HIV

Question 1

Risk factors for HIV infection? (4)

Answer 1

Vertical

Transfusion

IVDU

MSM/Sexual

Question 2

Clinical presentations of HIV - P in PRICMCP?

Answer 2

1. Initial symptoms that led to a diagnosis
2. Dx date
3. Has the patient had a seroconversion illness (≥50%): symptoms similar to glandular fever - fever, lymphadenopathy, rash, arthralgia, myalgia, N+V, meningism, oral candida.

Question 3

What are the complications of HIV & it’s treatment you need to ask in history?

Answer 3

• Infection: ask from top - have you ever had following infections that were thought to be caused by HIV? - brain (toxo, cryptococcal), eye (CMV retinitis), oral/food gullet/bowel (candida, oesophageal candida, CMV colitis), lungs (PJP, MAC), skin (chicken-pox/Herpes Zoster)
• Malignancy: KS, NHL, primary CNS lymphoma
• Accelerated atherosclerosis: CVD, CVD (+vascular/HIV dementia)
• Kidney: nephrotic syndrome - either HIV nephropathy or drug-induced
• Psychiatric: both disease & treatment side effects
• Drug side effects: lipodystrophy, metabolic*** (lipid, diabetes - PIs, OP - tenofovir), hepatotoxicity, renal toxicity, psychic, PN.

Question 4

HIV long PRICMCP?

Answer 4

P: initial symptoms, seroconversion illness (not associated with prognosis), date dx. Was there an AIDS-defining illness (e.g. PJP, KS, NHL. disseminated MAC, Toxoplasma, oesophageal candida, CMV).

R: Vertical, Transfusion, Sexual, IVDU.

I: current CD4 & VL (what were the lowest points - nadir?). Genotyping (?resistance, if so to what). How was the dx confirmed? Any LP, MRI/CT, BM biopsy (what did it show?)

C:

• Infection: ask from top - have you ever had following infections that were thought to be caused by HIV? - brain (toxo, cryptococcal), eye (CMV retinitis), oral/food gullet/bowel (candida, oesophageal candida, CMV colitis), lungs (PJP, MAC), skin (chicken-pox/Herpes Zoster)
• Malignancy: KS, NHL, primary CNS lymphoma
• Accelerated atherosclerosis: CVD, CVD (+vascular/HIV dementia)
• Kidney: nephrotic syndrome - either HIV nephropathy or drug-induced
• Hepatitis: from drugs
• Neuro-Psychiatric: both disease & treatment side effects, peripheral neuropathy**
• Drug side effects: lipodystrophy, metabolic*** (lipid, diabetes - PIs, OP - tenofovir), hepatotoxicity, renal toxicity, PN.

M: Current & previous regime, compliance, treatment failure/resistance? It is a big issue if the patient does not know their drug…!***

C:

• has the disease been under control? current CD4, VL, recent infective episodes
• current inpatient (or outpatient) issue / current complication
• Sexual contact***: contact traced? family & friends aware of diagnosis, have you disclosed sexuality, HIV status
• impact - work, life, family - do you face discrimination?
• Finance - how are they coping

P:

• Understanding of disease, why adherence is so important, life-style change (due to CV risk), awareness of drug interaction (hence not to start without talking to physician)

Question 5

When would you start the infection prophylaxis?

Answer 5

CD4 <200 → Bactrim for PCP and CNS toxo.

CD <50 → Azithromycin for MAC

Question 6

OIs when CD count 200-500? (4)

Answer 6

TB

Pneumococcal pneumonia

Oral candida

VZV

Question 7

OIs when CD4 50-200? (5)

Answer 7

PJP

Toxoplasma CNS

Cryptococcus

KS

NHL

Question 8

OIs when CD4 <50? (3)

Answer 8

Disseminated MAC

CMV retinitis/colitis

Cryptosporidiosis

Question 9

What investigations would you like to review for this patient with HIV?

Answer 9

T: HIV antibodies, HIV RNA VL, CD4 counts. Western blot (confirmatory).

E: concurrent diseases (Hep A/B/C), risk of latent infections (CMV Ab, syphilis Abs, Toxoplasma Abs), TB (quantiferon/TST), CD4+<200: Hep C RNA, Cryptococcal Ag, Stool for cyst/ova/parasites

CD4+<100: CMV PCR, Mycobacterial blood cultures, ECG, fundoscopy with pupils dilated.

