,

57 The sensitivity

for these fourth-generation combination assays is >99.7%, and test results can be

available within 3 hours which represents opportunity for more rapid engagement in

clinical care upon a positive test result.

55 Unless there is reason to suspect very early

infection, no further testing is required for a nonreactive antigen/antibody

combination assay. Specimen with reactive antigen/antibody results should be further

tested with an immunoassay to differentiate HIV-1 and HIV-2 antibodies. NATs for

HIV RNA should be used to confirm an indeterminate antibody differentiation

immunoassay or a negative antigen/antibody tests in patients where there is reason to

suspect very early infection.

55

SURROGATE MARKER DATA

While current guidelines recommend initiating therapeutic interventions for all HIVinfected persons ready to begin treatment,

3

the severity of immune damage and

potential for disease progression should still be assessed to determine the clinical

urgency for beginning treatment and if additional therapeutic interventions to prevent

opportunistic infection are needed. As stated previously, HIV predominantly infects

and destroys T cells. The larger the viral load, the greater the risk for T-cell

destruction and opportunistic infections. Therefore, quantitative measurements of

E.J.’s HIV viral load and T-cell counts will assist in “staging” the severity of

infection, assessing the risk for disease progression, and providing a reference point

(i.e., baseline) for future therapeutic decisions.

Identification and measurement of T-lymphocyte subsets (e.g., CD4, CD8) are

based on flow cytometry readings of fluorescent-labeled monoclonal antibodies.

58

These values can vary widely on repeated laboratory evaluations, even in clinically

stable patients. Patient samples can display up to 30% intralaboratory and

interlaboratory variabilities.

3 Consequently, it is important to realize that assessment

of T-cell measurements should always be interpreted as trends and not as individual

values. Variability can also be minimized by using the same laboratory and by

sampling patients at a consistent time of day.

The measurement of HIV viral load can be performed by one of three methods:

reverse transcriptase–polymerase chain reaction (RT-PCR), branched-chain DNA

assay, or nucleic acid sequence-based amplification.

59 Measurements using RT-PCR

are obtained when viral RNA is amplified and counted. In contrast, branched-chain

DNA amplifies and enumerates the signal from target probes attached to the viral

RNA. Nucleic acid sequence-based amplification allows real-time, high throughput

amplification of viral RNA. All methods report HIV RNA in plasma as the number of

copies per milliliter but have differing lower limits of quantitation.

3

It should be

recognized that plasma viral RNA values measure the amount of free virus in the

periphery and not the lymph nodes. Because viral concentrations are substantially

greater in the lymph node, plasma measurements of HIV indirectly reflect spillover

from replication in that compartment.

60

,

61

Similar to CD4 counts, viral load measurements (copies/milliliter) can vary by as

much as threefold (0.5 log) in either direction.

3 When obtaining a patient’s baseline

value, a number of issues must be considered. On initial infection with HIV, a burst

of viremia occurs until the host’s immune responses are able to control the infection.

Consequently, viral load measurements obtained during the first 6 months of infection

may not accurately reflect a true baseline value.

3

In addition, factors that activate the

immune system, such as the development of a new opportunistic infection or

immunizations,

62 can result in transient elevations of viral load measurements. In

these situations, concentrations obtained within 4 weeks of the event may not

accurately reflect the baseline viral load measurement.

3

Some clinicians would recommend that at least two separate viral load

measurements, which are obtained within 1 to 4 weeks of each other, be performed

before making decisions regarding therapeutic options.

3 As with T-cell values, viral

load measurements should be evaluated as trends.

In addition to quantifying the viral load, baseline resistance testing should be

performed, using either genotypic or phenotypic testing,

3

to guide the selection of the

initial regimen. Resistance testing is recommended in most clinical situations before

beginning treatment, because the rate of transmission of virus resistant to at least one

drug (i.e., transmitted drug resistance) has been noted in up to 11% to 12% of HIVinfected patients who have never been on antiretroviral therapy in North America and

Europe.

