1. HIV and Anti-Retroviral Therapy

2. Welcome to the module on the Initial Management of HIV!!
Please take this brief pre-module quiz

3. This module works a lot better in “presentation” mode

4. HIV Introduction
HIV is a virus spread through contact with body fluids (blood, semen, pre-semen, rectal, and vaginal fluids, or breast milk)
In the United States HIV is spread mainly through sex and sharing injection drug equipment, but it can also be spread through childbirth
The virus attacks the immune system, specifically CD4 type T cells
Without these immune cells, the body is prone to infections and certain types of cancer
HIV medicines are referred to as highly active antiretroviral therapy (HAART, or sometimes just ART)
These medications block replication of the virus, protect the immune system, and prevent the spread of the virus

5. Outline (click to jump to a section)
Pathophysiology of HIV
Testing for and diagnosing HIV
Baseline laboratory testing in new HIV diagnosis
Initial management of new HIV diagnoses
Building an initial treatment regimen

6. Outline (click to jump to a section)
Pathophysiology of HIV
Testing for and diagnosing HIV
Baseline laboratory testing in new HIV diagnosis
Initial management of new HIV diagnoses
Building an initial treatment regimen

7. Pathophysiology of HIV

8. The Virus Important components of the virus Glycoprotein 120
Integrase
Nucleocapsid (p24 antigen)
Protease
Lipid membrane
Reverse transcriptase
Viral RNA
Important components of the virus

9. The Viral Life Cycle
The virus may infect a host through sexual transmission (rectal or vaginal tissue), hematogenous spread or maternal-fetal transmission (during pregnancy, the birth process or through breast milk)
Sexual transmission is the most common mechanism of HIV acquisition in the US
In sexual transmission, the virus enters the host:
Through a break in the epithelium OR
Crossing intact mucosa with dendritic cells
Risk of HIV transmission per Act
Type of Exposure
Receptive anal intercourse
1/72
Insertive anal intercourse
1/900
Receptive vaginal intercourse
1/1,250
Insertive vaginal intercourse
1/2,500
Oral sex
1/10,000
Risk from sexual transmission is likely lower than you thought!

10. The Viral Life Cycle
Cell-to-cell signaling recruits more dendritic cells and CD4+ T cells
The dendritic cells help transport the virus through the lymphatic system
In the lymph nodes, activated CD4+ T cells are the source of viral replication

11. The Viral Life Cycle
CD4 Receptor
HIV Virus
CD4 Cell Membrane
Co-Receptor
(CCR5 or CXCR4)
gp120
The HIV virus utilizes CD4+ T cells for replication.
To enter these cells, the virus has specific envelope proteins (gp120) that bind to the CD4 receptor.
CD4 Cell
CD4 Cell Nucleus

12. The Viral Life Cycle
HIV Virus
Once gp120 binds to the CD4 receptor, a conformational change occurs in the gp120 protein allowing it to also bind to the chemokine co-receptor.
CD4 Receptor
CD4 Cell Membrane
gp120
Co-Receptor
(CCR5 or CXCR4)
CD4 Cell
CD4 Cell Nucleus

13. The Viral Life Cycle
HIV Virus
Once gp120 binds to the CD4 receptor, a conformational change occurs in the gp120 protein allowing it to also bind to the chemokine co-receptor.
CD4 Receptor
CD4 Cell Membrane
gp120
Co-Receptor
(CCR5 or CXCR4)
CD4 Cell
CD4 Cell Nucleus

14. The Viral Life Cycle
The virus is drawn towards the cell membrane leading to fusion and ultimately injection of the viral material into the host cell.
CD4 Cell Membrane
Integrase
Reverse transcriptase
CD4 Cell
Protease
Viral RNA
CD4 Cell Nucleus

15. The Viral Life Cycle
CD4 Cell Membrane
Once inside the cell, reverse transcriptase converts viral RNA into viral DNA.
CD4 Cell
Reverse transcriptase
Viral RNA
Viral DNA
CD4 Cell Nucleus

16. The Viral Life Cycle
CD4 Cell
The viral DNA then enters the cell nucleus where integrase helps it to “integrate” into the host DNA.
Integrase
Host DNA
Viral DNA
CD4 Cell Nucleus

