1. HIV Pharmacotherapy Focused Update
Drew Lambert, PharmD
Husson University School of Pharmacy

2. I have no conflicts of interest.
However, I will be using brand names extensively during the presentation
Majority of the drugs used are brand-only
Easier to say

3. Objectives Identify and describe new antiretroviral therapies
Review most recent HIV guidelines
Choose an appropriate antiretroviral regimen
History of HIV/AIDS
HIV life cycle and diagnosis
Baseline evaluation
Laboratory testing (HIV RNA, CD4 cell count, resistance)
New DHHS adult and adolescent antiretroviral treatment guidelines.
Overview of antiretroviral medications
When to initiate therapy
When to change therapy
Therapeutic options

4. Definitions HIV – Human Immunodeficiency Virus
AIDS – Acquired Immune Deficiency Syndrome
ARV – Antiretroviral
ART – Antiretroviral Therapy
HAART – Highly Active Antiretroviral Therapy
NRTI – Nucleoside Reverse Transcriptase Inhibitor
NNRTI – Non-nucleoside Reverse Transcriptase Inhibitor
PI – Protease Inhibitor
INSTI – Integrase Strand Transfer Inhibitor

5. Quick Stats About 1.2 million infected with HIV in the US
1 of every 265 people
~13% undiagnosed (down from ~20% previously)
~50,000 new cases per year in the US (2013)
~14,000 deaths per year in the US (2012)
Centers for Disease Control and Prevention. Results of the Expanded HIV Testing Initiative--25 jurisdictions, United States, MMWR Morb Mortal Wkly Rep. Jun ;60(24):

6. *= District represents district of residence at time of disease diagnosis. **= Risk for HIV infection is self identified and is defined as follows:
The eight public health districts are as follow: MSM= Men who have sex with other men
York= York County IDU= Injection drug users
Cumberland= Cumberland County MSM/IDU= Men who engage in both behaviors above
Western= Androscoggin, Franklin, and Oxford Counties HET= Heterosexuals who have a partner who is known to have, or be at
Mid Coast= Knox, Lincoln, Sagadahoc, and Waldo Counties high risk for HIV infection
Central= Kennebec and Somerset Counties Pediatric= Children whose infection was acquired from their mother
Penquis= Penobscot and Piscataquis Counties during pregnancy, birth, or breastfeeding
Downeast= Hancock and Washington Counties NRR/NIR= No reported risk or no identified risk (includes heterosexuals
Aroostook= Aroostook County with partners NOT known to have, or be at high risk for HIV infection.

7. *= District represents district of residence at time of disease diagnosis. **= Risk for HIV infection is self identified and is defined as follows:
The eight public health districts are as follow: MSM= Men who have sex with other men
York= York County IDU= Injection drug users
Cumberland= Cumberland County MSM/IDU= Men who engage in both behaviors above
Western= Androscoggin, Franklin, and Oxford Counties HET= Heterosexuals who have a partner who is known to have, or be at
Mid Coast= Knox, Lincoln, Sagadahoc, and Waldo Counties high risk for HIV infection
Central= Kennebec and Somerset Counties Pediatric= Children whose infection was acquired from their mother
Penquis= Penobscot and Piscataquis Counties during pregnancy, birth, or breastfeeding
Downeast= Hancock and Washington Counties NRR/NIR= No reported risk or no identified risk (includes heterosexuals
Aroostook= Aroostook County with partners NOT known to have, or be at high risk for HIV infection.

9. Pathophysiology
HIV attacks cells expressing the CD4+ receptor (CD4+ or CD4 cells)
T-helper cells
Normal range is cells/mm3 (CD4 count)
40-70% of total lymphocytes
New viruses bud off from the cell and enter the bloodstream
The number of copies of HIV RNA per mL is known as viral load
^This is important. Know this.

