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 in addition to the patient's clinical condition. Results of these laboratory tests provide clinicians with key information regarding the virologic and immunologic status of the patient and the risk for disease progression to acquired immunodeficiency syndrome (AIDS) (3–4). HIV viral load testing has been approved by the Food and Drug Administration (FDA) for determining prognosis and for monitoring the response to therapy only for the reverse transcriptase-polymerase chain reaction (RT-PCR) assay and in vitro nucleic amplification test for HIV–RNA (NucliSens® HIV-1 QT, manufactured by Organon Teknika). Multiple analyses among >5000 patients who participated in approximately 18 trials with viral load monitoring indicated a statistically significant dose-response–type association between decreases in plasma viremia and improved clinical outcome on the basis of standard results of new AIDS-defining diagnoses and survival. This relationship was observed throughout a range of patient baseline characteristics, including pretreatment plasma RNA level, CD4+ T cell count, and previous drug experience. Thus, viral load testing is an essential parameter in deciding to initiate or change antiretroviral therapies. Measurement of plasma HIV RNA levels (i.e., viral load) by using quantitative methods should be performed at the time of diagnosis and every 3–4 months thereafter for the untreated patient (AIII) (Table 2). CD4+ T cell counts should be measured at the time of diagnosis and every 3–6 months thereafter (AIII). These intervals between tests are recommendations only, and flexibility should be exercised according to the circumstances of each patient. Plasma HIV RNA levels should also be measured immediately before and again at 2–8 weeks after initiation of antiretroviral therapy (AIII). This second measurement allows the clinician to evaluate initial therapy effectiveness because, for the majority of patients, adherence to a regimen of potent antiretroviral agents should result in a substantial decrease ("1.0 log10) in viral load by 2–8 weeks. A patient's viral load should continue to decline during the following weeks and, for the majority of patients, should decrease below detectable levels (i.e., defined as <50 RNA copies/mL of plasma) by 16–24 weeks. Rates of viral load decline toward undetectable are affected by the baseline CD4+ T cell count, the initial viral load, potency of the regimen, adherence to the regimen, previous exposure to antiretroviral agents, and the presence of any OIs. These differences must be considered when monitoring the effect of therapy. However, the absence of a virologic response of the magnitude discussed previously should prompt the clinician to reassess patient adherence, rule out malabsorption, consider repeat RNA testing to document lack of response, or consider a change in drug regimen. After the patient is receiving 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 24 weeks should be undetectable (5). Data from clinical trials demonstrate that lowering plasma HIV RNA to <50 copies/mL is associated with increased duration of viral suppression, compared with reducing HIV RNA to levels of 50–500 copies/mL (6). If HIV RNA remains detectable in plasma after 16–24 weeks of therapy, the plasma HIV RNA test should be repeated to confirm the result and a change in therapy should be considered (see Changing a Failing Regimen) (BIII).