Septic work-up to exclude potential OIs (blood culture, CXR, CRP, urine) + further investigations guided by symptoms (previous CSF, CXR/CT, flexi-biopsy…etc).

S: review previous CD4/VL trends (is the patient progression or non-progressor?, resistance testing

T: FBC, EUC, LFTs, HBA1C, fasting lipids, HLA B5701 (Abacavir), Genotype testing

S: MMSE does not work as HIV-dementia is subcortical. Luria test + Heel-toe walk → if abnormal, refer to neuropsych, ECG (ischaemic changes), TTE, urine MCS, ACR, PCR (nephritis/nephrotic), HbA1C, lipid profile, DEXA, CTB (microvascular ischaemic changes / vascular dementia)

Question 10

How accurate is HIV Ab testing (i.e. ELISA or EIA)?

Answer 10

Sensitivity 99%

Specificity 90% in low-risk populations (FP due to recent vaccinations, other viral infections or autoimmune disease).

Question 11

What is the earliest detectable test? So why would you do Ab testing?

Answer 11

HIV PCR RNA is the earliest detectable test.

Ab testing is still needed as the level of RNA may still be below the detectable range.

Question 12

When would you start the HAART on this patient with newly diagnosed HIV?

Answer 12

Current guideline suggest that ALL should be treated regardless of CD4 counts or viral load.

This is based on START study → demonstrated that earlier treatment was a/w better composite outcome, prevention benefit, and public health.

Question 13

Which drug would you avoid if the HIV patient has…

1. IHD
2. Significant psychiatric conditions
3. Renal impairment

Answer 13

1. IHD: Avoid abacavir
2. Significant psychiatric conditions: avoid Efavirenze
3. Renal impairment: avoid Tenofovir

Question 14

What are the big 4 major side effects (groups) that are associated with HAART use?

Answer 14

1. Cardiovascular
2. Metabolic (DM, lipids, osteoporosis)
3. Neuropsychiatric (PN, dementia)
4. Renal (renal impairment, stone, FSGS, nephrotic syndrome)

Also lipodystrophy (facial, central adiposity, buffalohump)

Question 15

How would you manage PCP in HIV?

Presentation:

Diagnosis:

Management:

Answer 15

Presentation: pneumonia

Diagnosis: CXR/CT - bilateral interstitial infiltrates

Management: Bactrim +/- steroids (if hypoxic)

Question 16

How would you manage CMV in HIV?

Presentation:

Diagnosis:

Management:

Answer 16

How would you manage PCP in HIV?

Presentation: CMV retinitis or colitis

Diagnosis: biopsy + PCR

Management: Ganciclovir then Valganciclovir maintenance

Question 17

How would you manage Cerebral Toxoplasma in HIV?

Presentation:

Diagnosis:

Management:

Answer 17

How would you manage Cerebral Toxoplasma in HIV?

Presentation: neurological symptoms

Diagnosis: multiple ring-enhancing lesions on CTB, Toxoplasma Ab

Management: Sulfadiazine + Pyrimethamine (otherwise Bactrim - 2/3rd line)

Question 18

When would you cease Bactrim prophylaxis?

Answer 18

Once the CD4 count is >200 for at least 3 months.

Question 19

When would you give Acyclovir or Fluconazole/Ketoconazole prophylaxis in HIV?

Answer 19

As a secondary prevention (after one episode has already occurred)

Question 20

Differential diagnoses for neningism/focal neurology/seizures in patient with HIV? (5) what is your approach to investigating this?

Answer 20

Infection: Toxoplasma (CD4 200-500), TB (any CD4), Cryptococcus & other usual (e.g. HSV, EBV)

Malignancy: CNS lymphoma

Disease progression: HIV-encephalopathy

Others: Progressive multifocal leukoencephalopathy (PML)

Approach

Bloods: inflammatory markers, CD4/VL, cryptococcal, Toxoplasma serology.

CSF: raised protein, low glucose, HIV viral load (if high consider HIV-encephalopathy) cryptococcal/toxoplasma serology, mycobacterial culture, MCS, cytology, flow-cytometry, PCR for Ig-heavy chain (CNS lymphoma), PCR for JCV (PML).

