Page 51 - HIV/AIDS Guidelines

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with CD4 counts >350 cells/mm . A large proportion of the health care expenditure in patients with advanced
infection is from non-ARV drugs and hospitalization. However, no comparisons of costs for patients starting
3
ART with CD4 count 350 to 500 cells/mm and those for patients starting ART at >500 cells/mm have been
3
reported.
Historically, concerns about long-term toxicity, reduced quality of life, and the potential for emerging drug
resistance served as key reasons to defer HIV therapy in asymptomatic patients for as long as possible. Inherent
in this reasoning was the assumption that in asymptomatic patients the harm associated with viral replication
was less than the harm associated with the toxicities of ART. There is now more evidence that untreated HIV
infection has negative consequences on health at all stages of disease. Also, the currently preferred ART
regimens are better tolerated than previous regimens, leading to greater effectiveness, improved adherence, 131
and lower frequency of emerging drug resistance. Therefore, the current guidelines emphasize avoiding adverse
consequences of untreated HIV infection while managing potential drug toxicity associated with ART.

Conditions Favoring More Rapid Initiation of Therapy
Several conditions increase the urgency for therapy, including:

• Pregnancy (AI) (Clinicians should refer to the perinatal guidelines for more detailed recommendations
114
on the management of HIV-infected pregnant women. )
• AIDS-defining conditions (AI)
• Acute OIs (see discussion below)

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• Lower CD4 counts (e.g., <200 cells/mm ) (AI)
• HIVAN (AII)
• HIV/HBV coinfection (AII)
• Rapidly declining CD4 counts (e.g., >100 cells/mm decrease per year) (AIII)
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• Higher viral loads (e.g., >100,000 copies/mL) (BII)

Acute opportunistic infections
In patients with opportunistic conditions for which no effective therapy exists (e.g., cryptosporidiosis,
microsporidiosis, progressive multifocal leukoencephalopathy) but in whom ART may improve outcomes by
improving immune responses, the benefits of ART outweigh any increased risk; therefore, treatment should
be started as soon as possible (AIII).

In the setting of some OIs, such as cryptococcal meningitis or nontuberculous mycobacterial infections, for
which immediate therapy may increase the risk of immune reconstitution inflammatory syndrome (IRIS), a
short delay before initiating ART may be warranted (CIII). 132-133 In the setting of other OIs, such as
Pneumocystis jiroveci pneumonia (PCP), early initiation of ART is associated with increased survival; 3
therefore, therapy should not be delayed (AI).
In patients who have active TB, initiating ART during treatment for TB confers a significant survival
advantage; 134-138 therefore, ART should be initiated as recommended in Mycobacterium Tuberculosis Disease
with HIV Coinfection.
Clinicians should refer to the Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-
Infected Adults and Adolescents 139 for more detailed discussion on when to initiate ART in the setting of a
specific OI.

Conditions Where Deferral of Therapy May be Considered
Some patients and their clinicians may decide to defer therapy for a period of time on the basis of clinical or

Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents E-10

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