Control of HIV during a structured treatment interruption in chronically infected individuals with vigorous T cell responses.
OBJECTIVE
To study whether and under what circumstances HIV can be controlled in chronically infected patients.


METHODS
Nine patients treated with hydroxyurea and didanosine (PANDAs) were compared with 7 patients on highly active antiretroviral therapy (HAART) during an 8-week treatment interruption. Both groups had similar baseline viral load, CD4 count, and length of treatment. Treatment was resumed if viral rebound >10,000 copies/mL (virological failure) or CD4 count decrease below 200 cells/mm(3) (immunological failure) occurred in two consecutive measurements.


RESULTS
None of the PANDAs failed. Viral rebound was spontaneously contained, and CD4 count remained stable. Four out of 7 patients in the HAART group failed to control HIV by week 6 and had to restart therapy due to either viremia rebound or CD4 decrease. Before therapy interruption, the PANDAs had a vigorous HIV-specific T cell immune response (median CD4VIR 1.2%), while the HAART-treated patients did not (median CD4VIR 0.2%) (CD4VIR represents the percentage of HIV-specific CD4 subpopulation expressing IFN-gamma within the total CD4 population [CD3+, CD4+, IFN-gamma+]). This difference was statistically significant (p =.002).


CONCLUSIONS
This study shows that HIV can be controlled during therapy interruption in patients with established infection, and that control of viral replication correlates with vigorous anti-HIV specific immune responses.
Lori
Franco
F
Research Institute for Genetic and Human Therapy (RIGHT) at IRCCS Policlinico S. Matteo, Pavia, Italy. RIGHTPV@tin.it
Foli
Andrea
A
Maserati
Renato
R
Seminari
Elena
E
Xu
Jianqing
J
Whitman
Lucia
L
Ravot
Elisabetta
E
Alberici
Francesco
F
Lopalco
Lucia
L
Lisziewicz
Julianna
J
D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D002908:Chronic Disease; D015331:Cohort Studies; D016049:Didanosine / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000517:prevention & control; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use*; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000276:immunology*
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D016049:Didanosine; D006918:Hydroxyurea