Download presentation
Presentation is loading. Please wait.
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
Similar presentations
© 2025 SlidePlayer.com Inc.
All rights reserved.