ANTIRETROVIRAL THERAPY Dr Samuel Mwaniki BPharm MSc

ANTIRETROVIRAL THERAPY Dr. Samuel Mwaniki (BPharm. , MSc TID, Uo. N) University of Nairobi ISO 9001: 2008 1 Certified http: //www. uonbi. ac. ke

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 University of Nairobi ISO 9001: 2008 2 Certified http: //www. uonbi. ac. ke

Classification of Antiretroviral medicines NRTI (Nucleoside Reverse Transcriptase Inhibitors) Nt. RTI (Nucleotide Reverse Transcriptase Inhibitors) NNRTI ( Non-Nucleoside Reverse Transcriptase Inhibitors) PI (Protease Inhibitors) Entry Inhibitors Integrase Inhibitors University of Nairobi ISO 9001: 2008 3 Certified http: //www. uonbi. ac. ke

NRTIs Abacavir (ABC) Didanosine (DDI) Emtricitabine (FTC) Lamivudine (3 TC) Stavudine (D 4 T) Zidovudine (AZT) Tenofovir (TDF) - Nt. RTI University of Nairobi ISO 9001: 2008 4 Certified http: //www. uonbi. ac. ke

NNRTIs Efavirenz (EFV) Nevirapine (NVP) Etravirine Rilpivirine University of Nairobi ISO 9001: 2008 5 Certified http: //www. uonbi. ac. ke

PIs Atazanavir (ATV) Durunavir (DRV) Fosamprenavir (f-APV) Indinavir (IDV) Lopinavir (LPV) Nelfinavir (NFV) Ritonavir (RTV) Saquinavir (SQV) Tripranvir (TPV) University of Nairobi ISO 9001: 2008 6 Certified http: //www. uonbi. ac. ke

Other ARVs Entry inhibitors: Enfuvirtide, Maraviroc Integrase inhibitors: Raltegravir, Elvitegravir Maturation inhibitors: Beviramat University of Nairobi ISO 9001: 2008 7 Certified http: //www. uonbi. ac. ke

Uses of ART (Antiretroviral Therapy) PMTCT (Prevention of Mother To Child Transmission) PEP (Post Exposure Prophylaxis) Pr. EP (Pre Exposure Prophylaxis) University of Nairobi ISO 9001: 2008 8 Certified http: //www. uonbi. ac. ke

ART Combines at least 3 ARVs from at least 2 different classes. Why combination? § Synergism § Reduced toxicity § Prevent resistance University of Nairobi ISO 9001: 2008 9 Certified http: //www. uonbi. ac. ke

ART Combinations 2 NRTI + 1 NNRTI 1 NRTI + 1 Nt. RTI + 1 NNRTI 2 NRTI + boosted PI 1 NRTI + 1 Nt. RTI + boosted PI 3 NRTI (One must be Abacavir) University of Nairobi ISO 9001: 2008 10 Certified http: //www. uonbi. ac. ke

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 University of Nairobi ISO 9001: 2008 11 Certified http: //www. uonbi. ac. ke

Indications of ART Indicated in all HIV-positive adults and adolescents with the following: § WHO clinical stage 1 or 2 and a CD 4 count ≤ 350 cells/mm 3, § WHO clinical stage 3 or 4 regardless of CD 4 count, § HIV and TB co-infection regardless of the CD 4 count, § HIV/HBV co-infection with evidence of active liver disease. University of Nairobi ISO 9001: 2008 12 Certified http: //www. uonbi. ac. ke

First line ART regimens Recommended first-line antiretroviral regimens in treatment of naive adults and adolescents are: TDF + 3 TC + EFV or NVP or AZT + 3 TC + NVP or EFV University of Nairobi ISO 9001: 2008 13 Certified http: //www. uonbi. ac. ke

Changing to second line Treatment failure Clinical Immunological Virological Inability to tolerate a drug because of adverse effects University of Nairobi ISO 9001: 2008 14 Certified http: //www. uonbi. ac. ke

Second line ART regimens Recommended second-line for patients failing first line therapy First-line Second-line TDF + 3 TC + EFV or NVP AZT + 3 TC + LPV/r or ATV/r AZT + 3 TC + EFV or NVP TDF + 3 TC + LPV/r or ATV/r d 4 T + 3 TC + EFV or NVP TDF + 3 TC + LPV/r or ATV/r University of Nairobi ISO 9001: 2008 15 Certified http: //www. uonbi. ac. ke

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) University of Nairobi ISO 9001: 2008 16 Certified http: //www. uonbi. ac. ke

Interventions to reduce MTCT Prevention of HIV Infection among all women of reproductive age group from getting HIV Prevention of unintended pregnancies among HIVpositive 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 University of Nairobi ISO 9001: 2008 17 Certified http: //www. uonbi. ac. ke

PMTCT ART regimens When to start: CD 4 ≤ 350 cells/mm 3 irrespective of clinical symptoms OR WHO clinical stage 3 or 4 irrespective of CD 4 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, 3 TC or AZT. University of Nairobi ISO 9001: 2008 18 Certified http: //www. uonbi. ac. ke

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 University of Nairobi ISO 9001: 2008 19 Certified http: //www. uonbi. ac. ke

PEP regimens AZT/3 TC: 1 bd for 28 days TDF/3 TC: 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 University of Nairobi ISO 9001: 2008 20 Certified http: //www. uonbi. ac. ke

Pr. EP Studies carried out to evaluate efficacy i. Pr. Ex 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 University of Nairobi ISO 9001: 2008 21 Certified http: //www. uonbi. ac. ke

Thank you END University of Nairobi ISO 9001: 2008 22 Certified http: //www. uonbi. ac. ke