HIV Flashcards
What is the mode of transmission of HIV?
specific body fluids - blood, semen, genital fluids, and breast milk
- unprotected sex w an infected person
- sharing infected syringes and needles (IV drug users)
- Mother-to-child transmission during preg, at birth or through breast-feeding
- transfusion w contaminated blood and blood products
Who should be tested for HIV?
- IV drug users
- unprotected sex w multiple partners
- MSM
- CSW
- Persons treated for STDs
- recipients of multiple blood transfusion
- people who have been sexually assaulted
- preg women
How to diagnose HIV infection?
- serum antibody detection
~ HIV enzyme immunoassay antibody tests
~ Western Blot - HIV RNA detection/ quantification (viral load): PCR
What are the different stages of HIV presentation?
A) Acute (Primary) HIV Infection
B) The Asymptomatic Stage
C) Persistent Generalised Lymphadenopathy
D) AIDS and Related Conditions
What S&S are present in Acute (Primary) HIV Infection?
soon after contracting HIV, flu-like illness with swollen lymph nodes, fever, malaise and rash lasting about 2-3wks
Are there any S&S for The Asymptomatic Stage?
No, stage persists for many years
What presentation is seen in Persistent Generalised Lymphadenopathy?
Persistent unexplained lymph node enlargement in the neck, underarms and groin for > 3mths
What is the presentation/ seriousness when HIV has progressed into AIDs and related conditions?
- AIDS = CD4 <200/mm3 or presence of AIDS-defining diseases
- Advanced stage of disease and person succumb to infections by unusual organisms that the uninfected person can resist
- organs affected: lungs, eyes, GIT, nervous system, skin
- systemic smx like fevers, unexplained weight loss and diarrhoea are also common
- rare cancers (e.g. Lymphoma and Kaposi sarcoma) may be found
What are the primary goals of anti-retroviral therapy?
- reduce HIV-associated morbidity and mortality
- prolong duration and quality of survival
- restore and preserve immunologic fn
- maximally and durably suppress plasma HIV viral load
- Prevent HIV transmission
What are the surrogate markers in HIV?
- CD4
- Viral load
How is CD4 used to indicate presence of HIV?
- CD4 (T-lymphocyte) count (healthy) = 500-1200 cells/mm3
- most impt lab indicator of immune fn in HIV-infected patients
- also strongest predictor of subsequent disease progression and survival
- use to determine urgency for initiating antiretroviral therapy (now, once person has HIV, initiate therapy)
- use to assess response to antiretroviral therapy
~ assessed at baseline and every 3-6mths after treatment initiation, every 12mths after adequate response
~ adequate CD4 response is defined as an inc in CD4 count in range of 50-150 cells/mm3 during 1st yr of therapy - use to assess the need for initiating or discontinuing prophylaxis for opportunistic infections: e.g. prophylaxis for pneumocystis pneumonia is started when CD4 cells are <200 cells/mm3
How is viral load used to indicate presences of HIV?
- Viral load (plasma HIV RNA) = amt of virus in plasma
- most impt indicator of response to antiretroviral therapy and can be useful in predicting clinical progression
- viral load measured before initiation of therapy and within 2-4wks (not later than 8wks) after treatment initiation or modification, thereafter, every 4 to 8 weeks until viral load suppressed
- effective regimen generally achieve viral suppression (i.e. undetectable HIV RNA level) by 8-24 wks
- In patients on stable regimen and suppressed viral load, monitoring can be done evry 3-6mths
When to start ART?
- ART recommended for all HIV-infected ind, regardless of CD4 cell count, to reduce morbidity and mortality associated with HIV infection
- ART also recommended for HIV-infected ind to prevent HIV transmission
- when initiating ART, impt to educate pts regarding benefits and considerations regarding ART, and to address strategies to optimise adherence
- case-by-case basis, ART may be deferred because of clinical and/or psychosocial factors, but therapy should be initiated ASAP
Benefits of earlier treatment?
- maintenance of a higher CD4 count and prevention of potentially irreversible damage to the immune system
- Decreased risk for HIV-associated complications that can sometimes occur at CD4 counts >350cells/mm3, incl TB, non-Hodgkins’s lymphoma, Kaposi’s sarcoma, peripheral neuropathy, and HIV-associated cognitive impairment
- Decreased risk of non-opportunistic conditions, incl CVD, renal disease, liver disease, and non-AIDS-associated malignancies and infections
- Dec risk of HIV transmission to others, which will have positive public health implications
Limitations of earlier initiation?
