The HIV Diagnosis
Management of the HIV-infected patient in the
primary care setting
Lauren Pence, PharmD
Ambulatory Care Clinical Pharmacy Specialist, Eskenazi Health
Thursday, September 18, 2014
This speaker has no actual or potential conflicts of interest to disclose in
relation to this presentation
 Identify the role of the primary care healthcare team in
management of HIV patients
 Describe how current antiretroviral medications inhibit the
mechanism of infection of the HIV retrovirus
 Develop a “checklist” for appropriate considerations in
primary care patients with HIV
 Identify common adverse effects of current antiretroviral
medication
The HIV
Diagnosis
 You are a successful and cheerful pharmacist in 2014
 You attend a conference with a presentation on HIV infection in
the primary care setting. There is a special at Jimmy John’s
across the street and they are giving your favorite sandwich
away for free.
 What do you choose to do?
A
SKIP IT
I won’t be
seeing HIV
patients in my
practice,
anyway
B
SKIP IT
I feel comfortable
with HIV
management, and
Jimmy John’s is
delicious
C
ATTEND
They have free
lunch at the
conference,
anyway
• Unfortunately, your friend who told you about this Jimmy
John’s giveaway was mistaken, and it turns out they gave away
free sandwiches yesterday. The store is closed and you get no
lunch.
• You return to your ambulatory care practice after the
conference with a new patient with HIV on your physicians’
schedule. You forget the names of the HIV medications, but
don’t have the handout to reference that was given at the
lecture. You are hungry and sad.
Here’s to better luck next time…
• You attend the presentation and learn a few new things about
how to monitor HIV patients.
• You return to your ambulatory care clinic after the conference
with a new patient with HIV on one of your physicians’
schedule. You remember the adverse effects of the patients
HAART regimen from the lecture, and recommend the
appropriate labs. Your physician is very impressed with your
HIV knowledge.
Congratulations! Continue to the next adventure…
Danish HIV cohort study - 2006
“By 2015, more than 50% of HIV-positive patients will
be older than 50 years.”
Atherosclerosis. 2011;219:384-389
Cause of Death in HIV-Infected Patients
8%
AIDS Related Death
7%
Non-AIDS malignancy
Non-AIDS infection
CVD
8%
CVD Death:
MI/Ischemic:
49%3.2%
Stroke: 1.4%
Other: 3.3%
8%
Violence
Hepatic
Other
8%
12%
Antiretroviral Cohort Collabortation Clin Infect Dis. 2010;15;50(10):1387-96
Cardiovascular
disease
AIDS
enteropathy
Reduced bone
mineral density
Neurocognitive
disorders
Dyslipidemia,
metabolic
abnormalities
Nephropathy
Complications of HIV Infection: A Systems-Based Approach. American Family Physician. 2011:83:4
http://colgateimmunology.blogspot.com
Nucleoside Reverse
Transcriptase
Inhibitors (NRTI)
Non-Nucleoside
Protease Inhibitor (PI)
Reverse Transcriptase  Atazanavir (ATV)
Inhibitors (NNRTI)
 Darunavir (DRV)












Abacavir (ABC)
Didanosine (ddI)
Emtricitabine (FTC)
Lamivudine (3TC)
Stavudine (d4T)
Tenofovir (TDF)
Zidovudine (AZT,ZDV)
Integrase Inhibitor
 Raltegravir (RAL)
 Elvitegravir (EVG)*
 Dolutegravir (DOL)
Delaviridine (DLV)
Efavirenz (EFV)
Etravirine (ETR)
Nevirapine (NVP)
Rilpivirine (RPV)
Fusion Inhibitor







Fosamprenavir (FPV)
Indinavir (IDV)
Lopinavir (LPV)*
Nelfinavir (NFV)
Ritonavir (RTV)
Saquinavir (SQV)
Tipranavir (TPV)
 Enfuvirtide (ENF)
CCR5 Antagonist
 Maraviroc (MVC)
www.aidsinfo.nih.gov. January 2014
NNRTI
Atazanavir +
ritonavir
Two NRTIs
- Tenofovir
Efavirenz
Protease Inhibitor
- Emtricitabine
Darunavir +
ritonavir
Integrase
Inhibitor
Raltegravir
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of
antiretroviral agents in HIV-1 infected adults and adolescents. DHHS
Advantages