63

(see Resistance, Viral Genotyping, Phenotyping, and Viral Fitness section

for further discussion).

CASE 76-1, QUESTION 2: E.J.’s HIV-1/2 antigen/antibody combination immunoassay is reactive and the

antibody differentiation immunoassay detects HIV-1 antibodies. He is informed of his HIV status the next week

at his follow-up examination. Before making any decisions regarding therapeutic options, what additional

laboratory tests should be obtained?

E.J. should have a baseline T-cell count, viral load measurement, and viral

genotype obtained. A complete blood count, electrolyte panel, renal, and liver

function tests and hepatitis B and C serology should be performed. If specific

therapies are being considered, such as abacavir and maraviroc, specific testing is

available to guide the appropriate use of these agents. HLA-B5701 screening is

performed before starting a patient on abacavir because of an increased risk for

exhibiting a hypersensitivity reaction in patients positive for this allele. Co-receptor

tropism assay is performed before initiating maraviroc to determine whether the

patient has a virus that predominantly uses CCR5 receptors (vs. ones

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that use primarily CXCR-4 receptors or ones that can use both).

3 These laboratory

results help in selecting therapeutic options (see subsequent discussion) and establish

baseline values in the event that problems are encountered in the future.

ANTIRETROVIRAL THERAPY

CASE 76-1, QUESTION 3: E.J.’s T-cell count and viral load measurement return at 225 cells/μL and

145,000 copies/mL (by RT-PCR assay), respectively. Should antiretroviral therapy be initiated?

In deciding to initiate antiretroviral therapy, it is important to consider both the

potential benefits of therapy and the potential risks of therapy, including both shortterm and long-term side effects and potential for the development of drug resistance

(and cross-resistance; see subsequent discussion). Antiretroviral therapy should be

offered to all patients who are willing and able to commit to lifelong treatment after

an in-depth discussion of the benefits and risks of HAART and the importance of

adherence. Recently, the Department of Health and Human Services (DHHS) HIV

Treatment Guideline Panel issued a statement modifying their 2015 guidelines. This

modification was based on the results of two large randomized clinical trials

(START; The Strategic Timing of AntiRetroviral Treatment and the TEMPRANO

ARNS 12136 Study). These trials investigated the risks and benefits of initiating

HAART at a CD4 count >500 cell/μL versus delaying until the CD4 count declined

to <350 cell/μL. A significant increase in morbidity and mortality was observed

when HAART was delayed prompting the Guideline Panel to upgrade the strength of

their former recommendation to start HAART at any baseline CD4 count to the

highest level of evidence (AI; strong recommendation supported by data from

randomized controlled trials).

64 Previously, the strength of evidence in support of

initiating HAART was prioritized across three categories of increasing baseline CD4

cell count (>500 cell/μL: lowest strength; 350–500 cell/μL: intermediate strength;

<350 cell/μL: highest strength).

3

In further support of starting HAART regardless of

baseline CD4 count, the 2015 guidelines recognize the benefits of initiating HAART

for HIV prevention and support initiating HAART to prevent perinatal and

heterosexual transmission (AI evidence rating) or other transmission risks (AIII

evidence rating). Clinical situations which favor more urgent initiation of HAART

include pregnancy; AIDS-defining condition such as an opportunistic infection; CD4

count of <200 cells/μL; HIV-associated nephropathy (HIVAN); hepatitis B and/or C

coinfection; rapidly declining CD4 count (>100 cells/μL decrease per year); higher

baseline viral load (>100,000 copies/mL); and acute/early HIV infection.

3

In patients

who are asymptomatic, assessment of the patient’s surrogate marker data (T-cell

count, viral load measurements), concurrent medical conditions, medication

adherence history (if any), and motivation to initiate therapy are necessary. The

results of resistance testing should be considered before initiating therapy.