10. Fauci A et al. Ann Intern Med 1996;124:654
Viral transmission -> 2-3 weeks-> acute retroviral syndrome -> 2-3w-> recovery + seroconversion -> 2-4 w -> asymptomatic chronic HIV infection -> avg 8 yrs -> symptomatic HIV infection -> avg 1.3 y -> death (Bartlett page 1)
False negative serologies may be seen during acute retroviral syndrome
Fauci A et al. Ann Intern Med 1996;124:654

11. Kahn JO, Walker BD. Acute human immunodeficiency virus type 1 infection. NEJM. 1998;339(1):33-39.

12. Life cycle of human immunodeficiency virus with potential targets where replication may be interrupted. Italicized compounds were in development at the time of this writing. (Reprinted with permission, Courtney V. Fletcher, 2012.)

13. HIV vs. AIDS Patients may be infected with HIV but not have AIDS AIDS
Stage 1 – CD4 count ≥500 cells/mm3 or CD4% ≥29
Stage 2 – CD4 count cells/mm3 or CD4% 14-28
AIDS
Stage 3 – CD4 count <200 or CD4% <14 OR
AIDS defining illness
Only seen with severe immunodeficiency

14. New Drug Approvals All FDA approved drugs:

15. Stribild – August 2012
Elvitegravir 150mg + cobicistat 150mg + emtricitabine 200mg + tenofovir disoproxil fumarate 300mg
INSTI based single tablet regimen
Common adverse events
Nausea and diarrhea
Take with food
Take antacids 2 hours before or after Stribild

16. Tivicay – August 2013 Dolutegravir 50mg daily
Increase to 50mg twice daily when given with UGT1A1 inducers (e.g., rifampin, efavirenz, fosamprenavir, tipranavir) or with INSTI resistance
2nd generation INSTI
Common adverse effects
Headache, insomnia, fatigue
No food effects
Take 2 hours prior or 6 hours after antacids

17. Triumeq – August 2014
Dolutegravir 50mg + abacavir 600mg + lamivudine 300mg
Integrase inhibitor based single tablet regimen
2nd generation INSTI
Only combination with abacavir/lamivudine NRTI backbone

18. Tybost – September 2014 Cobicistat (cobi) 150mg daily
Pharmacokinetic booster (3A4 inhibitor) approved to be used in combination with
Darunavir 800mg daily
Atazanavir 300mg daily
Elvitegravir 150mg as part of Stribild or Genvoya
Not active against HIV
Inhibits creatinine excretion but does not change GFR

19. Vitetka – September 2014
Elvitegravir 85mg or 150mg

20. Vitetka – September 2014
Must be given with ritonavir boosted protease inhibitors
Take with food
Diarrhea is the most common adverse event
Avoid with CYP 3A4 inducers
No data yet on taking it with…

21. Protease inhibitor + booster combinations - January 2015
Prezcobix
Evotaz
Atazanavir (Reyataz) 300mg + cobicistat (Tybost) 150mg
Darunavir (Prezista) 800mg + cobicistat (Tybost) 150mg
Both approved for use in combination with other ARV drugs
Previously approved to be boosted with ritonavir
Take with food
Metabolic ADRs (diabetes, fat redistribution, dyslipidemia)

22. Genvoya – November 2015
Elvitegravir 150mg + cobicistat 150mg + emtricitabine 200mg + tenofovir alafenamide 10mg
INSTI based single tablet regimen
Similar to Stribild
Disoproxil fumarate 300mg
Nausea is most common ADR
Take with food

23. Odefsey – March 2016
Rilpivirine 25mg + emtricitabine 200mg + tenofovir alafenamide 25mg
NNRTI based single tablet regimen
Similar to Complera
Disoproxil fumarate 300mg
Take with food
Depression, insomnia, headache, nausea are common

24. Tenofovir alafenamide (TAF) vs. Tenofovir disoproxil fumarate (TDF)
TDF conversion to tenofovir occurs mainly in the plasma; TAF conversion occurs intracellularly
Plasma levels 91% lower; intracellular levels 4.1x higher
Less serum creatinine increase
Less effects on BMD
Less proteinuria
Less renal dysfunction
Same price
More comparison studies are ongoing
BMD = bone mineral density
Genvoya – A New 4-Drug Combination for HIV. The Medical Letter. 2016;15(1488):19-21.

