The document discusses pharmacy essentials for HIV screening and management, supported by educational grants. It includes data on the prevalence and demographics of HIV in the U.S., risk assessment, testing recommendations, and details about antiretroviral pharmacology. Key topics also include treatment adherence, drug interactions, and the societal influences on the HIV epidemic.

1. Pharmacy Essentials for HIV Screening and
Management
This activity is supported by independent educational grants from
Gilead Sciences and ViiV Healthcare.

2. About These Slides
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permissions@clinicaloptions.com for details
Slide credit: clinicaloptions.com

3. Faculty
Jennifer Cocohoba, PharmD
Professor
Department of Clinical Pharmacy
University of California, San Francisco
San Francisco, California
Jennifer Cocohoba, PharmD, has no real or apparent conflicts of interest to
report.

4. Program Overview
 A Contemporary Picture of HIV in the United States
 Assessing Risk and Testing for HIV
 ARV Pharmacology
 Treatment of HIV
 Essential ART Drug–Drug Interactions
 Supporting Treatment Adherence
Slide credit: clinicaloptions.com

5. A Contemporary Picture of
HIV in the United States

6. HIV by the Numbers
1.1
Million people living
with HIV/AIDS
38,739
New HIV diagnoses
(2017)
6465
Deaths due to HIV
(2015 estimate; final
2015 analysis: 6160)
Slide credit: clinicaloptions.com
CDC. HIV Surveillance Report, 2017;29. Xu. Natl Vital Stat Rep. 2018;67:1.
CDC. HIV Surveillance Supplemental Report. 2018;23.

7. Estimated HIV Prevalence in US Among Persons Aged
≥ 13 Yrs, by Area of Residence, 2015
Slide credit: clinicaloptions.com
Total = 1,122,900
*Estimate has relative standard error of 30% to 50%, should be used with caution because does not meet standard of reliability.
CDC. HIV Surveillance Supplemental Report. 2018;23.
Number
330-2900
2901-10,800
10,801-23,500
23,501-142,600
WA
14,500
OR
7500
CA
141,700
NV
10,800
AZ
18,000
UT
3200
ID
1100
MT
670*
WY
330*
CO
13,100
NM
3800
TX
99,600
OK
6700
KS
3300
NE
2400
SD
560*
ND
400* MN
9000
IA
2900
MO
13,700
AR
6200
LA
23,700
IL
40,900
WI
7000 MI
17,600
IN
12,900
OH
23,500
MS
10,600
AL
14,500
GA
58,700
124,400
FL
SC
19,200
TN 19,300 NC 34,800
VA
24,900
PA
36,800
NY
142,600
ME 1700
NH 1400
MA 22,600
RI 2700
CT 11,500
NJ 38,800
MD 37,900
DE 3700
DC 17,400
WV 2000
VT 710
KY 7800
AK 790* HI 3200

8. HIV by the Numbers
1.1
Million people living
with HIV/AIDS
38,739
New HIV diagnoses
(2017)
6465
Deaths due to HIV
(2015 estimate; final
2015 analysis: 6160)
Slide credit: clinicaloptions.com
75% male
75% aged 40 yrs or older
48% heterosexual
41% black/African American
98% with health insurance
or other ART coverage
46% living at/below federal
poverty threshold
CDC. HIV Surveillance Report, 2017;29. Xu. Natl Vital Stat Rep. 2018;67:1.
CDC. HIV Surveillance Supplemental Report. 2018;23. CDC. HIV Surveillance Special Report 20.

9. Estimated HIV Incidence in US Among Persons Aged
≥ 13 Yrs, by Area of Residence, 2015
Total = 38,500
Slide credit: clinicaloptions.com
*Estimate has relative standard error of 30% to 50%, should be used with caution because does not meet standard of reliability.
CDC. HIV Surveillance Supplemental Report. 2018;23.
Number
Relative standard error
> 50%; data not shown
120-390
391-810
811-5100
WA
450
OR
170*
CA
5100
NV
500
AZ
18,000
UT
120*
ID
MT
WY
CO
340*
NM
TX
4400
OK
260*
KS
NE
SD
ND
MN
270*
IA
MO
390
AR
230*
LA
100
IL
1400
WI
250* MI
700
IN
800
OH
770
MS
350*
AL
540
GA
2400
5100
FL
SC
590
TN 730 NC 1300
VA
970
PA
810
NY
3300
MA 640
RI --
CT 270*
NJ 880
MD 1100
DE --
DC 420
VT
KY 310*
AK HI 150*
WV
NH
ME

