• Risk factors for MTCT:
Maternal (high viral load, advanced HIV disease,
mixed feeding )
Obstetric (Vaginal delivery, prolonged rupture of
membranes >4 hours, placental infection)
Infant (prematurity <37 weeks, low birth
weight, oral candidiasis)
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Interventions to reduce MTCT
• Prevention of HIV Infection among all women of
reproductive age group from getting HIV
• Prevention of unintended pregnancies among
HIV-positive women
• Effective interventions to reduce HIV
transmission to infants during pregnancy, labor,
delivery and post.
• Chronic care and support for the HIV-infected
women, their infants, partners and families
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PMTCT ART regimens
• When to start:
– CD4 ≤350 cells/mm3 irrespective of clinical symptoms
OR
– WHO clinical stage 3 or 4 irrespective of CD4 cell count
• What to start:
– As adult/adolescent first-line
– AZT preferred but TDF acceptable
– EFV included as a NNRTI option (not in first trimester)
– Infants: NVP, 3TC or AZT.
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PEP
Indications for PEP
•Occupational exposure (healthcare workers,
police)
•After RTA where there has been exposure to
other people’s blood
•Discordant couples following condom bursts
•Rape
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PEP regimens
• AZT/3TC: 1 bd for 28 days
• TDF/3TC: 1 od for 28 days
• Add Alluvia/ Kaletra: 2 bd for 28 days in case of high risk
• Given at earliest possible opportunity, within 1-72 hours of
exposure
• Use fixed dose combination to enhance adherence
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PrEP
• Studies carried out to evaluate efficacy
• iPrEx study– Preexposure Prophylaxis Initiative
• Multinational (Peru, Ecuador, South Africa, Brazil, Thailand,
United States)
• Effect of FTC/TDF compared with placebo on reducing HIV
acquisition among men and transgender women who have sex
with men
• Disproportionately affected by the epidemic
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Thank you
END
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