POZ - Treatment News : Early Treatment Linked to CD4 Gains

A new report suggests that early HIV treatment is more likely to result in "normal" CD4 (T4 cell) counts, compared to treatment started in accordance with current treatment guidelines. Only patients with CD4 cell counts above 350 at the time of starting therapy, Johns Hopkins University (JHU) School of Medicine researchers found, had normal or near-normal CD4 counts after six years of treatment.

HIV care guidelines produced by the U.S. Department of Health and Human Services (DHHS) recommend that antiretroviral therapy be started when the CD4 cell count drops below 350. However, this cutoff is only a suggestion; some doctors prefer to prescribe therapy earlier, whereas others suggest holding off until the CD4 count teeters around 200.

Proponents of delayed therapy argue that starting treatment too early can increase the risk of adherence problems, long-term side effects, and drug resistance. Supporters of early treatment contend that the sooner antiretroviral therapy is started the more beneficial it will be in terms of immune system function.

The new report, researched and written by JHU's Richard Moore, MD, and Jeanne Keruly, CRNP, lends credence to the early therapy argument.

To determine if there is an association between the CD4 cell count at the start of treatment and the magnitude of the CD4 count response to therapy, Moore and Keruly turned to patients enrolled in the Johns Hopkins HIV Clinical Cohort who had been on treatment for at least a year and maintained viral loads below 400. They analyzed the annual change in the patients' CD4 counts for up to six years after starting antiretroviral treatment, comparing those who started therapy with 200 or fewer CD4 cells to those with counts between 201 and 350 and those with counts greater than 350.

As is reported in the February 1 issue of Clinical Infectious Diseases, a total of 655 patients in the cohort were followed and evaluated. Across the board, 92% of the patients saw their CD4 cell counts increase in response to treatment. The average CD4 increase was 274 cells among all those included in the analysis.

After six years of treatment, the average CD4 count was 493 among those who began therapy with 200 or fewer CD4 cells. Among those with CD4 counts between 201 and 350 at the time of treatment commencement, the CD4 count was approximately 508 after six years. Finally, among those who began therapy with CD4 cell counts above 350, the average CD4 count six years later was 829.

In addition to the CD4 cell count at the time of beginning treatment, injection drug use and older age were associated with smaller CD4 cell count responses. Of interest, the choice of either a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor did not differ in terms of the CD4 cell count gains seen in the cohort. Similarly, there were no differences in CD4 count gains among women, or people of color, or those coinfected with hepatitis C.

Moore and Keruly concluded that, "only patients with baseline CD4 counts [greater than 350] returned to nearly normal CD4 cell counts after six years of follow-up." While they noted that significant CD4 count increases were seen in most of the patients followed, those with lower pre-treatment levels were more likely to see their CD4 counts "plateau" at a below-normal level.

Given limitations of the collected data, it was not possible to conclude that higher CD4 cell counts in those who began treatment early were necessarily associated with longer disease-free survival than those who achieved less pronounced CD4 count increases. Additional clinical trials evaluating the timing of treatment initiation on AIDS diagnosis and survival rates will likely be needed to answer this long-standing question.

Source:

Moore RD and Keruly JC. CD4+ cell count 6 years after commencement of highly active antiretroviral therapy in persons with sustain virologic suppression. Clin Infect Dis 44:441-6, 2007.