Impact of pre-therapy viral load on virological response to modern first-line HAART.
BACKGROUND
We tested whether pre-HAART viraemia affects the achievement and maintenance of virological success in HIV-1-infected patients starting modern first-line therapies.


METHODS
A total of 1,430 patients starting their first HAART (genotype-tailored) in 2008 (median; IQR: 2006-2009) were grouped according to levels of pre-HAART viraemia (≤ 30,000, 30,001-100,000, 100,001-300,000, 300,001-500,000 and > 500,000 copies/ml). The impact of pre-therapy viraemia on the time to virological success (viraemia ≤ 50 copies/ml) and on the time to virological rebound (first of two consecutive viraemia values > 50 copies/ml after virological success) were evaluated by Kaplan-Meier curves and Cox regression analyses.


RESULTS
Median pre-HAART viraemia was 5.1 log10 copies/ml (IQR 4.5-5.5), and 53% of patients had viraemia > 100,000 copies/ml. By week 48, the prevalence of patients reaching virological success was > 90% in all pre-HAART viraemia ranges, with the only exception of range > 500,000 copies/ml (virological success = 83%; P < 0.001). Higher pre-HAART viraemia was tightly correlated with longer median time to achieve virological success. Cox multivariable estimates confirmed this result: patients with pre-HAART viraemia > 500,000 copies/ml showed the lowest hazard of virological undetectability after adjusting for age, gender, pre-HAART CD4+ T-cell count, transmitted drug resistance, calendar year and third drug administered (adjusted hazard ratio [95% CI]: 0.27 [0.21, 0.35]; P < 0.001). Pre-HAART viraemia > 500,000 copies/ml was also associated with higher probability of virological rebound compared with patients belonging to lower viraemia strata at weeks 4, 12 and 24 (P = 0.050).


CONCLUSIONS
At the time of modern HAART, and even though an average > 90% of virological success, high pre-HAART viraemia remains an independent factor associated with delayed and decreased virological success. Patients starting HAART with > 500,000 copies/ml represent a significant population that may deserve special attention.
University of Rome Tor Vergata, Rome, Italy.
Maria Mercedes
MM
Santoro
Daniele
D
Armenia
Claudia
C
Alteri
Philippe
P
Flandre
Andrea
A
Calcagno
Mario
M
Santoro
Caterina
C
Gori
Lavinia
L
Fabeni
Rita
R
Bellagamba
Vanni
V
Borghi
Federica
F
Forbici
Alessandra
A
Latini
Guido
G
Palamara
Raffaella
R
Libertone
Valerio
V
Tozzi
Evangelo
E
Boumis
Chiara
C
Tommasi
Carmela
C
Pinnetti
Adriana
A
Ammassari
Emanuele
E
Nicastri
Annarita
A
Buonomini
Valentina
V
Svicher
Massimo
M
Andreoni
Pasquale
P
Narciso
Cristina
C
Mussini
Andrea
A
Antinori
Francesca
F
Ceccherini-Silberstein
Giovanni
G
Di Perri
Carlo Federico
CF
Perno
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012307:Risk Factors; D017211:Treatment Failure; D016896:Treatment Outcome; D019562:Viral Load; D014766:Viremia / Q000188:drug therapy / Q000821:virology