HIV Flashcards
What is HIV?
HIV is a single-stranded RNA retrovirus that uses the machinery in host CD4 T-helper cells (T cells) to replicate. The viral copies burst through the CD4 cell membrane, destroying the cell in the process
What happens when HIV continues to replicate?
When HIV continues to replicate, the viral load increases and the CD4 count decreases
When is AIDS diagnosed?
AIDS is diagnosed when the CD4 count falls below 200 cells/mm3 or the patient develops an AIDS-defining condition
What happens when a patient has AIDS?
The immune system is very weak and can no longer ward off opportunistic infections and specific malignancies that are indicative of AIDS
How is HIV treated and what is an important counseling point given to patients about the therapy?
Antiretroviral therapy is used to treat HIV. The ART regimens currently available allow people with HIV to live long and healthy lives if adherent to treatment
How is HIV transmitted?
Infection is spread by direct contact with blood, semen, vaginal secretions, rectal secretions and breast milk. Most infections are caused by unprotected vaginal and rectal sex, and sharing injection drug equipment, including needles. Infection can spread from a woman with HIV to her child during pregnancy, childbirth of breastfeeding (mother-to-child or vertical transmission)
What does the CDC recommend with regards to HIV screening?
The CDC recommends HIV routine screening at least once for all patients who are 13-64 years old. If a person is high-risk for infection, testing should be done at least annually
What are high risk indicators for becoming infected with HIV?
- Sharing drug-injection equipment: needles, syringes and cookers (used to mix up or “cook drugs”)
- High-risk sexual behaviors: men who have sex with men, multiple sexual partners, sex with a person known to be infected or a history of sexually transmitted infections
- History of hepatitis or tuberculosis (TB) infection
How does acute HIV infection present?
Acute HIV infections presents with non-specific flu-like symptoms that can last a few days to several weeks, including fever, myalgias, headache, lymphadenopathy, pharyngitis and rash
What happens after an acute HIV infection presents?
An antibody response can take weeks or months to develop and, in most cases, is not fully able to fend off the virus. Patients become asymptomatic after this initial phase, but the virus is still replicating and capable of being transmitted. Over time, the CD4 count decreases, but it can take several years for an untreated patient to develop AIDS
What happens ~2 weeks post-infection?
The viral load is high enough for HIV RNA and HIV p24 antigens to be detected with an initial HIV-1/HIV-2 antigen/antibody screening test
What does a positive result of theHIV-1/HIV-2 antigen/antibody screening test indicate?
Positive results should be confirmed with an antibody differentiation immunoassay which differentiates HIV-1 from HIV-2 antibodies. Antibodies can be detected in most people about 4-12 weeks after contracting the disease, but it can take up to 6 months for some and repeat testing may be needed
What is an example of over-the-counter HIV testing?
The OraQuick In-Home HIV Test detects the presence of HIV antibodies and provides immediate results. Individuals with a positive OraQuick result must follow up with a confirmatory laboratory test
How do you use the OraQuick test?
The upper and lower gums are swabbed with a test stick, which is then inserted into a test tuber containing liquid. After 20 minutes, the test stick can be read. The tests should be used > 3 months from exposure due to the lag in antibody production; testing sooner can cause a false negative result
What are different HIV replication stages?
1) Binding/attachment
2) fusion
3) Reverse Transcription
4) Integration
5) Replication
6) Assembly
7) Budding and Maturation
What happens in the binding stage?
HIV attaches to a CD4 receptor and the CCR5 and/or CXCR4 co-receptors on the surface of the CD4 host cell
What are the drug/drug classes that target the binding/attachment stage?
- CCR5 antagonist: maraviroc
- Attachment inhibitor: fostemsavir
- Post-attachment inhibitor: ibalizumab-uiyk
What happens in the fusion phase?
The HIV viral envelope fuses with the CD4 cell membrane. HIV enters the host cell and releases HIV RNA, viral proteins and enzymes needed for replication
What drug works in the fusion phase?
Fusion inhibitor: enfuvirtide
What happens in the reverse transcription phase?