10. HIV by the Numbers
1.1
Million people living
with HIV/AIDS
38,739
New HIV diagnoses
(2017)
6465
Deaths due to HIV
(2015 estimate; final
2015 analysis: 6160)
Slide credit: clinicaloptions.com
CDC. HIV Surveillance Report, 2017;29. Xu. Natl Vital Stat Rep. 2018;67:1.
CDC. HIV Surveillance Supplemental Report. 2018;23. CDC. HIV Surveillance Special Report 20.
82% male
Increasing among persons
aged 25-34 yrs
68% male-to-male sexual
contact
Highest proportion among
Black/African Americans vs
other races/ethnicities
75% male
75% aged 40 yrs or older
48% heterosexual
41% black/African American
98% with health insurance
or other ART coverage
46% living at/below federal
poverty threshold

11. Age-Adjusted* Rates† of Death Among Persons With
Diagnosed HIV Infection by State, 2015
Slide credit: clinicaloptions.comCDC. HIV mortality (through 2015).
Rates per 1000 persons living
with diagnosed HIV infection
6.4-11.2
11.3-13.2
13.3-15.3
15.4-33.3
WA
14.7
OR
14.5
CA
10.3
NV
11.6
AZ
11.8
UT
6.6
ID
11.4
MT
12.3
WY
13.2
CO
7.0
NM
21.2
TX
14.2
OK
19.6
KS
18.0
NE
10.8
SD
10.2
ND
33.3 MN
13.5
IA
11.5
MO
11.2
AR
13.8
LA
17.5
IL
11.6
WI
11.1* MI
14.9
IN
14.3
OH
11.8
MS
20.3
AL
11.5
GA
16.4
15.4
FL
SC
14.8
TN 17.5 NC 16.3
VA
8.3
PA
14.6
NY
9.9
KY 13.7
AK 16.2 HI 7.0
ME 9.7
NH 15.3
MA 11.5
RI 9.1
CT 12.7
NJ 12.5
MD 13.5
DE 13.6
DC 12.7
WV 16.4
VT 6.4
Deaths may be due to any cause. *Standard: age distribution
of 2000 US population. †Per 100,000 persons living with diagnosed HIV infection.

12. Modern Influences on the HIV Epidemic
 Potent modern ART
 HIV treatment in primary
care
 Continued efforts to test
and treat hard to reach
populations
 Advent of pre-exposure
prophylaxis
 Persistent socioeconomic
disparities
 Continued stigma,
trauma, and violence
 Opioid epidemic
Slide credit: clinicaloptions.com

13. HIV by the Numbers
1.1
Million people living
with HIV/AIDS
38,739
New HIV diagnoses
(2017)
6465
Deaths due to HIV
(2015 estimate; final
2015 analysis: 6160)
Slide credit: clinicaloptions.com
Median age: 52 yrs
Highest rate in black/African
Americans
Second highest rate among
Hispanics/Latinos
CDC. HIV Surveillance Report, 2017;29. Xu. Natl Vital Stat Rep. 2018;67:1. CDC. HIV Surveillance Supplemental Report.
2018;23. CDC. HIV Surveillance Special Report 20. CDC. HIV mortality (through 2015).
75% male
75% aged 40 yrs or older
48% heterosexual
41% black/African American
98% with health insurance
or other ART coverage
46% living at/below federal
poverty threshold
82% male
Increasing among persons
aged 25-34 yrs
68% male-to-male sexual
contact
Highest proportion among
Black/African Americans vs
other races/ethnicities

14. Assessing Risk and Testing for HIV

15. Patient Case
 25-yr-old male brings a home HIV test kit to the pharmacy counter to
purchase
 Had sex with new partner of unknown HIV status last night
 Worried about acquiring HIV
Slide credit: clinicaloptions.com

16. HIV Transmission and Risk
Infectious fluid +
 Blood
 Semen
 Vaginal secretions
 Breast milk
 CSF
Portal of entry
 Mucous membrane
 Open cut
Slide credit: clinicaloptions.comCDC. HIV Risk Behaviors.
Estimated per Act Probability of Acquiring HIV From
Infected Source by Type of Exposure*
Risk per 10,000
Exposures
Parenteral
 Blood transfusion
 Needle-sharing during IDU
 Percutaneous (needlestick)
9250
63
23
Sexual
 Receptive anal intercourse
 Insertive anal intercourse
 Receptive penile-vaginal intercourse
 Insertive penile-vaginal intercourse
 Receptive or insertive oral intercourse
138
11
8
4
Low
Other
 Biting, spitting, throwing body fluids (including
semen or saliva), or sharing sex toys
Negligible
*Factors that may increase (STDs, acute or late-stage HIV, high viral load) or decrease (condom
use, male circumcision, ART, PrEP) risk not accounted for in these estimates.