17. The Viral Life Cycle
New “Immature” virion
The virus utilizes host mechanisms to convert the DNA into long chains of proteins. The protein chains and viral RNA move towards the cell membrane to be packaged into new virions.
CD4 Cell
Viral RNA
Viral Poly-protein
CD4 Cell Nucleus

18. The Viral Life Cycle
Protease splices the long protein chains into individual proteins. The mature virus can now infect more CD4 cells.
New “immature” virion
Viral Poly-protein
Viral RNA
Protease
Mature virion

19. The Viral Life Cycle Step 1 Step 2 Step 3 Step 7 Step 6 Step 4 Step 5
Medications for controlling HIV infection target several of these steps
…but more on that later!
HIV Virus
Step 1
CD4 Receptor
Step 2
CD4 Cell Membrane
Co-Receptor
(CCR5 or CXCR4)
Step 3
CD4 Cell
Reverse transcriptase
Step 7
Viral RNA
Integrase
Viral DNA
Host DNA
Protease
CD4 Cell Nucleus
Step 4
Step 6
Step 5

20. The Viral Life Cycle
As the virus replicates in the host, there are high levels of the virus, low levels of CD4 + T cells, and increasing markers of the presence of the virus.
For approximately 10 days, there is an ”eclipse” period during which time the virus is replicating but would not be detected through any available testing modalities.
At approximately 10 days, viral RNA can be detected, and within a few days, antigen-antibody tests can detect viral components.
…Let’s learn more about how to test for and diagnose HIV

21. Outline (click to jump to a section)
Pathophysiology of HIV
Testing for and diagnosing HIV
Baseline laboratory testing in new HIV diagnosis
Initial management of new HIV diagnoses
Building an initial treatment regimen

22. Diagnosing HIV
And initial laboratory testing

23. Diagnosing HIV
HIV testing should be recommended as a part of routine medical care to all patients
Testing should be voluntary and should be done alongside counseling on risk reduction strategies
Testing algorithms advocate for the use of the 4th generation antigen-antibody test.
This tests for the presence of antibodies to HIV-1 and HIV-2 as well as the HIV p24 antigen

24. Recommended HIV Testing Algorithm
Downloaded from Oxford Medicine Online. © Oxford University Press

25. Sequence of Appearance of Laboratory Markers
HIV Testing

26. Question
A 29 year old male presents to your clinic to establish care. He recently went to a local STD clinic and was informed that he had HIV. He carries a paper acknowledging the diagnosis was made by a 4th generation rapid HIV test, confirmed with an elevated HIV viral load of 12,456. He had unprotected anal intercourse with an unknown partner 8 weeks prior. He is interested in antiretroviral therapy.
How would you advise the patient?
Draw additional labs and have the patient follow-up in 2 weeks to review the results
Discuss patients understanding of the disease and social supports surrounding this new diagnosis
Describe the medications
All of the above

27. Answer
Priority in this first visit should be given to educating the patient about the disease and ensuring that they are well supported. There are important labs that will need to be obtained to understand the patient’s risk for opportunistic infections and co-morbid illness. While antiretroviral agents can be initiated in a first meeting, there is no rush to do so. The choice of initial medication regimen should be based on discussion with the patient and should take into consideration their medical, social and family history.

28. Question
What are the important initial labs to obtain in a patient with a new diagnosis of HIV infection?

29. Answer
Baseline testing should assess the strength of the immune system, the degree of viremia and any inherited mutations, organ system dysfunction, and other infections.

30. Outline (click to jump to a section)
Pathophysiology of HIV
Testing for and diagnosing HIV
Baseline laboratory testing in new HIV diagnosis
Initial management of new HIV diagnoses
Building an initial treatment regimen

31. Initial Laboratory Testing
Complete blood count and differential
CD4 Cell Count
Glucose, BUN/Creatinine, liver function tests
HgbA1c and fasting lipid profile
HIV viral load
HIV genotype test
HLA-B*5701 testing
Hepatitis A antibody
Hepatitis B surface antigen, Hepatitis B surface antibody, Hepatitis B core antibody
Hepatitis C antibody
Gonorrhea and chlamydia testing (may include throat, urine and/or rectal based on risk)
Toxoplasmosis IgG serology
PPD or quantiferon-gold testing
RPR

32. Question
In this patient with a new diagnosis of HIV, his baseline lab testing returns with a CD4 count of What medications would you recommend to the patient at this time?

