Immune restoration during HAART: 8-year follow-up in HIV-positive patients with sustained virological suppression

Purpose of the study

Durable virological suppression during HAART is associated with immunological recovery in patients with HIV infection. Current guidelines recommend to initiate HAART when CD4+ cell count falls <350/μl. However, recent studies have shown a higher immune restoration when HAART was started at CD4+ baseline level > 350 cells/μl. We retrospectively assessed the long-term immunological outcome in patients with sustained virological suppression during HAART, for up to 8 years.

Methods

HIV-infected consecutive patients attending to our clinic were included, with the following inclusion criteria: follow-up >1 year while on HAART and sustained virologic suppression (HIV-RNA <400 copies/ml) for at least 6 consecutive months. We analyzed the immunological outcome by of annual determination of: 1) CD4+ cell count; and 2) change in CD4+ cell count from baseline. Complete immunological recovery was defined as CD4+ cell count ≥700/μl. Patients were stratified according to baseline CD4+ cell (counts of <200/μl, 200–350/μl and >350/μl), age, HIV risk group, HCV co-infection, HAART regimen, sex, and race. A statistical analysis was performed by linear regression.

Summary of results

352 patients were observed: 172, 85 and 95 patients had baseline CD4+ cell count <200/μl, 200–350/μl and >350/μl, respectively. After 5 years of therapy, 29%, 69% and 82% of patients with baseline CD4+ cell count, respectively, <200/μl, 200–350/μl and >350/μl, exceeded the threshold of 500 cells/μl (p = 0.034).

Among patients with baseline CD4+ cell count >350/μl, mean CD4+ cell count reached a plateau with a complete immunological recovery by 4 years of suppressive HAART. CD4+ cell count increased even after 8 years without ever reaching a full immunological recovery in patients with baseline CD4+ cell count <200/μl.

Patients aged ≥50 years had a slower but similar immune recovery (p > 0.05). We found no significant differences in immunological response according to baseline viral load, HIV risk factor, sex, HCV co-infection and HAART regimen.

Conclusion

In our study, patients with sustained viral suppression experienced a significant immune recovery over 8 years of HAART. We found that complete immune recovery was achieved only in patients with baseline CD4+ cell count >350/μl. This observation strengthens the hypothesis that starting HAART at CD4+ cell counts < 50/μl could not be adequate to obtain a complete immunological recovery.