Over the past few years, data has accumulated underlining the benefits of earlier antiretroviral therapy. The most recent U.S. and European treatment guidelines recommend that HAART should be started when the CD4 cell count falls below 350 cells/mm3, but some experts believe even earlier would be better.

A study presented last week at the 9th International Congress on Drug Therapy in HIV Infection (HIV9) in Glasgow, Scotland, added further evidence that starting treatment with a relatively high CD4 count increases the likelihood of eventually achieving full recovery to a near-normal level.

Italian investigators retrospectively assessed long-term immunological outcomes for up to 8 years, in patients with sustained virological suppression on HAART. A total of 352 participants were followed at a clinic in Perugia for at least 1 year while on HAART and had HIV RNA < 400 copies/mL for at least 6 consecutive months.

Patients were stratified by sex, age, race/ethnicity, HIV risk group, hepatitis C virus (HCV) coinfection status, HAART regimen, and baseline CD4 cell (< 200, 200-350, or > 350 cells/mm3). Complete immunological recovery was defined as attaining a CD4 count of 700 cells/mm3 or higher. (A range of 500 to 1500 cells/mm3 is usually considered normal for HIV negative individuals.)

Results

• At baseline, 172 patients (49%) had a CD4 count < 200 cells/mm3, 85 (24%) had 200-350 cells/mm3, and 95 (27%) had > 350 cells/mm3.

• After 5 years on therapy, 82% of patients with > 350 cells/mm3 at baseline exceeded a threshold of 500 cells/mm3, compared with 69% in the middle CD4 stratum, and just 29% of those who started with < 200 cells/mm3 (P = 0.034).

• Among patients with > 350 cells/mm3 at baseline, the mean CD4 cell count reached a plateau, with complete immunological recovery by year 4 of suppressive HAART.

• Among patients with < 200 cells/mm3 at baseline, however, CD4 counts continued to increase even after 8 years without reaching full immunological recovery.

• Patients age 50 years or older had slower immune recovery, but ultimately attained the same CD4 levels as younger participants (P > 0.05).

• No significant differences in immunological response were observed according to sex, HIV risk factor, baseline HIV viral load, or HAART regimen.

• HCV coinfection, however, was associated with a lower CD4 count after 7 years on therapy.

"In our study, patients with sustained viral suppression experienced a significant immune recovery over 8 years of HAART," the investigators concluded.

But, they added, "We found that complete immune recovery was achieved only in patients with baseline CD4 cell count > 350 [cells/mm3]."

This observation, they suggested, "strengthens the hypothesis" that starting HAART at a CD4 cell count < 500 cells/mm3 may not be early enough to enable complete immunological recovery for some patients.

These results are similar to those from a recent analysis of the Dutch ATHENA cohort, which found that 73% of people who started therapy with 350-500 cells/mm3 achieved a level of at least 800 cells/mm3 within 7 years on HAART. Among those who started treatment with > 500 cells/mm3, however, 89% attained this level.

In another study presented at HIV9, U.K. researchers analyzed about 3500 treatment-naive participants who started HAART with 350-500 cells/mm3 and achieved undetectable viral load. Over 4 years of follow-up, although patients who started treatment with < 100 cells/mm3 still had a significantly lower median CD4 count than those who started earlier, their CD4 cell gains relative to baseline were significantly larger, leading the researchers to suggest that "any disadvantage may be lost over time if patients can maintain viral load suppression."

11/21/08

References

E Malincarne, A Sgrelli, G Camanni, and others. Immune restoration during HAART: 8-year follow-up in HIV-positive patients with sustained virologic suppression. 9th International Congress on Drug Therapy in HIV Infection. Glasgow, Scotland. November 9-13, 2008. Journal of the International AIDS Society 11(Suppl 1):P10. November 10, 2008.

LJ Waters, M Fisher, J Anderson, and others. Do the disadvantages of late initiation of HAART persist in patients achieving and maintaining viral load (VL) suppression for a year on HAART? 9th International Congress on Drug Therapy in HIV Infection. Glasgow, Scotland. November 9-13, 2008. Journal of the International AIDS Society 11(Suppl 1):O422. November 10, 2008.