Management of the patient with HIV and AIDs Flashcards
How prevalent is HIV in the UK?
- 91,500 people living with HIV in the UK (2010)
- > 36 million living with HIV worldwide
- 22 million deaths from HIV since 1981
Describe the typical progression of HIV infection WRT viral load and CD4.
- Acute phase; asymptomatic or flu-like symptoms (Weeks 0-12), CD4 (white cells) fighting HIV infection; clearing viral load to 10^3 odd, CD4 count recovers slightly
- Chronic phase; breakdown of immune system from HIV replication within it, viral load creeps up over time as immune system starts to break down - generally symptomatic, but then eventually develop AIDs syndrome
- AIDs; lose a lot of weight, tired, fevers; if CD4 below 200 cells per micro litre, can present with various AIDs defining illnesses:
• PCP (pneumonia)
• Cytomegalovirus
• Toxoplasmosis
»> Infections that present in the immunocompromised
How many people with HIV present at the AIDs stage?
- 30% of first-time HIV people present with a CD4 count below 200 cells per micro litre
- Already at AIDs stage (advanced, not asymptomatic any more)
What is the aim of HAART therapy?
- Undetectable viral load (in the blood etc)
- To slow down the progression line (chronic phase) into the full-blown AIDs syndrome
What is the treatment timeline for HIV?
- Lifelong antiretroviral therapy (ARV/T) aka HAART (highly active antiretroviral therapy) or CART (combination antiretroviral therapy)
»> No cure of preventive vaccine; aim is to prolong life and improve QoL (keep CD4 count up by keeping viral load down)
How is life expectancy affected if first diagnosed at 20 years of age? What is this similar to?
- At least 2/3 of normal life expectancy, with it not being uncommon to live to full life expectancy (w/ARV/HAART/CART)
- Same scenario as being diagnosed with T2DM at the same age
- ‘Chronic illness’
What are the HAART treatment objectives?
- Suppress viral load to undetectable (< 50 copies/ml)
- Increase CD4 count (surrogate marker for immune system function)
- Prevent opportunistic infections and progression to AIDs (vigilance)
»> Saw opportunistic first in the 90s (diagnosing factor); but much rarer now
What are the different types of ARV (antiretroviral therapy) availible?
Reverse Transcriptase Inhibitors (13):
• Nucleoside analogues:
- Zidovudine (AZT, ZDV)
- Didanosine (ddI)
• Nucleotide analogues:
- Tenofovir (TFV)
• Non-nucleotide analogues:
- Nevirapine (NVP)
- Etravirine (ETV)
Integrase Inhibitors:
- Raltegravir (RAL)
- Elvitegravir
Fusion inhibitor:
- Fuzeon
Entry inhibitors (CCR5): - Fuzeon (T20)
Protease inhibitors (10):
- Saquinavir (SQV)
- Darunavir (DRV)
What are the factors to consider WRT choosing first-line HAART therapy?
- Patient’s willingness to commit to therapy (denial? compliance?)
- Baseline resistance (10-11% in treatment naive patients in UK; HIV is already resistant to one or more medicines availible)
- Efficacy data
- Tolerability
- Convenience
- Efficacy data
- Tolerability (S/Es)
- Convenience
- Commodities (drugs safe in DM/heart disease/CKD etc?)
- Consequences of failure (resistance; designing regimen)
What is the first-line HAART for treatment-naive, non-resistant standard HIV patient?
BHIVA 2013 preferred:
- 2 NRTIs + efavirenz
E.g:
• Tenofovir + Emtricitabine (one nucleoside, one nucleotide)
• Abacavir + Lamivudine (older regimen)
»> Both + Efavirenz (non-nucleotide)
»> 3 drugs w/different mechanisms of action
If patient cannot take Efavirenz as part of first line HAART, what are they given instead to initiate HAART?
BHIVA 2013 alternative:
- 2 NRTIS + ritonavir-boosted protease inhibitor (e.g. lopinavir + ritonavir, saquinavir + ritonavir)
NRTI Example:
• Didanosine + Lamivudine (+ the above PI + ritonavir)
If a patient presents with a low CD4 count, what third antiretroviral is used in HAART instead of efavirenz?
Nevirapine
If a patient has cardiac disease, what are they given instead of the protease inhibitors of BHIVA 2013 Alternative HAART, and why?
- Atazanavir (newer protease inhibitor)
- Lots of antiretrovirals can cause water retention and arrhythmias; bad for heart disease
How does when HAART first-line therapy is initiated affect 5-year survival?