- treatment-related side effects and toxicities
- drug resistance because of incomplete viral suppression, resulting in loss of future treatment options
- transmission of drug-resistant virus in patients who don’t maintain full virologic suppression
- less time for pt to learn about HIV and its treatment and less time to prepare for need for adherence
- increased total time on medication, with greater chance of treatment fatigue,
- increased cost
What are the factors to consider when selecting an initial regimen?
regimen selection should be individualised and should be based on a no. of factors:
- pt’s HIV understanding
- cost and availability
- adherence issues, convenience ~ pill burden, dosing freq, food and fluid considerations
- virologic efficacy
- potential adv effects (comorbidities, drug interactions)
- childbearing potential
- genotypic drug resistance testing
What is the life cycle of HIV?
- Attachment to CD4 receptor
- Binding to co-receptor CCR5 or CXCR4
Drug targets: CCR5/CXCR4 receptor inhibitors - Fusion
Drug targets: Fusion inhibitors - Reverse transcription
Drug targets: NRTIs and NNRTIs - Integration
Drug targets: integrase inhibitors - Transcription
- Translation
- Cleavage of polypeptides and assembly
Drug targets: protease inhibitors - Viral release
What are the recommended combinations for patients naive to ART?
2 NRTIs + 1 INSTI:
a) Tenofovir + emtricitabine + bictegravir OR
b) Tenofovir + emtricitabine + dolutegravir OR
c) Abacavir + lamivudine + dolutegravir (3-in-1, Triumeq)
OR
1 NRTI + 1 INSTI: emtricitabine + dolutegravir
NOT for ind with:
- HIV RNA > 500,000 copies/ml
- HBV co-infection OR
- In whom ART is to be started before the HIV genotypic resistance testing results or HBV testing results are available
HBV required 2 antivirals (tenofovir, emtricitabine, or lamivudine)
What are the drugs under Nucleoside Reverse Transcriptase Inhibitors (NRTIs)?
tenofovir, emtricitabine, lamivudine, abacavir, zidovudine (early art, used in preg women)
What are the advantages of NRTIs?
- established dual backbone of combination ART
- Renal elimination, little concerns for drug interactions
What are the disadvantages of NRTIs?
- adv effect related to mitochondrial toxicity (rare but serious):
~ lactic acidosis and hepatic steatosis (fatty infiltrate)
~ lipoatrophy (lost of fat)
~ Zidovudine > Tenofovir = Abacavir = Lamivudine - Requires dose adjustment in renal impaired pts (Except abacavir)
What are the adv effects of specific NRTIs?
Lamivudine - minimal toxicity, N/V/D
Emtricitabine - minimal toxicities, hyperpigmentation, N/D
Tenofovir - N/V/D, can cause renal impairment, dec in bone mineral density (Tenofovir Alafenamide (TAF) less than Tenofovir Disoproxil Fumarate (TDF))
Abacavir - N/V/D, Hypersensitivity rxn in pts with HLA B5701
Smx: rash, fever, malaise/fatigue, loss of appetite, sore throat, cough, SOB) Can be fatal.
Discontinue if it occurs, do not rechallenge.
Testing for the absence of HLA-B5701 is required before initiating abacavir. Concern for assoc with MI - not be used in high cardiovascular risk pts.
Zidovudine - N/V/D, myopathy, BM suppression causing anaemia or neutropenia
What are the drugs under Integrase Strand Transfer Inhibitor (INSTI)?
Raltegravir, Elvitegravir, Dolutegravir, Bictegravir
What are the advantages of INSTIs?
- Bictegravir, dolutegravir good virologic effectiveness
- high genetic barrier to resistance (B, D > R, E)
- generally well tolerated
What are the disadvantages of INSTIs?
- ADR: weight gain, N/D, HA, depression, and suicidality rarely reported with INSTI use, primarily in pts with pre-existing psychiatric conditions
- DDI: F lowered by concurrent adm of polyvalent cations; Bictegravir, dolutegravir and elvitegravir are CYP3A4 substrates (concern wirh CYP3A4 inducers and inhibitors)
What are the adverse effects of INSTIs?
