Antiretroviral therapy

Treatment of HIV/AIDS, HAART

1. ANTIRETROVIRAL TREATMENT OF ADULT HIV INFECTION D R.MD SHAHID IQUBAL 1 st year PG MEDICINE NMCH,PATNA

2. INTRODUCTION ART is defined as Treatment with antiretroviral medicines, against the retrovirus (HIV ), which resides and multiplies within the human body HAART (Highly Active Antiretroviral Therapy)-regimens combining several antiretroviral drugs As of mid-2016 8.2 million people are receiving antiretroviral treatment worldwide Current recommendation to start ART - is to treat everyone infected with hiv irrespective of CD4 count Goal of therapy is maximal and durable suppression of HIV replication

3. Classification of Antiretroviral drugs Are grouped into five categories NRTI (Nucleoside and nucleotide Reverse Transcriptase Inhibitors ) NNRTI ( Non-Nucleoside Reverse Transcriptase Inhibitors) PIs (Protease Inhibitors) Entry Inhibitors Integrase Inhibitors

4. Classification of drugs contd … NRTIs NNRTIs Nucleoside analogues Zidovudine (AZT) Didanosine (DDI) Zalcitabine ( ddC ) Stavudine (D4T) Lamivudine (3TC) Emtricitabine (FTC) Abacavir (ABC) Delavirdine Nevirapine (NVP) Efavirenz (EFV) Etravirine Rilpivirine Nucleotide analogues Tenofovir

5. Classification of drugs contd … Protease inhibitors( Pis ) Entry inhibitors- Saquinavir (SQV) Ritonavir (RTV) Indinavir (IDV) Nelfinavir (NFV ) Fosamprenavir (f-APV) Lopinavir (LPV ) Atazanavir (ATV) Tripranvir (TPV) Durunavir (DRV ) Enfuvritide - Maraviroc

6. ART initial therapy- Combines at least 3 ARVs from at least 2 different classes . Generally consists of combination of two NRTIS,usually plus an NNRTI,an integrase inhibitors or a boosted PIs. Why combination? Synergism Reduced toxicity Prevent resistance Many of the first line regimens are co-formulated as single tablet daily regimens

7. ART initial therapy cond ….. Current first line regimens are- 1.NNRTI based Efavirenz+tenofovir+emtricitabine 2.Protease inhibitor based Atazanavir / ritonavir+tenofovir+emtricitabine Darunavir / ritonavir+tenofovir+emtricitabine 3.Integrase inhibitor based Dolutegravir+tenofovir+emtricitabine Raltegravir+tenofovir+emtricitabine

8. Treatment monitoring- Viral load should be checked after initiation of ART and should decrease by 10 fold in 4 weeks Treatment failure- i s defined as less than 10 fold(1 log drop) reduction of the viral load in 4 weeks after initiation of ART Persistently declining CD4 cell count Clinical deterioration confirmed treatment failure are indication of changing antiretroviral therapy

9. MTCT(Mother to child transmissin )- 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)

10. Interventions to reduce MTCT- MTCT can reduce to 50%by 3 intervention- 1. intrapartum zidovudine 2.elective cesarian delivery 3.early cord clamping of baby Current guidelines recommend that all HIV infected partners in a couple planning pregnancy should attain virological suppression before attempting conception If a pregnant woman is already taking ART,it shouldnot change regardless of regimen Newly HIV + ve pregnant woman should be started on a one daily fixed dose combination of Tenofovir + lamivudine+efavirenz ` If treated early in her pregnacy , a woman’s risk of transmitting HIV to her baby can be reduced to 1%.