Also do usual screen: EBV, HSV, VZV.

Imaging: MRI/CTB with contrast: ring-enhanced lesions, SOL.

Neurocognitive assessment.

Question 21

How would you manage disseminated MAC in HIV?

Presentation:

Diagnosis:

Management:

Answer 21

How would you manage disseminated MAC in HIV?

Presentation: insidious fever, diarrhoea

Diagnosis: AFB and Blood culture

Management: anti-mycobacterials: ethambutol, azithromycin, rifabutin.

Question 22

How would you manage Cryptococcal in HIV?

Presentation:

Diagnosis:

Management:

Answer 22

How would you manage Cryptococcal in HIV?

Presentation: headache, fever, meningism

Diagnosis: serum + CSF cryptococcal Ag + CSF culture

Management: Fluconzaole or Amphotericin B

Question 23

Management of Kaposi’s sarcoma in HIV? (3)

Answer 23

1. HAART is the 1st line (1B) - i.e. optimal tx of HIV is essential. For some, this is all they need
2. For limited disease-causing symptoms or cosmetic disfigurement - local chemotherapy (intralesional) or RTx
3. Systemic chemotherapy (e.g. liposomal daunorubicin) is indicated for extensive cutaneous or visceral disease (symptomatic). Also indicated in IRIS (i.e. rapidly progressive KS within weeks after initiation of ART).

Question 24

What is IRIS?

Answer 24

Immune Reconstitution Inflammatory Syndrome, where there is paradoxical worsening of pre-existing infectious process following the initiation of ART.

Question 25

How would you manage IRIS in HIV? (3)

Answer 25

Must measure the balance between the benefit of early ART vs. induction of potentially serious IRIS. Usually starts from 1 week to a few months. Risk is higher if CD4/HIV RNA VL is very low prior to commencing ART. Approach: 1. Treat the OI as early as possible 2. Delay initiating ART for 2 weeks, but in setting of certain OIs (e.g. meningitis), ART may have to be delayed for longer: speak to ID. 3. If already on ART, can generally be continued and commence Anti-microbials ASAP.

Question 26

Would you recommend organ transplant (say, kidney) for this patient with HIV? Could there be an issue?

Answer 26

HIV is **not** a contraindication. Must have a serological control. Overall survival similar to non-HIV patients However but the rejection rate is higher.

Question 27

What is your approach to treatment failure in HIV patient? (4)

Answer 27

1. Confirm **compliance** with family + optimize (check side effects, understanding) 2. Exclude **mal-absorption** (from celiac disease, PPI) 3. Exclude drug **interaction**: is patient taking any OTC, herbal, other medications? 4. Viral **genotype** / **resistance** testing (tells you which drugs you can't use) - however, do not stop the drug even if they are resistant (high-risk of clinical events)

Question 28

What is your approach to HIV and Hep B (a particularly good regime?) or C co-infection?

Answer 28

**Monitor** carefully for cirrhosis and HCC **Non-pharmacological** Mx - e.g. moderation of ETOH consumption Involve **experts** - however, principles are Hep B: use **Tenofovir based regime** (active against both HBV and HIV) → Truvada (Tenofovir + Emtricitabine) is very effective so try and include this drug into the regime. Hep C: use **same DAAs**, they have same outcome as HIV -ves.

Question 29

How would you manage HIV-TB coinfection?

Answer 29

Latent disease (TST \>5mm is positive or Quntiferon) → treat with INH Active disease: specialised area so consult ID but the principles are 1. Start anti-TB ASAP 2. The timing of commencing ART depends on CD4 and other clinical features. Generally aim to commence ART within the first 2 months of anti-TB therapy. However if CD4 count is low (\<50), can consider commencing simultaneousl.y

Question 30

Pregnancy and HIV - approach?

Answer 30

The aim is to minimize vertical transmission whilst achieving/maintaining disease control for the mother (given complication of disease will be detrimental to fetus) In general, the patient **should be on ART** _regardless of CD4 or VL_. Consider pregnancy-safer drugs: TDF, emtricitabine (i.e. **Trvada**) + **Dolutegravir** or Darinavir. Both partners (HIV +Ve and -ve) should have **Post-exposure prophylaxis**. Infant need to be treated for 6 weeks. Vaginal delivery is OK, unless **VL \<1000 copies** (if so for **c-section**) **No breast feeding**

Question 31

Is this HIV patient on contraceptive pill? Any concerns?

