Page 50 - HIV/AIDS Guidelines

should discuss with patients the potential individual and public health benefits of therapy and the need for
adherence to the prescribed regimen and counsel patients that ART is not a substitute for condom use and
behavioral modification and that ART does not protect against other STDs (also see Preventing Secondary
Transmission of HIV).

Potential Limitations of Earlier Initiation of Therapy
Although there are benefits associated with earlier initiation of ART, there also are some limitations to using
this approach in all patients. Concerns about long-term toxicity and development of resistance to ARV drugs
have served as a rationale for deferral of HIV therapy. However, evidence thus far indicates that resistance
occurs more frequently in individuals who initiate therapy later in the course of infection than in those who
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initiate ART earlier. Earlier initiation of ART at higher CD4 counts (e.g., >500 cells/mm ) results in greater
cumulative time on therapy. Nevertheless, assuming treatment will continue for several decades regardless of
when therapy is initiated, the incremental increase in drug exposure associated with starting therapy at higher
CD4 counts will represent a small percentage of the total time on ART for most patients.

Newer ARV drugs are generally better tolerated, more convenient, and more effective than drugs used in
older regimens but there are fewer longer term safety data for the newer agents. Analyses supporting
initiation of ART at CD4 counts >350 cells/mm (e.g., NA-ACCORD and ART-CC) were based on
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observational cohort data where patients were largely treated with regimens less commonly used in current
clinical practice. In addition, these studies reported on clinical endpoints of death and/or AIDS disease
progression but lacked information on drug toxicities, emergent drug resistance, or adherence. Therefore, in
considering earlier initiation of therapy, concerns for some adverse consequences of ART remain.

Antiretroviral Drug Toxicities and Quality of Life
Earlier initiation of ART extends exposure to ARV agents by several years. The D:A:D study found an
increased incidence of CVD associated with cumulative exposure to some drugs in the nucleoside reverse
transcriptase inhibitor (NRTI) and PI drug classes. 52, 126 In the SMART study, compared with interruption or
deferral of therapy, continuous exposure to ART was associated with significantly greater loss of bone
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density. There may be unknown complications related to cumulative use of ARV drugs for many decades. A
list of known ARV-associated toxicities can be found in Adverse Effects of Antiretroviral Agents.
ART frequently improves quality of life for symptomatic patients. However, some side effects of ART may
impair the quality of life for some patients, especially those who are asymptomatic at initiation of therapy.
For example, efavirenz (EFV) can cause neurocognitive or psychiatric side effects and all the PIs have been
associated with gastrointestinal (GI) side effects. Furthermore, some patients may find that the inconvenience
of taking medication every day outweighs the overall benefit of early ART and may choose to delay therapy.

Nonadherence to Antiretroviral Therapy
At any CD4 count, adherence to therapy is essential to achieve viral suppression and prevent emergence of
drug-resistance mutations. Several behavioral and social factors associated with poor adherence, such as
untreated major psychiatric disorders, active substance abuse, unfavorable social circumstances, patient
concerns about side effects, and poor adherence to clinic visits, have been identified. Clinicians should
identify areas where additional intervention is needed to improve adherence both before and after initiation
of therapy. Some strategies to improve adherence are discussed in Adherence to Antiretroviral Therapy.

Cost
In resource-rich countries, the cost of ART exceeds $10,000 per year (see Appendix C). Several modeling
studies support the cost effectiveness of HIV therapy initiated soon after diagnosis. 127-129 One study reported
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that the annual cost of care is 2.5 times higher for patients with CD4 counts <50 cells/mm than for patients
Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents E-9

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