- Bicetegravir: inc in serum creatinine (Cr)*
- Dolutegravir: inc in serum Cr*
- inhibits tubular secretion of Cr, no impact on glomerular function
- Raltegravir: pyrexia (fever), Cr kinase elevation (rhabdomyolysis)
What are the drugs under Non-nucleoside reverse transcriptase inhibitors (NNRTIs)?
Efavirenz, Rilpivirine
What are the advantages of NNRTIs?
- long half-lives
- less metabolic toxicity (hyperlipidaemia, insulin resistance) than with some Protease inhibitors (PIs)
What are the disadvantages of NNRTIs?
- low genetic barrier to resistance
- cross resistance among approved NNRTIs
- skin rash, SJS (R < E)
- potential for CYP450 drug interactions (some are inducers and inhibitors)
- QTc prolongation
What are the adv effects of NNRTIs?
- Efavirenz: rash, hyperlipidaemia, neuropsychiatric SE (dizziness, depression, insomnia, abnormal dreams, hallucination), inc in LDL-C and TGs, hepatotoxicity
- Rilpivirine: depression, HA
- Mixed CYP inducer/inhibitor
~ Efavirenz: CYP3A4 substrate, CYP2B6 and 2C19 inducer
~ Rilpivirine: CYP3A4 substrate, oral abs is reduced with inc gastric pH; used with PPIs are CONTRAINDICATED (low pH is favourable)
What are the drugs under protease inhibitors (PIs)?
Ritonavir, Lopinavir, Atazanavir, Darunavir, Fosamprenavir (pre-formulated with ritonavir or cobicistat)
What are the advantages of PIs?
- High genetic barrier to resistance
- PI resistance less common
What are the disadvantages of PIs?
- Metabolic complications (dyslipidaemia, insulin resistance)
- GI side effects (N/V/D)
- Liver toxicity (esp with chronic hep B or C)
- CYP3A4 inhibitors and substrates: potential for drug interactions
- Morphologic complications: fat maldistribution (lipohypertrophy); similar to a buffalo hump
- inc risk of osteopenia/ osteoporosis
What are the adv effects of PIs?
- Ritonavir: potent CYP3A4, 2D6 inhibitor, frequently combined with other PI to “boost” their levels (e.g. Lopinavir/ ritonavir)
Additional SE: paresthesia (numbness of extremities), taste perversion - Darunavir: good GI tolerability, less lipids effects. Skin rash (10%), concern for SJS (sulphonamide)
- Atazanavir: good GI tolerability, less lipids effects. Absorption depends on low pH (CONTRAINDICATED concurrent use with PPIs)
Additional SE: hyperbilirubinaemia, prolong QT interval, skin rash
What is a fusion inhibitor and what are the ADR?
- enfuvirtide (less commonly used)
- no appreciable drug interactions
- SC injection, 2x/day
- ADR:
injection site rxn (erythema/induration, nodules/cyst, pruritis, ecchymosis in 98%),
rare hypersensitivity rxn reported (fever, rash, chills, dec BP).
Inc bacterial pneumonia
What is a CCR5 Antagonist and what are the ADR?
- Maraviroc (Selzentry)
- used only in ppl whose strain of HIV uses the CCR5 receptor to enter the CD4 cells
~ need co-receptor tropism assay before initiation
~ must be CCR5 predorminant to use maraviroc (not to use if CXCR4 or dual/mixed tropism) - CYP3A4 substrate
- ADR: abdominal pain, cough, dizziness, musculoskeletal smx, pyrexia (fever), rash, URTI, hepatoxicity, orthostatic hypotension
How to combine the drugs available for HIV ART?
2 NRTIs (backbone) + 1 INSTI/NNRTI/PI
or
1 NRTIs + 1 INSTI/NNRTI/PI
PI replaces INSTI
What are the 7 reasons for failure in HIV ART?
- drug toxicities
- dosing schedule and requirements
- DDI
- Viral resistance
- regimen potency
- provider experience
- adherence > 95%
What are the strategies to improve adherence to ART?
- establish readiness to start therapy
- provide education on medication dosing
- review potential side effects
- anticipate and treat SE
- utilise educational aids incl pictures, pillboxes, and calendars
- engage family, friends
- simplify regimens, dosing, and food requirements (talking ART w or wo food)
- utilise team approach with nurses, pharmacists and peer counsellors
- provide accessible, trusting health care team
