Strategic Decisions

With improving longevity for HIV-infected persons receiving antiretroviral treatment, but also acknowledging the finite durability of each regimen and a limited number of regimens, the optimal strategy for the use of antiretroviral therapy is crucial to maximize clinical benefit. Significant unanswered questions include the optimal initiation of antiretroviral therapy and the timing of a switch from a failing regimen to a secondary one.

Treatment Initiation

Most clinicians follow HIV-infected persons not receiving antiretroviral treatment every 3 to 6 months with a careful history and physical examination and monitoring of plasma HIV RNA levels and absolute CD4+ cell counts. In asymptomatic HIV-infected persons the potential benefits of antiretroviral therapy should outweigh their imposition, toxicities, and cost. Many asymptomatic HIV-infected persons may be at low risk for clinical progression of disease due to host and virologic factors.

Therefore, antiretroviral therapy should ideally be offered to those patients at greatest risk of clinical progression. Before considering treatment initiation, it is prudent to repeat plasma HIV RNA levels and absolute CD4+ cell counts because of potential variability. The risk of disease progression is related to a patient's symptoms, plasma HIV RNA level, and absolute CD4+ cell number. Therapy is strongly recommended for all symptomatic patients. The optimal levels of plasma HIV RNA and absolute CD4+ cells to guide the initiation of therapy are not known, but most clinicians recommend therapy at conservative thresholds of more than 20,000 copies HIV RNA/mL or CD4+ cells less than 300/mm³ .

Critical to the success of treatment interventions is a patient who is prepared and committed to beginning therapy. Therefore, decisions on treatment initiation must be highly individualized. Many clinicians never initiate treatment for a patient during his or her first visit; rather, they evaluate and educate the patient during several visits.

Physicians must recognize the essential role of strict adherence to antiretroviral regimens and optimize circumstances such as patient education, emotional support, substance abuse rehabilitation, and the resources to obtain a continuing supply of medications. Studies of adherence have demonstrated that socioeconomic status, race/ethnicity, gender, and educational level do not predict successful adherence; therefore, physicians should not preclude treatment based on these factors.

With an expanding number of available antiretroviral drugs, clinicians can tailor regimens based on potency, convenience, predicted toxicities, and drug interactions. The importance of convenience and its relationship to adherence should not be underestimated. Significant issues may include dosing schedules, pill burden, food interactions, drug interactions, and toxicities. Clinicians should take a careful history regarding daily activities including employment and meals and project alternative medication schedules in discussions with their patients. When an initial regimen has been chosen, many clinicians will have patients return in 1 to 4 weeks to reinforce adherence and assess possible toxicities. Continuing attention to adherence at the time of all follow-up visits may assist in achieving long-term treatment success.