25. (Old) Drugs Drug Class & Individual Agent Overview Guidelines
Nucleoside Reverse Transcriptase Inhibitors
Non-nucleoside reverse transcriptase inhibitors
Protease Inhibitors
Integrase strand transfer inhibitors

26. 2007 1987 2003 1995 1996 CCR-5 Antagonists & Integrase Inhibitors
Nucleoside Reverse Transcriptase Inhibitors
2003
Fusion Inhibitors
July 12, 2006: Atripla approved
1995
Protease Inhibitors
1996
Non-Nucleoside Reverse Transcriptase Inhibitors

27. NRTIs Generic Abbreviation Brand Abacavir* ABC Ziagen Didanosine* ddI
Videx (EC)
Emtricitabine
FTC
Emtriva
Lamivudine*
3TC
Epivir
Tenofovir
TDF
Viread
Stavudine*
d4T
Zerit
Zidovudine*
AZT or ZDV
Retrovir
* – generic (tablet dosage form)

28. Mechanism of Action and notes
Nucleoside/nucleotide analogs
Stop reverse transcriptase because of replacement of 3’ end
Actively compete with endogenous substrates
Mimic different bases
Choose two that mimic different base pairs
Require phosphorylation for activation
Generally renal elimination
Form the backbone for HAART (highly active antiretroviral therapy)

29. Class Adverse Reactions
Headache
N/V/D
Rash
Lipoatrophy—primarily caused by the thymidine analogs zidovudine and stavudine
Fatty liver
Lactic acidosis

30. Nucleoside Reverse Transcriptase Inhibitors
Abacavir (Ziagen, ABC)
600mg once daily or 300mg BID
Must test for HLA-B*5701 because of possible hypersensitivity reaction
May have higher rates of failure in individuals with an viral load of >100,000 copies/mL
Zidovudine (Retrovir, AZT or ZDV)
300mg BID
Possible anemias and fatigue
Renal dose adjustments with CrCl <15mL/min
Bone marrow suppression
Fingernail Hyperpigmentation

31. Nucleoside Reverse Transcriptase Inhibitors
Emtricitabine (Emtriva, FTC)
200mg daily
May cause skin discoloration
Generally well tolerated
Active against HBV
Lamivudine (Epivir, 3TC)
300mg daily
Would not use these together as they are both cytosine analogs

33. Nucleoside Reverse Transcriptase Inhibitors
Tenofovir disoproxil fumarate (Viread, TDF)
300mg daily
NucleoTIDE reverse transcriptase inhibitor
Possible decreases in BMD
Fairly well tolerated
Activity against HBV
May cause renal dysfunction
Dose adjustments needed for CrCL <50mL/min, <30mL/min, and is not recommended with CrCl <10 unless receiving hemodialysis

34. NRTI Combinations Combivir* Epzicom Trizivir* Truvada
Epivir (lamivudine) and Retrovir (zidovudine)
Epzicom
Epivir (lamivudine) and Ziagen (abacavir)
Trizivir*
Epivir (lamivudine), Retrovir (zidovudine), and Ziagen (abacavir)
Truvada
Emtriva (emtricitabine) and Viread (tenofovir disoproxil)
* – generic (tablet dosage form)

35. NNRTIs Generic Abbreviation Brand Delavirdine DLV Rescriptor
Nevirapine*
NVP
Viramune (XR)
Efavirenz
EFV
Sustiva
Etravirine**
ETV
Intelence
Rilpivirine**
RPV
Edurant
* – generic
** – second generation NNRTI

36. Mechanism of Action and notes
Inhibit reverse transcriptase directly
Does not require activation
Low genetic barrier to resistance
Single mutation can cause resistance to multiple drugs
Second generation NNRTIs have a higher barrier to resistance
Come in single tablet combinations
Metabolized by and induce CYP 3A4

37. Adverse Reactions Rash (including SJS) N/V/D Increased LFTs
Other drug-specific adverse reactions
Newer NNRTIs are better tolerated

38. Non-Nucleoside Reverse Transcriptase Inhibitors
Efavirenz (Sustiva, EFV)
600mg daily
Do not use in moderate to severe hepatic impairment
Pregnancy class D
CNS adverse effects
Depression
Insomnia/abnormal dreams or nightmares
Dizziness
May give a false positive test for marijuana
Generally given at bedtime
Available as a combination tablet
Neuropsychiatric effects
Occurs in the first 2 days and resolves by 2 to 4 weeks
Increased risk in patients with history of psychiatric disorders

