429   Immunologic Response to HAART by Duration of Viral Suppression and Continuity of Antiretroviral Therapy.

R. E. Chaisson*, J. Keruly, and R. D. Moore.
Johns Hopkins Univ., Baltimore, MD.

Background:The objective of this study was to assess the immunologic response to HAART by duration of viral suppression and continuity of treatment.

Methods:We studied 515 patients on a first HAART regimen who continued treatment for at least 6 months and achieved at least 1 viral load <400 copies per mL. Changes in CD4 counts were determined for the following groups: Group 1—sustained virologic response with no VL >1000 ever; Group 2a—virologic rebound >1000 but continued HAART with subsequent VL <400; Group 2b—sustained virologic rebound >1000 but continued HAART; Group 3—virologic rebound to >1000 and discontinued HAART.

Results:515 patients were studied, 240 in Group 1, 118 in Group 2a, 84 in Group 2b and 73 in Group 3. Patients in Group 1 were more likely than other groups to be white and non-injection drug users, with no difference by sex between groups. Mean follow-up was >2 years in all groups. Median CD4 changes at 6, 12, 18 and 24 months, respectively, by group were as follows: Group 1—+82, +141, +174, + 200; Group 2a—+66, +96, +105, +123; Group 2b—+76, +99, +116, +116; Group 3—+78, +79, +69, +41. CD4 increases in Group 1 were significantly greater than other groups after 12 months, whereas the CD4 changes in Groups 2a and 2b didn't differ throughout follow-up. By contrast, Group 3 patients, who stopped HAART after virologic rebound, had significantly poorer CD4 cell responses than Group 2a and 2b patients at 24 months. Though not significant, Group 3 patients were twice as likely as patients in Groups 1 and 2a/b to have clinical disease progression.

Conclusions:Patients with sustained suppression of VL on HAART have better CD4 responses at 24 months than patients with virologic failure. Among those with virologic rebound who continue HAART, CD4 count increases are >100 cells after 24 months, even in those who do not achieve re-suppression of VL to <400. In patients with virologic failure who stop HAART, CD4 responses are markedly poorer than in those continuing HAART. These data support the hypothesis that continuing HAART in the presence of virologic failure may lead to attenuation of viral pathogenicity.