Human Immunodeficiency Virus (HIV) Pharmacotherapy and Clinical Management

Comprehensive vocabulary flashcards covering the pathophysiology, epidemiology, life cycle, diagnostic timelines, pharmacotherapy classes, drug-drug interactions, and PrEP/PEP clinical guidelines for Human Immunodeficiency Virus (HIV).

HIV Transmission Routes

Transmission occurring when infected body fluids (blood, semen, pre-seminal fluid, rectal fluid, vaginal fluid, breastmilk) contact mucous membranes, open wounds, or bloodstream via sexual intercourse, sharing injection equipment, vertical transmission, or breastfeeding; it is not spread through respiratory droplets, skin-to-skin contact, or contaminated water.

Acute HIV Syndrome

The initial clinical stage presenting typically within 28 days of infection with symptoms including fever, fatigue, myalgia, skin rash, headache, pharyngitis, and cervical adenopathy, though some patients remain entirely asymptomatic.

HIV Diagnostic Window Period

The post-acquisition timeframe required before specific biomarkers reach detectable thresholds: approximately 10 to 12 days for HIV RNA, 16 to 18 days for laboratory antigen-antibody tests, 19 to 21 days for point-of-care (POC) antigen-antibody tests, 22 to 25 days for laboratory antibody tests, 30 to 35 days for POC antibody tests, and over 36 days for Western blot.

Undetectable = Untransmittable (U=U)

The public health concept demonstrating that individuals living with HIV who achieve and durably maintain an undetectable plasma viral load through antiretroviral therapy have effectively no risk of transmitting HIV to sexual partners.

Nucleoside Reverse Transcriptase Inhibitors (NRTIs) MoA

Antiretroviral drug class that blocks the conversion of viral RNA into DNA

Nucleoside Reverse Transcriptase Inhibitors (NRTIs) AEs

Associated with class adverse effects including nausea, diarrhea, headache, elevated liver transaminases (LFTs), and boxed warnings for lactic acidosis and severe hepatomegaly with steatosis.

HLA-B*5701 Screening

Mandatory pharmacogenetic test performed prior to initiating abacavir (ABC) to identify patients at high risk for developing a severe, potentially life-threatening multiorgan hypersensitivity reaction.

Tenofovir Disoproxil Fumarate (TDF)

An NRTI associated with acute renal failure, Fanconi syndrome (proximal renal tubular injury with hyperphosphatemia), and decreased bone mineral density; must be avoided in patients with osteoporosis or severe renal dysfunction ($CrCl < 60\,mL/min$ or stage IV chronic kidney disease).

Tenofovir Alafenamide (TAF)

A targeted tenofovir prodrug with reduced nephrotoxicity and bone mineral density loss compared to TDF, but associated with elevated serum lipid profiles.

Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) MoA

Antiretroviral drug class that allosterically blocks HIV reverse transcriptase

Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) AEs

Class adverse effects include hepatotoxicity and rash, with nevirapine posing the greatest risk for Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).

Rilpivirine (RPV)

An NNRTI that should not be initiated in treatment-naïve patients with a baseline HIV viral load $> 100{,}000\,\text{copies/mL}$ or CD4+ count $< 200\,\text{cells/mm}^3$; requires an acidic stomach environment for absorption (contraindicated with proton pump inhibitors).

Efavirenz (EFV)

An NNRTI characterized by prominent central nervous system adverse effects—such as dizziness, impaired concentration, and vivid or abnormal dreams—and psychiatric disturbances (depression, suicidality) that typically improve after 2 to 4 weeks.

Protease Inhibitors (PIs) MoA

Antiretroviral class that prevents viral polyprotein cleavage to block immature virions from becoming infectious

Protease Inhibitors (PIs) AEs

Class effects include metabolic abnormalities (hyperglycemia, insulin resistance, dyslipidemia, lipodystrophy) and potent CYP3A4 substrate and inhibitory activity.

Atazanavir (ATV)

A protease inhibitor that inhibits UGT1A1, commonly causing indirect benign hyperbilirubinemia with jaundice ("bananavir"), and requires an acidic gastric environment for oral absorption.

