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Dynamic of HIV-1 RNA and DNA in Plasma and Cervico-Vaginal Secretions after HAARTInitiation: ANRS EP24 GYNODYN Study
Odile Launay*1, L Bélec2, M Tod1, A Si Mohamed2, N Matignon3, I Tschope3, C Goujard4, A M Taburet4, O Lortholary5, V Leroy3, and ANRS EP24 Study Group
1Hosp Cochin, Paris, France; 2Hosp Europeen Georges Pompidou, Paris, France; 3INSERM U593, Univ Victor Segalen, Bordeaux, France; 4Hosp Bicetre, Le Kremlin-Bicetre, France; and 5Necker-Enfants Malades Hosp, Paris, France
Background: HIV shedding in cervicovaginal
secretions (CVS) is a major determinant of HIV transmission. We studied the
18-month dynamics of HIV RNA and DNA levels in plasma and CVS after HAART
initiation.
Methods: A prospective multicentric
open cohort of 23 ART-naïve women with HIV-1 infection initiating zidovudine
(AZT)/lamivudine (3TC) combined with lopinavir (LPV) (n
= 17) or indinavir (IDV) (n = 6) boosted with low-dose ritonavir (RTV)
was designed. Paired samples of plasma and CVS (obtained by cervicovaginal lavage with a dilution of 1:10) were collected at baseline, and at 1, 6, 12, and 18 months to measure viral
markers and ART concentrations. Viral HIV RNA and proviral
HIV DNA were measured using real-time polymerase chain reaction (PCR) assay. The
threshold of detection was 50 copies/mL (1.7 log) for viral RNA and 10 copies/106 cells (1.0
log) for proviral DNA. ART
concentrations were determined by high performance liquid chromatography at different points in time after
ART intake. Mean HIV RNA and proviral DNA
in plasma and CVS after log10
transformation were described. We compared mean HIV RNA in plasma and dilution
factor adjusted HIV RNA in CVS using
a Wilcoxon non parametric test, all HIV RNA values
lower than the adjusted CVS threshold
being replaced by 2.7 log.
Results: From October 2003 to October 2005, 23 women were
included for 16 of whom longitudinal analyses to date were available. At month 1,
median LPV H+2 concentrations were
7.70 mg/L (range 5.5 to 8.8) in plasma and 0.39 mg/L (range 0.1 to 1.0) in CVS;
IDV concentrations were
detectable in the 2 plasma (0.1, 2.5 mg/L) and the 3 CVS (1.1, 3.0, and 14.6
mg/L) samples available of the 6 women in this stratum.
Conclusions: Baseline viral markers were significantly
lower in CVS than plasma. HIV RNA decreased significantly in both body
compartments after HAART initiation reaching durable undetectable values from 1
month until 18 months. By contrast, HIV DNA levels remained detectable in all
plasma samples and most CVS samples over time. A differential diffusion of IDV
and LPV in the CVS was observed.
|
|
J0
|
M1
|
M6
|
M12
|
M18
|
|
HIV-1 RNA
% undetectable
|
|
|
|
|
|
|
plasma (<1.7 log10
copies/mL)
|
6
|
19
|
71
|
70
|
75
|
|
CVS (<2.7 log10 copies/mL)
|
19
|
81
|
93
|
91
|
100
|
|
mean (SD)
|
|
|
|
|
|
|
Plasma
|
4.87 (0.80)
|
2.99 (0.39)
|
2.7 (0)
|
3.00 (0.50)
|
3.30 (1.11)
|
|
CVS
|
3.88 (0.91)
|
2.74 (0.17)
|
2.80 (0.38)
|
2.72 (0.06)
|
2.7 (0)
|
|
p-value
|
0.0019
|
NS
|
NS
|
NS
|
NS
|
|
Proviral DNA
% undetectable
|
|
|
|
|
|
|
Plasma
|
0
|
0
|
0
|
0
|
0
|
|
CVS
|
38
|
56
|
53
|
73
|
56
|
|
mean (SD)
|
|
|
|
|
|
|
plasma
|
3.40 (0.45)
|
3.24 (0.60)
|
2.76 (0.59)
|
2.83 (0.47)
|
2.80 (0.30)
|
|
CVS
|
1.84 (0.88)
|
1.52 (0.69)
|
1.58 (0.83)
|
1.30 (0.53)
|
1.30 (0.52)
|
|
