Risk factor for poor adherence - behavioral (denial, nondisclosure of HIV status, fear of stigma),
- psychosocial (mental illness or low levels of social support), and
- structural (poverty, homelessness, inconsistent access to medications) barriers;
- low health literacy;
- active substance use; and
- age (young adults have increased difficulty with adherence)
Opportunistic Infection Prophylaxis - PCP < 200, but more points are there
- Toxoplasmosis: Pyrimethamine if < 100, but bacterium has activity against Toxo . Leucovirin is given alongside to decrease the risk of cytopenia, side effect of Toxolasmosis
- MAC < 50
- CMV : Treat if symptomatic, ART otherwise
- Cryptosporodiosis: Treat if symptomatic, ART otherwise
HIV Pre-exposure prophylaxis - Emtricitabine + Tenofovir (Truvada) (Two drug regimen is approved)
HIV post-exposure prophylaxis
HIV Treatment Scenario:
- Treatment (Go to Page IV to access table)
- Page 9,10 of ART Guidelines
- Antiretroviral Regimen Considerations as Initial Therapy based on Specific Clinical Scenarios Table 7 (Page 11,12,13) ART Guidelines
- Pre-ART Characteristics
- CD4 count <200 cells/mm3
- HIV RNA >100,000 copies/mL
- HLA-B*5701 positive
- Do not use Abacavir based regimen
- Must treat before HIV drug resistance results available
- ART Specific Characteristics
- One pill once daily regimen desired
- Food effects
- Presence of Other Conditions or Side effects
- Chronic kidney disease (defined as eGFR<60 mL/min)
- Osteoporosis
- Usually seen with tenofovir disoproxil fumarate a component of Truvada. However, TAF (tenofovir alafenamide fumarate) is can be used with close monitoring. Abacavir can be used. NRTI sparing regimen are better but if needed can use 3TC (lamivudine) or FTC (emtricitabine)
- Example:
Triumeq (abacavir sulfate / dolutegravir sodium / lamivudine, ABC / DTG / 3TC) Combivir (Ziduvidine + Lamivduine) + Kaletra (Lopinavir/ritonavir)
- Psychiatric illnesses
- As a side effect: Mostly with NNRTI (EFV, RPV). Can switch to INSTI based regimen however, INSTI causes insomnia, and depression and suicidability has been infrequently reported to increase in patient with primary psychiatric illness
- HIV-associated dementia (HAD)
- Narcotic replacement therapy required
- High cardiac risk
- Benefits of HIV treatment is more on CV disease due to decreased inflammation than the metabolic complications of HIV treatment
- Insulin resistance is seen with PI based of regimen. INSTI or RPV can be used.
- Hyperlipidemia
- Mostly seen with COBI or RTV boosted regimen, also seen in EFV. INSTI based regimen can be used. RPV can also be used (NNRTI based)
- Because of the interaction with Ritonavir, Atorvastatin should be started at lower dose
- Pregnancy
- Based on recent published data and recommendations, the treatment regimen of zidovudine, lamivudine, and lopinavir-ritonavir is no longer the most effective/best therapy for pregnant women newly diagnosed with HIV. Recommendations now indicate a dual nucleoside reverse transcriptase inhibitor (NRTI) combination (abacavir-lamivudine, tenofovir disoproxil fumarate (tenofovir)-emtricitabine or lamivudine, or zidovudine-lamivudine) in combination with either a ritonavir-boosted protease inhibitor (atazanavir/ritonavir or darunavir/ritonavir), a non-NRTI (efavirenz initiated after 8 weeks of pregnancy) or an integrate inhibitor (raltegravir).
- Ref: MKSAP
- Cytopenia: Avoid Ziduvine
- GI side effects (N, Diarrhea)
- Mostly with PI based regimen and is due to Ritonavir. Often can decrease with time if patient can tolerate.