33. Outline (click to jump to a section)
Pathophysiology of HIV
Testing for and diagnosing HIV
Baseline laboratory testing in new HIV diagnosis
Initial management of new HIV diagnoses
Building an initial treatment regimen

34. Initial Management
Of Patients with a new diagnosis of HIV

35. Answer
Trimethoprim-sulfamethoxazole*, 1 double-strength tablet daily, should be initiated immediately to prevent against Pneumocystis jiroveci (PCP) infection
Antiretroviral medications would be recommended once the patient feels prepared to start
*Alternative dosing for PCP prophylaxis may include: 1 single-strength tablet daily or one double- strength tablet three times per week. In patients with a documented sulfa allergy, alternative medications include dapsone, aerosolized pentamidine, and atovaquone.

36. Initial Management Should focus on…
Educating the patient about the disease, expected disease course, and ways to prevent complications
Establishing baseline testing to understand the patient’s immune status
Initiating medications to prevent against opportunistic infections where indicated
Immunizing the patient as indicated
Preventative health screening as indicated
Discussing antiretroviral options, side effects and medication interactions
Initiating antiretroviral medications when the patient is ready

37. Prevention Against Opportunistic Infections
CD4 Count <200
PCP
Trimethoprim-sulfamethoxazole
1 DS tablet daily OR
1 SS tablet daily
Alternative:
Dapsone, aerosolized pentamidine, atovaquone
CD4 count < 100
Toxoplasmosis
Trimethoprim-sulfamethoxazole (DS daily)
Alternative
Atovaquone
Dapsone + pyrimethamine + leucovorin
CD4 count < 50
Mycobacterium avium complex (MAC)
Azithromycin
1200mg once weekly
600mg twice weekly

38. Immunization Schedule for HIV Infected Patients
Annual influenza
Tdap
Pneumococcal (PCV13 followed by PPSV23 8 weeks later)
Meningococcal conjugate (two doses, 8 weeks apart, repeat every 5 years)
Hepatitis B (if not immune)
HPV series
For HIV Infected Patients with a CD4 count > 200:
MMR and varicella (if not previously vaccinated)
These are contraindicated in immunocomprised hosts because these are live-virus vaccines; if used in HIV patients, CD4 must be over 200

39. When should antiretrovirals be initiated?
Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents
aidsinfo.nih.gov/guidelines

40. Benefits to the patient Reduction in transmission
What is the evidence for early initiation of antiretroviral medications?
Benefits to the patient
Reduction in transmission
START TRIAL:
4,685 HIV infected patients with a CD4 count >500 who were treatment-naïve
Randomized to start antiretrovirals immediately or defer until CD4 count <350
Primary end point = any serious AIDS-related or non-related event, or death
After 3 years of follow-up, interim analysis found that primary outcome was significantly reduced in the early initiation arm
Serious AIDS events HR 0.28 (95% CI )
Non-AIDS events HR 0.61 (95% CI )
HPTN 052 Trial:
1763 HIV serodiscordant couples
Randomized to start antiretrovirals at enrollment or delay until CD count < 250 or after and AIDS- related illness
Primary end point = partner acquiring HIV
After 5.5 years of follow-up, there were no linked transmissions when the HIV-infected partner had achieved stable viral suppression
N Engl J Med 2015;373:
N Engl J Med 2016;375:

41. Question
After discussion with your patient, he opts to start antiretrovirals.
What medication options exist for this patient?

42. Answer
Highly active antiretroviral regimens (HAART) consist of a combination of medications aimed at suppressing viremia and reconstituting the immune system. Monotherapy leads to the development of viral resistance within weeks to months. Current regimens are not curative because of “sanctuary sites” in the body, including the central nervous system and gonads, in which these drugs do not penetrate well.
…Continue on to the next section for more information on HAART!