17. Get Comfortable Asking Questions
Health history
 Occupational and other blood exposures
 Sexual history (currently having sex, number of partners, gender of
partners, sexual practices)
Assessing other risk behaviors
 Legal drug use (types, how much, how often)
 Illicit drug use (types, how much, how often)
What is known about people they have sex with or use with (eg, HIV
status)?
Slide credit: clinicaloptions.com

18. HIV Testing: Who, When, How Often
Population Testing Notes
Persons aged 13-64 yrs At least once
If population prevalence < 0.1%,
may be deferred; USPSTF
recommends testing individuals
aged 15-65 yrs
Patients with TB or STDs Routinely (during episode)
Pregnant women
Early during prenatal care, also in
third trimester if high risk
High risk for HIV (including
gay, bisexual, MSM, IDU)
Annually
Some clinicians offer screening
more frequently (every 3-6 mos)
Slide credit: clinicaloptions.com
Branson. MMWR Recomm Rep. 2006;55:RR-14. Moyer. Ann Intern Med. 2013;159:51.
DiNenno. MMWR Morb Mortal Wkly Rep. 2017;66:830.

19. Detection of HIV Particles and Testing
Slide credit: clinicaloptions.comCDC. HIV testing. 2014, 2018.
Detects
Ab only
Detects Ab + p24
Standard test type
for rapid testing or
home testing kits
Recommended for
lab use; rapid test
available
Not routinely used for screening; useful
for identifying early/acute infection
0 10 20 30 40 50 60 70 80 90 100
Time Since Infection, d
11 17 22
HIV RNA (plasma)
HIV p24 antigen
HIV antibody
First-generation EIA
Second-generation EIA
Third-generation EIA
Fourth-generation EIA
NAT
Detects HIV-1 RNA

20. CDC Recommended Laboratory HIV Testing Algorithm
for Serum or Plasma Samples
Slide credit: clinicaloptions.comCDC. HIV testing. 2014, 2018.
HIV-1/2 antigen/antibody immunoassay
(-)
Negative for HIV-1 and HIV-2
antibodies and p24 Ag
(+)
HIV-1/HIV-2 antibody differentiation immunoassay
HIV-1 (+)
HIV-2 (-)
HIV-1 antibodies
detected
HIV-1 (-)
HIV-2 (+)
HIV-2 antibodies
detected
HIV-1 (+)
HIV-2 (+)
HIV antibodies
detected
HIV-1 (-) or indeterminate
and
HIV-2 (-) or indeterminate
HIV-1 NAT (+)
Acute HIV-1 infection
HIV-1 NAT (-)
Negative for HIV-1
(+) indicates reactive test result
(-) indicates nonreactive test result
HIV-1 NAT

21. HIV Testing in Community Pharmacies
Slide credit: clinicaloptions.com
Weidle PJ. J Am Pharm Assoc (2003). 2014:54;486. Amesty. AIDS Patient
Care STDS. 2015:29;437. Darinl. J Am Pharm Assoc (2003). 2015;55:81.
Common Features
 Assessment of local context/need
 Relationships with local health
department
 CLIA waiver/use of rapid oral fluid
HIV tests
 Training of > 1 staff member
 Time to administer ~ 30 mins
Program Considerations
 Best forms of advertisement/
recruitment
 Charge for test or not
 Private counseling area
 Investment required to train staff
 Establishing linkage to care

22. CDC Toolkit for HIV Testing in Retail Pharmacies
Slide credit: clinicaloptions.comCDC. Effective Interventions. Prevention that works.

23. Diagnosed Infection Among Persons Aged ≥ 13 Yrs
Living With HIV: 2015
Total = 85.5%
Slide credit: clinicaloptions.comCDC. HIV Surveillance Supplemental Report. 2018;23.
Percentage
81.5-84.5
84.6-85.7
85.8-89.9
90.0-94.3
Data classified manually
WA
85.4
OR
86.9
CA
85.7
NV
82.1
AZ
84.3
UT
84.7
ID
94.3
MT
85.0
WY
85.2
CO
87.5
NM
84.0
TX
81.5
OK
85.2
KS
85.9
NE
85.1
SD
89.8
ND
82.5 MN
85.4
IA
83.7
MO
86.4
AR
84.5
LA
81.7
IL
86.0
WI
84.2 MI
81.9
IN
82.3
OH
87.3
MS
86.2
AL
84.1
GA
83.5
84.5
FL
SC
83.8
TN 84.4
NC 84.8
VA
85.7
PA
91.7
NY
88.4
ME 85.4
NH 86.6
MA 85.6
RI 85.2
CT 88.8
NJ 90.3
MD 86.0
DE 87.1
DC 85.1
WV 87.1
KY 84.9
AK 82.5 HI 86.3

24. Antiretroviral Pharmacology

25. Mechanism of Action of ARVs
Maturation
Entry and attachment
at gp41 and CCR5
Penetration
Viral uncoating
Nucleic acid synthesis
via reverse transcriptase
Protein synthesis
via HIV protease
Packaging/assembly
Integration
via integrase
Release
maraviroc
enfuvirtide
ibalizumab
abacavir, emtricitabine,
lamivudine , tenofovir DF or AF
doravirine, efavirenz, rilpivirine
bictegravir, dolutegravir,
raltegravir
atazanavir, darunavir, ritonavir
Slide credit: clinicaloptions.comAdapted from Katzung. Basic and Clinical Pharmacology.

