Antiretrovirals Flashcards
WHO HIV clinical stage 1
Persistent generalised lymphadenopathy Asymptomatic
Unexplained persistent hepatosplenomegaly
Papular pruritic eruptions
Extensive wart virus infection
Extensive molluscum contagiosum
Fungal nail infections
CLINICAL STAGE 2 who hiv
WHO clinical stage 2 of HIV
Recurrent oral ulcerations
Unexplained persistent parotid enlargement
Lineal gingival erythema
Herpes zoster
Recurrent or chronic upper respiratory tract infections (otitis media, otorrhoea, sinusitis or tonsillitis)
Unexplainedi moderate malnutrition not adequately responding to standard therapy
Unexplained persistent diarrhoea (14 days or more) Unexplained persistent fever (above 37.5°C intermittent or constant, for longer than one month)
HIV WHO clinical stage 3
Persistent oral candidiasis (after first 6–8 weeks of life) Oral hairy leukoplakia
Acute necrotizing ulcerative gingivitis or periodontitis
WHO HIV Clinical stage 3
Lymph node tuberculosis
Pulmonary tuberculosis
Severe recurrent bacterial pneumonia
HIC WHO clinical stage 3
Describe the pneumonitis, anaemia and lung disease of WHO clinical stage 3
Symptomatic lymphoid interstitial pneumonitis
Chronic HIV-associated lung disease including brochiectasis
Unexplained anaemia (<8 g/dl), neutropaenia (<0.5 × 109 per litre) and or chronic thrombocytopaenia (<50 × 109 per litre)
Unexplained severe wasting, stunting or severe malnutrition not responding to standard therapy
Pneumocystis pneumonia
Recurrent severe bacterial infections (such as empyema, pyomyositis, bone or joint infection or meningitis but excluding pneumonia)
HIV WHO clinical stage 4
Chronic herpes simplex infection (orolabial or cutaneous of more than one month’s duration or visceral at any site)
Extrapulmonary tuberculosis
Kaposi sarcoma
WHO HIV clinical stage 4
Oesophageal candidiasis (or candidiasis of trachea, bronchi or lungs)
Central nervous system toxoplasmosis (after one month of life)
HIV encephalopathy
Cytomegalovirus infection: retinitis or cytomegalovirus infection affecting another organ, with onset at age older than one month
HIV WHO Clinicl stage 4
Extrapulmonary cryptococcosis (including meningitis)
Disseminated endemic mycosis (extrapulmonary histoplasmosis, coccidiomycosis)
Chronic cryptosporidiosis
Chronic isosporiasis
WHO clinical stage 4
Disseminated non-tuberculous mycobacterial infection
Cerebral or B-cell non-Hodgkin lymphoma
Progressive multifocal leukoencephalopathy
Symptomatic HIV-associated nephropathy or HIV-associated cardiomyopathy
WHO HIV clinical stage 4
Immunological criteria for diagnosing advanced HIV in adults and children five years or older with confirmed HIV infection
CD4 count less than 350 per mm3 of blood in an HIV-infected adult or child
Immunological criteria for diagnosing advanced HIV in a child younger than five years of age with confirmed HIV infection:
%CD4+ <30 among those younger than 12 months %CD4+ <25 among those aged 12–35 months %CD4+ <20 among those aged 36–59 months
AIDS diagnosis in adults an children
clinical diagnosis (presumptive or definitive ) of any stage 4 condition (as defined in Annex 1) with confirmed HIV infection; OR
immunological criteria in adults and children with confirmed HIV infection and >5 years of age;
first-ever documented %CD4 count less than 200 per mm3 or %CD4+ <15; or,
among children aged 12–35 months first-ever documented CD4 of +<20; or among infants less than 12 months of age first-ever documented %CD4+ <25.
viral suppression
defined as having less than 200 copies of HIV per milliliter of blood
Nucleoside and nucleotide reverse transcriptase inhibitors
zidovudine, lamivudine, abacavir, tenofovir, emtricitabine, stavudine)
MOA Zidovudine
It inhibits the activity of HIV-1 reverse transcriptase (RT) via DNA chain termination after incorporation of the nucleotide analogue.