- Initiate with a CD4 count of > 200 cells/mm^3
- If starting HAART < 200 cells/mm^3 CD4, risk of death/progression to AIDs is 12%; DOUBLE that of if starting between 351-500 cells (6%)
- 201-350 cells CD4 = 7% risk at 5 years
What are the reasons for delayed vs earlier initiation of HAART therapy?
For delayed:
- Drug toxicity
- Preservation of limited Rx options (later before you develop resistance)
- Cost
For earlier:
- Potency, durability, simplicity and safety of current regimens (compared to OG antiretrovirals)
- Improves formulations and PK (don’t have to take drugs five times a day for example)
- New classes of drugs
- Excess morbidity/mortality at lower CD4 (risk of death doubles)
- Public health; if patient does not get treated down to an undetectable viral load, they are much more likely to transmit the infection
When is HAART first-line therapy initiated in patients with a primary (first-time) HIV infection? What other circumstances mirror this approach?
- Treat in clinical trial (evidence not clear)
Same in:
- Neurological involvement (HIV in the CNS)
- < 200 CD4 cell/micro L for > 3 months
- AIDs defining illness
For an established HIV infection, when is HAART first-line therapy initiated in patients with varying CD4 counts?
CD4 cells/micro L:
- < 200 = Treat
- 201-350 = Treat ASAP when patient is ready (counsel)
- 351-500 = Treat in specific situations e.g. Hep B (develop symptoms more early)
- > 500 = Consider enrolment in ‘when to start trial’
- AIDS diagnosis = Treat
Describe the importance of early HIV diagnosis.
- Late diagnosis is most important predictor of dying of AIDs (OR 10.55; 10x more likely to die from AIDs)
- 1-year mortality rate: 31.6 per 1000 persons diagnosed in 2010:
• Adults diagnosed late: 40.3/1000
• Prompt diagnosis: 5.2/1000 (w/high CD4 count)
What is a ‘late diagnosis’ of HIV WRT CD4?
Diagnosed/presenting with a CD4 < 350.
Which groups are more liable to presenting later/being diagnosed with HIV later? (asymptomatic for longer?)
- > 50 years or older (67%) vs. 15-24 years (31%)
- Heterosexual men (64%) vs. Women (46%), Homoesexual men (36%)
- Black African adults (66%)
- Black African adults born abroad (96%)
What are the public health implications of not knowing you’re HIV+? (asymptomatic etc.)
- If 25% of the HIV infected populace were unaware they were infected, they go on to be the root cause of 54% (more like 70%) of new HIV infections
- Compared to the remaining 75% who are aware, who cause 46% of new infections
What are meant by ‘indicator diseases’?
The range of diseases that are more common among people that are HIV+; patient should be tested for HIV as a precautionary measure.
List some common indicator diseases for HIV.
Respiratory:
- Bacterial pneumonia
- Aspergillosis (fungal)
Neurology:
- Aseptic meningitis/encephalitis
- Cerebral abscess
- Lesion of unknown cause
- GBS; Guillain-Barré syndrome (immune system attacks myelin sheath of PNS)
- Peripheral neuropathy
- Dementia
Dermatology:
- Severe/recalcitrant seborrhoeic dermatitis/psoriasis
- Recurrent herpes zoster
Gastroenterology:
- Oral candidiasis/hairy leukoplakia
- Chronic diarrhoea/weight loss of unknown cause
- Salmonella, shigella or campylobacter
- Hep B/C
Oncology: - Anal cancer or anal intraepithelial dysplasia - Lung cancer - Seminoma - H&N cancer - Hodgkin's lymphoma (HIV may be trigger of CAN)
Gynaecology:
- Vaginal/cervical intraepithelial neoplasia Grade II or above
Haematology:
- Thrombocytopenia
- Neutropenia
- Lymphopenia
Ophthalmology
- Infective (herpes, toxoplasma)
- Unexplained retinopathy
ENT:
- Lymphadenopathy of unknown cause
- Chronic parotitis
Other:
- Mononucleosis-like syndrome (primary HIV)
- Pyrexia
- Lymphadenopathy of unknown cause
- Any STI
What are the benefits of HAART?
- Prevention of mother to child transmission (if undetectable viral load)
- Post exposure prophylaxis (PEP)
- Secondary prevention of HIV transmission
- Primary prevention (PrEP)
- Clinical management of patients with HIV
Main points:
• Reduces HIV replication
• Increase or maintain CD4 numbers
• Maintain ‘less fit’ mutated HIV
• Delay progression to AIDs (becomes terminal then)
• Infection at 20 years of age; 2/3 normal life expectancy
What are the short-term S/Es of HAART?