26. Nucleoside/tide Reverse Transcriptase Inhibitors
(NRTIs)
Mechanism of
action
Inhibit HIV viral DNA synthesis by competing with
endogenous nucleosides, causing chain termination
Class-related
adverse events
Lactic acidosis, mitochondrial toxicity, hepatic
steatosis (rare)
Metabolism Renally cleared (except abacavir)
Resistance
Due to mutations in reverse transcriptase,
cross-resistance possible
 Abacavir
 Didanosine
 Emtricitabine
 Lamivudine
 Stavudine
 Tenofovir disoproxil
fumarate
 Tenofovir alafenamide
 Zidovudine
Slide credit: clinicaloptions.com

27. Abacavir
300 mg orally twice daily or 600 mg orally once dailyDose
Headache, fatigue, malaise, nausea
Hypersensitivity reactionAdverse events
None majorDrug interactions
HLA-B*5701 testing required before initiation to predict
hypersensitivity reaction
Clinical
considerations
Slide credit: clinicaloptions.comAbacavir PI.

28. Emtricitabine
200 mg orally dailyDose
Dizziness, headache, hyperpigmentation of soles and palms,
nauseaAdverse events
Do not use in combination with lamivudine to avoid therapeutic
duplicationDrug interactions
Adjust dose in renal dysfunction
May cause HBV viral rebound if abruptly discontinued in an
HIV/HBV-coinfected patient
Clinical
considerations
Slide credit: clinicaloptions.comEmtricitabine PI.

29. Lamivudine
300 mg orally once daily or 150 mg orally twice dailyDose
Headache, fatigue, malaiseAdverse events
Do not use in combination with emtricitabine to avoid therapeutic
duplicationDrug interactions
Adjust dose in renal dysfunction
May cause HBV viral rebound if abruptly discontinued in an
HIV/HBV-coinfected patient
Clinical
considerations
Slide credit: clinicaloptions.comLamivudine PI.

30. Tenofovir Disoproxil Fumarate
300 mg orally once daily with foodDose
Fatigue, depression, nausea, diarrhea
Renal insufficiency, Fanconi’s syndrome, proximal renal
tubulopathy, osteomalacia, decreased BMD
Adverse events
AtazanavirDrug interactions
Adjust dose in renal dysfunction
May cause HBV viral rebound if abruptly discontinued in an
HIV/HBV-coinfected patient
Clinical
considerations
Slide credit: clinicaloptions.comTenofovir Disoproxil Fumarate PI.

31. Tenofovir Alafenamide
25 mg orally once daily or 10 mg orally once daily (if used in
pharmacologically boosted regimen)Dose
Nausea, increased lipids
Renal dysfunction, decreased BMD (< TDF); Fanconi’s syndrome or
proximal renal tubulopathy (no cases reported with TAF)
Adverse events
None majorDrug interactions
Do not administer if CrCL < 30 mL/min
May cause HBV viral rebound if abruptly discontinued in an
HIV/HBV-coinfected patient
Clinical
considerations
Slide credit: clinicaloptions.comTenofovir Alafenamide PI.

32. Nonnucleoside Reverse Transcriptase Inhibitors
(NNRTIs)
Mechanism of
action
Inhibits HIV viral DNA synthesis via binding/
allosterically inhibiting the active site of reverse
transcriptase
Class-related
adverse events
Hepatotoxicity, rash
Metabolism Hepatically cleared
Resistance Due to mutations in reverse transcriptase,
cross-resistance possible
 Efavirenz
 Etravirine
 Delavirdine
 Doravirine
 Nevirapine
 Rilpivirine
Slide credit: clinicaloptions.com

33. Efavirenz
600 mg orally once daily or 400 mg orally once daily on an empty
stomachDose
Rash, neuropsychiatric symptoms (dizziness, “groggy” feeling, vivid
dreams), hyperlipidemiaAdverse events
Many potential interactionsDrug interactions
Discuss prior to use in women of childbearing age
Clinical
considerations
Slide credit: clinicaloptions.comEfavirenz PI.

34. Rilpivirine
25 mg orally once daily with foodDose
Rash, headache, depression, insomniaAdverse events
Proton pump inhibitorsDrug interactions
May be less efficacious with high baseline HIV-1 RNA
Monitor ECG if used with other QT prolonging agents
Clinical
considerations
Slide credit: clinicaloptions.comRilpivirine PI.