Knowledge of both the T-cell count and the baseline viral load values is important

to “stage” the severity of infection (Table 76-1). In otherwise healthy,

immunocompetent persons, T-cell measurements are greater than 1,200 cells/μL. In

patients who have been chronically infected with HIV, significant T-cell destruction

occurs. When T-cell counts fall to less than 500 cells/μL, patients are at increased

risk for opportunistic infections. Data from both clinical trials and observational

cohort studies have long shown a clear benefit for antiretroviral therapy when CD4

cell counts are ≤350 cells/μL, and many cohort analyses have shown benefit for

starting therapy at CD4 counts ≤500 cells/μL.

3 Early, less definitive evidence also

suggested initiating HAART in patients with CD4 counts of >500 cells/μL improves

immune recovery, reduces HIV transmission risk, and potentially reduces the risk of

non–AIDS-defining diseases. These suggestive data were recently confirmed by the

two previously mentioned randomized trials, START and Temprano ANRS 12136

study, both of which found definitive benefit when initiating HAART at a CD4 Count

>500 cells/μL versus delaying.

65

,

66 The risk of disease progression is closely tied to

CD4 cell counts, with low CD4 counts (<200 cells/μL) predicting both short-term

and long-term risk of disease progression.

67–69 High viral load (>100,000

copies/mL), increasing age, acquisition of infection through intravenous drug use, and

a previous AIDS diagnosis also increase the risk of disease progression in

observational cohorts.

The decision to initiate therapy should not be taken lightly. Antiretroviral regimens

may improve the quality and duration of a patient’s life, but they are not without

risks. Once therapy is initiated, antiretroviral therapy is a lifetime commitment. For

some patients, this may be a difficult realization, particularly if the patient is

relatively healthy. In addition, the risk of adverse events/toxicities and the costs of

HAART should be considered before beginning treatment. These guidelines,

therefore, should be used to initiate discussions with the patient regarding the risks

and benefits of therapy. It is critical for practitioners to talk openly with patients

about their fears and concerns and make an assessment about their motivation to

initiate therapy and ability to adhere to a lifelong regimen. The patient should always

make the final decision after careful discussions with the practitioner.

E.J. has a number of significant risk factors for disease progression. He is

clinically symptomatic with oral thrush and nonspecific constitutional symptoms

(e.g., fevers, night sweats, and weight loss). His surrogate maker data place him at

risk for greater disease progression (T-cell count <500 cells/μL and viral load

>100,000 copies/mL). Based on these values, E.J. should be counseled on his risk of

disease progression, potential adverse events associated with both starting and

deferring treatment, and his willingness to adhere to a regimen.

Before developing a patient-specific regimen, it is important to recognize the

benefits and limitations of therapy and identify obtainable and realistic goals.

CASE 76-1, QUESTION 4: After careful discussions, E.J. agrees to initiate therapy. What should be the

goals of therapy? What other factors or information should be considered in selecting an appropriate regimen?

Goals of Therapy

GOAL 1: MAXIMALLY AND DURABLY SUPPRESS VIRAL LOAD

Maximal viral suppression often results in significant increases in T-cell counts and

improved clinical outcomes. Based on our understanding of viral pathogenesis, this

finding is not surprising. Lower amounts of replicating virus result in decreased risk

for T-cell infection and destruction and, subsequently, a more intact immune

response. Therefore, therapy should suppress viral replication to undetectable levels

in the plasma (<50 copies/mL), for as long as possible.

3

,

5 The development of new

antiretroviral agents with improved potency, higher genetic barrier to resistance, low

adverse event profiles, and more convenient dosing regimens (including once daily

single tablet regimens) makes viral suppression a reasonable goal in most patients,

even those who previously have received multiple suboptimal regimens or failed

therapy. In the treatment-experienced patient, however, special care must be given to

designing a regimen that will suppress viral

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load, yet not contribute to the development of drug resistance that limits future

treatment options. Consultation with an expert in antiretroviral resistance patterns is

critical to designing a salvage regimen in such patients.