Answer 31

Potential drug-drug interaction may make OCP ineffective, can also affect drug concentration. Patients should be educated on drug-drug interaction, provide written advice.

Question 32

Why do you want to do a viral genotype testing for HIV for treatment naive patient?

Answer 32

Because the prevalence of HIV drug resistance is about 6-16%. So must do a pre-treatment viral genotype testing.

Question 33

How does this patient's comorbidities influence your choice of ART? (patient has a significant IHD, CKD, osteoporosis, depression/pSavesychosis, and on methadone program). (3)

Answer 33

Avoid Tenofovir as it is a/w tubulopathy (CKD) → phosphaturia → osteomalacia + osteoporosis. Avoid Efavirenz (worsens HIV-associated dementia + neuropsychiatric) Avoid PIs or Abacavir if Cardiovascular disease (worsens metabolic state) - use INSTIs

Question 34

What is your approach to managing this patient with HIV in the long-run?

Answer 34

**Goal:** suppression of VL, restoration of CD4, treatment adherence, minimise complications. **_C_**onfirm dx: review HIV VL, CD4, genotype testing. _**A**:_ screen & treat \*\*\*depression + neuropsych as these affect adherence that is critical. **_S:_** screen for complications of disease & treatment * **Cardiac**: ECG (ischaemic changes), lipid profile, HbA1C (or OGTT), previous TTE/Angio * **Metabolic**: DEXA, Vitamin D, Calcium. * **Renal**: EUC, ACR, PCR looking for evidence of tubulopathy (tenofovir), hypophosphataemia * **Neuropsych**: previous neuropsychiatric assessment, if not examine for sub-cortical dementia (fine-motor control looking for slowing - e.g. Luria test + heel-toe walk) **_T: non-pharm_** * Educate: risk of non-adherence → treatment failure, CV risk, drug-drug interactions, written information, HIV Australia * Preventing transmission\*\*\*\*\*: barrier contraception, inform partner of HIV+ve status, PEP * Infection prophylaxis: HIV patients has x150 risk of pneumococcal pneumonia * CV risk modification: diet (salt restriction, high fibre, avoid sat-fat, Mediterranean), weight loss, mod-exercise 5/7, smoking cessation\*\*\* - as they thnk they will die of HIV, moderation of ETOH * OP: calcium + vitamin D replacement, denosumab/bisphos if OP * Adherence: continued support, regularly check their understanding, warn side effects, write down side effects * Malignancy screening: age-appropriate + HPV/Anal cancer surveillance **_T: Pharm_** * Manage HTN, dyslipidemia, DM * Infection prophylaxis: Bactrim (CD4\<200), Azithrom (CD4\<50), secondary if previous fungal * Usual regime: 2xNRTIs + INSTI (or PI). Usually 3-drugs, ask why if not on 3. * Close monitoring of OIs and appropriate treatment **_I_**nvolve: family support, counselling, SW (financial support), neuropsychiatric assessment, HIV clinic **_C_**omplications + **_E_**nsure follow-up * 3 monthly CD4/VL monitor + for virologic failure * Depression, ongoing education, insight, social issues * Monitor for cardiovascular, metabolic, renal and neuropsychiatric complications as above.

Question 35

Which groups of non-HIV medications should you most lookout for complications in HIV long-case?

Answer 35

1. **Fluticasone**: severe Cushing's, OP, neuropsychiatric 2. **PPI**: impairs drug absorption\*\*\* common, high-yield problem 3. **Methadone**\*\*\* (some drugs, e.g. Efavirenz increases clearance of Methadone - acute withdrawal symptoms) 4. **Anti-arrhythmic** (Amiodarone, Flecainide)

Question 36

What are the side effects of NRTIs? (3) Examples?

Answer 36

Zidovudine, Didanosine, Lamivudine, Stavudine, Abacavir. BM supporession Pancreatitis Peripheral neuropathy

Question 37

Side effects of NNRTIs? (2)

Answer 37

Efavirenz, Nevirapine Neuropsychiatric\*\*\* Hepatitis

Question 38

Side effects of protease inhibitors? (3)

Answer 38

PIs = -navirs. Lipodystrophy Insulin resistance & diabetes Hepatitis