35. Doravirine
100 mg orally once dailyDose
Fatigue, nausea, headache, dizziness, rashAdverse events
Strong inducers (eg, rifampin, St John’s wort, antiepileptics)
Rifabutin (increase dose to twice daily)Drug interactions
Active against HIV viruses with common NNRTI mutations, but
novel doravirine-specific mutations resulted in virologic failure
Clinical
considerations
Slide credit: clinicaloptions.comDoravirine PI.

36. Integrase Strand Transfer Inhibitors (INSTIs)
Mechanism of
action
Blocks incorporation of HIV proviral DNA into the
host CD4+ cell
Class-related
adverse events
Inhibition of renal tubular secretion of creatinine
(without decrease in renal function), weight gain (?)
Metabolism Hepatically cleared
Resistance Accumulated mutations in integrase cause resistance;
second-generation INSTIs rare resistance to date
 Bictegravir
 Dolutegravir
 Elvitegravir
 Raltegravir
Slide credit: clinicaloptions.com

37. Bictegravir
50 mg orally once dailyDose
Headache, diarrhea, nauseaAdverse events
Rifampin
Polyvalent cations
Metformin
Drug interactions
Only available in single-tablet regimen (not as stand-alone agent)
STR contains FTC/TAF; do not abruptly discontinue in an HIV/HBV-
coinfected patient
Clinical
considerations
Slide credit: clinicaloptions.comBictegravir PI.

38. Dolutegravir
50 mg orally once dailyDose
Insomnia, fatigue, headacheAdverse events
Rifampin
Polyvalent cations
Metformin
Drug interactions
INSTI-experienced patients should receive twice-daily dosing
Treatment emergent resistance is rare
See DHHS guidelines on use in women of childbearing age
Clinical
considerations
Slide credit: clinicaloptions.comDolutegravir PI. DHHS ART. Oct 2018.

39. RITONAVIR
 Dose: 100-200 mg once/twice daily
 Used with: many PIs, elvitegravir
 Adverse events: gastrointestinal
adverse events, taste disturbances,
hyperlipidemia, insulin resistance
 Clinical considerations: anti-HIV
activity at higher doses (eg, 600 mg
BID), but adverse events limit its use
COBICISTAT
 Dose: 150 mg daily
 Used with: atazanavir, darunavir,
elvitegravir
 Adverse events: gastrointestinal adverse
events, inhibits renal tubular creatinine
secretion (without affecting GFR)
 Clinical considerations: no anti-HIV
activity; pharmacokinetic boosting effect is
not equivalent to ritonavir
Slide credit: clinicaloptions.com
CYP3A4-Based Pharmacokinetic Enhancers
Ritonavir PI. Cobicistat PI.

40. Protease Inhibitors (PIs)
Mechanism of
action
Peptide-like molecules that compete at the protease
active site and block cleavage of viral polyproteins
Class-related
adverse events
Gastrointestinal adverse events (nausea, vomiting,
diarrhea), metabolic adverse events (insulin
resistance, hyperlipidemia), fat accumulation
Metabolism Hepatic
Resistance
Accumulated mutations in protease; typically several
mutations required to impair activity of modern PIs;
cross-resistance across class
 Atazanavir
 Darunavir
 Fosamprenavir
 Amprenavir
 Indinavir
 Lopinavir/ritonavir
 Nelfinavir
 Saquinavir
 Tipranavir
Slide credit: clinicaloptions.com

41. Darunavir
800 mg orally + 100 mg ritonavir or 150 mg cobicistat once daily
with food
600 mg orally + 100 mg ritonavir orally twice daily with food
Dose
Nausea, vomiting, diarrhea, rash (sulfonamide), headache,
abdominal painAdverse events
Many potential drug interactionsDrug interactions
Multiple mutations required for clinical resistance
Clinical
considerations
Slide credit: clinicaloptions.comDarunavir PI.

42. Single-Tablet Regimens
Brand Name Components Notes
NNRTI Based
Atripla, Symfi, Symfi Lo Efavirenz + emtricitabine + tenofovir disoproxil fumarate Avoid if CrCl < 50 mL/min
Delstrigo Doravirine + lamivudine + tenofovir disoproxil fumarate Avoid if CrCl < 50 mL/min
Odefsey Emtricitabine + rilpivirine + tenofovir alafenamide Avoid if CrCl < 30 mL/min
Complera Emtricitabine + rilpivirine + tenofovir disoproxil fumarate Avoid if CrCl < 50 mL/min
INSTI Based
Biktarvy Bictegravir + emtricitabine + tenofovir alafenamide Avoid if CrCl < 30 mL/min
Genvoya Cobicistat + elvitegravir + emtricitabine + tenofovir alafenamide Avoid if CrCl < 30 mL/min
Stribild Cobicistat + elvitegravir + emtricitabine + tenofovir disoproxil fumarate Avoid if CrCl < 70 mL/min
Triumeq Abacavir + dolutegravir + lamivudine Avoid if CrCl < 50 mL/min
PI Based
Symtuza Cobicistat + darunavir + emtricitabine + tenofovir alafenamide Avoid if CrCl < 30 mL/min
Slide credit: clinicaloptions.comhttps://www.accessdata.fda.gov/scripts/cder/daf/

