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What are Antiretrovirals?

What are Antiretrovirals?. ARV Nurse Training Programme Prepared by Marcus McGilvray and Nicola Willis Modified by Megan Rohm. What is……. ART ARV HAART Triple therapy ??????. Confusing terminology….!. ART = A nti R etroviral T reatment ARV = A nti R etro V irals

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What are Antiretrovirals?

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  1. What are Antiretrovirals? ARV Nurse Training Programme Prepared by Marcus McGilvray and Nicola Willis Modified by Megan Rohm ARV Nurse Training, Africaid, 2004

  2. What is…… • ART • ARV • HAART • Triple therapy • ?????? ARV Nurse Training, Africaid, 2004

  3. Confusing terminology….! • ART = AntiRetroviral Treatment • ARV = AntiRetroVirals • HAART = Highly Active AntiRetroviral Treatment • Triple Therapy = Three Antiretrovirals • Basically it all means the same thing! ARV Nurse Training, Africaid, 2004

  4. But what are Antiretrovirals? Medicines used to treat OIs Immune Boosters Herbal Remedies Medicines that are used to actually fight the HIV virus Versus ARV Nurse Training, Africaid, 2004

  5. What do ARVs do….? ARVs can change HIV from a terminal (fatal) disease to a “chronic disease”. ARV Nurse Training, Africaid, 2004

  6. What is a Chronic Disease?? An illness which cannot be “cured” but can be controlled Examples of chronic diseases: • Diabetes • High Blood pressure • Asthma • Schizophrenia ARV Nurse Training, Africaid, 2004

  7. ARVs reduce the ability of the HIV virus to replicate In turn, this increases the ability of the body to fight disease HIV Replication Immune Response How do they control HIV? ARV Nurse Training, Africaid, 2004

  8. Primary Goal of ARVs Decrease or reverse immune system damage associated with HIV infection, thus improving quality of life and reducing HIV-related morbidity and mortality ARV Nurse Training, Africaid, 2004

  9. How HIV Works 3. Integration into host cell’s nucleus HIV 4. Reproduction of viral components 1. Attachment to host CD4 cell • Assembly of new HIV viruses • Reverse transcriptase makes DNA from the virus’s RNA 6. Release ARV Nurse Training, Africaid, 2004

  10. ARVs at Work…. • Remember – HIV uses the CD4 cell as an HIV factory……. • ARVs get inside the factory, and at different places, reduce the ability of the virus to replicate • So, less virus can be made CD4 ARV Nurse Training, Africaid, 2004

  11. 3 Main Classes of ARVs NRTIs – ”nukes”e.g. AZT, 3TC, DDI, D4T NNRTIs – ”non nukes”e.g. EFV, NVP (Nevirapine) PIs– protease inhibitorse.g. Lopinavir, Ritonavir Each class acts at a different stage and in a different way, to prevent HIV replicating within the CD4 cell ARV Nurse Training, Africaid, 2004

  12. ARVs at Work….. Remember the enzymes involved in HIV replication….? • Reverse Transcriptase(essential for copying viral RNA into DNA in the early stages of replication) • Protease( required for assembly and maturation of fully-infectious new virus in final stages of replication) ARVs INHIBIT these enzymes, thus slowing down the replication cycle ARV Nurse Training, Africaid, 2004

  13. How NRTIs Work HIV Nucleoside reverse transcriptase inhibitors (NRTIs) latch onto the new strand of DNA that reverse transcriptase is trying to build. ARV Nurse Training, Africaid, 2004

  14. How NNRTIs Work HIV Non-nucleoside reverse transcriptase inhibitors (NNRTIs) hook onto reverse transcriptase and stop it from working ARV Nurse Training, Africaid, 2004

  15. How PIs Work HIV Protease inhibitors (PIs) prevent final assembly and completion of new HIV viruses within the cell ARV Nurse Training, Africaid, 2004

  16. Does everyone with HIV need ARVs ? NO It depends on the ‘Stage’ of HIV Infection Which depends on…………….. ARV Nurse Training, Africaid, 2004

  17. Who needs ARVs…..? The ‘Stage’ of HIV depends upon: • Immunological markers (CD4 count) • Clinical symptoms (Opportunistic infections) It also depends on whether the patient is READY to start! ARV Nurse Training, Africaid, 2004

  18. WHO Guidelines (2010 updates) HIV infected adults and adolescents should start ARV therapy when they have: • WHO stage 3 of HIV disease, regardless of CD4 count • WHO stage II of HIV disease, with a CD4 count below 350/mm3 (where resources are available for testing and treatment) ARV Nurse Training, Africaid, 2004

  19. Starting ARVs in Children(WHO 2010) NB: Children differ in their immunology and virological response to HIV And are managed differently! ARV Nurse Training, Africaid, 2004

