HIV AND TB Flashcards

(55 cards)

1
Q

What are the main steps in the HIV life cycle?

A

Attachment (CD4 + CCR5/CXCR4)
Fusion
Reverse transcription
Integration (by integrase)
Transcription/translation
Assembly
Budding/maturation (by protease)

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2
Q

What are the 6 main classes of ART drugs?

A

NRTIs (Nucleoside Reverse Transcriptase Inhibitors)
NNRTIs (Non-Nucleoside Reverse Transcriptase Inhibitors)
PIs (Protease Inhibitors)
INSTIs (Integrase Strand Transfer Inhibitors)
Entry/Fusion Inhibitors
CCR5 Antagonists

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3
Q

What is the goal of ART (antiretroviral therapy)?

A

To reduce HIV viral load to undetectable levels, restore and preserve immune function, reduce HIV-related morbidity and mortality, and prevent transmission.

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4
Q

How is HIV diagnosed?

A

Adults: Rapid antibody tests (screening + confirmatory) - ELISA
Infants <18 months: HIV DNA PCR

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5
Q

What is the mechanism of NRTIs?

A

Analogues of natural nucleosides → get incorporated into viral DNA → terminate elongation.

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6
Q

What is the mechanism of NNRTIs?

A

Bind directly to reverse transcriptase at an allosteric site → inhibit enzyme activity.

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7
Q

What is the mechanism of PIs?

A

Inhibit HIV protease enzyme → prevent cleavage of viral polyproteins → immature, non-infectious viral particles.

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8
Q

What is the mechanism of INSTIs (integrase inhibitors)?

A

Block integration of viral DNA into host genome by inhibiting HIV integrase enzyme.

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9
Q

Name 4 NRTIs and their side effects

A

Zidovudine (AZT): anemia, neutropenia
Lamivudine (3TC): pancreatitis (rare)
Abacavir (ABC): hypersensitivity (test for HLA-B*5701)
Tenofovir (TDF): nephrotoxicity, ↓ bone mineral density

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10
Q

Name 3 NNRTIs and their concerns.

A

Nevirapine (NVP): hepatotoxicity, rash
Efavirenz (EFV): CNS effects (vivid dreams, dizziness), teratogenicity
Etravirine (ETR): fewer CNS side effects, used in resistance

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11
Q

Name 3 Protease Inhibitors (PIs).

A

Lopinavir/ritonavir (LPV/r): GI effects, hyperlipidemia
Atazanavir (ATV): hyperbilirubinemia
Darunavir (DRV): skin rash, sulfa allergy risk

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12
Q

Name 2 INSTIs and their benefits.

A

Dolutegravir (DTG): high barrier to resistance, well tolerated
Raltegravir (RAL): minimal interactions, good for TB coinfection

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13
Q

How are most PIs metabolised and boosted?

A

Metabolised by CYP3A4 and boosted by ritonavir or cobicistat (inhibit CYP3A4 to ↑ PI levels).

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14
Q

Which ART drugs interact with rifampicin?

A

Efavirenz is safe with rifampicin.
Avoid protease inhibitors and dolutegravir with rifampicin unless adjusted.

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15
Q

What drugs must be dose-adjusted in renal impairment?

A

Tenofovir, Lamivudine, Zidovudine.

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16
Q

Which ART is contraindicated in pregnancy?

A

Efavirenz in the first trimester (due to teratogenicity risk).

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17
Q

What is South Africa’s 1st-line ART regimen?

A

TDF + 3TC (or FTC) + DTG

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18
Q

What is 2nd-line ART after NNRTI failure?

A

AZT + 3TC + LPV/r

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19
Q

When is 3rd-line ART considered?

A

After confirmed virologic failure of 2nd-line regimen with resistance
Needs genotyping
May include: DRV/r + RAL + optimized NRTIs

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20
Q

What are the key monitoring tests in HIV therapy?

A

Viral load (gold standard): every 6 months
CD4 count: used to guide OI prophylaxis
Creatinine (for TDF), LFTs (for NVP, EFV), Hb (for AZT)

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21
Q

What defines virologic failure?

A

Two consecutive viral loads >1000 copies/mL despite good adherence over 6 months.

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22
Q

What ART is preferred in pregnancy?

A

TDF + 3TC + DTG (safe in all trimesters)
Avoid EFV in 1st trimester

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23
Q

What is the HIV management protocol during labour?

A

Continue ART
IV AZT if VL >1000 or unknown status
Neonate: nevirapine and AZT prophylaxis

24
Q

What is the protocol for TB–HIV co-infection?