43. Additional Fixed-Dose Combinations
Brand Name Components Notes
NRTI Fixed-Dose Combination Tablets
Cimduo Lamivudine + tenofovir disoproxil fumarate Avoid if CrCl < 50 mL/min
Combivir Lamivudine + zidovudine (twice daily) Avoid if CrCl < 50 mL/min
Descovy Emtricitabine + tenofovir alafenamide Avoid if CrCl < 30 mL/min
Epzicom Abacavir + lamivudine Avoid if CrCl < 50 mL/min
Trizivir Abacavir + lamivudine + zidovudine (twice daily) Avoid if CrCl < 50 mL/min
Truvada Emtricitabine + tenofovir disoproxil fumarate Adjust dose if CrCl 30 to < 50 mL/min
Avoid if CrCl < 30 mL/min
PI Fixed-Dose Combination Tablets
Kaletra Lopinavir + ritonavir
Evotaz Atazanavir + cobicistat
Prezcobix Darunavir + cobicistat
Slide credit: clinicaloptions.comhttps://www.accessdata.fda.gov/scripts/cder/daf/

44. Treatment of HIV

45. Patient Case: New HIV diagnosis
 A 29-yr-old man reluctantly presents to the pharmacy to pick up a new
prescription for PCP prophylaxis and tells you that his doctor wants him
to start ART; “I just don’t see why I have to start right away,” he says. “I
feel just fine”
Slide credit: clinicaloptions.com

46. Antiretroviral Therapy Principles
Startearly
 Assess readiness
 Anticipate barriers
Efficacyandtoxicity
 Clinical trial
evidence
 Short- and long-
term toxicities
 Comorbidities
 Regimen barrier to
resistance
 Resistance profiles
 Drug interactions
Tailortheregimen
 Regimen
characteristics
 Administration
logistics
 Access
 Patient’s ability to
adhere
Slide credit: clinicaloptions.com

47. Evidence for Starting ART Early
 START study: large RCT with 4685 patients with CD4+ cell count > 500 cells/mm3
‒ Comparison: immediate vs delayed ART start until CD4+ cell count < 350 cells/mm3
‒ Primary endpoint: serious AIDS-related or non–AIDS-related event or death (any cause)
‒ Results: halted by DSMB, primary endpoint: 1.8% vs 4.1% with immediate vs deferred
ART; HR: 0.43 for immediate vs deferred ART (95% CI: 0.30-0.62; P < .001)
 TEMPRANO study: 2x2 factorial design study of 2056 patients
‒ Comparison: early ART, deferred ART (to WHO criteria), early ART + isoniazid
preventive therapy, or deferred ART (to WHO criteria) + isoniazid preventive therapy
‒ Primary endpoint: AIDS-defining condition, non-AIDS cancer/invasive bacterial disease,
death (any cause) at 30 mos
‒ Results: 2.8% vs 4.9% with early vs deferred ART; HR: 0.56 for early vs deferred ART
(95% CI: 0.41-0.76)
Slide credit: clinicaloptions.comLundgren. NEJM. 2015;373:795. TEMPRANO ANRS 12136 Study Group. NEJM. 2015;373:808.

48. Structure of Typical ART Regimens
2 NRTIs
plus either
NNRTI
PI + PK
enhancer
INSTI
Slide credit: clinicaloptions.com

49. Initial Treatment of HIV: DHHS Guidelines
Recommended for Most People With HIV Recommended in Certain Clinical Situations
 Bictegravir/tenofovir alafenamide/emtricitabine
 Dolutegravir/abacavir/lamivudine*†#
 Dolutegravir plus tenofovir/emtricitabine†‡#
 Raltegravir plus tenofovir/emtricitabine†‡
Boosted PI + 2 NRTIs
(darunavir preferred over atazanavir)
 Darunavir/(cobicistat or ritonavir) plus
tenofovir/emtricitabine†‡ or abacavir/lamivudine*†
 Atazanavir/(cobicistat or ritonavir) plus
tenofovir/emtricitabine†‡
NNRTI + 2 NRTIs
 Doravirine plus tenofovir/lamivudine†‡
 Efavirenz plus tenofovir/emtricitabine†‡
 Rilpivirine/tenofovir/emtricitabine†‡ǁ§
INSTI + 2 NRTIs
 Elvitegravir/cobicistat/tenofovir/emtricitabine‡
 Raltegravir plus abacavir/lamivudine*ǁ
*Only if HLA-B*5701 negative. †Lamivudine may be substituted with emtricitabine or vice versa. ‡“Tenofovir” denotes TDF or TAF. ǁOnly if HIV-1
RNA < 100,000 c/mL. §Only if CD4+ cell count > 200 cells/mm3. #Important considerations for use before conception/in early pregnancy based
on interim reports of potential dolutegravir teratogenicity. See full guidance on use in women of childbearing age.
Slide credit: clinicaloptions.comDHHS ART. Oct 2018.

