Viral tropism by geno2pheno as a tool for predicting CD4 decrease in HIV-1-infected naive patients with high CD4 counts.
OBJECTIVE
To investigate the value of tropism (determined by genotypic testing) to predict CD4 depletion in HIV-infected antiretroviral-naive patients with high CD4 counts.


METHODS
Viral tropism was determined by geno2pheno (false positive rate = 10%) in 223 HIV-infected subjects naive to antiretrovirals with CD4 count ≥350 cells/μL and HIV-RNA >500 copies/mL enrolled in the ICONA Foundation Study for whom a stored plasma sample (baseline) was retrospectively tested. We monitored CD4 cell count and identified predictors of decline before antiretroviral therapy initiation, applying a mixed linear model with covariates (age, gender, tropism, HIV risk factor, calendar year of HIV infection, months from HIV diagnosis to baseline, hepatitis C virus status, CD4 and HIV-RNA at sample collection and duration of follow-up).


RESULTS
Two hundred and twenty-three subjects met the eligibility criteria; 137 (61%) were male and the median age was 35 (31-40) years. Median follow-up was 16.4 (3.2-37.2) months. Median CD4 decrease during follow-up was -157 (-278 to -13) cells/μL. At baseline, 192 (86%) subjects were defined as harbouring R5 virus and 31 (14%) non-R5. Median CD4 count was 571 (458-729) cells/μL and median HIV-RNA was 4.08 (3.57-4.55) log(10) copies/mL. At multivariable analysis, a greater mean CD4 decrease was associated with non-R5 viral tropism (-159.9 ± 12.22, P = 0.0002) at baseline. Other significant covariates were female gender, older age, intravenous drug use, longer duration of follow-up, and higher CD4 cell count and higher HIV-RNA at sample collection.


CONCLUSIONS
In patients with CD4 counts ≥350 cells/μL, non-R5 viral tropism by geno2pheno is predictive of CD4 decrease independent of their viral set point and CD4 counts.
San Raffaele Scientific Institute, Milan, Italy. silvia.nozza@hsr.it
Silvia
S
Nozza
Filippo
F
Canducci
Laura
L
Galli
Alessandro
A
Cozzi-Lepri
Maria Rosaria
MR
Capobianchi
Elisa Rita
ER
Ceresola
Pasquale
P
Narciso
Raffaella
R
Libertone
Paula
P
Castelli
Mariacristina
M
Moioli
Antonella
A
D'Arminio Monforte
Antonella
A
Castagna
D000328:Adult; D018791:CD4 Lymphocyte Count / Q000379:methods; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology / Q000472:pathogenicity*; D006801:Humans; D008297:Male; D012367:RNA, Viral / Q000097:blood; D015728:Receptors, HIV / Q000378:metabolism; D019562:Viral Load; D056189:Viral Tropism
D012367:RNA, Viral; D015728:Receptors, HIV