Page 43 - HIV/AIDS Guidelines

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cells/mm and AII for CD4 count 350 to 500 cells/mm ).
The recommendation to initiate therapy at CD4 count >500 cells/mm (BIII) is based on growing awareness that
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untreated HIV infection or uncontrolled viremia may be associated with development of many non-AIDS-
defining diseases, including cardiovascular disease (CVD), kidney disease, liver disease, neurologic
complications, and malignancy; availability of ART regimens that are more effective, more convenient, and better
tolerated than earlier ART combinations no longer widely used; and evidence from one observational cohort study
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that showed survival benefit in patients who started ART when their CD4 counts were >500 cells/mm .
Tempering the enthusiasm to treat all patients regardless of CD4 count is the absence of randomized data that
definitively demonstrate a clear benefit of ART in patients with CD4 count >500 cells/mm and mixed results
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on the benefits of early ART from observational cohort studies. In addition, potential risks of short- or long-
term drug-related complications and nonadherence to long-term therapy in asymptomatic patients may offset
possible benefits of earlier initiation of therapy. When resources are not available to initiate ART in all
patients, treatment should be prioritized for patients with the lowest CD4 counts and those with the following
clinical conditions: pregnancy, history of an AIDS-defining illness, HIV-associated nephropathy (HIVAN), or
HIV/hepatitis B virus (HBV) coinfection.

The decision to initiate ART should always include consideration of other conditions and considerations
listed in the Panel’s boxed recommendations, the willingness and readiness of the patient to initiate therapy,
and the availability of resources. The known benefits and limitations of ART are discussed below.

Benefits of Antiretroviral Therapy
Reduction in Mortality and/or AIDS-Related Morbidity According to Pretreatment CD4
Cell Count

Patients with a history of an AIDS-defining illness or CD4 count <350 cells/mm 3
HIV-infected patients with CD4 counts <200 cells/mm are at higher risk of opportunistic diseases, non-AIDS
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morbidity, and death than HIV-infected patients with higher CD4 counts. Randomized controlled trials in
patients with CD4 counts <200 cells/mm and/or a history of an AIDS-defining condition provide strong
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evidence that ART improves survival and delays disease progression in these patients. 1-3 Long-term data from
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multiple observational cohort studies comparing earlier ART (initiated at CD4 count >200 cells/mm ) with later
treatment (initiated at CD4 count <200 cells/mm ) also have provided strong support for these findings. 4-9
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Few large, randomized controlled trials address when to start therapy in patients with CD4 counts >200
cells/mm . CIPRA HT-001, a randomized clinical trial conducted in Haiti, enrolled 816 participants without
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AIDS. Participants were randomized to start ART at CD4 counts of 200 to 350 cells/mm or to defer
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treatment until their CD4 counts dropped to <200 cells/mm or they developed an AIDS-defining condition.
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An interim analysis of the study showed that, compared with participants who began ART with CD4 counts
of 200 to 350 cells/mm , patients who deferred therapy had a higher mortality rate (23 vs. 6 deaths, hazard
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ratio [HR] = 4.0, 95% confidence interval [CI]: 1.6–9.8) and greater incident tuberculosis (TB) (HR = 2.0,
95% CI: 1.2–3.6). 10

Collectively, these studies support the Panel’s recommendation that ART should be initiated in patients with
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a history of an AIDS-defining illness or with a CD4 count <350 cells/mm (AI).
Patients with CD4 counts between 350 and 500 cells/mm 3
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Data supporting initiation of ART in patients with CD4 counts ranging from 350 to 500 cells/mm are
derived from large observational studies and secondary analysis of randomized controlled trials. Analysis of
the findings from the observational studies involved use of advanced statistical methods that minimize the
bias and confounding that arise when observational data are used to address the question of when to start

Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents E-2

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