50. Initial Treatment of HIV: IAS-USA Guidelines
Category IAS-USA Guidelines (2018)
Recommended initial
treatment
Bictegravir/tenofovir alafenamide/ emtricitabine
Dolutegravir/abacavir/lamivudine*†
Dolutegravir plus tenofovir alafenamide/emtricitabine
When integrase
inhibitors are not an
option
Darunavir/cobicistat plus tenofovir/emtricitabine‡
Darunavir plus ritonavir plus tenofovir/emtricitabine‡
Efavirenz/TDF/emtricitabine
Elvitegravir/cobicistat/tenofovir/emtricitabine‡
Raltegravir plus tenofovir/emtricitabine‡
Rilpivirine/tenofovir/emtricitabine‡ǁ
*Only if HLA-B*5701 negative. †Important considerations for use before conception/in early pregnancy based on interim reports of potential
dolutegravir teratogenicity. See full guidance on use in women of childbearing age. ‡“Tenofovir” denotes either TDF or TAF can be used.
ǁIf baseline HIV-1 RNA < 100,000 c/mL and CD4+ cell count > 200 cells/mm3.
Slide credit: clinicaloptions.comSaag. JAMA. 2018;320:379.

51. On-Treatment Monitoring
 Virologic failure defined as not virally suppressed after 24 wks (HIV-1 RNA
persistently > 200 copies/mL) or inability to maintain HIV-1 < 200 copies/mL
Slide credit: clinicaloptions.comDHHS ART. Oct 2018.
Timepoint HIV-1 RNA CD4+ Cell Count
Entry to care, prior to ART initiation + +
After ART initiation 2-4 wks, then every
4-8 wks until suppressed
3 mos
During first 2 yrs of ART Every 3-4 mos Every 3-6 mos
After 2 yrs of ART if consistent HIV-1 RNA
suppression and CD4+ count 300-500 cells/mm3
Every 6 mos Every 12 mos
After 2 yrs ART if consistent HIV-1 RNA
suppression and CD4+ count > 500 cells/mm3
Every 6 mos Optional

52. Monitoring for Adverse Events
NRTIs NNRTIs INSTIs PIs
Fusion
Inhibitor
CCR5 Inhibitor
Monitoring
parameters
Serum creatinine
Ca++, Mg++,
Phos++, UA
(tenofovir), HBsAg
AST, ALT, Alk phos,
ECG (rilpivirine)
Serum
creatinine,
weight
AST, ALT, Alk phos,
lipid panel, fasting
glucose and/or
A1C
--
AST, ALT, Alk
phos, CK,
blood pressure
Short term Renal
insufficiency,
lactic acidosis
CNS (efavirenz),
insomnia,
depression (EFV
and RPV),
hepatotoxicity
Insomnia,
gastrointestinal,
dizziness,
creatinine
changes
Gastrointestinal Injection-site
reactions
Orthostatic
hypotension,
hepatotoxicity,
myositis
Long term Hepatic steatosis,
lipoatrophy,
bone (TDF),
lipids (TAF)
See above Insomnia/psych
effects
Hyperlipidemia,
insulin resistance,
fat accumulation
See above See above
Slide credit: clinicaloptions.com

53. Essential ART Drug–Drug Interactions

54. ART Interaction Potential by Drug Class
Class Examples Effects
PIs and cobicistat Atazanavir, darunavir, ritonavir,
cobicistat
Typically inhibit CYP3A4 and
enhance levels of other drugs
NNRTIs Efavirenz, etravirine,
nevirapine
Mixed effects, often induce
CYP3A4
*Exceptions* Tenofovir, elvitegravir (with
cobicistat), rilpivirine,
doravirine
Tenofovir: few odd interactions
Elvitegravir boosted with
cobicistat!
Rilpivirine and doravirine fairly
neutral
NRTIs, INSTIs, entry
inhibitors, CCR5
inhibitors
Lamivudine, emtricitabine,
abacavir, raltegravir,
dolutegravir, maraviroc,
enfuvirtide
Usually no effects on other drugs
but may be substrate
Slide credit: clinicaloptions.comDHHS ART. Oct 2018.

55. Nucleoside/tide Reverse Transcriptase Inhibitors
 Tenofovir interactions
‒ With atazanavir: lowers atazanavir levels (ameliorate by using PK
boosting)
‒ With rifampin: lowers levels of tenofovir (more data required for TAF)
Slide credit: clinicaloptions.comDHHS ART. Oct 2018.