Abacavir (ABC)
Didanosine (ddI)
Emtricitabine (FTC)
Lamivudine (3TC)
Stavudine (d4T)
Tenofovir (TDF)
Zidovudine (AZT,ZDV)
• Well tolerated medications
• Minimal drug interactions
• Once daily combination products
Disadvantages:
• Possible increase in cardiovascular
events (ABC/3TC)
• Tenofovir: potential for renal
impairment, decreased BMD
• Zidovudine: bone marrow
suppression, GI intolerance
NNRTI
Two NRTIs
- Tenofovir
- Emtricitabine
Efavirenz
Atazanavir +
ritonavir
Protease
Inhibitor
Integrase
Inhibitor
Darunavir +
ritonavir
Raltegravir
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of
antiretroviral agents in HIV-1 infected adults and adolescents. DHHS
Advantages




Delaviridine (DLV)
Efavirenz (EFV)
Etravirine (ETR)
Nevirapine (NVP)
 Rilpivirine (RPV)
• Well tolerated medications
• Minimal drug interactions
Disadvantages:
• Greater risk of resistance with
treatment failure
• Cross resistance potential
• Serious skin rash
• Rilpivirine - meal requirement
• Efavirenz – teratogenicity, lipid
abnormalities
NNRTI
Two NRTIs
- Tenofovir
- Emtricitabine
Protease
Inhibitor
Integrase
Inhibitor
Efavirenz
Atazanavir +
ritonavir
Darunavir +
ritonavir
Raltegravir
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of
antiretroviral agents in HIV-1 infected adults and adolescents. DHHS









Atazanavir (ATV)
Darunavir (DRV)
Fosamprenavir (FPV)
Indinavir (IDV)
Lopinavir (LPV)
Nelfinavir (NFV)
Ritonavir (RTV)
Saquinavir (SQV)
Tipranavir (TPV)
Advantages
• Higher barrier to resistance
Disadvantages:
• Metabolic complications:
• Dyslipidemia
• Insulin resistance
• Hepatotoxicity
• GI adverse effects
• Drug interactions
• Strong CYP3A4 inhibitors
NNRTI
Two NRTIs
- Tenofovir
- Emtricitabine
Efavirenz
Atazanavir +
ritonavir
Protease
Inhibitor
Darunavir +
ritonavir
Integrase
Inhibitor
Raltegravir
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of
antiretroviral agents in HIV-1 infected adults and adolescents. DHHS
Advantages:
Integrase Inhibitor
 Raltegravir (RAL)
 Elvitegravir (EVG)
 Dolutegravir (DOL)
• Well tolerated medications
• Fewer drug interactions
Disadvantages:
• Lower barrier to resistance
• Newer agents = higher cost
• Elvitegravir w/ cobicistat
• Decreased CrCl
• Drug interactions: CYP3A4 inhibitor
• Raltegravir: rhabdomyolysis and
hypersensitivity reactions
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


46 yo AA female with HIV, HTN, and tobacco dependence
HAART regimen of boosted darunavir/tenofovir/emtricitabine
ASCVD 10-year risk of 7.8%, LDL of 176
Is a statin indicated in this patient? If so, what regimen would you
initiate?
AYES
Initiate
atorvastatin 40
mg daily
B YES
Initiate
simvastatin
40 mg daily
CYES
Initiate
rosuvastatin
20 mg daily
 Per the lipid guidelines, this patient qualifies for a moderate or
high intensity statin.
 However, it is recommended to start a lower dose of
atorvastatin in patients also taking a protease inhibitor.
 Your patient develops muscle aches and myalgias shortly after
initiating treatment and stops therapy.
Here’s to better luck next time…
 Per the lipid guidelines, this patient qualifies for a moderate or
high intensity statin.
 However, simvastatin is contraindicated in patients taking
protease inhibitors.
 Your patient develops muscle aches and myalgias shortly after
initiating treatment and stops therapy.
Here’s to better luck next time…
 Per the lipid guidelines, this patient qualifies for a moderate or
high intensity statin.
 The patient presents to your next visit in 3 months, and her
LDL is 98. She has no complaints or concerns.
Congratulations! Continue to the next adventure…
Statin
Protease Inhibitor
NNRTI
Atorvastatin
Use lowest starting dose
Efavirenz – may need higher dose
Fluvastatin
Lovastatin
Etravirine – may need lower dose
CONTRAINDICATED
Pitavastatin
No data available
Pravastatin
Caution with darunavir
Rosuvastatin
Caution with
lopinavir/ritonavir
Simvastatin
CONTRAINDICATED
Efavirenz – may need higher dose
Efavirenz – may need higher dose
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of
antiretroviral agents in HIV-1 infected adults and adolescents. DHHS