43. Outline (click to jump to a section)
Pathophysiology of HIV
Testing for and diagnosing HIV
Baseline laboratory testing in new HIV diagnosis
Initial management of new HIV diagnoses
Building an initial treatment regimen

44. Building an Antiretroviral Regimen

45. The Building Blocks of a Regimen
HIV treatment regimens are aimed at:
Suppressing HIV viral RNA
Restoring and preserve immunologic function
Reducing HIV-associated morbidity and prolong the duration and quality of survival
Preventing HIV transmission
All regimens consistent of multiple medications (at least three) to minimize the chances of mutations developing. Mutations occur because of the rapid turnover of HIV and the many random errors that occur during its replication
Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents
aidsinfo.nih.gov/guidelines

46. The Building Blocks of a Regimen
There are six classes of medications, each targeting different steps in the viral replication process
HIV Virus
Step 1
CD4 Receptor
Step 2
CD4 Cell Membrane
Co-Receptor
(CCR5 or CXCR4)
Step 3
CD4 Cell
Reverse transcriptase
Step 7
Viral RNA
Integrase
Viral DNA
Host DNA
Protease
CD4 Cell Nucleus
Step 4
Step 6
Step 5

47. The Building Blocks of a Regimen
The six classes of medications include:
Entry inhibitors
Fusion Inhibitors
Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs)
Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
Integrase Inhibitors (INSTIs)
Protease Inhibitors (PIs)
Target Step 1 &2: Binding & Fusion
Target Step 3: Reverse Transcriptase
Target Step 4: Integrase
Target Step 7: Protease

48. The Building Blocks of a Regimen
Two NRTIs make up the backbone of all initial regimens in treatment-naïve patients
A third medication is added from one of three classes of medications
NRTI
NNRTI
Protease Inhibitor
NRTI
Integrase Inhibitor

49. The Building Blocks of a Regimen
Now let’s walk through each class of medication and its mechanism of action,
in order of its effect on the viral life cycle

50. HAART: Entry Inhibitors*
Never used as first line treatment
HIV Virus
Entry Inhibitors: Maraviroc
300mg PO BID
Requires testing for CCR5 tropism – can only be used in patients who have virus that does NOT utilize CXCR4
Patients may fail this regimen due to development of CXCR4 tropic virus
Side effects: hepatoxicity
CD4 Receptor
CD4 Cell Membrane
gp120
Co-Receptor
(CCR5 or CXCR4)
CD4 Cell
CD4 Cell Nucleus

51. HAART: Fusion Inhibitors
Never used as first line treatment
Fusion Inhibitors:
Enfuvirtide (Fuzeon, T-20)
90mg SC BID
Only used in treatment-experienced patients where there are no other 3-drug regimens available
Low barrier to resistance
Side effects: local injection site reaction
CD4 Cell Membrane
Integrase
Reverse transcriptase
CD4 Cell
Protease
Viral RNA
CD4 Cell Nucleus

52. HAART: NRTIs Nucleoside Reverse Transcriptase Inhibitors (NRTI’s):
Competitively bind to viral reverse transcriptase, terminating DNA chain elongation
Class-wide Side Effects: Secondary to mitochondrial toxicity including peripheral neuropathy, lipodystrophy, pancreatitis, and hepatic steatosis
(Minimal in currently used NRTIs)
Few drug-drug interactions
CD4 Cell Membrane
CD4 Cell
Reverse transcriptase
Viral RNA
Viral DNA
CD4 Cell Nucleus

53. HAART: NRTIs, specific medications
Tenofovir
Tenofovir disoproxil fumarate (TDF, Viread)
Dosing: 300 mg po daily
Side Effects: Renal dysfunction, bone loss, hypophosphatemia, GI intolerance
Dose reduce in patients with CrCl < 60 mL/m
Also active against hepatitis B
Tenofovir alafenamide (TAF)
Dosing: dependent on drug combination, not available as single drug
Side Effects: Lactic acidosis; no bone/renal issues like TDF
Safe for use in patients with CrCl > 30 mL/m
Emtricitabine (FTC, Emtriva)
Dosing: 200 mg po daily
Side effects: Rare palmar hyperpigmentation
Co-formulated as:
TDF 300 mg +FTC 200 mg (Truvada) po once daily
TAF 25 mg +FTC 200 mg (Descovy) po once daily
CD4 Cell Membrane
CD4 Cell
Reverse transcriptase
Viral RNA
Viral DNA
CD4 Cell Nucleus