t competes with the natural substrate dGTP and incorporates itself into viral DNA
Zidovudine adverse drug reactions
fatigue, headache, gastrointestinal upset, lipoatrophy, bone marrow suppression, and myopathy
Emtricitabine MOA
emtricitabine 5’-triphosphate, competes with deoxycytidine 5’-triphosphate for HIV-1 reverse transcriptase
As HIV-1 reverse transcriptase incorporates emtricitabine into forming DNA strands, new nucleotides are unable to be incorporated, leading to viral DNA chain termination.5 I
nhibition of reverse transcriptase prevents transcription of viral RNA into DNA, therefore the virus is unable to incorporate its DNA into host DNA and replicate using host cell machinery.
ADRs emtricitabine
discoloration of the skin, nails, and tongue
STavudine mOA
Stavudine inhibits the activity of HIV-1 reverse transcriptase (RT) both by competing with the natural substrate dGTP and by its incorporation into viral DNA.
Stavudine ADRs
peripheral neuropathy, lactic acidosis, and facial and body lipoatrophy.[57] In addition, cases of severe neuromuscular weakness have been described
Lamivudine MOA
This nucleoside analogue is incorporated into viral DNA by HIV reverse transcriptase and HBV polymerase, resulting in DNA chain termination.
Lamivudine ADRs
discoloration of the skin, nails, and tongue
Abacavir MOA
converted by cellular enzymes to the active metabolite carbovir triphosphate
inhibits the activity of HIV-1 reverse transcriptase (RT) both by competing with the natural substrate dGTP and by its incorporation into viral DNA.
Viral DNA growth is terminated
Abacavir ADRs
Hypersensitivity reaction
Risk of cardiac disease
Tenofovir MOA
inhibition of viral polymerase causing chain termination and the inhibition of viral synthesis
potent inhibitor of the viral reverse transcriptase
Tenofovir ADRs
mild gastrointestinal effects (nausea, vomiting, diarrhea)
Nevirapine MOA
binds directly to reverse transcriptase (RT) and blocks the RNA-dependent and DNA-dependent DNA polymerase activities
Non-nucleoside reverse transcriptase inhibitors
(nevirapine, efavirenz
Nevirapine ADRs
Hypersensitivity reaction with rash and he[atotoxicity
Rash may be accompanied by fever, general malaise, fatigue, myalgias, arthralgias, blisters, oral lesions, conjunctivitis, facial edema, eosinophilia, granulocytopenia, lymphadenopathy, or renal dysfunction.
Efavirenz moa
inhibits the activity of viral RNA-directed DNA polymerase (i.e., reverse transcriptase
Efavirenz side effects
Cardiac QTc Interval Prolongation:
Dyslipidemia
Hepatotoxicity
Neuropsychiatric
Rash
Teratogenicity
Protease inhibitors
(lopinavir, atazanavir,ritonavir)
Lopinavir MOA
an inhibitor of the HIV-1 protease enzyme
the enzyme responsible for cleaving the Gag polyprotein which coordinates assembly, budding and maturation in HIV lifecycle
Lopinavir ADRs
Hyperlipidaemia
Diarrhoea
Alcohol in Liquid Formulation
atazanavir moa
Atazanavir selectively inhibits the virus-specific processing of viral Gag and Gag-Pol polyproteins in HIV-1 infected cells by binding to the active site of HIV-1 protease, thus preventing the formation of mature virions
Atazanavir ADRs
Hyperbilirubinemia
Nephrolithiasis
Cholelithiasis
Ritonovir MOA
inhibits the HIV viral proteinase enzyme that normally cleaves the structural and replicative proteins that arise from major HIV genes, such as gag and pol.
Ritonavir ADRs
gastrointestinal effects, including diarrhea, nausea, vomiting, and abdominal pain. These side effects are greater with higher doses of ritonavir.
