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

ARV Nurse Training, Africaid, 2004

ARV Nurse Training Programme

Prepared by Marcus McGilvray and Nicola Willis

Modified by Megan Rohm

What are Antiretrovirals?


What is……

ART ARV HAART Triple therapy

??????


Confusing terminology….!

ART = AntiRetroviral Treatment ARV = AntiRetroVirals HAART = Highly Active AntiRetroviral

Treatment Triple Therapy = Three Antiretrovirals

Basically it all means the same thing!


But what are Antiretrovirals?

Medicines used to treat OIs Immune BoostersHerbal Remedies

Medicines that are used to actually fight the HIV virus

Versus


What do ARVs do….?

ARVs can change HIV from a terminal (fatal) disease to a “chronic disease”.


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


How do they control HIV?

ARVs reduce the ability of the HIV virus to replicate

In turn, this increases the ability of the body to fight disease

HIVReplication

Immune Response


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


How HIV WorksHIV

1. Attachment to host CD4 cell

2. Reverse transcriptase makes DNA from the virus’s RNA

3. Integration into host cell’s nucleus

4. Reproduction of viral components

5. Assembly of new HIV viruses

6. Release


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


3 Main Classes of ARVs

NRTIs – ”nukes” e.g. AZT, 3TC, DDI, D4T

NNRTIs – ”non nukes” e.g. EFV, NVP (Nevirapine)

PIs – protease inhibitors e.g. Lopinavir, Ritonavir

Each class acts at a different stage and in a different way, to prevent HIV replicating within the CD4 cell


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


How NRTIs Work

HIV

Nucleoside reverse transcriptase inhibitors (NRTIs) latch onto the new strand of DNA that reverse transcriptase is trying to build.


How NNRTIs WorkHIV

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) hook onto reverse transcriptase and stop it from working


HIV

Protease inhibitors (PIs) prevent final assembly and completion of new HIV viruses within the cell

How PIs WorkHow PIs Work


Does everyone with HIV need ARVs ?

NO

It depends on the ‘Stage’ of HIV Infection

Which depends on……………..


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!


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)


Starting ARVs in Children(WHO 2010)

NB: Children differ in their immunology and virological response to HIV

And are managed differently!

• 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 forsurveillance. 2006.

Table 8. WHO clinical staging of HIV disease in adults and adolescents

• 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

WHO HIV update

• http://whqlibdoc.who.int/publications/2010/9789241599764_eng.pdf

• http://www.who.int/hiv/en/


http://whqlibdoc.who.int/publications/2010/9789241599764_eng.pdf

http://whqlibdoc.who.int/publications/2010/9789241599764_eng.pdf

http://www.who.int/hiv/en/


What to Start…..?

The most effective regimens utilise drugs from different classes

This promotes maximum viral suppression by inhibiting replication in different ways, at different places in the life cycle

NRTIs: AZT, D4T, 3TC, ddI

NNRTIs:NVP, EFV

PIs:NFV, IDV, LPV, SQV


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!


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)

Adverse Drug Effects

Mitochondrialdysfunction

Metabolic abnormalities

Hematologiccomplications

Allergic reactions

Lactic acidosis

Hepatic toxicity

Pancreatitis

Peripheral neuropathy

LipodystrophyFat accumulationLipoatrophy

Hyperlipidemia/ ? Premature CAD

Hyperglycemia

Insulin resistance/DM

Bone disorders: oesteoporosis and osteopenia

Bone marrowsuppression

Hypersensitivityreactions

Skin rashes

Medication Side Effects

– Anorexia– Sore/dry/painful mouth– Swallowing difficulties– Constipation/Diarrhea– Nausea/Vomiting/Altered Taste– Depression/Tiredness/Lethargy


Achievable…..?

YESARVs 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……….


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


“It is not like just giving 2 aspirins…” (National AIDS conference, RSA, August 2003)

This is true


And……

What may work for one, may not work for another

Everybody Everybody is different!is different!


Why is HIV so hard to treat?

It’s a cheeky little devil!

10 billion copies of the virus are made every day


The problem of resistance (a biological issue)

The challenge of adherence (a human issue)

And…

Side effects……..


What can we do……?

Understanding the way in which ARVs work and the challenges our patients face, helps us to help them!

Documents

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