HIV RNA is converted to HIV DNA by reverse transcriptase (an HIV enzyme). HIV DNA can then enter the CD4 cell nucleus
What drug/drug classes target the reverse transcription stage?
- Nucleoside reverse transcriptase inhibitors (NRTIs): e.g. emtricitabine, tenofovir)
- Non-nucleoside reverse transcriptase inhibitors (NNRTIs) (e.g. efavirenz, rilpivirine)
What happens in the integration stage?
Once inside the CD4 cell nucleus, integrase (an HIV enzyme) is released and used to insert HIV DNA into the host cell DNA
What drug/drug classes work in the integration phase?
Integrase strand transfer inhibitors (INSTIs): e.g. bictegravir, dolutegravir, raltegravir)
What happens in the replication stage?
Host cell machinery is used to transcribe and translate HIC DNA into HIV RNA and long-chain proteins (the HIV building blocks)
What happens in the assembly phase?
New HIV RNA, proteins and enzymes (including protease) move to the cell surface and assemble into immature HIV
What happens in the budding and maturation stage?
Immature HIV pushes out of the CD4 cell and protease (an HIV enzyme) breaks up the long viral protein chains, creating mature virus that can infect other cells
What drug/drug classes work in the budding and maturation phase?
Protease inhibitors (PIs): e.g. atazanavir, darunavir
What are the routine labs tests needed for patients with HIV?
- CD4 count: the major indicator of immune function used to determine the need for OI prophylaxis
- HIV viral load: indicates how much HIV RNA is in the blood. It is the most important indicator of response to ART. A high viral load can be due to medication nonadherence or drug resistance. The treatment goal is an undetectable HIV viral load
- Drug resistance genotyping testing
- Comprehensive metabolic panel (including LFTs), CBC with differential , random or fasting lipid panel, random or fasting glucose level and urinanalysis
- Hepatitis B and C screening
- Pregnancy test (women)
- HLA-B*5701 allele (if considering abacavir) or a tropism assay (if considering using maraviroc)
When should ART be started?
ART should be started as soon as possible in all HIV-infected individuals.
What is the goal of initiating ART therapy?
The goal is to reduce disease progression by suppressing the HIV viral load, preserving the immune system and reducing HIV-associated morbidity and mortality
Why is treatment adherence important with ARTs?
Treatment adherence is essential to prevent drug resistance
What is the preferred initial ART regimens in most treatment naive adults?
One-pill, once daily (single tablet regimens), two-pills (once daily for most)
What are some examples of one-pill once daily (single tablet regimens)?
- Biktarvy: Bictegravir/Emtricitabine/Tenofovir alafenamide
- Triumeq: Dolutegravir/Abacavir/Lamivudine
- Dovato: Dolutegravir/Lamivudine
What are some examples of two-pills (once daily for most)?
- Tivicay + Truvada: Dolutegravir + Emtricitabine/Tenofovir disoproxil fumarate
- Tivicay + Descovy: Dolutegravir + Emtricitabine/Tenofovir alafenamide
- Isentress + Truvada: Raltegravir + Emtricitabine/Tenofovir disoproxil fumarate
- Isentress + Descovy: Raltegravir + Emtricitabine/Tenofovir alafenamide
What do the most preferred ART regimens contain?
2 NRTIs and 1 INSTI
What medications make up the backbone in most regimens?
Emtricitabine/tenofovir disoproxil fumarate (Truvada) or emtricitabine/tenofovir alafenamide (Descovy) make up the NRTI backbone in most regimens
*Lamivudine and emtricitabine are interchangeable but should not be used together (both are cytosine analgos and are therefore antagonistic)
What is an important note about Dovato (1 NRTI + 1 INSTI)?
Do not use in treatment-naive patients if HIV RNA > 500,00 copies/mL, known hepatitis B virus (HBV) co-infection or HIV genotypic testing not yet available
What is an important note about Triumeq?
Test for the HLA-B*5701 allele before using. A positive result indicates a higher risk for a severe hypersensitivity reaction (HSR) and any abacavir-containing product is contraindicated
Which fixed dose combinations have less flexibility with renal dosing?
