ID Lectures 56, 58-59: HIV | Quizlet

Where did HIV originate?

cross species transmission from chimps in Central Africa

Where is HIV-1 commonly found?

in the US and around the world

Where is HIV-2 commonly found?

West Africa

HIV prevalence

Number of diagnosed and undiagnosed persons living with HIV

HIV Prevalence Rate

Number of persons living with HIV per 100,000 population

HIV Incidence

number of new HIV infections in a fixed time period

HIV incidence rate

number of new HIV infectios in a fixed time period per 100,000 population

The prevalence of HIV is higher in what populations?

Men who have sex with men

Transgender women

African Americans

Hispanics

Latinx populations

Does HIV effect everyone equally?

NO

Who is most at risk for contracting HIV?

MSM

Transgender women

IVDU

Describe the HIV life cycle.

1) Viral Entry via attachment to CD4 cell receptors and co receptors on the host cell

2) Reverse transcription

3) Integration into the host cell's DNA

4) Transcription Viral DNA to RNA

5) Translation (Replication)

6) Cleavage - long proteins are broken down into core proteins

7) Assembly - HIV RNA and viral proteins migrate to the host cell membrane

8) Budding and maturation - immature HIV virus buds from the host cell to go infect more host cells

What poses the highest risk of HIV transmission?

Blood

Semen

Vaginal fluids

Breast milk

Vaginal fluids

Sexual contact

Sharing dirty needles

What poses a lower risk of HIV transmission?

Vertical transmission

Needle sticks (HCW)

Does every exposure cause HIV transmission?

No!

What HIV virus is considered to be capable of causing infection?

Founder virus

What happens to CD4 T cell counts during the early stage of HIV infection when left untreated?

Decreases until week 6 where it increases for a number weeks until it gradually decreases again

What are the CDC HIV screening recommendations?

routine annual screening for everyone aged 13-64

Every pregnancy

What are the USPSTF HIV screening recommendations?

All adults aged 15-65 years old

Repeated screening for those known to be at risk

Every pregnancy

What are the FIRST three things to be detected in HIV following exposure?

1. HIV RNA (~10 days)

2. p24Ag (~15 days)

3. EIA (~21 days)

What should be done if a patient comes to you after they screen themselves for HIV?

HIV Antigen/Antibody Immunoassay

What should the next step be for a patient with a negative result on their HIV Antigen/Antibody Immunoassay?

Nothing, the negative test rules out the possibility of them having HIV

What should the next step be for a patient with a positive result on their HIV Antigen/Antibody Immunoassay?

Do a HIV Antibody Differentiation Immunoassay

What should be the next step for a patient with a result of HIV-1 negative and HIV-2 negative differentiation immunoassay?

Perform HIV-1 NAT test which rules HIV-1 in or out

When is "Acute HIV"?

days 10-24 following infection

What components of health history are important to gather to determine if a person is at risk of HIV?

Diagnosis date

Vaccinations

Opportunistic infections

Blood work

Drug history

Sexual history

What laboratory values are critical to evaluate in people living with HIV?

CD4 Count

Viral load

Genotype

What is the purpose of genotype testing in HIV?

determines drug resistant mutations present in viral genes

What are the different stages of HIV?

Acute infection

Asymptomatic

Symptomatic

Advanced immunosuppression

What are the different stages of HIV infection?

Exposure event

Prime infection

Initial propagation

Local expansion

Regional lymphatic spread

Hematogenous spread

CD4 Count

predictor of disease progression and survival

What is the true marker of HIV drug action?

Viral load testing

Viral load testing

amount of virus in the blood

*goal is to be undetectable!*

At what CD4 level are patients at risk for developing opportunistic infections?

>500 = normal

201-499 = may have sx

<200 = advanced immunosuppression

Why do we want to have patients achieve therapeutic HIV drug levels?

Mutations occur when there is some drug in the blood because the virus is not fully suppressed

What is the main goals of HIV treatment?

Maximally and durably suppress plasma HIV RNA levels

Restore and preserve immunologic function

Reduce HIV associated morbidity and prolong the duration and quality of survival

Prevent transmission

When should antiretroviral therapy (ART) be started?

on the day of HIV diagnosis regardless of CD4 counts

What are some reasons for a more rapid initiation of ART in patients?

Acute HIV

HCV/HBV

CVD/HIVAN

Pregnancy

Opportunistic infections

Lower CD4 counts or rapidly declining

Higher viral loads

What are some reasons to delay ART initiation if patients with HIV?

Psyche

Adherence

What is the backbone and anchor drugs of ART therapy?

