Predictors of virological outcome and safety in primary HIV type 1-infected patients initiating quadruple antiretroviral therapy: QUEST GW PROB3005.
BACKGROUND
Initiation of antiretroviral therapy during primary human immunodeficiency virus (HIV)-1 infection may confer long-term benefit.


METHODS
After initiation of zidovudine, lamivudine, abacavir, and amprenavir therapy in patients in the QUEST cohort, predictors of virological outcome, virological and immunological changes, and adverse events were evaluated over 48 weeks.


RESULTS
One hundred forty-eight patients started antiretroviral therapy during primary HIV-1 infection with < or =3 bands on Western Blot (median plasma HIV-1 RNA load, 5.4 log copies/mL; median CD4 cell count, 517 cells/mm(3)). By week 48, 36% of patients had stopped treatment or were lost to follow-up. Among the 115 patients receiving follow-up care at week 48 (102 of whom were receiving antiretroviral therapy), the median viral load decrease was -5.4 log copies/mL (interquartile range [IQR], -6.4 to -3.9 log copies/mL), and the median increase in CD4 cell count was 147 cells/mm(3) (IQR, -1 to 283 cells/mm(3)); 84.2% of patients had a viral load < or =50 copies/mL, and 44.7% of patients had a viral load < or =3 copies/mL. The median cell-associated RNA level decreased from 3.4 log copies/million PBMCs (IQR, 2.9-4.1 log copies/million PBMCs) to 0.8 log copies/million PBMCs (IQR, 0.5-1.4 log copies/million PBMCs), and the median cell-associated DNA level decreased from 2.8 log copies/million PBMCs (IQR, 2.4-3.0 log copies/million PBMCs) to 1.6 log copies/million PBMCs (IQR, 1.2-1.9 log copies/million PBMCs); 33.3% of patients had an undetectable RNA level, and 9.5% of patients had an undetectable cell-associated DNA level. The median CD8(+)/CD38(++) T cell count decreased from 459 cells/mm(3) (IQR, 208-974 cells/mm(3)) to 33 cells/mm(3) (IQR, 19-75 cells/mm(3)). Baseline CD8(+)/CD38(++) T cell count and cell-associated DNA level were independent inverse predictors for reaching a viral load < or =3 copies/mL. Eighty-three patients experienced a serious adverse event (median duration of an adverse event, 15 days).Conclusions. Initiation of antiretroviral therapy during primary HIV-1 infection was associated with very significant antiretroviral activity and a decrease in immune activation. Lower baseline CD8(+)/CD38(++) T cell count and cell-associated DNA level were predictive of achieving a viral load < or =3 copies/mL.
Hoen
Bruno
B
Department of Infectious Diseases, University Medical Centre, Besancon, France.
Cooper
David A
DA
Lampe
Fiona C
FC
Perrin
Luc
L
Clumeck
Nathan
N
Phillips
Andrew N
AN
Goh
Li-Ean
LE
Lindback
Stefan
S
Sereni
Daniel
D
Gazzard
Brian
B
Montaner
Julio
J
Stellbrink
Hans-Jurgen
HJ
Lazzarin
Adriano
A
Ponscarme
Diane
D
Staszewski
Shlomo
S
Mathiesen
Lars
L
Smith
Don
D
Finlayson
Robert
R
Weber
Rainer
R
Wegmann
Laurence
L
Janossy
George
G
Kinloch-de Loes
Sabine
S
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D005006:Ethnicity; D005060:Europe; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D019562:Viral Load
D019380:Anti-HIV Agents