Biktarvy, Triumeq, Dovato, Truvada, Descovy (do not use if CrCl < 30 mL/min
*Except for Biktarvy, individual components of these drugs can be given separately to allow for more flexible dosing with renal-dose adjustments
What are some examples of alternative ART regimens?
- PI-based (boosted with cobicistat or ritonavir): Darunavir or atazanavir
- NNRTI-based: Efavirenz or rilpivirine
- INSTI-based (co-formulated in one pill): Elvitegravir/cobiscistat/TDF or TAF
- NRTI backbone (2 drugs, 1 from each row): TDF or TAF or abacavir PLUS emtricitabine or lamuvudine
*A complete HIV ART regimen has one “base” plus two NRTIs to serve as the “backbone”
What are some examples of nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs)?
Abacavir(Ziagen), Emtricitabine (Emtriva), Lamivudine (Epivir), Tenofovir disoproxil fumarate or TDR (Viread), Tenofovir alafenamide (TAF, Zidovudine (Retrovir)
What is the MOA of NRTIs?
Competitively inhibit the reverse transcriptase enzyme, preventing the conversion of HIV RNA to HIV DNA in stage 3 (reverse transcription) of the HIV life cycle. NRTIs have a low barrier to resistance
How often is Tenofovir administered?
Once daily
How often is Abacavir and Lamivudine administered?
Once daily and twice daily regimens
How often is Zidovudine?
Twice daily
Do the NRTIs needed to be renally dose adjusted?
All NRTIs, except abacavir: decrease dose with renal impairment
How is TDF oral powder administered?
Mix with 2-4 oz of soft food (applesauce, yogurt) to avoid bitter taste; do not use liquid; contains lactose
What special time is Zidovudine administered?
Administered IV during labor and delivery in women with HIV RNA > 1000 copies/mL (to protect the baby)
What are some key features and safety issues of all NRTIs?
- Warning for lactic acidosis and hepatomegaly with steatosis (fat build up in the liver); boxed warning for didanosine, stavudine and zidovidine
- Common side effects: nausea, diarrhea, headache, increasd LFTs
What are some HBV and HIV coinfection boxed warnings?
- Severe acute HBV exacerbation can occur if emtricitabine, lamivudine or tenofovir-containing productis are discontinued
- Do not use Epivir-HBV for the treatment of HIV (contains a lower dose of lamivudine)
What are some key features and safety issues specific to abacavir?
- Boxed warning: risk for hypersensitivity reaction (HSR)
- Screen for HLA*5701 allele before starting; abacavir is contraindicated if positive (higher risk of HSR)
- Patient must carry a medication card indicating that HSR is an emergency
- Never-rechallenge if history of HSR
- Consider avoiding with CVD due to potential increased risk for MI
What is a specific key feature and safety issue specific to emtricitabine?
Hyperpigmentation of the palms of the hands or soles of the feet
What are some key features and safety issues specific to Tenofovir Formulations (higher risk with TDF)?
- Renal impairment, including acute renal fallure and Fanconi syndrome (renal tubular injury with hyperphosphatemia)
- Decrease dose with renal impairment and avoid other nephrotoxic drugs (e.g. NSAIDs)
- Decrease bone mineral density; consider calcium/vitamin D supplementation and DEXA scan if at risk
- Note; monitor lipids if switching from TDF to TAF for improved side effect profile (TAF associated with higher risk of lipid abnormalities)
What are some key features and safety issues of Zidovudine?
- Hematologic toxicity: neutropenia and anemia (increases MCV is a sign of adherence)
- Myopathy
What are some examples of integrase strand transfer inhibitors?
Bictegravir, Cabotegravir (Vocabria), Dolutegravir (Tivicay), Elvitegravir (only in combination drugs Genvoya and Stribild), Raltegravir (Isentress, Isentress HD)
What is the MOA of integrase strand transcriptase inhibitors?
Block the integrase enzyme, preventing the HIV DNA from inserting into the host cell DNA in stage 4 (integration) of the HIV life cycle
- INSTIs have higher barrier to resistance than NRTIs and NNRTIs