Highly active antiretroviral therapy (HAART) regimens have greatly diminished the morbidity and mortality associated with human immunodeficiency virus (HIV) infection. Early identification of patients who are not responding to HAART should help to minimize viral resistance caused by suboptimal regimens and better prevent disease progression. Kitchen and associates present long-term follow-up data from patients with HIV infection who had been taking HAART for longer than two years and identify some early predictors of later disease progression.

The study involved 213 patients who were randomly drawn at an outpatient HIV treatment facility. Of the study participants, 92 percent were men, and 91 percent had homosexual contact as their HIV risk factor. The median viral load of HIV-1 RNA at the study onset was 4.2 log copies per mL, and the median baseline CD4⁺ count was 230 cells per mm³ (230 × 10⁶ per L). Before the trial, opportunistic infections had already been diagnosed in 19 percent of patients, and only 17 percent were “treatment naive” (i.e., they had no previous antiretroviral therapy).

Patients were evaluated regularly for at least two years for changes in viral load, CD4⁺ count and clinical progression of the disease. Suppression of the viral load below detectable levels after three months of HAART was accomplished in 69 percent of patients. Almost all of the patients who failed to suppress had been treated previously with at least three different anti-HIV medications. Of patients with initial suppression, 38 percent had a viral load rebound during the two-year follow-up period, and this was more common among patients treated previously for HIV infection.

The single best predictor of disease progression during long-term follow-up was a failure to decrease the viral load by at least 0.5 log copies per mL after the first three months of HAART. A combination of an increase in CD4⁺ count of more than 200 cells per mm³ (200 × 10⁶ per L) and a decrease of at least 0.5 log copies per mL in viral load was associated with the best long-term outcome.

The authors conclude that a decrease in viral load of at least 0.5 log copies per mL after three months of HAART is an important predictor of decreased risk of disease progression. Even more protection is conferred with a concurrent increase of CD4⁺ count of more than 200 cells per mm³.

editor's note: Shorter-term studies have postulated that a high initial viral load or failure to achieve complete viral suppression is associated with the greatest risk of disease progression. This long-term trial, involving a typical HIV-infected population (i.e., with previous anti-HIV treatment and opportunistic infections already documented), suggests that any failure of HAART to suppress viral load within three months of starting therapy should prompt a reassessment of compliance and perhaps a change in therapy.—b.z.