A

Start TB treatment first, then ART after 2–8 weeks
Preferred ART: TDF + 3TC + EFV
Monitor for IRIS

25
What is PEP and when must it be started?
Post-exposure prophylaxis: within 72 hours Regimen: TDF + 3TC + DTG for 28 days
26
What is PrEP and who gets it?
Pre-exposure prophylaxis for high-risk HIV-negative individuals TDF + FTC once daily
27
How is adherence monitored in PrEP users?
HIV test every 3 months Monitor renal function (due to TDF)
28
What factors contribute to ART resistance?
Poor adherence Inadequate drug levels Pre-existing mutations
29
What are the key toxicities of ART drugs?
AZT: anemia TDF: renal toxicity, ↓ BMD NVP: hepatotoxicity, rash EFV: CNS effects LPV/r: metabolic effects
30
What causes TB and what is its characteristic staining property?
Mycobacterium tuberculosis—a slender, waxy-coated, acid-fast bacillus. Ziehl–Neelsen stain or fluorochrome stain is used for detection
31
How is TB transmitted and what factors increase risk?
Airborne droplet nuclei from coughing/sneezing. Risks ↑ with HIV, chemo, immunosuppressants, poor ventilation, malnutrition, or crowding
32
What are key symptoms of active pulmonary TB?
Cough ≥2 weeks (or any duration if HIV+), fever, night sweats, weight loss. Sputum sent for bacteriological confirmation
33
What are the 4 main first-line TB drugs?
Rifampicin (R) Isoniazid (H) Pyrazinamide (Z) Ethambutol (E)
34
Isoniazid mechanism of action?
Prodrug activated by KatG enzyme → inhibits mycolic acid & nucleic acid synthesis → cell death
35
Isoniazid pharmacokinetics?
Oral; take on empty stomach Hepatic metabolism via NAT2 (slow/fast acetylators) Distributes to CNS Renal elimination (no dose adjustment needed)
36
Isoniazid adverse effects?
Hepatotoxicity (↑ with age, alcohol, ARVs) Peripheral neuropathy (prevented by pyridoxine 25mg/day) CNS: seizures (↓GABA) Haematologic: sideroblastic anaemia, neutropenia
37
Rifampicin mechanism and spectrum?
Inhibits RNA polymerase → bactericidal against intra/extracellular TB. Also active vs. Staph, Neisseria, Haemophilus
38
Rifampicin pharmacokinetics?
↓ absorption with food Autoinduces metabolism (CYP3A4) Bile/faecal elimination CSF penetration ↑ in meningitis
39
Key rifampicin interactions and side effects?
Potent inducer (↓ levels of ARVs, warfarin, OCPs) ADRs: hepatotoxicity, GI upset Harmless red-orange body fluid discoloration
40
Pyrazinamide mechanism?
Converted by pyrazinamidase → pyrazinoic acid → disrupts cell membrane transport. Works best in acidic pH (macrophages)
41
Pyrazinamide kinetics & caution?
Good GI absorption CSF = plasma levels Hepatic metabolism, renally excreted Renal impairment: dose adjust if eGFR <30 ml/min
42
Pyrazinamide side effects?
Hepatotoxicity Hyperuricaemia → arthralgia GI upset Contraindicated in severe hepatic damage
43
Ethambutol mechanism?
Inhibits arabinosyl transferase → blocks arabinogalactan → disrupts cell wall; enhances entry of other TB drugs
44
Ethambutol kinetics & precautions?
Poor CNS penetration unless meningitis Renally excreted (dose adjust if eGFR <30 mL/min) Half-life: 3–4 hours
45
Ethambutol adverse effects?
Optic neuritis (reversible): ↓ visual acuity, red-green colour blindness Hyperuricaemia Needs monthly visual monitoring
46
Define MDR-TB and XDR-TB.
MDR-TB: resistance to INH + RIF XDR-TB: MDR + resistance to fluoroquinolone + ≥1 second-line injectable agent
47
Key drugs for MDR/RR-TB?
Bedaquiline Linezolid Levofloxacin Clofazimine Delamanid Terizidone PAS Pretomanid
48
Bedaquiline – MOA and risk?
nhibits ATP synthase CYP3A4 metabolism (no efavirenz!) Long t½ (5.5 months) QT prolongation (ECG monitoring needed)
49
Linezolid – MOA, toxicities, interactions?
23s site of 50s ribosome → ↓ protein synthesis Bone marrow suppression (esp. with AZT), thrombocytopenia Interactions: SSRIs, tyramine (MAOI activity)
50
Levofloxacin – MOA, side effects?
Inhibits DNA gyrase/topoisomerase Side effects: GI upset, QT prolongation, tendonitis Chelation with antacids/minerals
51
Clofazimine – MOA, elimination, side effects?
Binds guanine in bacterial DNA Very long half-life (2–3 months) Side effects: skin pigmentation, QT prolongation
52
Terizidone – MOA, neurotoxicity?
Inhibits cell wall synthesis Side effects: depression, psychosis (Efavirenz interaction!) Supplement with pyridoxine
53
PAS (para-aminosalicylic acid) – MOA and side effects?
Folic acid synthesis inhibitor GI upset, hepatotoxicity, hypothyroidism Renal adjustment required
54
Delamanid – MOA, special uses?
Inhibits mycolic acid synthesis Safe in kids 6–12 yrs QT prolongation (ECG monitoring)
55
Pretomanid – MOA and dual action?
Mycolic acid inhibition (aerobic) NO₂ release (anaerobic killing) Long t½, CYP3A4 metabolism Used in BPaL-L 6-month regimen