54. HAART: NRTIs, specific medications
Abacavir (ABC, Ziagen)
Dosing: 300 mg po BID
Side Effects: Hypersensitivity reaction (test for HLA B*5701 before initiating), not recommended in patients with known CAD or risk factors for CAD
Also active against hepatitis B
Lamivudine (3TC, Epivir)
Dosing: 150 mg po BID or 300mg daily
Side effects: Rare
Co-formulated as:
ABC 600 mg + 3TC 300 mg (Epzicom) po once daily
*Other medications in this class exist but are not considered first line regimens. These include didanosine, stavudine, and zidovudine.
CD4 Cell Membrane
CD4 Cell
Reverse transcriptase
Viral RNA
Viral DNA
CD4 Cell Nucleus

55. HAART: NNRTIs
Non-nucleoside reverse transcriptase inhibitors (NNRTIs):
Non-competitively bind to viral reverse transcriptase, terminating DNA chain elongation
Many drug-drug interactions
Low barrier to resistance: single mutation can confer class-wide resistance
CD4 Cell Membrane
CD4 Cell
Reverse transcriptase
Viral RNA
Viral DNA
CD4 Cell Nucleus

56. HAART: NNRTIs, specific medications
Efavirenz (EFV, Sustiva)
Dosing: 600 mg po daily
Side Effects: CNS (vivid dreams, headache, depression)
Pregnancy category D
Rilpivirine (RPV, Edurant)
Dosing: 25 mg po daily
Side Effects: depression (less CNS side effects than EFV)
Approved for use in patients with HIV viral load < 100,000 copies/mL
*Other medications in this class exist but are not considered first line regimens. These include delavirdine, etravirine, and nevirapine.
CD4 Cell Membrane
CD4 Cell
Reverse transcriptase
Viral RNA
Viral DNA
CD4 Cell Nucleus

57. HAART: Integrase Inhibitors
Block binding of the ”pre-integration complex” to host DNA, preventing integration
Well tolerated
Minimal drug-drug interactions
Integrase
Host DNA
Viral DNA
CD4 Cell Nucleus

58. HAART: Integrase Inhibitors
Dolutegravir (DTG, Tivicay)
Dosing: 50 mg po daily
Side Effects: Uncommon insomnia, headache
Highest barrier to resistance
Raltegravir (RAL, Isentress)
Dosing: 400 mg po BID
Side Effects: CK elevation
Elvitegravir (EVG)
Most commonly co-formulated with cobicistat, a potent CYP3A inhibitor without activity against HIV, but serves as a PK enhancer allowing for once daily dosing
Dosing: 150mg po daily with cobicistat
150mg po daily Side Effects: diarrhea, nausea, headache
Cobicistat has many drug-drug interactions
Elvitegravir drug levels may be altered by CYP3A inhibitors and inducers
Integrase
Host DNA
Viral DNA
CD4 Cell Nucleus

59. HAART: Protease Inhibitors
Mature virion
Protease Inhibitors:
Competitively inhibit protease, preventing cleavage of the polyproteins into individual and active proteins
High barrier to resistance
Administered with a boosting agent (either ritonavir or cobicistat)
Many drug-drug interactions
Viral Poly-protein
Protease
“Immature” virion

60. HAART: Protease Inhibitors
Mature virion
Darunavir (DRV, Prezista)
Dosing:
800 mg po daily with ritonavir 100 mg po daily
Co-formulated as DRV 800 mg + COBI 150 mg (Prezcobix) po once daily
Side Effects: Nausea, diarrhea, increased transaminases, rare drug induced liver injury
Atazanavir (ATZ, Reyataz)
Dosing: 300 mg with ritonavir 100 mg po daily or cobicistat 150 mg po daily
Side Effects: Increased indirect bilirubin
Requires gastric acid for absorption: take with food, do not use PPIs
*Other medications in this class exist but are not considered first line regimens. These include lopinavir, fosamprenavir, indinavir, nelfinavir, saquinavir, tipranavir
Viral Poly-protein
Protease
“Immature” virion