39. Non-Nucleoside Reverse Transcriptase Inhibitors
Rilpivirine (Edurant, RPV)
25mg daily
Should be taken with food
Higher barrier to resistance
More virologic failures as compared to efavirenz in patients with a viral load of >100,000 copies/mm3
Depressive disorders
Contraindicated with CYP 3A4 inducers and PPIs
Only NNRTI to not inhibit or induce CYP enzymes
Available as a combination tablet
Not studied in patients with severe hepatic impairment
Newest NNRTI

40. NNRTI Combinations Atripla – 600/200/300mg Complera – 200/25/300mg
Sustiva (efavirenz), Emtriva (emtricitabine), Viread (tenofovir)
Sustiva (efavirenz), Truvada (emtricitabine and tenofovir)
Complera – 200/25/300mg
Emtriva (emtricitabine), Edurant (rilpivirine), Viread (tenofovir)
Edurant (rilpivirine), Truvada (emtricitabine and tenofovir)
Odefsey – 200/25/25mg
Edurant (rilpivirine), Emtriva (emtricitabine), tenofovir alafenamide

41. PIs Generic Abbreviation Brand Ritonavir RTV Norvir Indinavir IDV
Crixivan
Nelfinavir
NFV
Viracept
Saquinavir
SQV
Invirase
Tipranavir
TPV
Aptivus
Fosamprenavir
FPV
Lexiva
Lopinavir/r
LPV/r
Kaletra
Darunavir
DRV
Prezista
Atazanavir
ATV
Reyataz
No generics

42. Mechanism of Action and notes
Inhibit HIV protease enzyme, which cleaves polyproteins into mature, active proteins. This results in production of immature, non-infections virus particles.
Occurs post-translation, so PIs are active in acutely and chronically infected cells
High barrier to resistance
Strong CYP 3A4 inhibitors
Many drug interactions
Most require pharmacokinetic “boosting” with ritonavir or cobicistat

43. Boosting with ritonavir almost singlehandedly cause the downfall of therapeutic drug monitoring of PIs in AIDS patients.
Acosta, EP. Pharmacokinetic enhancement of protease inhibitors. JAIDS. 2002;29:S11-18.

44. Adverse Effects Most increase cholesterol and triglycerides
Lipodystrophy
Diabetes and insulin resistance
Immune Reconstitution Inflammatory Syndrome (IRIS)
N/V/D
Abdominal pain
Elevated LFTs

45. What is the difference between lipoatrophy and lipodystrophy?
In lipoatrophy, there is wasting of the subcutaneous fat, often accompanied by an increase in triglycerides. This occurs most commonly with the NRTIs, specifically stavudine and didanosine.
In lipodystrophy, there is accumulation of visceral fat. This occurs most commonly with the protease inhibitors.

46. Protease Inhibitors Ritonavir (Norvir, RTV)
Used to boost other PIs—100mg with each dose of the other protease inhibitor
Available as tablets and capsules—tablets much more palatable
Tingling or numbness of the hands or feet, or around the mouth

47. Protease Inhibitors Atazanavir (Reyataz, ATV)
300mg daily boosted, or 400mg daily unboosted
Use boosted regimen when given with tenofovir or in treatment experienced patients
Take with food
Least metabolic side effects of the PI class
Dizziness and lightheadedness
Jaundice
Total bilirubin will likely increase, and can be a marker of adherence
PR prolongation
Interaction with PPIs and acid-decreasing agents

48. Protease Inhibitors Darunavir (Prezista, DRV)
800mg daily boosted with ritonavir for treatment naïve patients, 600mg BID boosted for treatment experienced
Take with food
Very high barrier to resistance
Not recommended in severe liver disease
Less metabolic side effects than older PIs
Possible rash on initiation

49. PI Combinations Evotaz – 300mg/150mg Prezcobix – 800mg/150mg
Reyataz (atazanavir) + Tybost (cobicistat)
Prezcobix – 800mg/150mg
Prezista (darunavir) + Tybost (cobicistat)
Kaletra – 800mg/200mg
Lopinavir/ritonavir
Lopinavir not available separately
NOT single tablet regimens
Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) in trials now