- N&V, diarrhoea (to the point of dehydration), abdominal bloating & flatulence (real bad)
- Headaches ‘banging headaches’
- Mild to moderate rash; rarely leading to Steven-Johnson syndrome
What are the long-term S/Es of HAART?
- Osteopenia; changes in bone mineral density (lower)
- Changes in renal function (dropping)
- Dyslipidemia (atherosclerosis)
- DM and changes in glucose control
- Peripheral neuropathy
- Lipodystrophy & changes in body shape (random depositions of fat in the body)
»> Newer antiretrovirals have fewer of these though
What are the issues of antiretrovirals and potential drug interactions?
- Most ARVs are enzyme inducers/inhibitors/substrates of various Cytochrome P450 isoenzymes
- Clinical significance not always known; weighing up reduced efficacy vs. increased toxicity (juggle interacting drug regimens)
- Interactions are not class-based; one protease inhibitor may be fine, whilst another may cause a major interaction
How does the effect on CYP450 enzymes vary with if their induced or inhibited by antiretrovirals?
- Enzyme induction; can take 2 weeks to manifest, or 2 weeks to stop
- Enzyme inhibition; occurs quickly
»> Drug interactions have potential to continue even after interacting medicine has been stopped.
Why can’t the ARVs atazanavir and rilpivirine be taken w/acid suppressing drugs e.g. PPIs?
Both rely on an acidic environment for absorption
Why are Ritonavir and Cobicistat potentially a problem for asthmatics?
- Powerful enzyme inhibitors
- Can cause v. elevated levels of other other drugs resulting in toxicity e.g. Cushing’s disease w/steroid inhalers (like Fluticasone), and joint injections
What are some important, common drug interactions with ARVs, and the actions required?
Clarithromycin:
- Decrease dose in renal failure, consider azithromycin
Rifampicin:
- Increase efavirenz (w/TDM), increase other ARV doses
H2-receptor blockers:
- Give 2-12 hours after atazanavir; not within 12 hours before
PPIs:
- Avoid, use alternative
Simvastatin:
- Avoid, use alternative
St. John’s Wort:
- Avoid
MDMA:
- Avoid
Methadone:
- Monitor for withdrawal and increase dose slowly
Warfarin:
- Frequent INR monitoring (high variance in patients)
Fluticasone:
- Avoid, use alternative (can lead to steroid syndrome)
Why is medicine adherence paramount for ARV therapy?
- Very high levels of adherence essential to delay development of resistance; to maintain therapeutic level
- Need at least 95% of regimen
What are common reasons for non-adherence of ARVs?
- Failure to acknowledge need for treatment (denial?)
- Not understanding the benefits of treatment
- Perceived harm from taking ARVs and fear of stigmatising S/Es (e.g. lipodystrophy, debilitating diarrhoea)
- Intolerance to S/Es
- Complex regimens leading to misunderstanding how to take ARV and forgetting to take ARV (but loads of new combination therapies now)
- Fear of disclosure of HIV status
- Cost of ARV (especially in sub-Saharan Africa etc. where there is poor access)
Describe how ARV regimens have changed from 1996 to 2006.
1996: - Didanosine + stavudine + saquinavir • 24 pills/dose, 5 times a day • Saquinavir; 6 Q8H w/fatty food • Didanosine; 2 BD 30 mins AC or 2 hours PC • Stavudine; 1 tab BD
2006:
- Emtricitabine/tenofovir DF + efavirenz (Atripla)
• 1 tablet OD
• No food restrictions, though taking with high fat meals increases absorption and S/Es
How doe HIV co-infection w/TB infect the patient?
- HIV+ people 30x more likely to develop TB (immunocompromised)
- TB most common cause of AIDS related death (26%, especially in sub-Saharan Africa)
- Extrapulmonary TB common; spread from lungs to bones etc.
How prevalent is TB/TB + HIV coinfection?
- > 1 million people in the world with HIV and TB coinfection
- 1/3 world population may have latent TB infection
In TB + HIV coinfection, why is TB treated first, then HIV?
- Treating both at the same time can lead to IRIS (Immune Reconstitution Inflammatory Syndrome)
- TB and ARVs put immune system into overdrive
- Thus TB treated first, then ARV once eradicated
»> Unless CD4 count already < 200
»> Rifampicin is also an enzyme inducer (erythromycins)
How is HIV/TB co-infection treated?
- Treat TB immediately w/rifampicin-containing regimen
- OR, treat HIV immediately (2 weeks - 2 months after starting TB therapy) if CD4 < 200 cells/micro L
- CD4 201 < 350; treat after initial TB treatment phase
- Complex drug interactions and additive toxicities