61. The Building Blocks of a Regimen
Now that we have a better understanding of the available medications in each class,
let’s look at the recommended regimens
NRTI
NNRTI
Protease Inhibitor
NRTI
Integrase Inhibitor

62. Recommended Initial Regimens
* Several available as one pill once daily regimens!
These are the regimens that have excellent efficacy, good tolerability and minimal toxicities.
Abacavir + lamivudine + dolutegravir
Tenofovir disoproxil fumarate + emtricitabine + dolutegravir
Tenofovir alafenamide + emtricitabine + dolutegravir
Tenofovir disoproxil fumarate + emtricitabine + elvitegravir + cobicistat
Tenofovir alafenamide + emtricitabine + elvitegravir + cobicistat
Tenofovir disoproxil fumarate + emtricitabine + raltegravir
Tenofovir alafenamide + emtricitabine + raltegravir
Tenofovir disoproxil fumarate + emtricitabine + darunavir + ritonavir
Tenofovir alafenamide + emtricitabine + darunavir + ritonavir
Triumeq
Stribild
Genvoya
Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents
aidsinfo.nih.gov/guidelines

63. Alternative Initial Regimens
* Several available as one pill once daily regimens!
These are effective and tolerable regimens. They may have limitations in certain patient populations and less supporting data in randomized clinical trials.
Tenofovir disoproxil fumarate + emtricitabine + efavirenz
Tenofovir alafenamide + emtricitabine + efavirenz
Tenofovir disoproxil fumarate + emtricitabine + rilpivirine
Tenofovir alafenamide + emtricitabine + rilpivirine
Atripla
Complera
Only use rilpivarine if HIV viral load is <100,000 copies/ml
Odefsey
Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents
aidsinfo.nih.gov/guidelines

64. Safe Initial Regimens in Pregnancy
ABC + 3TC
Atazanavir/ritonavir OR OR
TDF + FTC
Darunavir/ritonavir OR OR
Raltegravir
TAF + FTC

65. Factors to consider when choosing a medication regimen
Pretreatment immune status and HIV viral load
HIV genotypic drug resistance testing
Likelihood of adherence
Convenience of regimen (pill burden, dosing frequency, food and fluid requirements)
Co-morbidities (liver or renal disease, hepatitis, cardiovascular disease)
Side effects
Medication interactions
Pregnancy or potential for pregnancy

66. Now let’s practice choosing a regimen…

67. Question
A 33 year old otherwise healthy man was recently diagnosed with HIV. He has an initial CD4 count of 300 and a viral load of 230,000 copies/ml. He has normal kidney function and his HLA B*5701 was negative. He takes no medications. His priority is taking the fewest pills possible as he has a hard time remembering medications.
Which is the best regimen option for him?
Tenofovir alafenamide + emtricitabine + raltegravir
Tenofovir disoproxil fumarate + emtricitabine + darunavir + ritonavir
Tenofovir alafenamide + emtricitabine + dolutegravir
Abacavir + lamivudine + dolutegravir

68. Answer D) Abacavir + lamivudine + dolutegravir
Tenofovir alafenamide + emtricitabine + raltegravir
This regimen contains a total of two pills (tenofovir alafenamide + emtricitabine co-formulated as Descovy and raltegravir). Descovy is given once a day but raltegravir is dosed twice a day.
Tenofovir disoproxil fumarate + emtricitabine + darunavir + ritonavir
This regimen contains three pills. Tenofovir disoproxil fumarate + emtricitabine is co-formulated as Truvada given once a day. Darunavir and ritonavir are each separate pills and dosed once a day.
Tenofovir alafenamide + emtricitabine + dolutegravir
This regimen contains a total of two pills each given once a day (tenofovir alafenamide + emtricitabine co- formulated as Descovy and dolutegravir).
Abacavir + lamivudine + dolutegravir
This regimen is available in a one pill once daily regimen (Triumeq) with few side effects. Remember that you would need to check HLA-B*5701 before starting abacavir to avoid a hypersensitivity reaction.

