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Could Cerebrospinal Fluid ART Penetration Scores Predict Viral Rebound in ART-naïve Individuals Who Achieve Plasma Viral Load Suppression on Their First Therapy?
Andrea Antinori*1, A Cozzi-Lepri2, P Cinque3, M Giancola1, A De Luca4, C Mussini5, C Torti6, L Sighinolfi7, V Colangeli8, A d'Arminio Monforte9, and ICoNA Cohort
1Natl Inst of Infectious Diseases, L Spallanzani, Rome, Italy; 2Royal Free and Univ Coll London Med Sch, UK; 3Inst San Raffaele, Milan, Italy; 4Univ Cattolica Sacro Cuore, Rome, Italy; 5Policlin of Modena, Italy; 6Univ degli Studi, Brescia, Italy; 7Hosp St Anna, Ferrara, Italy; 8Univ of Bologna, Italy; and 9Azienda Hosp, Polo Univ San Paolo, Milan, Italy
Background: Enhanced penetration
of combination ART (cART) in the central nervous system (CNS) is associated
with increased HIV suppression in cerebrospinal fluid (CSF). However, whether
the degree of cART penetration in CSF has an effect on virologic response in
plasma has not been completely elucidated. It has been suggested that the
ability of each ART to penetrate in CSF can be predicted using a recently
developed score.
Methods: We
studied a total of 2785 participants starting cART, but had been ART-naïve, and
who achieved suppression to <80 copies/mL. We restricted the analysis to
this study population to eliminate the potential confounding effect of poor
adherence. A validated CSF penetration score (CPS) of 0 (low), 0.5
(intermediate), or 1 (high) based on pharmacodynamic and pharmacokinetic drug
properties (according to the CHARTER definition) was used. The score for a
regimen was constructed by summing the scores for individual drugs. The rate of
VF was estimated as number of rebounds (>400 copies/mL) per person years of
follow-up using Poisson regression, and a stratification by CD4 count was used
according with different risk of CNS compartmentalization.
Results: Patient characteristics
were: female 29%; median age 36 years
(IQR 32 to 41); injecting drug user 32%, heterosexual 39%, hepatitis C virus
antibody+ 37%, CDC C 9%; median CD4 and log10 HIV RNA at
cART initiation 260/mm3 (110 to 394), and 4.8 copies/mL (4.2 to 5.3),
respectively. Median year of starting cART was 2000 (range 1997 to 2006). In a
total of 4998 person years of follow-up, 311 VF ratings were registered with an
overall incidence rate of 6.2x100 person years of follow-up (95%CI 5.6 to 6.9).
In the crude analysis, higher values of current CPS was associated with
declining incidence rates of VFx100 person years of follow-up: 9.7 (5.7 to 15.6) if CPS 0.5; 8.1 (6.8 to 9.5)
if CPS 1 to 1.5; 4.9 (4.1 to 5.7) if CPS ³2. Adjusted RR of viral rebound, stratified by CD4
count at cART initiation, are reported in the table.
Conclusions: Although the crude incidence
rate of VF was lower with increasing ART penetration scores in CSF, this
association was no longer significant after adjusting for ART drugs currently
used and the adjusted RR was <1 only in people starting cART with low CD4
count. Further investigations are needed to assess whether larger reduction of
HIV replication in CNS may result in greater systemic efficacy of therapy in
ART-naïve patients who achieve viral suppression on first cART.
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