The debate continues concerning the optimal time to initiate highly active antiretroviral therapy (HAART) in patients with human immunodeficiency virus (HIV) infection. Clinical guidelines vary in regard to this issue: some advocate initiating HAART when CD4⁺ T lymphocyte counts fall below 350 cells per mm³ (350 × 10⁶ per L), while others recommend waiting until these counts fall to 200 cells per mm³ (200 × 10⁶ per L). Sterling and colleagues present observational data on the usefulness of initiating HAART in patients with CD4⁺ counts above 350 cells per mm³.

The authors compiled retrospective patient data from a cohort of outpatients with HIV infection who were followed at an academic medical center. The authors compared patients with CD4⁺ counts from 350 to 499 cells per mm³ (350 to 499 × 10⁶ per L) who had received at least 90 days of HAART after reaching this level (159 patients) or were being followed without antiretroviral therapy (174 patients). A HAART regimen was defined as two nucleoside reverse-transcriptase inhibitors and at least one protease inhibitor. Patients who received HAART were more likely to be male and nonblack, and to have homosexual contact as their primary risk factor than those who did not receive HAART while in this CD4⁺ cell count range. There was no difference in median age, baseline CD4⁺ T lymphocyte count, and HIV-1 RNA viral load between the two groups. Those receiving HAART had a longer average follow-up (31 months) than those who did not receive multidrug therapy (21 months).

There were no significant differences at follow-up in HIV disease progression or death rates between the two groups. The number of patients who developed acquired immunodeficiency syndrome (AIDS)–defining events was low in both groups: 20 patients in the group receiving HAART, and 23 patients in the group who did not receive HAART while in this CD4⁺ cell count stratum. Among those receiving HAART, 85 patients (53 percent) still had HIV-1 viral loads above 400 copies per mL at their latest clinic visit. Sixty-five patients (41 percent) receiving HAART had to change their drug regimen during follow-up because of adverse effects.

The authors conclude that the use of HAART in patients who have HIV infection with CD4⁺ counts between 350 and 499 cells per mm³ did not slow disease progression or improve survival, did not completely suppress viral load in many patients, and frequently caused side effects. They advise caution in interpreting this data because of the retrospective, nonrandomized nature of the study.