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

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

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

4.  Abacavir (ABC)  Didanosine (DDI)  Emtricitabine (FTC)  Lamivudine (3TC)  Stavudine (D4T)  Zidovudine (AZT)  Tenofovir (TDF) - NtRTI NRTIs University of Nairobi ISO 9001:2008 4 Certified http://www.uonbi.ac.ke

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

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

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

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

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

10.  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) ART Combinations University of Nairobi ISO 9001:2008 10 Certified http://www.uonbi.ac.ke

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

12. 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. Indications of ART University of Nairobi ISO 9001:2008 12 Certified http://www.uonbi.ac.ke

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

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

15. Recommended second-line for patients failing first line therapy Second line ART regimens University of Nairobi ISO 9001:2008 15 Certified http://www.uonbi.ac.ke First-lineSecond-line TDF + 3TC + EFV or NVPAZT + 3TC + LPV/r or ATV/r AZT + 3TC + EFV or NVPTDF + 3TC + LPV/r or ATV/r d4T + 3TC + EFV or NVPTDF + 3TC + LPV/r or ATV/r

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

17.  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 Interventions to reduce MTCT University of Nairobi ISO 9001:2008 17 Certified http://www.uonbi.ac.ke

18.  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. PMTCT ART regimens University of Nairobi ISO 9001:2008 18 Certified http://www.uonbi.ac.ke

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

20.  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 PEP regimens University of Nairobi ISO 9001:2008 20 Certified http://www.uonbi.ac.ke

21.  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 PrEP University of Nairobi ISO 9001:2008 21 Certified http://www.uonbi.ac.ke

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