Protease Inhibitor-Statin Drug Interaction

Marked CYP3A4-mediated interaction making simvastatin and lovastatin contraindicated with protease inhibitors due to severe rhabdomyolysis risk; atorvastatin and rosuvastatin are preferred alternatives.

Integrase Strand Transfer Inhibitors (INSTIs)

Antiretroviral drug class (e.g., bictegravir, dolutegravir, raltegravir) that inhibits integration of proviral DNA into host chromosomes

Integrase Strand Transfer Inhibitors (INSTIs) DDI considerations

Absorption is significantly impaired when co-administered with polyvalent metal cations (aluminum, calcium, magnesium, iron).

Dolutegravir-Metformin Drug Interaction

A clinically significant transporter-mediated interaction in which dolutegravir increases metformin plasma concentrations by up to $200\%$, increasing the risk of metformin adverse effects and lactic acidosis.

Maraviroc (Selzentry)

A chemokine receptor antagonist that binds to CCR5; strictly requires a baseline coreceptor tropism assay because it is completely ineffective against CXCR4-tropic or dual/mixed-tropic virus strains.

Enfuvirtide (Fuzeon)

A subcutaneously injected peptide fusion inhibitor that binds to viral gp41 to block host cell membrane entry; frequently causes injection site reactions (erythema, nodules, cysts) and is linked to an increased risk of bacterial pneumonia.

Lenacapavir

A first-in-class multistage HIV capsid inhibitor formulated as an oral lead-in with long-acting subcutaneous injections for heavily treatment-experienced infection (Sunlenca), co-formulated with bictegravir (Bixlenvo), and approved for PrEP (Yeztugo).

Islatravir

A nucleoside reverse transcriptase translocation inhibitor (NRTTI) co-formulated with doravirine as Idvysno for virologically suppressed adults without a history of failure; its viral susceptibility is diminished by the M184V/I mutation.

First-Line Antiretroviral Regimens

Standard initial treatment regimens for treatment-naïve patients comprising Biktarvy (bictegravir/TAF/emtricitabine), dolutegravir + (TDF or TAF) + (lamivudine or emtricitabine), or Dovato (dolutegravir/lamivudine, provided there is no HBV coinfection and baseline resistance testing is completed).

Virologic Failure

The inability to achieve or maintain viral suppression below an HIV RNA threshold of $< 200\,\text{copies/mL}$ while receiving antiretroviral therapy, requiring resistance evaluation without adding a single drug to a failing regimen.

M184V Mutation

A common reverse transcriptase mutation causing high-level resistance to lamivudine (3TC) and emtricitabine (FTC) and low-to-intermediate resistance to abacavir, while concurrently increasing viral susceptibility to zidovudine (AZT) and tenofovir (TDF).

Oral Pre-Exposure Prophylaxis (PrEP)

Daily preventive oral therapy indicated for at-risk individuals $\to$ Truvada (TDF/FTC) for individuals $\ge 35\,\text{kg}$ with $CrCl \ge 60\,mL/min$, or Descovy (TAF/FTC) for cisgender men and transgender women $\ge 35\,\text{kg}$ with $CrCl \ge 30\,mL/min$.

Injectable Pre-Exposure Prophylaxis (PrEP)

Long-acting parenteral PrEP formulations approved for individuals $\ge 35\,\text{kg}$, consisting of intramuscular cabotegravir (Apretude) given every 2 months or subcutaneous lenacapavir (Yeztugo) administered every 6 months.

PrEP Baseline Eligibility Criteria

Required pre-prescription screening factors consisting of a documented negative HIV test result within 1 week of initiation, absence of acute viral symptoms, confirmed hepatitis B status, and adequate renal function.

Post-Exposure Prophylaxis (PEP / nPEP)

An emergency 28-day antiretroviral regimen (typically Biktarvy or dolutegravir plus TDF/TAF and FTC/3TC) initiated as soon as possible and strictly within 72 hours following potential occupational or non-occupational HIV exposure.

NRTI Drugs

Abacavir (ABC), Emtricatabine (FTC), Lamivudine (3TC), Tenofovir disoprroxil fulmarate (TDF), Tenofovir alafenamide (TAF), Zidovudine (ZDV)

NRTI MoA

Block Conversion of HIV RNA to HIV DNA

NNRTI MoA

Block Conversion of HIV RNA to HIV DNA

NRTTI MoA

Block Conversion of HIV RNA to HIV DNA

PIs MoA

Block new/immature HIV from becoming mature

INSTI MoA

Block insertion of HIV DNA into host CD4 cell DNA

What is not an MoA of HIV Entry Inhibitors?

