Determinants of virologic and immunologic outcomes in chronically HIV-infected subjects undergoing repeated treatment interruptions: the Istituto Superiore di Sanita-Pulsed Antiretroviral Therapy (ISS-PART) study.
BACKGROUND
Factors influencing the outcome of structured treatment interruptions (STIs) in HIV chronic infection are not fully elucidated.


METHODS
In ISS-PART, 273 subjects were randomly assigned to arm A (137 assigned to continuous highly active antiretroviral therapy [HAART]) and arm B (136 assigned to 5 STIs of 1, 1, 2, 2, and 3 months' duration, each followed by 3 months of therapy). Main outcome measures were the proportion of subjects with a CD4 count >500 cells/mm3, the rate of virologic failure, and the emergence of resistance at 24 months.


RESULTS
The proportion of subjects with a CD4 count >500 cells/mm3 was higher in arm A than in arm B (86.5% vs. 69.1%; P = 0.0075). Pre-HAART CD4 cell count and male gender were independent predictors of a CD4 count >500 cells/mm3 in arm B. The overall risk of virologic failure was not increased in arm B; however, it was higher in the 38 subjects who had resistance mutations in the rebounding virus. Archived mutations at baseline and the use of a regimen that included an unboosted protease inhibitor (PI), compared with nonnucleoside reverse transcriptase inhibitor-based HAART, independently predicted the emergence of plasma mutations during STI (P = 0.002 for DNA mutations and P = 0.048 for PI-based HAART).


CONCLUSIONS
Our results suggest that patients with preexisting mutations and treated with unboosted PI-based HAART should not be enrolled in studies of time-fixed treatment interruptions, being at higher risk of developing plasma mutations during STI and virologic failure at therapy reinstitution.
Palmisano
Lucia
L
Department of Drug Research and Evaluation, Instituto Superiore di Sanità, Rome, Italy. l.palmisano@iss.it
Giuliano
Marina
M
Bucciardini
Raffaella
R
Fragola
Vincenzo
V
Andreotti
Mauro
M
Galluzzo
Clementina
C
Pirillo
Maria F
MF
Weimer
Liliana E
LE
Arcieri
Romano
R
Germinario
Elena A P
EA
Amici
Roberta
R
Mancini
Maria Grazia
MG
Monforte
Antonella d'Arminio
Ad
Castelli
Francesco
F
Caramello
Pietro
P
Vella
Stefano
S
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D004334:Drug Administration Schedule; D024921:Drug Resistance, Multiple, Viral; D005260:Female; D006678:HIV / Q000187:drug effects* / Q000502:physiology; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood
D019380:Anti-HIV Agents; D012367:RNA, Viral