By Liz Highleyman

Evidence has accumulated over the past few years showing that starting antiretroviral therapy early, before the immune system sustains severe damage, leads to more favorable outcomes. This strategy has become more attractive with the development of drugs that -- so far -- appear to be safe and effective over the long term.

Current U.S. and European treatment guidelines recommend that asymptomatic HIV patients should start therapy when their CD4 count falls below 350 cells/mm3, but a growing number of experts think starting sooner might be better.

A study presented in a late-breaker session at the 48th International Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2008), taking place this week in Washington, DC, offered further support for early treatment initiation.

Researchers with the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) analyzed data from multiple U.S. and Canadian cohorts including a total of more than 8000 treatment-naive HIV positive patients with a CD4 count of 351-500 cells/mm3 seen between 1996 and 2006. (For the presentation, an additional cohort was added to the data in the published abstract.)

The median age was about 40 years, the median baseline CD4 count was about 430 cells/mm3, and the median baseline viral load was about 15,000 copies/mL. Overall, approximately 20% were injection drug users and roughly 30% had hepatitis C virus (HCV) coinfection. Type of HAART used was similar in the immediate and deferred groups (mostly non-boosted protease inhibitor-based regimens).

Among the 8374 patients studied, 2473 (30%) initiated HAART with 351-500 cells/mm3 (median 420 cells/mm3), while the remaining 5901 (70%) deferred therapy (starting with a median 275 cells/mm3). The latter group included individuals who started as soon as their CD4 cell count fell to 350 cells/mm3, those who waited longer, and those who died without ever starting treatment. The investigators compared the relative hazard (RH) of death for patients who started HAART with 351-500 cells/mm3 versus those who deferred therapy.

Results

• 221 patients (8.9%) who initiated HAART with 351-500 cells/mm3 died of any cause during follow-up, compared with 446 (7.6%) in the deferred therapy group.

• In an analysis adjusting for cohort and calendar year, patients who deferred treatment had a significantly higher risk of death than those who initiated HAART with 351-500 cells/mm3 (RH 1.7 or 71% higher; P < 0.001).

• The risk of death fell by about 10% as the CD4 count at treatment initiation rose by 100 cells/mm3.

• Risk of death did not vary according to HIV viral load.

• The elevated risk of death in patients who deferred therapy was not attributable to injection drug use or HCV coinfection.

Based on these findings, the study investigators said they found a "higher risk of death for patients who deferred treatment rather than initiating HAART at a CD4+ count between 351-500 cells/mm3."

"Results from this large North American cohort collaboration support initiation of HAART at a CD4+ count of 351-500 cells/mm3, an earlier stage of HIV disease than currently recommended," they added.

In a press conference discussing the data, presenter Mari Kitahata went further, stating, "These data strongly support the use of antiretroviral treatment for patients at a CD4 count of 500 and below, regardless of the presence of symptoms."

The researchers are currently performing a new analysis looking at survival among individuals who start therapy even sooner, with a CD4 count above 500 cells/mm3.

North American AIDS Cohort Collaboration on Research and Design; Univ. of Washington, Seattle, WA; Johns Hopkins Univ., Baltimore, MD.

10/28/08

References
MM Kitahata, SJ Gange, and RD Moore. Initiating rather than deferring HAART at a CD4+ count between 351-500 cells/mm3 is associated with improved survival. 48th International Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2008). Washington, DC. October 25-28, 2008. Abstract H-896b.