The development of drug resistance is also a consideration in the selection of

regimens for patients who have not previously used antiretrovirals (antiretroviral

naïve). In any given viral population, the potential exists for a spontaneous mutation

to occur, which results in a resistant isolate. The larger the population, the greater the

risk for mutations. HIV replication is a highly error-prone process, especially with

the reverse transcriptase enzyme. Given the high rate of viral replication, the

potential exists for the daily production of thousands of replication-competent viral

mutations to each and every site on the HIV genome (~10,000 nucleotides in

length).

4

,

35 Under selective pressures from inadequate antiretroviral therapies,

spontaneously produced isolates with reduced susceptibility to the given regimen

eventually flourish and repopulate the host. This fact is of particular concern given

the potential for cross-resistance between antiretroviral agents (see the following

discussion of resistance). Therefore, the use of a regimen that fully suppresses viral

replication reduces the potential for mutations and the development of crossresistance.

Although more than 20 FDA-approved antiretroviral agents are currently available

to use in combination therapies, many of these agents display similar resistance

profiles. Developing resistance to one or more agents in a given regimen may result

in the loss of activity to other agents with similar resistance profiles (i.e., crossresistance).

4 Whether or not drug resistance develops is determined by the genetic

barrier associated with the individual antiretroviral drugs. Some drugs have low

genetic barriers; that is, only one or two critical changes in the virus are necessary

for resistance to occur. An example of a class of agents with a low genetic barrier is

the NNRTIs. While a number of individual point mutations in the viral genome can

confer the loss of activity for the first-generation NNRTIs (nevirapine and efavirenz),

second-generation NNRTIs (rilpivirine and etravirine) exhibit improved barriers to

resistance compared to these first-generation agents. In contrast, the PIs have a wide

genetic barrier, which requires multiple changes to the viral genome to incur

resistance.

4

It should be recognized, however, that just because an agent has a low genetic

barrier does not mean it is virologically inferior or less potent. Potent regimens

containing NNRTIs are highly effective and provide durable treatment responses.

The potency of the entire regimen

3

is critical to determining whether or not drug

resistance develops. If viral replication is suppressed, the development of resistance

will be minimal. When viral replication does occur, the greater the replication, the

greater the risk for development of resistance. In those situations in which viral

replication does occur, inclusion of a drug with a low genetic barrier in the

antiretroviral regimen may be risky and could result in the loss of activity of the drug,

the development of cross-resistance to other drugs, or both. As a result, an

antiretroviral regimen should be selected that has a high likelihood of suppressing

viral replication and to which the patient will strictly adhere.

GOAL 2: PRESERVE AND STRENGTHEN THE IMMUNE SYSTEM

Decreasing viral replication usually leads to increased CD4 cell counts, which

strengthens and preserves the immune system. With increased cell counts, patients are

at lower risk for exhibiting opportunistic infections and death. With newer and

improved regimens, strengthening and preserving the immune system may be possible

even in treatment-experienced patients, although drug regimens must be designed

carefully to prevent developing further resistance. Full immune reconstitution may not

be possible if the CD4 cell count is low for a long period of time; however, it is

reasonable to try and restore immune function as fully as possible. Despite advances

in drug therapy, it is important to remember that HIV remains an incurable condition.

GOAL 3: LIMIT DRUG ADVERSE EVENTS, PROMOTE ADHERENCE,

AND IMPROVE QUALITY OF LIFE

Treatment with combination therapy has been shown to be highly effective in

suppressing HIV replication and improving survival among patients who are HIV

infected. Lifelong adherence to an antiretroviral regimen is required and can be a

complex and difficult task, although advances in coformulation of drug products and

the advent of ritonavir-boosted protease inhibitors have simplified HIV treatment

considerably. Several once-daily regimens and single tablet regimens are

recommended as first-line therapy (Tables 76-3 and 76-4). The patient’s ability to

adhere to therapy may, however, still be the difference between a regimen that fails

and one that results in a clinical benefit. The first regimen generally provides the best

chance for treatment success. Although newer antiretrovirals tend to exhibit better

adverse event profiles compared to the early antiretrovirals, adverse events can still

make tolerating these regimens difficult, and affect drug adherence and response to

therapy. Changes in body composition (known as lipodystrophy), increases in lipids

and triglycerides, bone and joint fractures, increased risks for cardiac disease, and

the development of lactic acidosis are serious concerns.