46 yo AA female with HIV, HTN, tobacco dependence
HAART regimen of boosted darunavir/tenofovir/emtricitabine
ASCVD 10-year risk of 7.8%, LDL of 176
Is a statin indicated in this patient? If so, what regimen would you
initiate?
AYES
Initiate
atorvastatin 40
mg daily
B YES
Initiate
simvastatin
40 mg daily
CYES
Initiate
rosuvastatin
20 mg daily
Dyslipidemia
 Risk factors:
 Traditional risk factors
 HIV infection itself
 ARVs: PIs, efavirenz
Diabetes Mellitus
 Risk factors:
 Traditional risk factors
 HIV infection itself
 Older PIs: nelfinavir, lopinavir
Recommendations
Recommendations
 Screen: FLP prior and 1-3 months  Screen: HgA1c or fasting glucose
after ART
prior and 1-3 months after ART
 Treat: according to lipid guidelines  Treat: according to ADA guidelines
 Drug interactions with some
PIs/NRTIs and statins
Primary Care Guidelines for the Management of Persons Infected with HIV. Clin Infect Dis. 2013




54 yo AA male with HIV, type II DM, HTN, dyslipidemia
HAART regimen of boosted atazanavir/tenofovir/emtricitabine
Patients presents with symptoms of dyspepsia, heartburn
What acid suppressing agent would you start in this patient?
A PPI
Initiate
omeprazole 40
mg daily
B H2RA
Initiate
ranitidine
150 mg BID
C Antacid
Initiate calcium
carbonate
 Absorption of boosted atazanavir can be decreased with
simultaneous administration of PPIs. Therefore, PPIs are not
recommended in PI-experienced patients
 After prescribing your patient omeprazole 40 mg, the patient
is not adequately absorbing his boosted atazanavir, leading to
possible resistance.
Here’s to better luck next time…
 Absorption of boosted atazanavir can be decreased with
administration of certain acid suppressing agents, if not
administered at the appropriate time.
 After prescribing your patient ranitidine 150 mg BID but not
counseling him on the appropriate timing of the doses, the
patient takes it inappropriately and is not adequately
absorbing his boosted atazanavir, leading to possible
resistance.
Here’s to better luck next time…
 If patient takes calcium carbonate simultaneously with
boosted atazanavir, decreased atazanavir concentrations are
expected
 After prescribing your patient calcium carbonate but not
counseling him on the appropriate timing of the doses, the
patient takes it simultaneous with his HAART regimen and is
not adequately absorbing his boosted atazanavir, leading to
possible resistance.
Here’s to better luck next time…
Antiretrovirals with food
requirement
 Efavirenz - empty stomach
 Rilpivirine - at least 400 kcal
 Atazanavir - with food
 Ritonavir - with food
Antiretrovirals interacting with
acid suppressants
 Atazanavir/ritonavir
 Antacid: 2 hr before or 1 hr after
 H2RA: Simultaneous or > 10 hr before
 PPIs not recommended in
PI-experienced patients
 Rilpivirine
 Antacid: 2 hr before or 4 hr after
 H2RA: 12 hr before or 4 hr after
 PPIs contraindicated
 Elvitegravir
 Antacid: Separate by 2 hours