2 nucleoside reverse transcriptase inhibitors

PLUS one of the below:

Integrase inhibitor

OR

An NNRTI

OR

Protease inhibitor with a PK booster

What is the recommended therapy for HIV treatment naive patients?

Dovato (Dolutegravir-Lamivudine)

Tivicay AND Truvada OR Descovy

Biktarvy (bictegravir-TAF-Emtricitabine)

What two steps of the HIV life cycle do we target?

Reverse transcription

Integration

Dual NRTIs

Descovy (tenofovir AF + emtricitabine)

Truvada (tenofovir DF + emtricitabine)

NNRTIs

Edurant (Rilpivirine)

Pifeltro (Doravirine)

Integrase inhibitors

Isentress (Raltegravir)

Tivicay (Dolutegravir)

Biktarvy

bictegravir/emtricitabine/TAF

Dual NRTI and Integrase inhibitor

Protease inhibitors

Prezista (Darunavir)

Reyataz (Atazanavir)

When should viral load be monitored after starting therapy?

At baseline

2-8 weeks after initiating tx

then every 4-8 weeks until load is suppressed

Then every 3-4 months for at least 2 years

After 2 years, every 6 months

When do we want HIV viral loads to be undetectable after starting treatment?

after about 3 months

When should CD4 count be monitored after starting therapy?

At baseline

At 3 months

Then every 3-6 months for 2 years

After 2 years it depends on CD4 count

Besides CD4 count and viral load, what other labratory tests are routinely monitored?

CBC and CMP

Which class of HIV treatment should patients avoid taking with polyvalent cations?

Integrase inhibitors

- separate by 2-6 hours

Which ART agents need an acidic environment for absorption?

Atazanavir

Rilpivirine

What needs to be avoided in patients taking Atazanavir or Rilpivirine?

PPIs

Which ART therapies can be taken with food?

Atazanavir

Darunavir

Etravirine

Rilpivirine (calorie requirement)

Elvitegravir

Which ART agent has a calorie requirement? What is it?

Rilpivirine - at least 300 calories

Which ART agent can be taken without food?

Efavirenz

Cabenuva

Cabotegravir + Rilpivirine injection

Which ART agents have significant CYP450 interactions?

Protease inhibitors

Which ART agents have to be given with a PK booster (Ritonavir or Cobicistat)?

Protease inhibitors

Capsid inhibitor

Lenacapavir (PO or SQ)

When is Lenacapavir used?

treatment of HIV-1 in combo with other drugs in heavily treatment-experienced adults with multidrug resistant HIV

aka last resort

NOT FDA approved - HIV prevention

What are the contraindications of Lenacapavir?

CYP3A inducers

Most ART agents act ________________.

intracellularly

What is the difference between TDF and TAF?

TDF is a prodrug that has to be converted into TFV

TAF requires no conversion and has less ADRs

All Protease inhibitors are CYP3A4 _______________.

substrates

What is the purpose of giving Ritonavir or Cobicistat with Protease inhibitors?

Better dosing profile

Less pill burden

Better serum concentrations

When should boosing be added to antiretroviral therapy?

WITH EVERY PROTEASE INHIBITOR REGIMEN

Common interactions with ART

Statins

Estrogen OCs

Corticosteroids

CNS agents

Methadone

Anticoagulatns/platelets

Anti-infectives

ED medications

Acid suppressing medications

What ART agents should be adjusted at a CrCl less than 50 mL/min?

Tenofovir DF

Lamivudine

Emtricitabine

Lovastatin and Simvastatin are contraindicated with what ART agents?

ATV/RTV

ATV/COBI

DRV/RTV

DRV/COBI

EVG/COBI/TDF/FTC

Which statins are SAFE to use with ART?

Pitavastatin

Atorvastatin (with RPV)

Which ART agent has the strongest association with bone diseases?

Tenofovir DF

What is a long term side effect of ART?

Weight gain

PrEP

pre-exposure prophylaxis that when taken long enough can block replication after HIV exposure

What are the approved PrEP medications?

Truvada

Descovy

Who should recieve PrEP?

MSM

Heterosexual men and women at risk

IVDU

Transgender persons

How long after taking PrEP, would someone be protected?

Rectal tissue - 7 days

Vaginal tissue and blood - 20 days

On demand PrEP (2-1-1)

2 tabs of Truvada 2-24 hours before sex, then followed by 1 dose 24 and 48 hours after

Post Exposure Prophylaxis in Pocket (PIP)

patients are provided with a 1 month supply of 3 drugs (typical ART treatment) so they can start whenever they are exposed