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

US Health & Human Services, December 1998

Acute HIV Infection

The theoretical rationale for early intervention, as provided in Principle 10, is sixfold:

• to suppress the initial burst of viral replication and decrease the magnitude of virus dissemination throughout the body;

• to decrease the severity of acute disease;

• to potentially alter the initial viral "set point," which may ultimately affect the rate of disease progression;

• to possibly reduce the rate of viral mutation due to the suppression of viral replication;

• to possibly reduce the risk of viral transmission;

• to preserve immune function.

The risks of 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 which 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 and were discussed in greater detail in the section "Considerations in Initiating Therapy in the Asymptomatic HIV-infected Patient."

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 detectable HIV RNA in plasma using sensitive PCR or bDNA assays together with a negative or indeterminate HIV antibody test. While 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. It should be noted, however, that a negative p24 antigen test does not rule out acute infection. When suspicion for acute infection is high, such as in a patient with a report of recent risk behavior in association with symptoms and signs listed in Table XVI, a test for HIV RNA should be performed (BII). (Patients diagnosed with HIV infection by HIV RNA testing should have confirmatory testing performed [see Table II].) As noted earlier, individuals may or may not have symptoms of the acute retroviral syndrome. Viremia occurs acutely after infection prior to the detection of a specific immune response; an indeterminate antibody test may occur when an individual is in the process of seroconversion.

Apart from patients with acute primary HIV infection, many experts would also consider therapy for patients in who seroconversion has been documented to have occurred within the previous six months (CIII). Although the initial burst of viremia in infected adults has usually resolved by two 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 Chronic infection" algorithm mentioned previously (CIII). Except in the setting of post-exposure prophylaxis with antiretroviral agents^[21], no patient should be treated for HIV infection until the infection is documented. In this regard, all patients presenting without a formal medical record of a positive HIV test, such as those who have tested positive by available home testing kits, should undergo ELISA and an established confirmatory test such as the Western Blot (AI) to document HIV infection.

Treatment Regimen for Primary HIV Infection

Once the physician and patient have made the decision 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 nucleoside reverse transcriptase inhibitors and one potent protease inhibitor (AII). Although most experience to date with protease inhibitors in the setting of acute HIV infection has been with ritonavir, indinavir or nelfinavir^{[2, 22-24]}, there are insufficient data to make firm conclusions regarding specific drug recommendations. Potential combinations of agents available are much the same as those used in established infection, listed in Table VI. It is recognized that these aggressive regimens may be associated with several disadvantages, including drug toxicity, large pill burden, 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 (see above).

Since 1) the ultimate goal of therapy is suppression of viral replication to below the level of detection, and 2) the benefits of therapy are based primarily on theoretical considerations and 3) long term clinical outcome benefit has not been documented, any regimen that is not expected to maximally suppress viral replication is not considered appropriate for treating the acutely HIV-infected individual (EIII). 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 described above in "Use of Testing for Plasma HIV RNA levels..." i.e., on initiation of therapy, after 4 weeks, and every 3-4 months thereafter (AII). Some experts feel that testing for plasma HIV RNA levels at 4 weeks is not helpful in evaluating the effect of therapy for acute infection as 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). 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.