Impact of immune interventions on proviral HIV-1 DNA decay in patients receiving highly active antiretroviral therapy.
OBJECTIVE
To measure the evolution of proviral HIV-1 DNA levels in patients receiving highly active antiretroviral therapy (HAART) compared to those treated with HAART plus interleukin-2 (IL-2) and hydroxyurea.


METHODS
Prospective randomised trial.


METHODS
Twenty-two HIV-1 infected patients were randomly assigned to a five-drug antiretroviral regimen for 72 weeks, with or without IL-2, followed by a three-drug regimen up to week 120 with additional hydroxyurea in patients having received IL-2. HIV-1 DNA levels in peripheral blood mononuclear cells (PBMC) were measured regularly using the Amplicor Monitor kit from Roche Diagnostics (Meylan, France). Potentially infectious HIV-1 was cultured in enhanced conditions from circulating CD4 T cells at week 120.


RESULTS
During the study period of 120 weeks, HIV-1 DNA levels in PBMC decreased by -1.1 log in patients treated with HAART only compared with -1.8 log in patients with additional IL-2 and hydroxyurea. A two-phase decay rate was observed, with an inflexion point at 12 weeks. The second decay was slow, with mean half-lives of 130.1 +/- 21.3 weeks and 95.1 +/- 26.3 weeks for patients on HAART and those receiving additional IL-2 and hydroxyurea, respectively. At week 120, one out of 11 patients with HAART alone compared to six out of 11 in the group with IL-2 and hydroxyurea had undetectable proviral DNA levels and three of them had unsuccessful recovery of replication-competent HIV-1 from blood CD4 T cells.


CONCLUSIONS
Therapeutic strategies combining HAART and immune interventions have higher potency to decrease the number of infected cells than HAART alone.
Lafeuillade
A
A
Department of Infectious Diseases, and Laboratory of Virology, General Hospital, Toulon and Laboratory Alphabio, Marseilles, France. avps@club-internet.fr
Poggi
C
C
Chadapaud
S
S
Hittinger
G
G
Khiri
H
H
Halfon
P
P
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D004279:DNA, Viral / Q000187:drug effects*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D007376:Interleukin-2 / Q000627:therapeutic use*; D007963:Leukocytes, Mononuclear / Q000821:virology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016896:Treatment Outcome
D004279:DNA, Viral; D007376:Interleukin-2