56. Integrase Inhibitors
 With metformin
‒ Increases levels of metformin (OAT); limit metformin to 1000 mg/day with
dolutegravir
 With polyvalent cations (Ca++, Al/Mg++, Fe++)
‒ Decreased exposure/efficacy of INSTI. Recommendations may include avoiding
coadministration, taking together with food, or giving INSTI 2 hrs before or 6 hrs
after other medication
 With strong inducers (rifampin, rifapentine, carbamazepine, etc)
‒ Decreased exposure/efficacy of INSTI; refer to individual INSTI prescribing
information for management
Slide credit: clinicaloptions.comDHHS ART. Oct 2018.

57. Common Drug Classes Interacting With PIs,
PK Enhancers, NNRTIs
 Antacid agents: particularly lowers atazanavir levels, rilpivirine levels
 Statins: monitor for toxicity (PIs) or efficacy (with some NNRTIs)
 Hepatitis C drugs: some contraindicated with certain ART due to
interactions
 Azole antifungals: complex interactions, often bidirectional
 Rifampin, rifabutin, rifapentine: lower levels of ART
 Anticonvulsants: lower levels of ART (interactions may be bidirectional)
Slide credit: clinicaloptions.comDHHS ART. Oct 2018.

58. Supporting Treatment Adherence

59. Why Don’t People Take ART?
 Never started: healthcare provider said they didn’t need to, worried
about ART harming them or making them sick, don’t believe they need
ART
 Not currently taking ART: worried about ART harming them or making
them sick, money issues, don’t believe they need ART
 60%: proportion of people who reported taking 100% of their ART over
the last mo
Slide credit: clinicaloptions.comCDC. HIV Surveillance Special Report 20. May 2018.

60. Assessing Adherence
 Self-report
‒ “In the last 30 days, how good a job did you do at taking your HIV medications in the
way you were supposed to?” (excellent, very good, fair, poor, very poor)
‒ 3 (or 7) day recall
‒ Corroboration by family members/friends/partners
‒ Self-collection of dosing information via smartphone apps
 Pharmacy refill history: medication possession ratio or proportion of days covered
 Pill counts (unannounced vs scheduled)
 Patient familiarity with pills/routine
 Biologic markers: CD4, HIV-1 RNA, therapeutic drug monitoring (blood, hair, urine)
Slide credit: clinicaloptions.comAmico. J Int Assoc Provid AIDS Care. 2013;12:79.

61. *Participants may report > 1 reason for last missed dose.
Reason* % 95% CI
Forgot to take 37 34-39
Change in your daily routine or were out of town 25 23-28
Fell asleep early or overslept 20 18-22
Had a problem getting a prescription, a refill,
insurance coverage, or paying for HIV medicines
15 13-17
Felt depressed or overwhelmed 10 9-12
Did not feel like taking HIV medicines 8 7-8
Had adverse events from HIV medicines 7 6-8
In the hospital or too sick to take HIV medicine 7 5-8
Was drinking or using drugs 6 4-8
Reasons for Last Missed ART Dose Among Adults With
Diagnosed HIV and Receiving ART
Slide credit: clinicaloptions.comCDC. HIV Surveillance Special Report 20. May 2018.

62. Pharmacists Supporting Adherence
 Pharmacist as healthcare provider: provide education and promote
initiation of ART for patients who are ready
 Support around adverse events: educate regarding long-term vs short-
term adverse events; help patients symptomatically manage/monitor
adverse events; serve as advocate and link to healthcare team
 Financial barriers: prior authorizations, patient assistance programs,
simplifying therapy for reduced copays
 Forgetting: refill reminders, automatic refills, delivery, reminder
packaging
‒ What to do for missed doses
Slide credit: clinicaloptions.com

63. Potentially Modifiable Adherence Barriers
Knowledge
 Screen for health literacy (REALM-R)
 Education and counseling sessions
 Referral to Web sites, hotlines,
helplines
Forgetfulness
 Reminder devices (alarms/
smartphone apps)
 Medication diaries
 Reminder packaging
 Pharmacy reminders (auto refill)
Financial concerns
 Prescreening ART insurance coverage
 Simplify (may decrease copays)
 Copay assistance cards
 Patient assistance programs
Regimen characteristics
 Preplan ART schedule
 Simplify (few pills, lower frequency)
 Remove administration barriers
Slide credit: clinicaloptions.com

64. Supporting Adherence: A Process
 Relationship-centered communication
 Elicit information
‒ Short-term recall
‒ Multiple measures of adherence (if available)
‒ Nonjudgmental tone
 Explore barriers and facilitators
 Patient-centered support and resources
 Continual reassessment
Slide credit: clinicaloptions.com

65. clinicaloptions.com/hiv
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