50. Integrase Strand Transfer Inhibitors (INSTIs)
Generic
Abbreviation
Brand
Raltegravir
RAL
Isentress
Elvitegravir*
EVG
Vitekta
Dolutegravir*
DTG
Tivicay
* – Second generation
No generics

51. Mechanism of Action and notes
Inhibits HIV integrase, which integrates the viral DNA into the host cell’s DNA
Lower barrier to resistance than the PIs
Adverse Reactions
Generally well tolerated
N/D
Headache
Elevated LFTs

52. Integrase Strand Transfer Inhibitors (INSTIs)
Raltegravir (Isentress, RAL)
400mg BID
No food requirements
No renal dose adjustments
Not studied in severe hepatic impairment
Metabolized by UGT1A1 mediated glucuronidation
800mg twice daily with rifampin
Increased total bilirubin
Elevated CK – myopathy and rhabdomyolysis

53. INSTIs Combinations Stribild - 150/150/300/200mg daily
Elvitegravir/cobicistat/tenofovir/emtricitabine (EVG/cobi/TDF/FTC)
Genvoya - 150/150/10/200mg daily
Elvitegravir/cobicistat/tenofovir alafenamide/emtricitabine (EVG/cobi/TAF/FTC)
Triumeq - 50/600/300mg
Dolutegravir/abacavir/lamivudine (DTG/ABC/3TC)

54. HIV Treatment guidelines

55. Treatment Goals Suppression of HIV viral load
Undetectable - <50 copies/mL or the lower limit of detection (some assays detect a few as 20 copies/mL)
“The goal of ART is to suppress HIV replication to a level where drug-resistance mutations do not emerge.”
Preserve and restore immunologic function
Reduce morbidity and prolong survival
Prevent HIV transmission
Improve quality of life
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Available at

56. Predictors of Treatment Success
High potency antiretroviral regimen
Multiple active drugs
Adherence to antiretroviral regimen (>95%)
Tolerability
Convenience
Low baseline viral load
Higher (>200 cells/mm3) baseline CD4 count
Rapid reduction of viremia in response to therapy

57. Therapy Initiation Risk vs. Benefit
Risks
Drug related toxicities
Long-term effects may not be known
Resistance with nonadherance
Treatment fatigue
Less time for education and preparation for adherence
Transmission of resistant virus
Benefits
Reduces AIDS-related complications
Prolongation of disease-free survival
Viral suppression
Preservation of immune function
Decreased risk of disease transmission
Reduction of HIV-associated nephropathy, cardiovascular disease, malignancies, neurocognitive decline
Non opportunistic related disease – HIV-associated nephropathy, cardiovascular disease, malignancies, neurocognitive decline (HIV dementia), younger pts may have more robust response with CD4 count
Untreated HIV infection – high level inflammation and t-cell activation
Reduced transmission – mother to child and to partners, lower plasma RNA levels decreases amount in genital secretions
Risks
Drug related effects – cardiovascular risks?, bone toxicities (
DHHS Guidelines: Adults & Adolescents. Nov 2014

58. Considerations for Treatment Selection
Underlying conditions
Liver/renal disease
Chemical dependency
Cardiovascular disease
Underlying viral resistance
Potential medication toxicities
Drug interactions
Pregnancy or potential pregnancy
Lifestyle changes required
Dosing schedule, pill burden and food/fluid requirements
DHHS Guidelines: Adults & Adolescents. Nov 2014

59. Antiretroviral Treatment (ART)
Current standard is minimum of 3 drug regimen
Typically two (or more) classes
Panel on Antiretroviral Guidelines for Adults and Adolescents convened by the Department of Health & Human Services (DHHS)

60. Who and When to Initiate ART
“ART is recommended for all HIV-infected individuals…”
Especially in
History of AIDS-defining illness (including opportunistic infections)
Pregnancy
HIV-associated nephropathy
Hepatitis B & C coinfection
Low CD4+ counts
Acute HIV infection
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Available at 