  20. Table 8. WHO clinical staging of HIV disease in adults and adolescents • Clinical stage 1 • Asymptomatic • Persistent generalized lymphadenopathy • Clinical stage 2 • Moderate unexplained weight loss (under 10% of presumed or measured body weight) • Recurrent respiratory tract infections (sinusitis, tonsillitis, otitis media, pharyngitis) • Herpes zoster • Angular cheilitis • Recurrent oral ulcerations • Papular pruritic eruptions • Seborrhoeic dermatitis • Fungal nail infections • Clinical stage 3 • Unexplained severe weight loss (over 10% of presumed or measured body weight) • Unexplained chronic diarrhoea for longer than 1 month • Unexplained persistent fever (intermittent or constant for longer than 1 month) • Persistent oral candidiasis • Oral hairy leukoplakia • Pulmonary tuberculosis • Severe bacterial infections (e.g. pneumonia, empyema, meningitis, pyomyositis, bone or • joint infection, bacteraemia, severe pelvic inflammatory disease) • Acute necrotizing ulcerative stomatitis, gingivitis or periodontitis Source: Revised WHO clinical staging and immunological classification of HIV and case definition of HIV for surveillance. 2006.

  21. Clinical stage 4 • HIV wasting syndrome • Pneumocystis jiroveci pneumonia • Recurrent severe bacterial pneumonia • Chronic herpes simplex infection (orolabial, genital or anorectal of more than 1 month’s • duration or visceral at any site) • Oesophageal candidiasis (or candidiasis of trachea, bronchi or lungs) • Extrapulmonary tuberculosis • Kaposi sarcoma • Cytomegalovirus disease (retinitis or infection of other organs, excluding liver, spleen and • lymph nodes) • Central nervous system toxoplasmosis • HIV encephalopathy • Extrapulmonary cryptococcosis including meningitis • Disseminated nontuberculous mycobacteria infection • Progressive multifocal leukoencephalopathy • Chronic cryptosporidiosis • Chronic isosporiasis • Disseminated mycosis (histoplasmosis, coccidiomycosis) • Recurrent septicaemia (including nontyphoidal Salmonella) • Lymphoma (cerebral or B cell non-Hodgkin) • Invasive cervical carcinoma • Atypical disseminated leishmaniasis • Symptomatic HIV-associated nephropathy or HIV-associated cardiomyopathy Source: Revised WHO clinical staging and immunological classification of HIV and case definition of HIV for

  22. WHO HIV update • http://whqlibdoc.who.int/publications/2010/9789241599764_eng.pdf • http://www.who.int/hiv/en/ ARV Nurse Training, Africaid, 2004

  23. The most effective regimens utilise drugs from different classes This promotes maximum viral suppression by inhibiting replication in different ways, at different placesin the life cycle NRTIs: AZT, D4T, 3TC, ddI NNRTIs: NVP, EFV PIs: NFV, IDV, LPV, SQV What to Start…..? ARV Nurse Training, Africaid, 2004

  24. So…. Examples of drug regimens commonly used in ARV combinations d4T + 3TC + NVP d4T + 3TC + EFV AZT + ddI + Lopinavir/Ritonavir NB AZT + D4T should NEVER be used together! ARV Nurse Training, Africaid, 2004

  25. What to expect! Treatment success = • Decline in VL of at least 1.0 log from pre-treatment levels by 6-8 weeks after initiating ARVs • A decline in VL to <400 RNA copies/mL by 24 weeks after commencing ARVs Undetectable viral load = ultimate goal! (A sustained viral load of <50 RNA copies/mL is associated with the most durable virological benefit) ARV Nurse Training, Africaid, 2004

  26. Adverse Drug Effects

  27. Medication Side Effects • Anorexia • Sore/dry/painful mouth • Swallowing difficulties • Constipation/Diarrhea • Nausea/Vomiting/Altered Taste • Depression/Tiredness/Lethargy

  28. Achievable…..? YES ARVs are able to significantly reduce viral load, allowing immune reconstitution followed by an increase in quality of life and reduction in morbidity and mortality BUT they are not perfect………. ARV Nurse Training, Africaid, 2004

  29. Not perfect! Unfortunately, ‘treatment failure’ may occur for some people, where: • A sustained increase in VL >5000 copies/mL • A decline in VL of less than 1 log within 6-8 weeks after commencing ARVs • A sustained increase in VL of >0.6 log from its lowest point or a return to 50% of pre-treatment value ARV Nurse Training, Africaid, 2004

  30. “It is not like just giving 2 aspirins…” (National AIDS conference, RSA, August 2003) This is true ARV Nurse Training, Africaid, 2004

  31. And…… What may work for one, may not work for another Everybody is different! ARV Nurse Training, Africaid, 2004

  32. Why is HIV so hard to treat? It’s a cheeky little devil! 10 billion copies of the virus are made every day ARV Nurse Training, Africaid, 2004

  33. And… • The problem of resistance (a biological issue) • The challenge of adherence (a human issue) • Side effects…….. ARV Nurse Training, Africaid, 2004

  34. What can we do……? Understanding the way in which ARVs work and the challenges our patients face, helps us to help them! ARV Nurse Training, Africaid, 2004

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