3

Limit Adverse Events

Although new antiretrovirals offer marked improvement over early generation

agents’ toxicity profiles, lifelong HAART is not without risk. Metabolic

complications from antiretroviral therapy include abnormal distribution of body fat,

lipid abnormalities (e.g., hypercholesterolemia, hypertriglyceridemia, increases in

low-density lipoprotein [LDL] and decreases in high-density lipoprotein [HDL]),

and new-onset diabetes.

70–72 Coronary artery disease, myocardial infarctions, and

vascular complications among relatively young patients (30–40 years old) taking

HAART-containing regimens have been reported.

73–78 Large observational studies

suggest an increased risk for cardiovascular disease among patients taking HAART,

particularly among those receiving protease inhibitors.

79–81 Additionally, nucleoside

analogs can inhibit mitochondrial DNA polymerase and, as a result, have been

implicated in lipoatrophy; however, this appears to be less of a concern for newer

NRTIs.

82 Finally, metabolic abnormalities have also been reported in patients who

are HIV infected before receiving HAART, and it may also be a consequence of HIV

infection or preexisting metabolic disorders that are exacerbated by HAART.

71

Up to 40% of patients on PI-based HAART are reported to experience impaired

glucose tolerance because of significant insulin resistance.

83 Patients with type 2

diabetes mellitus are at increased risk, and PI-based regimens should be used with

caution in these patients. Fasting glucose measures for all patients are recommended

before and during therapy (e.g., every 3–6 months) with PI-based regimens.

3

Treatment of type 2 diabetes in HIV patients as a result of HAART therapy should be

handled similarly to any other patient.

Elevations in serum levels of triglycerides, total cholesterol, and LDL, with mild

decreases in HDL, are associated with HAART.

71

,

84

,

85 These abnormalities may be

seen as early as 2 weeks after the initiation of therapy.

71 Although all PIs have been

implicated, these laboratory abnormalities appear to occur more frequently in

ritonavir-containing regimens, and less frequently in patients receiving atazanavir

alone.

71 The NNRTIs can also cause lipid alterations, although their incidence is

lower. Both efavirenz and nevirapine have been shown to increase HDL

concentrations among patients receiving HAART. Nevirapine may have the least

detrimental lipid profile (i.e., greater increases in HDLconcentrations and less effect

on LDL elevations).

86 Of the NRTIs, stavudine appears to affect lipid profiles to the

greatest extent: two prospective clinical trials have shown greater increases in

triglycerides and total cholesterol among patients receiving stavudine-based HAART

compared with zidovudine- or tenofovir-based regimens.

88–93 The management of

HAART-associated hyperlipidemias should be handled similarly to hyperlipidemia

in other patients with close attention paid to preventing drug–drug interactions.

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Table 76-4

Recommended Antiretroviral Agents for Initial Treatment of Established

Human Immunodeficiency Virus Infection

Preferred

a Alternatives

PIs (one or two

PIs + two NRTIs)

Darunavir/ritonavir + emtricitabine/tenofovir

disoproxil fumarate or

emtricitabine/tenofovir alafenamide

Darunavir/ritonavir + abacavir/lamivudine

b

Darunavir/cobicistat

c +

abacavir/lamivudine

b or

emtricitabine/tenofovir disoproxil fumarate

or emtricitabine/tenofovir alafenamide

Atazanavir/ritonavir +

emtricitabine/tenofovir disoproxil fumarate

or emtricitabine/tenofovir alafenamide

Atazanavir/cobicistat

c +

emtricitabine/tenofovir disoproxil fumarate

or emtricitabine/tenofovir alafenamide

Integrase

inhibitors

Raltegravir twice daily +

emtricitabine/tenofovir disoproxil fumarate

or emtricitabine/tenofovir alafenamide

Elvitegravir/cobicistat/emtricitabine/tenofovir

disoproxil fumarate

c or

Elvitegravir/cobicistat/emtricitabine/tenofovir

alafenamide

Dolutegravir + emtricitabine/tenofovir

disoproxil fumarate or

emtricitabine/tenofovir alafenamide

Dolutegravir/abacavir/lamivudine

b

NNRTIs (one

NNRTI + two

NRTIs)