54 yo AA male with HIV, type II DM, HTN, dyslipidemia
HAART regimen of boosted atazanavir/tenofovir/emtricitabine
Patients presents with symptoms of dyspepsia, heartburn
What acid suppressing agent would you start in this patient?
A PPI
Initiate
omeprazole 40
mg daily
B H2RA
Initiate
ranitidine
150 mg BID
C Antacid
Initiate calcium
carbonate
 28 yo hispanic female with HIV, asthma
 HAART regimen of efavirenz/tenofovir/emtricitabine
 Patient states she is using condoms as her preferred birth
control method, and states she does not want to conceive.
 Is this an appropriate contraception regimen? What would you
recommend as the most appropriate regimen?
A YES
Condoms also
reduce HIV
transmission
and STD risk
B NO
Prescribe
combined oral
contraceptive in
addition to
condoms
C NO
Prescribe depoprovera in
addition to
condoms
 Condoms are recommended to prevent pregnancy, but also to
decrease HIV and other sexually-transmitted infections
 Recommendations encourage patients to use a secondary
method of contraception to decrease the risk of unplanned
pregnancy
 Your patient is not currently using effective contraception, and
is currently at risk for an unplanned pregnancy while on
efavirenz, which is teratogenic.
Here’s to better luck next time…
 A secondary type of contraception is recommended in
addition to condoms.
 Efavirenz decreases the concentrations of levornogestrel and
norgestimate.
 You choose a combined oral contraception product that does
not interact with efavirenz, and your patient is adequately
protected from unplanned pregnancy while on a teratogenic
medication (efavirenz)
Congratulations! Continue to the next adventure…
 A secondary type of contraception is recommended in
addition to condoms.
 Efavirenz does not interact with the depo-provera injection,
however, both depo-provera and tenofovir run the risk of
decreased bone mineral density
 Your patient is adequately protected from unplanned
pregnancy while on a teratogenic medication (efavirenz),
however, suffers a right tibia fracture five years later.
Here’s to better luck next time…
Recommendations:
 Condom use: Contraception, STD protection, HIV transmission
 Encourage second method of protection
 Drug interactions with combined hormonal contraceptives
 IUD use: Safe and effective. No increase in HIV viral shedding
ARV
Effect on hormone levels
Recommendation
Atazanavir/ritonavir
 Ethinyl estradiol
Contain at least 35 mcg
ethinyl estradiol
Other boosted PIs
 All hormone levels
Additional method
Efavirenz
 Levornogestrel and
norgestimate (progestins)
Additional method
Nevirapine
 Ethinyl estradiol
Additional method
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of
antiretroviral agents in HIV-1 infected adults and adolescents. DHHS
 28 yo hispanic female with HIV, asthma
 HAART regimen of efavirenz/tenofovir/emtricitabine
 Patient states she is using condoms as her preferred birth
control method, and states she does not want to conceive.
 Is this an appropriate contraception regimen? What would you
recommend as the most appropriate regimen?
A YES
Condoms also
reduce HIV
transmission
and STD risk
B NO
Prescribe
combined oral
contraceptive in
addition to
condoms
C NO
Prescribe depoprovera in
addition to
condoms
 Risk factors:
 HIV infection – as compared to individuals without HIV infection:
 Increase in fracture rate by 30-70%
 Three-fold increase in osteoporosis risk
 Increase in Vitamin D deficiency prevalence of 60-75%
 Antiretrovirals or uncontrolled viremia
 Recommendations:
 Screen: Baseline DXA scan should be completed in
postmenopausal women and men aged > 50 years
 Periodic monitoring thereafter – assess other risk factors
 Treat: According to NOF guidelines:
 Vitamin D and/or calcium supplementation
 Bisphosphonate if indicated
Primary Care Guidelines for the Management of Persons Infected with HIV. Clin Infect Dis. 2013
 DHHS Treatment Guidelines
 www.aidsinfo.nih.gov/guidelines
 Database of antiretroviral drug interactions
 http://hivinsite.ucsf.edu
 HIV-drug interactions – University of Liverpool
 www.hiv-druginteractions.org
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
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