- Hypersensitivity reaction
- Abacavir and INSTI based regimen
- Presence of Co- Infections
- HBV infection
- Primarily based on Truvada (both emtricitabine and tenofovir has activity against hepatitis B)
- eg. Genvoya
- HCV treatment required
- TB infection
- New vs Old (with TDF vs TAF)
- COSG
- Complera - Odefsey
- Stribild - Genvoya
- Truvada - Descovey
- Treatment Naive Patient: Table 6 (Page 9 of ART Guidelines)
- Advantage or Disadvantage of Therapy on Initiation: Table 7, Pg 10, 11, 12 of ART Guidelines
- Regimens not to use on Initiation: Table 8 (Page 13,14 of ART Guidelines
- Regimens not to be used at any time: Table 9 (Page 15, 16 of ART Guidelines
- HIV + HCV Patient: Table 12 (Page 18, 19, 20 of ART Guidelines
Preferred Regimen include: INSTI Based: Triumeq (abacavir sulfate / dolutegravir sodium / lamivudine, ABC / DTG / 3TC) Truvada + Tivicay (dolutegravir sodium, DTG) Genvoya (elvitegravir / cobicistat / emtricitabine / tenofovir alafenamide, EVG / COBI / FTC / TAF) Truvada + Isentress ( Raltegravir potassium,RAL )
Boosted PI: Truvada + Prezista + Norvir (Darunavir ethanolate/Ritonavir, DRV/r)
Alternate Regimen: NNRTI Based: - Atripla (efavirenz / emtricitabine / tenofovir, efavirenz / emtricitabine / tenofovir DF, EFV / FTC / TDF)
- RPV requires acidic pH for absorption. Use of PPI is contraindicated.
- Side effects and Cost and Drug Interaction: (Go to Page IV and V to access table)
- Common and/or Severe Side Effects: Table 14 , Page 24-30 of ART Guidelines
- Contraindications and Drug Interaction: Table 17, 18, 19 , Page 38-75 of ART Guidelines
3 Main HIV Regimen Includes the following
Truvada (Two NRTI): Emtricitabine / Tenofovir
NNRTI-based: Atripla: Truvada + Sustiva (Efavirenz);Complera: Truvada + Rilpivirine (Edurant)
Boosted PI-Based: Truvada + atazanavir/ritonavir (Riyataz) or Truvada + (darunavir/ritonavir)(Prezista) Combivir (Ziduvidine + Lamivduine) + Kaletra (Lopinavir/ritonavir) INSTI-Based (Integrase Strand Transfer Inhibitor): Truvada + dolutegravir (Tivicay) or Truvada + raltegravir (Isentress) or Truvada + elvitegravir, cobicistat
http://www.cshp-bc.com/events/2016/clinicalsymposium/Lepik_HIV%202016_final-handout-2-pg.pdf
Additional reading
Following group of patients have additional treatment options
HLA-B*5701 negative (in no nephrotoxity regimen)
pre-ART CrCl >70 mL/min
pre-ART plasma HIV RNA <100,000 copies/mL
CD4 count >200 cells/mm3
Coreceptor tropism assay : If CCR5 entry inhibitor are used
Special Circumstances
Efavirenz: Not to be used during first trimester, in women trying to conceive, or who are not
using effective contraception
Pregnancy: Preferred Regimen: (Lopinavier/ritonavir; twice daily) + (Ziduvadine / Lamivudine)
ATV/r: Not indicated if using >20 mg / day omeprazole equivalent
Abacavir (NRTI): Should not be used if HLA-B 5701 positive, use with caution in high risk CV disease,
pretreatment HIV RNA >100,000 copies / ml
Case
BJ 63 yo is seen for HIV. PMHx: ESRD on HD, A Fib, HFrEF (25% EF), Hep C
What HIV regimen to start?
TD 55 yo M with AIDS is seen for headache. CD4 count is LP is done. CSF and other study are as follow
Case Study 1 LW 57 yo AAF is seen for HIV follow up. Patient has been on HIV medication for 5 years. Her HIV regimen includes the following.
- Emtricitabine 200 mg Oral (NRTI) every 3 days
- Tenofovir (VIREAD) 300 mg tablet BID (NRTI)
- Raltegraivir (ISENTRESS) 400 mg tablet BID (INSTI)
What kind of HIV regimen is patient on? INSTI Based regimen. Patient is on INSTI + 2 NRTI
What is Truvada? Emtricitabine + Tenofovir is Truvada
Patient CD4 count over the time is as below
Now the CD4 count is 63, what is the next course of action? - Prophylaxis for infection
- Bactrim for PCP prevention
- Azithromycin is not yet indicated as CD4 count is > 50 (For MAI, and Toxoplasmosis)
- Work up for Treatment Failure
- HIV PCR for viral load
- Genotype Drug testings
- Tropism Testing if considering CCR5 antagonist
- HLA- B*5701 Testing if considering AB
- Search for adverse events of treatment
- Emtricitabine:
- Tenofovir:
- Raltegraivir
- Since, there is likely going to be treatment modification
- Hepatitis B Serology
- CMP
- CBC with Diff
- A1C
- Fasting Lipid
- Pregnancy Test for women
Which drug testing to order and for what purpose?