Efavirenz/emtricitabine/tenofovir disoproxil

fumarate

Rilpivirine/emtricitabine/tenofovir disoproxil

fumarate

d or

rilpivirine/emtricitabine/tenofovir

alafenamide

Not

recommended:

Should not be

offered

All monotherapies, dual-nucleoside

regimens, triple-NRTI regimens

aThis table provides a guide to the use of available treatment regimens for individuals with no prior or limited

experience on HIV therapy. In accordance with the established goals of HIV therapy, priority is given to regimens

in which clinical trial data suggest the following: sustained suppression of HIV plasma RNA (particularly in

patients with high baseline viral load), sustained increase in CD4+ T-cell count (in most cases >48 weeks), and

favorable clinical outcome (i.e., delayed progression to AIDS and death). Additional consideration is given to the

regimen’s pill burden, dosing frequency, food requirements, convenience, toxicity, and drug interaction profile

compared with other regimens. It is important to note that all antiretroviral agents have potentially serious toxic and

adverse events associated with their use.

bOnly for patients who are HLA-B*5701 negative.

cOnly for patients with pretreatment estimated CrCl >70 mL/minute.

dOnly for patients with pretreatment HIV RNA <100,000 copies/mL and CD4 count >200 cells/μL.

AIDS, acquired immunodeficiency syndrome; HIV, human immunodeficiency virus; NRTI, nucleos(t)ide analog

reverse transcriptase inhibitor; NNRTI, non-nucleos(t)ide analog reverse transcriptase inhibitor; PI, protease

inhibitor.

Up to 40% to 50% of patients have been reported to experience alterations in body

composition (fat loss [arms, legs, face, buttocks] and fat accumulation [dorsocervical

fatty deposits or “buffalo humps”], increased abdominal girth), although the exact

rate is confounded by differences in definition and assessment.

71 Risk factors for this

complication include higher baseline body mass index, increased duration of

exposure to antiretroviral agents, lower CD4 nadir at time of initiation of HAART,

increasing age, female sex, and prolonged duration of HIV infection. The nucleoside

analogs are likely responsible for lipoatrophy, whereas the PIs are believed to be

responsible for lipoaccumulation,

71 although it is difficult to precisely identify which

class of agents is responsible for which adverse event because they are given in

combination.

The causes of lipodystrophy are unknown. It appears that there is greater

propensity for lipoatrophy by those nucleoside analogs which greatly inhibit

mitochondrial DNA polymerase in vitro (e.g., stavudine). Although substituting

stavudine with an alternate NRTI such as zidovudine, tenofovir, or abacavir is

associated with significant increases in arm and leg fat, and decreases in trunk fat

(using radiographic tests such as dual-energy x-ray absorptiometry, computed

tomography scans), these improvements are so modest that they may not be clinically

relevant.

72

,

89–93 The use of recombinant human growth hormone, an agent with

lipolytic effects, decreases the size of buffalo humps and abdominal girth; however,

the growth often returns once growth hormone therapy is stopped.

71 Tesamorelin, a

growth hormone–releasing factor given as a 2-mg once daily subcutaneous injection,

was approved in 2010. It is specifically indicated for the reduction of excess

abdominal fat in HIV-infected patients with lipodystrophy.

94 Surgical excision or

liposuction may be effective; however, recurrences, along with adverse events

(intestinal perforation, intraperitoneal bleeding), have been reported.

95 For facial

wasting, injection of fat or synthetic polymers into the recessed areas of the cheeks

has shown good results, but it requires frequent costly administration and lacks longterm safety data.

96

Other important long-term complications include nucleoside-associated lactic

acidosis, osteonecrosis, and osteopenia.

