Use of Testing for Plasma HIV RNA Levels and CD4⁺ T Cell Count in Guiding Decisions for Therapy

Decisions regarding initiation or changes in antiretroviral therapy should be guided by monitoring the laboratory parameters of plasma HIV RNA (viral load) and CD4⁺ T cell count, as well as the clinical condition of the patient. Results of these two laboratory tests give the physician important information about the virologic and immunologic status of the patient and the risk of disease progression to AIDS (3,4). It should be noted that HIV viral load testing has been approved by the FDA for determining prognosis and for monitoring the response to therapy only for the RT- PCR assay (Roche). Multiple analyses in over 5000 patients who participated in approximately 18 trials with viral load monitoring showed a statistically significant dose-response type association between decreases in plasma viremia and improved clinical outcome based on standard endpoints of new AIDS-defining diagnoses and survival. This relationship was observed over a range of patient baseline characteristics including: pretreatment plasma RNA level, CD4⁺ T cell count, and prior drug experience. Thus, it is the consensus of the Panel that viral load testing is the essential parameter in decisions to initiate or change antiretroviral therapies. Measurement of plasma HIV RNA levels (viral load), using quantitative methods, should be performed at the time of diagnosis and every 3-4 months thereafter in the untreated patient (AIII) (See Table II). CD4⁺ T cell counts should be measured at the time of diagnosis and generally every 3-6 months thereafter (AIII). These intervals between tests are merely recommendations and flexibility should be exercised according to the circumstances of the individual case. Plasma HIV RNA levels should also be measured immediately prior to and again at 2*8 weeks after initiation of antiretroviral therapy (AIII). This second time point allows the clinician to evaluate the initial effectiveness of therapy, since in most patients adherence to a regimen of potent antiretroviral agents should result in a large decrease (~ 1.0 log₁₀) in viral load by 2-8 weeks. The viral load should continue to decline over the following weeks and in most individuals becomes below detectable levels (currently defined as <50 RNA copies/mL) by 16-20 weeks. The rate of viral load decline towards undetectable is affected by the baseline CD4⁺ T cell count, the initial viral load, potency of the regimen, adherence to the regimen, prior exposure to antiretroviral agents, and the presence of any OIs. These individual differences must be considered when monitoring the effect of therapy. However, the absence of a virologic response of the magnitude discussed above should prompt the physician to reassess patient adherence, rule out malabsorption, consider repeat RNA testing to document lack of response, and/or consider a change in drug regimen. Once the patient is on therapy, HIV RNA testing should be repeated every 3-4 months to evaluate the continuing effectiveness of therapy (AII). With optimal therapy viral levels in plasma at 6 months should be undetectable, that is, below 50 copies of HIV RNA per mL of plasma (5). Data from clinical trials strongly suggest that lowering plasma HIV RNA to below 50 copies/mL is associated with a more complete and durable viral suppression, compared with reducing HIV RNA to levels between 50-500 copies/mL (6). If HIV RNA remains detectable in plasma after 16-20 weeks of therapy, the plasma HIV RNA test should be repeated to confirm the result and a change in therapy should be considered, according to the guidelines in the section Considerations for changing a failing regimen (BIII).

When making decisions regarding the initiation of therapy, the CD4⁺ T lymphocyte count and plasma HIV RNA measurement should ideally be performed on two occasions to ensure accuracy and consistency of measurement (BIII). However, in patients who present with advanced HIV disease, antiretroviral therapy should generally be initiated after the first viral load measurement is obtained in order to prevent a potentially deleterious delay in treatment. It is recognized that the requirement for two measurements of viral load may place a significant financial burden on patients or payers. Nonetheless, the Panel feels that two measurements of viral load will provide the clinician with the best information for subsequent follow-up of the patient. Plasma HIV RNA levels should not be measured during or within four weeks after successful treatment of any intercurrent infection, resolution of symptomatic illness, or immunization. Because there are differences among commercially available tests, confirmatory plasma HIV RNA levels should be measured by the same laboratory using the same technique in order to ensure consistent results.

A minimally significant change in plasma viremia is considered to be a 3-fold or 0.5 log₁₀ increase or decrease. A significant decrease in CD4⁺ T lymphocyte count is a decrease of >30% from baseline for absolute cell numbers and a decrease of >3% from baseline in percentages of cells (7). Discordance between trends in CD4⁺ T cell numbers and plasma HIV RNA levels can occur and was found in 20% of patients in one cohort studied (8). Such discordance can complicate decisions regarding antiretroviral therapy and may be due to a number of factors that affect plasma HIV RNA testing. In general, viral load and trends in viral load are felt to be more informative for guiding decisions regarding antiretroviral therapy than are CD4⁺ T cell counts; exceptions to this rule do occur, however. For further discussion refer to "Considerations for changing a failing regimen;" in many such cases, expert consultation should be considered.

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