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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