69. Question
A 56 year old man with a history of coronary artery disease, hypertension and chronic kidney disease (last creatinine 2.3, estimated GFR 40) presents with a new diagnosis of HIV. His initial blood work shows a CD4 count of 190 and an HIV viral load of 290,000.
Which is the best initial regimen for him?
Abacavir + lamivudine + dolutegravir
Tenofovir disoproxil fumarate + emtricitabine + dolutegravir
Tenofovir alafenamide + emtricitabine + dolutegravir
Tenofovir alafenamide + emtricitabine + rilpivirine

70. Answer C) Tenofovir alafenamide + emtricitabine + dolutegravir
Abacavir + lamivudine + dolutegravir
Abacavir may increase cardiovascular risk and in patients with known CAD it is not recommended
Tenofovir disoproxil fumarate + emtricitabine + dolutegravir
The patient’s GFR is <50 so tenofovir disoproxil fumarate would not be recommended
Tenofovir alafenamide + emtricitabine + dolutegravir
This a strong regimen. It has less renal toxicity with the newer formulation of tenofovir (TAF), and is two pills once a dayTenofovir alafenamide + emtricitabine + dolutegravir
Tenofovir alafenamide + emtricitabine + rilpivirine
The patient’s viral load is >100,000 thus rilpivarine would not be recommended.

71. Question
A 29 year old female with presents with a new diagnosis of HIV. Initial blood work shows a CD4 count of 450 and HIV viral load of 90,000. She takes a combined oral contraceptive pill most days, but occasionally forgets to take it.
Which would be the best initial regimen for this patient?
Tenofovir disoproxil fumarate + emtricitabine + efavirenz
Tenofovir alafenamide + emtricitabine + dolutegravir
Tenofovir disoproxil fumarate + emtricitabine + elvitegravir + cobicistat
Tenofovir alafenamide + emtricitabine + darunavir + ritonavir

72. Answer B) Tenofovir alafenamide + emtricitabine + dolutegravir
Tenofovir disoproxil fumarate + emtricitabine + efavirenz
Efavirenz is teratogenic and not recommended for initiation in women of childbearing age
Tenofovir alafenamide + emtricitabine + dolutegravir
This regimen would not interact with her hormonal contraception, would be safe if she unintentionally became pregnant, and has a high genetic barrier to resistance if she missed pills.
Tenofovir disoproxil fumarate + emtricitabine + elvitegravir + cobicistat
The cobicistat component would alter the levels of her hormonal contraception potentially making it less effective or more likely to lead to adverse effects such as thromboembolism
Tenofovir alafenamide + emtricitabine + darunavir + ritonavir
The ritonavir component would alter the levels of her hormonal contraception potentially making it less effective or more likely to lead to adverse effects such as thromboembolism

73. Question
A 38 year old man with a history of chronic hepatitis B (viral load 1,250,345) presents with a new diagnosis of HIV.
Which of the following medications, if included in his regimen, would also act as treatment of his hepatitis B?
Tenofovir alafenamide
Tenofovir disoproxil fumarate
Lamivudine
Emtricitabine

74. Answer
A, B and C: All of these medications have activity against hepatitis B. Emtricitabine does not have activity against hepatitis B.
In patients with chronic hepatitis B, it is very important that they remain on their antiretroviral medications, as stopping these medications could precipitate an acute hepatitis.

75. Follow-up After Initiation of Medications
All patients should have an in-person visit with their clinician 1 month after initiation of medications to discuss:
Tolerability of medications
Adherence to medications
Concerns about medications
And to check:
Immune response (viral load and CD4 count)
Safety labs (kidney function, liver function, electrolytes)

76. Initial Management of HIV: Conclusions
HIV infection is most commonly acquired through sexual transmission but can also occur with hematogenous spread and maternal-fetal transmission
Patients with a new diagnosis of HIV should be provided with education surrounding the diagnosis, treatment to prevent complications, and medications to control the virus once they are ready
Highly active antiretroviral therapy (HAART) is a multi-drug regimen targeted towards impeding the viral life cycle. One-pill once a day regimens exist and are well tolerated

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