61. Why initiate ART immediately?
Decreased risk of death
START and TEMPRANO Trials
Higher CD4 count (>500 cells/mm3)
Higher incidence of 1 year viral suppression
Lower viral load = decreased risk of transmission
Public health benefit
INSIGHT START Study Group. Initiation of antiretroviral therapy in early asymptomatic HIV infection. N Engl J Med. 2015;373(9):
TEMPRANO ANRS Study Group, Danel C, Moh R, et al. A trial of early antiretrovirals and isoniazid preventive therapy in Africa. N Engl J Med. 2015;373(9):

62. Starting HAART <12 months after seroconversion improves immune health
Median CD4 count in uninfected patients is
900 cells/mm3
38.4% of patients beginning HAART <12 months after seroconversion achieved this
28.3% of patients beginning HAART >12 months after seroconversion achieved this
Better overall immune health
Fewer patients progressed to AIDS
Okulicz, Jason F., et al. "Influence of the Timing of Antiretroviral Therapy on the Potential for Normalization of Immune Status in Human Immunodeficiency Virus 1–Infected Individuals." JAMA internal medicine 175.1 (2015):

63. Monitoring Parameters
Viral Load = Amount of virus per mL of blood
Goal: As low as possible!
<50 copies/mL correlates with durable response to HIV medications and is considered “undetectable”
Newer assays may detect < 20 copies/mL
CD4 count = Number of immune cells in blood
Goal: As high as possible!
>200 cells/mm3 to prevent most opportunistic infections
DHHS Guidelines: Adults & Adolescents. Nov 2014

64. Definitions of Guideline Regimens
Recommended Regimen
Optimal and durable efficacy, favorable tolerability and toxicity profile and ease of use
Alternative Regimen
Effective and tolerable but have potential disadvantages compared with preferred regimens. An alternative regimen may be the preferred regimen for some patients.
DHHS Guidelines: Adults & Adolescents. Nov. 2014

65. Recommended Regimens for All Treatment Naïve Patients (6 regimens)
NRTI Backbone
Combination drug
Class
Emtricitabine + Tenofovir (TDF)
Darunavir/r PI
Raltegravir
INSTI
Elvitegravir/cobi*
Dolutegravir
Emtricitabine + Tenofovir alafenamide (TAF)
Abacavir + Lamivudine
Dolutegravir*
* – Available as a single tablet regimen
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Available at 

66. Recommended Regimens for Treatment Naïve Patients
Stribild ……………….
Triumeq ……………..
Genvoya……………
Prezista + Norvir + Truvada
Tivicay + Truvada
Isentress + Truvada
70 mL/min minimum 50 mL/min minimum 30 mL/min minimum Dose adjust <50mL/min for Truvada only
Stribild - Must change if CrCl falls < 50 mL/min
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Available at

67. Alternative Regimens for Treatment Naïve Patients
NRTI Backbone
Combination drug
Class
Emtricitabine + Tenofovir (TDF)
Efavirenz*
NNRTI
Rilpivirine*
Atazanavir/r PI
Atazanavir/cobi**
Darunavir/cobi**
Abacavir + Lamivudine
Darunavir/r
* - Available as a single tablet regimen
** - Co-formulated
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Available at
AIDSInfo. Recommendation on Integrase Inhibitor Use in Antiretroviral Treatment-Naive HIV-Infected Individuals from the HHS Panel on Antiretroviral Guidelines for Adults and Adolescents. Dec. 30, Available at

68. Other Regimens for Treatment Naïve Patients
NRTI Backbone
Combination drug
Class
Abacavir + Lamivudine
Raltegravir
INSTI
Efavirenz*
NNRTI
Atazanavir/r* PI
Atazanavir/cobi*
Lopinavir/r
Emtricitabine + Tenofovir
Lamivudine
NONE
Darunavir/r + Raltegravir*
PI + INSTI
* - Viral load <100,000 copies/mL (and CD4+ >200 for DRV/RAL)
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Available at

69. Regimen Notes
Patients receiving any regimen with abacavir must be HLA-B*5701 negative
Patients receiving a regimen with cobicistat and TDF must have a pre-treatment CrCl ≥70 mL/min
Patients must have a viral load <100,000 when initiating Complera (RPV/FTC/TDF) and the 2 other regimens noted in the Other Regimens slide
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Available at