Now that we have the results of viral testing, appropriate medication is started. What is the next course of action? - Viral load monitoring 2-4 weeks after, then every 4-8 weeks until viral load is suppressed
What if viral suppression not possible? - Repeat Viral load every 3 months
Case 2
56 y-o M with ESRD, AIDS (CD4 70), HTN is seen in the clinic for HIV. Genotyping assay shows patient is sensitive to all medications. HIV PCR is 49,000. Patient also has HCV, with log of 4.5. What is the best HIV regimen for this patient? - 1. Atripla or (Truvada + Sustiva)
- 2. Truvada + Tivicay
- 3. Truvada + Riyataz
- 4. Truvada + Prezista (Prezista not used due to CD 4 < 200)
- 5. Combivir + Kaletra
- 6. Complera (Truvada + Edurant). Edurant is not used due to CD4 < 200
Patient was started on Truvada + Tivicay Following should not be used due to CD 4 < 200 due to risk of treatment failure - RPV-based regimens (Rilpivirine or Edurant - NNRTI)
- DRV/r (Prezista) plus RAL
Case 3
26 yo AAM with 1 mth history of worsening of mental status. HIV of ??? duration. MRI is normal. LP is normal. CD 4 count is 7. Viral load is very high.
DDx. in this patient includes the following
Delirium - EEG shows diffuse slowing. Normal EEG does not rule out delirium
- Can cause psychotic symptoms
- Fluctuating mental status is the key
- Substance abuse
HIV-associated Dementia - HIV Dementia Scale (with scores of 10 or less indicat- ing HIV-associated dementia)
- The typical presentation is a progressive dementia with subcortical features (apathy, inattention, and loss of retentive memory) and abnormalities of motor function, such as psychomotor slowing
- AIDS Mania: When psychosis (prominent agitation, irritability, and delusions) occurs in patient with HIV-associated dementia
- The extent of the cognitive impairment will require reexamination with a full battery of neuropsychological tests after his acute illness has resolved
Primary Psychiatry Disorder- A first episode of schizophrenia is unlikely, since the onset of schizophrenia is typically not sudden but instead involves a prodromal period of several years, with gradual loss of function and social competence
- Reactive Psychosis: the very sudden onset of psychosis during the course of a day or so has been called “reactive psychosis,” in response to stressors
Infection and Malignancy in HIV host - Toxo: Not seen in MRI
- Cryptococcal: LP CSF cell count can be normal, but CSF antigen was negative
- CMV: CMV in blood and CSF PCR was negative. Yet, cannot rule out when CD4 is that low. Retinal exam will be useful as well.
- M Tb: Less likely based on MRI and CSF but cannot be ruled out.
- PMLE: MRI rules out
- Lymphoma : MRI rules out
Metabolic - B12 deficiency
- Thiamine Deficiency
Treatment - Olanzapine, an antipsychotic agent. proven efficacy and relatively low risk of causing extrapyramidal symptoms and tar dive dyskinesia, which are highly prevalent among patients with HIV.
- HIV-associated damage to the dopaminergic basal ganglia system and increased plasma levels of antipsychotic agents because of interactions with antiret- roviral drugs puts hiv patient at risk of extrapyramidal symptoms
- Dysfunction of the basal ganglia also heightens the risk for neuroleptic malignant syndrome in hiv, which has been well documented to occur in patients with HIV
- Refernces:
Case 4 DB 57 yo F with CD, DM - 2, Genital Herpes and HIV is being followed in the HIV clinic. She is on the following medication regimen.
Patient has been previously on following medication regimen. In the parenthesis is the time when medications were discontinued. - efavirenz-emtrictabine-tenofovir (ATRIPLA) 600-200-300 mg per tablet oral nightly (DC 2 / 2014) NNRTI-based
Patient had already build up resistance to efavirenz. Hence, Atripla was discontinued. - emtricitabine-tenofovir (TRUVADA) 200-300 mg per tablet daily (DC 5/2014) Truvada (Two NRTI)
patient had developed resistance to tenofovir, hence, Truvada was discontinued as well.