Interfere with structure and function of HIV Capsid

Capsid Inhibitor MoA

Interfere with structure and function of HIV Capsid

DOR - Name - Class

Doravirine - NNRTI

DRV - Name - Class

Darunavir - PI

DTG - Name - Class

Dolutegravir - INSTI

EFV - Name - Class

Efavirenz - NNRTI

ETR - Name - Class

Etravirine - NNRTI

3TC - Name - Class

Lamivudine - NRTI

EVG - Name - Class

Elvitegravir - INSTI

NVP - Name - Class

Nevirapine - NNRTI

LPV - Name - Class

Lopinavir - PI

ABC - Name - Class

Abacavir - NRTI

ZDV - Name - Class

Zidovudine - NRTI

RPV - Name - Class

Rilpivirine - NNRTI

RTV - Name - Class

Ritonavir - PI

RAL - Name - Class

Raltegravir - INSTI

NRTTI class medication - Name

Islatravir

TDF - Name - Class

Tenofovir disoproxil fulmarate - NTRI

TAF - Name - Class

Tenofovir alafenamide - NTRI

TPV - Name - Class

Tipranavir - PI

Do not use with Strong CYP3A4 inhibitors

(DOR) Doravirine - NNRTIs

CYP2B6 substrate, moderate CYP3A4 inducer, hyperlipidemia, and psych symptom warnings

(EFV) Efavirenz - NNRTI

moderate CYP3A4 inducer only

(ETR) Etravirine - NNRTI

Do not use with PPIs and HIV viral load must be below 100,000 and CD4 count must be less than 200

(RPV) Rilpivirine - NNRTI

Which NNRTI has the highest risk of SJS and TEN

Nevirapine (NVP)

What is the alternative name of Atazanavir?

Bananavir

(ABC) Abacovir requires what testing prior to giving and why?

HLA-B*5701 due to hypersensitivity rxns

(ABC) Acacovir has what increased risk?

Myocardial infarction (MI)

(TDF) Tenofovir disoproxil fulmarate has what notable concerns?

CKD (CrCL<60) and Osteoporosis

(ATV) should not be given with what lab result?

Hyperbilirubinemia

PIs have DDIs with Statins except these two

Rosuvastatin and Atorvastatin

(RTV) Ritonavir is unique amond the PIs for what reason?

Only used for PK boosting

Which INSTI has no risk for depression and suicidal ideations?

(BIC) Bictegravir

Which two INSTIs can be taken with oral Calcium or Iron if taken with food?

(BIC) Bictegravir and (DTG) Dolutegravir

What INSTI must be avoided with all Cations?

(RAL) Raltegravir

What INSTI has a Hyperlipidemia warning?

(EVG) Elvitegravir

Before a patient can take Selzentry what must occur for testing?

Tropism assay results before beginning therapy

What is ART?

Antiretroviral Therapy

What HIV medication is safe during pregnancy?

Biktarvy or if already on effective therapy no change is nessecary

First line HIV tablets

Biktarvy and Dovato

Complete injectable regimens

Cabenuva

Patients with poor adherence to HIV meds should be given which classes?

Boosted PIs, BIC, or DTG

ART is made up of what combination of drug classes?

2 NRTIs + either an INSTI, PI, or NNRTI

Who is eligible for PrEP?

Anyone whom asks

How long do patients have to recieve PEP?

72 hours

What options are there for Oral PrEP?

Truvada and Descovy

What options are there for Injectable PrEP?

Cabotegravir (Apretude) and Lenacapavir (Yeztugo)

Which of the following is wrongly matched in CrCl requirements?

Lenacapavir CrCL>30mL/min

Patients eligibility for PrEP relies on what 4 results?

• Negative HIV Ag/Ab test result within 1 week of PrEP initiation

• No HIV Acute Signs of infection

• HBV screening

• Renal Function

After a patient starts HIV therapy what monitoring should occur immediately afterwards?

Follow-up to check viral load in 4-8 weeks