70. Regimen Notes
Emtricitabine/tenofovir (Truvada) and abacavir/lamivudine (Epzicom) are the preferred NRTI backbones
No CCR5 antagonists or fusion inhibitors are Recommended, Alternative, or Other regimens
There are a total of 6 single tablet regimens; 3 are preferred
Genvoya, Triumeq, Stribild
Other 3 are alternatives
Atripla, Complera, Odefsey (anticipated by me)
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Available at

71. Regimen Notes
Tenofovir disoproxil fumarate – use with caution in patients with renal insufficiency
Efavirenz is teratogenic; do not include in regimens for women who may become pregnant
Atazanavir should not be used with >20mg of omeprazole (or equivalent PPI dose). Administer ATV >12 hours after a dose of a PPI
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Available at

72. Regimen Notes
Rilpivirine is not recommended in patients with a viral load > 100,000 copies/mL
PPIs are contraindicated with RPV
Do not start EVG/cobi/TDF/FTC (Stribild) in patients with CrCl <70mL/min
Change regimen if CrCl falls below 50mL/min
EVG/cobi/TAF/FTC (Genvoya) may be used in all patients with CrCl >30mL/min

73. Choosing a Regimen Least adverse effects Durability Drug interactions
INSTI-based
Durability
PI-based
Drug interactions
INSTI based (usually)
Single tablet regimen
INSTI- or NNRTI-based

74. Emphasize Benefits of Therapy
Reduces AIDS-related complications
Prolongation of disease-free survival
Viral suppression
Preservation of immune function
Decreased risk of disease transmission
Reduction of HIV-associated nephropathy, cardiovascular disease, malignancies, neurocognitive decline
Non opportunistic related disease – HIV-associated nephropathy, cardiovascular disease, malignancies, neurocognitive decline (HIV dementia), younger pts may have more robust response with CD4 count
Untreated HIV infection – high level inflammation and t-cell activation
Reduced transmission – mother to child and to partners, lower plasma RNA levels decreases amount in genital secretions
Risks
Drug related effects – cardiovascular risks?, bone toxicities (
DHHS Guidelines: Adults & Adolescents. Feb 12, 2013

75. Interventions to Improve Adherence
Delivery of prescriptions
Often disadvantaged populations
Automatic refills
Paying for medications
Ryan White programs
PAPs
Other state and federal programs
Dealing with insurance issues to ensure there is not a lapse in therapy

76. XY is a 45 year old patient newly diagnosed with HIV
XY is a 45 year old patient newly diagnosed with HIV. His CD4+ count is 373 cells/mm3 and viral load is 210,794 copies/mL. He also has CKD with a CrCl of 40mL/min. What is the only first line single tablet regimen recommended for XY?
Genvoya
Atripla
Triumeq
Stribild
Complera

77. Which of the following Patients with HIV should begin therapy?
16 year old pregnant female with a CD4 count of 797 cells/mm3 and a viral load of 7,384 copies/mL
26 year old otherwise healthy male with a CD4 count of 797 cells/mm3 and a viral load of 984 copies/mL
36 year old female with Kaposi’s sarcoma and a CD4 count of 77 cells/mm3 and a viral load of 797,384 copies/mL
51 year old male with diabetes and a CD4 count of 501 cells/mm3 and a viral load of 97,384 copies/mL
All of these patients should begin therapy

78. Which set of the following drugs all contain the pharmacokinetic booster cobicistat (Tybost®)?
Prezista, Stribild, and Tivicay, Vitekta
Evotaz, Prezista, Tivicay, Vitekta
Genvoya, Kaletra, Prezcobix, Triumeq
Evotaz, Genvoya, Prezcobix, Stribild
Prezcobix, Triumeq, Tivicay, Vitekta

79. Summary & Questions?
Many new therapies are available which give new options to patients seeking alternatives
All patients should be treated regardless of CD4+ count or viral load
Regimens should be individualized based on specific patient parameters
Adherence
Drug interactions
Adverse effects
Durability

80. Resources AIDSinfo Centers for Disease Control and Prevention (CDC)
Guidelines and other resources
Centers for Disease Control and Prevention (CDC)
Fact sheets, slide sets, testing and surveillance
World Health Organization
International data, facts and statistics
Positively Aware
Annual HIV Drug Guide and other resources