71 Lactic acidosis has been predominantly

associated with the use of older NRTIs (stavudine, zidovudine, and didanosine)

which are no longer preferred antiretrovirals but has been reported with other

nucleoside analogs. This complication is managed by discontinuing therapy until

lactate levels return to normal and then reinitiating

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therapy with a non-stavudine or non-nucleoside analog-containing HAART

regimen.

3 Tenofovir alafenamide (TAF), a novel formulation of tenofovir, is

associated with improved long-term bone and renal outcomes compared to tenofovir

disoproxil fumarate (TDF) in patients initiating therapy. [Ref 97: Wang H et al. The

efficacy and safety of tenofovir alafenamide versus tenofovir disoproxil fumarate in

antiretroviral regimens for HIV-1 therapy Meta-analysis. Medicine. 2016;

95:41(e5146).] With the availability of generic tenofovir disoproxil fumarate (FDA

approved in June 2017), balancing lower cost vs improved safety will be an

important consideration for clinicians in selecting a tenofovir based regimen.

Promote Adherence

While the exact degree of adherence required for clinical success is currently

unknown and varies by antiretroviral class, taking 90% to 95% of prescribed doses

is generally believed to be necessary to prevent the development of resistance. Data

from studies evaluating adherence among HIV-infected patients indicates that

approximately 62% of patients take ≥90% of the prescribed doses of

antiretrovirals.

98 Although it is important to note that adherence patterns vary widely

based on patient-specific factors. The four most common reasons for skipping

antiretroviral doses are simple forgetfulness, a change in daily routine, being too

busy with other things, and being away from home.

99 Factors associated with poor

adherence include (a) the number of medications (the greater the number, the greater

the likelihood of poor adherence); (b) the complexity of the regimen (special meal

requirements, escalating or de-escalating doses, dose frequency); (c) special storage

requirements; (d) interference of medication with lifestyle and daily activities; and

(e) poor communication with primary care providers and other health care

professionals. Comorbid psychiatric conditions, as well as substance abuse issues,

are also significant barriers to adherence in the HIV-infected population.

Incorporating these factors into the selection of a patient-specific regimen may

improve adherence and, subsequently, the chance for an improved clinical outcome

and quality of life.

To better address the complex, multidimensional, patient-specific structures that

can influence adherence behavior and retention in care, the DHHS HIV Treatment

Guidelines recommend that clinics adopt a multidisciplinary team approach which

provides access to trustworthy case managers, pharmacists, social workers, nurses,

psychiatric care providers, etc.

3 Additionally, before selecting an HIV treatment

regimen clinicians should provide adherence-related education (including

information regarding why adherence is important) and involve the patient in the

antiretroviral selection process. Selecting a treatment plan that the patient can (1)

understand and (2) commit to for the long term is critical for fostering lifelong

adherence. Thus, considering the patient’s daily schedule and their ability to comply

with antiretroviral specific requirements (i.e., food requirements, drug interactions,

etc.) is important. For example, rilpivirine should be consumed with a full meal

(ideally ≥500 kcal) and therefore may not be the best option for a patient who

frequently skips meals or does not have a consistent eating schedule. Efavirenz which

may cause drowsiness and is generally taken before bed on an empty stomach to

mitigate this CNS effect might not be the best option for a person who works night

shifts where they are on for 7 days then off for 7 days. Involving patients in the

selection of their antiretroviral regimen maximizes the possibility of selecting a

regimen which is least burdensome to their daily routine and helps to reduce certain

barriers which lead to poor adherence. After the antiretroviral regimen has been

selected and treatment initiated, quickly identifying patients who are struggling with

adherence (via patient self-report, pharmacy records, pill counts, etc.); identifying

their specific barriers to adherence (i.e., pill fatigue, high co-pays, forgetfulness,

etc.); and employing targeted interventions to improve adherence are essential.

Examples of specific strategies to improve adherence can be found in Table 13

(https://aidsinfo.nih.gov/contentfiles/lvguidelines/AA_Tables.pdf) of the 2015

DHHS HIV treatment guidelines.

3