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Single-agent Therapy with Lopinavir/ritonavir Controls HIV-1 Viral Replication in the Central Nervous System
Rosa F Yeh*1,2, Rosa F Yeh*1,2, S Letendre3, I Novak2,4, I Novak2,4, B Lipman5, A Hermes5, C Mayberry6, B Miguel1, J Nemecek6, M Norton5, and J Gathe, Jr1
1Therapeutic Concepts, Houston, TX, US; 2Univ of Texas, Houston, US; 3Univ of California, San Diego, US; 4Park Plaza Hosp, Houston, TX, US; 5Abbott Labs, Abbott Park, IL, US; and 6Donald R Watkins Fndn, Houston, TX, US
Background: Success of single-agent therapy may be limited by an
inability to control HIV replication in sanctuary
sites
such as
the central nervous system (CNS).
Lopinavir/ritonavir (LPV/r) has demonstrated
control of HIV replication when used
in combination with other ART. We analyzed the control of HIV replication in
the cerebrospinal fluid (CSF) with
LPV/r single-agent therapy.
Methods: IMANI-2 is
an ongoing, prospective, open-label
investigation of LPV/r single-agent therapy in 40 ART-naïve HIV-1-infected subjects.
We enrolled in this sub-study
11 subjects
who had at least 24 weeks of LPV/r single-agent
therapy and 2 consecutive viral load
< 75 copies/mL in plasma
via branched DNA assay (Bayer Versant™
HIV-1 RNA 3.0) at least 4 weeks apart, and at the most
recent study visit. All subjects
achieved viral load suppression of
<75 copies/mL in plasma
by week 24. A board certified
neurologist performed 11 lumbar
punctures using standard technique. Lumbar punctures were performed at week 38 (24 to 48) on average. Viral
load in CSF was measured via real time polymerase chain reaction (RT-PCR)
with limits of detection at <50
copies/mL. We
obtained 3 CSF samples for HIV RNA 0 to 6 hours
after dose, and 8, 6 to 12 hours
after dose. Viral load and CD4 are presented as
median (interquartile range).
Results: Of the 11 CSF samples, 10 were evaluable; 1
CSF sample was
excluded because of a traumatic tap. We evaluated 5 males
(2 African American, 1 Caucasian, 2 Hispanic) and 5 females (3 African American, 2 Caucasian) whose mean age was
42 (30 to 51) years. Before treatment, subjects
had median CD4 counts of 264 (200 to 491)
cells/µL and viral loads of 4.28 (3.72
to 4.78) log10 copies/mL. At time of analysis, median CD4 counts
were 493 (429 to 558) cells/µL. All 10 evaluable
subjects
achieved CSF viral loads <50
copies/mL.
Conclusions: This study is the first to examine CSF viral
load in naive subjects treated with LPV/r single-agent therapy for at least 24
weeks. Subjects were sampled throughout the dosing interval, and all achieved suppression
of CSF viral load <50 copies/mL. This suggests that
LPV/r given as single-agent therapy effectively suppresses viral replication in
the CSF.
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