38 yo caucasian female with HIV, asthma, hyperlipidemia, HTN
HAART regimen of efavirenz/tenofovir/emtricitabine
CD4 count of 284 cells/mcL
PPV23 (Pneumovax) received 8/2/2011
Does the patient require further pneumococcal vaccination?
A NO
Patient’s CD4
count is too low
to vaccinate
B YES
One dose of
PCV13 today,
then PPV23 in 5
years
C YES
Another dose of
PPV23 five
years after the
original dose
 Patients with HIV are eligible for all vaccinations if the CD4
count is > 200 cells/mcL
 Without further vaccinations, this patient is not appropriately
immunized and is at risk for pneumococcal infection.
Here’s to better luck next time…
 After receiving the PCV13 vaccination today, the patient is
appropriately immunized against pneumococcal infection.
 The patient receives the second dose of PPV23 in five years,
and does not develop pneumonia.
Congratulations! Continue to the next adventure…
 It is recommended that this patient receive a dose of PCV13
one year after the original PPV23 vaccination, prior to
revaccination with PPV23 in 5 years.
 Without the PCV13 vaccination, this patient is not
appropriately immunized and is at risk for pneumococcal
infection.
Here’s to better luck next time…
• If no previous pneumococcal vaccination:
PCV 13
PPV23
in 8 weeks
PPV23
5
years later
• If previous pneumococcal vaccination:
PCV 13 after
at least one
year
PPV23
5 years later
Adapted from the Advisory Committee on Immunization Practices (ACIP) 2013 Adult Immunization Schedule
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
32 yo caucasian male with HIV, Type II DM, HTN, GERD
Newly diagnosed with HIV
HAART regimen of efavirenz/tenofovir/emtricitabine
CD4 count of 184 cells/mcL, viral load of 19,438 copies/mL
Does this patient require prophylaxis for an OI?
A YES
Initiate
TMP/SMX DS
daily
B NO
OI prophylaxis
not indicated
until CD4 count
< 100 cells/mcL
C YES
Initiate
TMP/SMX DS
daily and
itraconazole
200 mg
 This patient begins taking one TMP/SMX DS tablet daily per
your request.
 The patient is appropriately protected against pneumocystis
jirovecci pneumonia
Congratulations! Continue to the next adventure…
 Opportunistic infection prophylaxis is indicated after CD4
count decreases below 200 cells/mcL
 The patient is not appropriately protected against
pneumocystis jirovecci pneumonia
Here’s to better luck next time…
 This patient begins taking one TMP/SMX DS tablet daily per
your request.
 The patient is appropriately protected against pneumocystis
jirovecci pneumonia. However, the itraconazole is not
indicated until CD4 count decreases below 150 cells/mcL.
 The patient experiences significant nausea, to which he stops
both the TMP/SMX DS and itraconazole 10 days after
initiation.
Here’s to better luck next time…
Bug
Prophylaxis
Agents
Prophylaxis
Initiation
Stopping
prophylaxis
Pneumocystis
jiroveccii
(Fungus/Protozoa)
TMP/SMX DS
daily
CD4 < 200
or AIDS-defining
illness
CD4 > 200
for > 3 months
Toxoplasma gondii
(protozoa)
TMP/SMX DS
daily
CD4 < 100
CD4 > 200
for > 3 months
Histoplasmosis
capsulatum
(fungus)
Itraconazole
200 mg
CD4 < 150 living
in endemic areas
CD4 > 150
for > 6 months
Mycobacterium
Avium
Azithromycin or
Clarithromycin
CD4 < 50
CD4 > 100
for > 3 months
2014 CDC, NIH, HIV IDSA Guidelines for the prevention and
treatment of opportunistic infections in HIV-infected adults and adolescents





32 yo caucasian male with HIV, Type II DM, HTN, GERD
Newly diagnosed with HIV
HAART regimen of efavirenz/tenofovir/emtricitabine
CD4 count of 184 cells/mcL, viral load of 19,438 copies/mL
Does this patient require prophylaxis for an OI?
A YES
Initiate
TMP/SMX DS
daily
B NO
OI prophylaxis
not indicated
until CD4 count
< 100 cells/mcL
C YES
Initiate
TMP/SMX DS
daily and
itraconazole
200 mg
 HIV is a complex disease state that will be seen more
commonly in the primary care setting due to the “chronic”
nature of the disease when treated appropriately
 Important items to monitor in the primary care setting include:
 Metabolic abnormalities
 Contraceptive choice and interactions
 GI complaints and drug interactions
 Osteoporosis
 Vaccinations
 Opportunistic infection prophylaxis
The HIV Diagnosis
Management of the HIV-infected patient in the
primary care setting
Lauren Pence, PharmD
Ambulatory Care Clinical Pharmacy Specialist, Eskenazi Health
Thursday, September 18, 2014