Raltegravir MOA
Raltegravir inhibits HIV integrase to prevent the viral genome being incorporated into the human genome
Raltegravir ADRs
Elevated Creatine Kinase
Proximal Myopathy
Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis
dolutegravir MOA
It inhibits HIV integrase by binding to the active site and blocking the strand transfer step of retroviral DNA integration in the host cell
When to start ART among adults (>19 years old)
ART should be initiated among all adults with HIV regardless of WHO clinical stage and at any CD4 cell count (strong recommendation, moderate-quality evidence).
o As a priority, ART should be initiated among all adults with severe or advanced HIV clinical disease (WHO clinical stage 3 or 4) and adults with CD4 count ≤350 cells/mm3
When to start ART among pregnant and breastfeeding women
ART should be initiated in all pregnant and breastfeeding women living with HIV regardless of WHO clinical stage and at any CD4 cell count and continued lifelong
When to start ART among adolescents (10–19 years of age)
ART should be initiated among all adolescents living with HIV regardless of WHO clinical stage and at any CD4 cell count (conditional recommendation, low-quality evidence). o As a priority, ART should be initiated among all adolescents with severe or advanced HIV clinical disease (WHO clinical stage 3 or 4) and adolescents with CD4 count ≤350 cells/mm3 (
When to start ART among children (younger than 10 years of age)
ART should be initiated among all children living with HIV, regardless of WHO clinical stage or at any CD4 cell count.
o Infants diagnosed in the first year of life (strong recommendation, moderate-quality evidence). o Children living with HIV one year old to less than 10 years old (conditional recommendation, low-quality evidence).
As a priority, ART should be initiated among all children ≤2 years old or with WHO stage 3 or 4 or CD4 count ≤750 cells/mm³ or CD percentage <25% among children younger than 5 years and CD4 count ≤350 cells/mm³ among children 5 years and older.
Factors that should be monitored when on ART
TB screen
WHO staging
side effects
CD 4 count
viral load
creatinine
FBC
ALT
Fasting TC TG
Causes of treatment failure
- Drug resistance
- Adherence issues
Factors contributing to development of resistance
Poor adherance
Insufficient drug level
Viral replication in presence of drug
resistant viru
transmission
Howto diagnose virological failure
HIV RNA >1000 copies
Check VL in 2 months if still>100 copies change treatment
- Clinical deterioration - poor growth / FTT - delay in developmental milestones - development of opportunistic infections
- Immunological deterioration - steady decline in CD4+ count
Failed 1st line NNRTI based regimen
Abacavir + Lamivudine + Efavirenz (or Nevirapine)
What is Recommended second line regimen?
Zidovudine + Lamivudine + Lopinavir/ritonavir
Failed 1st line NNRTI based regimen
First line NNRTI-based regimen:
Stavudine + Lamivudine + Efavirenz (or Nevirapine)
what is the Recommended second line regimen:
Zidovudine + Lamivudine + Lopinavir/ritonavir
Failed 1st line Protease Inhibitor (PI) based regimen
Abacavir + Lamivudine + Lopinavir/ritonavir
Stavudine + Lamivudine + Lopinavir/ritonavir Unboosted
PI-based regimen Rifampicin while on Lopinavir/ritonavi
*Manage as for 3rd line regimens
Should be managed by a Paediatric Infectious Disease Specialist on the basis of genotype resistance testing.
Indications for resistance testing:
• Infants = 1000 copies/ml (>=log 3) at least 8-12 weeks apart after adherence has been addressed.
Stavudine + Lamivudine + Lopinavir/ritonavir Unboosted PI-based regimen Rifampicin while on Lopinavir/ritonavi
Resistance Testing
Can only be used to detect resistance to drugs currently being taken or within 4 weeks of stopping them -won’t necessarily show resistance to drugs patient was previously exposed to • Is useful to exclude drugs from a future regimen -won’t necessarily indicate which drugs will work
Initial antiretroviral therapy regimens for the previously untreated patient
• TDF + emtricitabine (FTC) (or 3TC) + efavirenz (EFV)
or
• TDF + emtricitabine (FTC) (or 3TC) + dolutegravir (DTG)
or
• TDF + emtricitabine (FTC) (or 3TC) + rilpivirine (RPV) provided VL < 100 000 copies/mL.
Recommended second-line antiretroviral therapy regimen
We recommend a regimen of two NRTIs and a RTV-boosted (/r) PI. Boosting of PIs involves the addition of low-dose RTV, which inhibits PI metabolism, thereby boosting PI plasma concentration and prolonging half-life. We recommend against the use of unboosted PIs
