Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents
ACUTE HIV INFECTION
Considerations for Treatment of Patients Who Have Acute HIV Infection
Various studies indicate that 50% & 90% of patients acutely
infected with HIV will experience at least some symptoms of the acute retroviral
syndrome (Table 15) and can thus be identified as candidates for early
therapy (16 & 19). However, acute HIV infection is often not
recognized in the primary-care setting because of the similarity of the
symptom complex with those of the “flu” or other common illnesses. Also,
acute primary infection may occur without symptoms. Physicians should maintain
a high level of suspicion for HIV infection in all patients with a compatible
clinical syndrome (Table 15) and should obtain appropriate laboratory confirmation.
Information regarding treatment of acute HIV infection from clinical trials
is limited. There is evidence for a short-term effect of therapy on viral
load and CD4+T cell counts (20), but there are as yet no outcome data
demonstrating a clinical benefit of antiretroviral treatment of primary
HIV infection. Clinical trials completed to date also have been limited
by small sample sizes, short duration of follow up, and often by the use
of treatment regimens that have suboptimal antiviral activity by current
standards. However, results from these studies generally support antiretroviral
treatment of acute HIV infection. Ongoing clinical trials are addressing
the question of the long-term clinical benefit of more potent treatment
regimens.
The theoretical rationale for early intervention (see Principle 10) is fourfold:
The physician and the patient should be aware that therapy of primary HIV infection is based on theoretical considerations, and the potential benefits, described above, should be weighed against the potential risks (see below). Most experts endorse treatment of acute HIV infection based on the theoretical rationale, limited but supportive clinical trial data, and the experience of HIV clinicians.
The risks associated with therapy for acute HIV infection include adverse effects on quality of life resulting from drug toxicities and dosing constraints; the potential, if therapy fails to effectively suppress viral replication, for the development of drug resistance that may limit future treatment options; and the potential need for continuing therapy indefinitely. These considerations are similar to those for initiating therapy in the asymptomatic patient (see Considerations in Initiating Therapy in the Asymptomatic HIV-infected Patient).
Deciding Whom to Treat During Acute HIV Infection
Many experts would recommend antiretroviral therapy for all patients
who demonstrate laboratory evidence of acute HIV infection (AII). Such
evidence includes HIV RNA in plasma that can be detected by using sensitive
PCR or bDNA assays together with a negative or indeterminate HIV antibody
test. Although measurement of plasma HIV RNA is the preferable method of
diagnosis, a test for p24 antigen may be useful when RNA testing is not
readily available. However, a negative p24 antigen test does not rule out
acute infection. When suspicion for acute infection is high (e.g., as in
a patient who has a report of recent risk behavior in association with
suggestive symptoms and signs [Table 15]), a test for HIV RNA should be
performed (BII).* Persons may or may not have symptoms of the acute retroviral
syndrome. Viremia occurs acutely after infection before the detection of
a specific immune response; an indeterminate antibody test may occur when
a person is in the process of seroconversion.
Apart from patients who have acute primary HIV infection, many experts
also would consider therapy for patients in whom seroconversion has been
documented to have occurred within the previous 6 months (CIII). Although
the initial burst of viremia in infected adults has usually resolved by
2 months, treatment during the 2 & 6 & month period after
infection is based on the likelihood that virus replication in lymphoid
tissue is still not maximally contained by the immune system during this
time. Decisions regarding therapy for patients who test antibody positive
and who believe the infection is recent but for whom the time of infection
cannot be documented should be made using the Asymptomatic HIV Infection
algorithm mentioned previously (CIII). No patient should be treated for
HIV infection until the infection is documented, except in the setting
of post-exposure prophylaxis of healthcare workers with antiretroviral
agents (21).§ All patients without a formal medical record of
a positive HIV test (e.g., persons who have tested positive by available
home testing kits) should be tested by both the ELISA and an established
confirmatory test (e.g., the Western Blot) to document HIV infection (AI).
*Patients diagnosed with HIV infection by HIV RNA testing should have
confirmatory testing performed (Table 2).
§ Or treatment of neonates born to HIV-infected mothers.
Treatment Regimen for Primary HIV Infection
Once the physician and patient have decided to use antiretroviral therapy
for primary HIV infection, treatment should be implemented with the goal
of suppressing plasma HIV RNA levels to below detectable levels (AIII).
The weight of current experience suggests that the therapeutic regimen
for acute HIV infection should include a combination of two NRTIs and one
potent PI (AII). Although most experience to date with PIs in the setting
of acute HIV infection has been with ritonavir, indinavir or nelfinavir
(2,22 & 24), insufficient data are available to make firm conclusions
regarding specific drug recommendations. Potential combinations of agents
available are much the same as those used in established infection (Table
6). These aggressive regimens may be associated with several disadvantages
(e.g., drug toxicity, large numbers of pills, cost of drugs, and the possibility
of developing drug resistance that may limit future options); the latter
is likely if virus replication is not adequately suppressed or if the patient
has been infected with a viral strain that is already resistant to one
or more agents. The patient should be carefully counseled regarding these
potential limitations and individual decisions made only after weighing
the risks and sequelae of therapy against the theoretical benefit of treatment.
Any regimen that is not expected to maximally suppress viral replication is not considered appropriate for treating the acutely HIV-infected person (EIII) because a) the ultimate goal of therapy is suppression of viral replication to below the level of detection, b) the benefits of therapy are based primarily on theoretical considerations, and c) long-term clinical outcome benefit has not been documented. Additional clinical studies are needed to delineate further the role of antiretroviral therapy in the primary infection period.
Patient Follow-up
Testing for plasma HIV RNA levels and CD4+T cell count and toxicity
monitoring should be performed as previously described in Use of Testing
for Plasma HIV RNA levels and CD4+T cell Count in Guiding Decisions for
Therapy, that is, on initiation of therapy, after 4 weeks, and every 3 & 4
months thereafter (AII). Some experts suggest that testing for plasma HIV
RNA levels at 4 weeks is not helpful in evaluating the effect of therapy
for acute infection because viral loads may be decreasing from peak viremia
levels even in the absence of therapy.
Duration of Therapy for Primary HIV Infection
Once therapy is initiated, many experts would continue to treat the
patient with antiretroviral agents indefinitely because viremia has been
documented to reappear or increase after discontinuation of therapy (CII).
However, some experts would treat for one year and then reevaluate the
patient with CD4+T cell determinations and quantitative HIV RNA measurements.
The optimal duration and composition of therapy are unknown, and ongoing
clinical trials are expected to provide data relevant to these issues.
The difficulties inherent in determining the optimal duration and composition
of therapy initiated for acute infection should be considered when first
counseling the patient regarding therapy.
Go to the NIH Report & Guidelines Menu
Go to the HIVpositive.us Main Menu