Lab as of 12/2015 Following medications were discontinued due to resistance to ziduvidien. - lamiVUDine-zidovudine (COMBIVIR) 150-300 mg per tablet BID (DC 12/2015) NRTI : Combivir (Ziduvidine + Lamivduine)
- raltegravir (ISENTRESS) 400 mg tablet BID (DC 12/2015)
- INSTI-Based (Integrase Strand Transfer Inhibitor):raltegravir (Isentress)
- ritonavir (NORVIR) 100 mg capsule BID (DC 12/2015) Boosted PI-Based
Lab as of 2/2016 is as follow
Patient lab as of 4 / 2016 are as follow
Patient lab results as of 8/2016 is as follow
darunavir-cobicistat (PREZCOBIX) 800-150 mg-mg Tablet oral daily (12/2016 medication) - CYP3A4 inhibitor cobicistat (brand name Tybost) - acts as a “boosting” agent, raising the drug levels of other ARVs.
- PI darunavir
HIV-Rx
Case Based Learning
56 y-o M with ESRD, AIDS (CD4 70), HTN is seen in the clinic for HIV. Genotyping assay shows patient is sensitive to all medications. HIV PCR is 49,000. Patient also has HCV, with log of 4.5. What is the best HIV regimen for this patient? - 1. Atripla or (Truvada + Sustiva)
- 2. Truvada + Tivicay
- 3. Truvada + Riyataz
- 4. Truvada + Prezista (Prezista not used due to CD 4 < 200)
- 5. Combivir + Kaletra
- 6. Complera (Truvada + Edurant). Edurant is not used due to CD4 < 200
Patient was started on Truvada + Tivicay Following should not be used due to CD 4 < 200 due to risk of treatment failure - RPV-based regimens (Rilpivirine or Edurant - NNRTI)
- DRV/r (Prezista) plus RAL
Case Based Learning 65 yo M with new HIV diagnosis, CD4 15, Viral Load of 200000, and PCP. Asymptomatic CMV infection.
HIV medication was to be started. Genotype shows no viral resistance.
What medication options are available.
Triumeq (abacavir sulfate / dolutegravir sodium / lamivudine, ABC / DTG / 3TC) Genvoya (elvitegravir / cobicistat / emtricitabine / tenofovir alafenamide, EVG / COBI / FTC / TAF) Atripla (efavirenz / emtricitabine / tenofovir, efavirenz / emtricitabine / tenofovir DF, EFV / FTC / TDF)
Ideal will be to start patient on either Boosted PI regimen or INSTI based regimen
Note, both INSTI or PI based regimen has another drug added to Truvada (Emtricitabine and Tenofavir) except for one INSTI regimen which is
DTG/ABC/3TC (DTG = dolutegravir;ABC = abacavir; 3TC = lamivudine) if HLB*5701 is negative Triumeq
This particular patient was started on
Case Based Learning 32 yo M is seen for HIV with PCP. CD 4 is 46. Viral load and HIV resistance study and HLV B 5701 tests are pending. Which medication to start?
4 most important point in consideration of treatment include
Ideal to treat with Truvada + either PI or INSTI based regimen that starts with D DRV/r or DTG . However, most important thing is to avoid NNRTI based regimen
Why ? See table above in highlights.
This particular patient was started on
GENVOYA (elvitegravir, cobicistat, emtricitabine, tenofovir alafenamide)
This is also one of the preferred regimen
BM 58 yo M is seen for HIV. Also, has Hep B. How should the patient be treated?
How should the next step? Genetic testing ? HBV DNA level
Also check for Hep C.
Hep C is positive. However, viral count is not detectable.
Case study: 40 yo F is seen for AIDS. CD4 count is 30. Viral load is 400000. Any of the following medication can be started? - Darunavir, Ritonavir, Lamivudine, Abacavir
- Do not use ABC/3TC (;ABC = abacavir; 3TC = lamivudine) with EFV or ATV/r (Atazanavir/Ritonavir) if viral load is > 100000
- Do not use ABC if HLB*5701 is positive
- Atazanavir/Ritonavir
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