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Early Viral Load Reduction in Pregnant Women Differs according to Antiretroviral Regimen
C Bell1, M Douglas2, Y Gilleece1, N Desmond3, and Graham Taylor*2
1Royal Sussex County Hosp, Brighton, UK; 2Imperial Coll Hlth Care, NHS Trust, London, UK; and 3Garden Clin, Slough, UK
Background: Nevirapine (NVP) has been widely and
effectively used but with concerns about toxicity. Consequently protease
inhibitors (PI) are increasingly used in pregnancy, despite reports that plasma
concentrations may be sub-optimal. We therefore examined the rate of reduction
of HIV viral load in plasma during the first 14 days of therapy in pregnant
women starting a first antiretroviral combination of 2 nucleoside analogues
(usually zidovudine [ZDV] + lamivudine [3TC]) + either NVP or a PI.
Methods: From 3 centers, prospective data were collection
to study the change in viral load in consecutive pregnant women starting either
NVP or ritonavir-boosted lopinavir (LPV/r) or nelfinavir (NFV) and in
non-pregnant women starting LPV/r. HIV plasma RNA copies pre-treatment and at
first routine review (usually14 days) and baseline CD4 counts were collated.
Plasma viral decay (half-life) over 14 days was calculated and therapies
compared by t-test.
Results: HIV plasma half life during the first 14
days of therapy was shortest in women taking NVP while the tablet formulation
of LPV/r appears to out-perform NFV. Higher CD4 counts were associated with a
slower viral load decline with the protease inhibitors but not with NVP (data
not shown). Viral decays with LPV/r capsules in pregnant women were slower than
in non-pregnant women but this did not reach statistical significance.
|
|
Nevirapine
200 mg od
|
LPV/r Capsules 400mg/100mg bd
|
LPV/r Tablets
400mg/100mg bd
|
Nelfinavir 1250mg/bd
|
LPV/r capsules
400mg/100mg bd non-pregnant
|
|
# Subjects
|
25
|
20
|
9
|
12
|
10
|
|
Mean days on therapy (range)
|
12.7 (7 to 21)
|
13.3 (7 to 16)
|
13.8 (13 to14)
|
15.4 (10 to 21)
|
13.8 (12 to14)
|
|
Mean baseline CD4 cells/L (range)
|
189.6 (10 to 470)
|
401 (40 to 730)
|
369 (20 to 650)
|
454 (16 to1230)
|
162 (20 to300)
|
|
Mean baseline HIV RNA copies/mL
|
66,215 (4900 to 500,000)
|
20,286 (751 to 121,797)
|
10,542 (1531 to 24070)
|
14,773 (4580 to 36424)
|
176,745 (1443 to 500,000)
|
|
Viral decay (T/2) days (range)
|
1.84 (0.74 to 2.86)
|
2.63 (1.5 to 4.2)
|
2.3 (1.93 to 2.83)
|
3.00 (2.24to4.06)
|
2.2 (1.43 to 3.43)
|
|
|
Days
|
Decay
|
CD4
|
Viral load
|
|
LPV/r pregnant v non-pregnant
|
0.86
|
0.28
|
0.0008
|
0.014
|
|
NVP v NFV
|
0.04
|
0.00004
|
0.01
|
0.04
|
|
Nevirapine v LPV/r capsules
|
0.50
|
0.0002
|
0.0004
|
0.06
|
|
LPV/r capsules v NFV
|
0.09
|
0.12
|
0.4
|
0.6
|
|
LPV/r tablets v NFV
|
0.15
|
0.01
|
0.4
|
0.4
|
|
LPV/r capsules v tablets
|
0.42
|
0.13
|
0.8
|
0.2
|
Conclusions: These data support the continued use of
NVP in pregnant women with CD4 counts <250 cells/mL and may have implications for the type and timing of PI-based
therapy in pregnancy.
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