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Erschienen in:

01.12.2012

Neurocognitive impairment in patients randomized to second-line lopinavir/ritonavir-based antiretroviral therapy vs. lopinavir/ritonavir monotherapy

verfasst von: Torsak Bunupuradah, Ploenchan Chetchotisakd, Supunnee Jirajariyavej, Victor Valcour, Chureeratana Bowonwattanuwong, Warangkana Munsakul, Virat Klinbuayaem, Wisit Prasithsirikul, Jiratchaya Sophonphan, Apicha Mahanontharit, Bernard Hirschel, Sorakij Bhakeecheep, Kiat Ruxrungtham, Jintanat Ananworanich, On behalf of the HIV STAR Study Group

Erschienen in: Journal of NeuroVirology | Ausgabe 6/2012

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Abstract

We compared rates of neurocognitive impairment (NCI) among 93 Thai adults failing non-nucleoside reverse transcriptase inhibitor (NNRTI)-based combination antiretroviral therapy (cART) before and after switching to lopinavir/ritonavir monotherapy (mLPV/r) vs. tenofovir/lamivudine/LPV/r (TDF/3TC/LPV/r). Participants completed the Color Trails 1 and 2, Digit Symbol, and Grooved Pegboard at weeks 0, 24, and 48. We calculated z-scores using normative data from 451 healthy HIV-negative Thais. We defined NCI as performance of <-1 SD on ≥2 tests. The Thai depression inventory was used to capture depressive symptoms. Lumbar puncture was optional at week 0 and 48. At baseline, median (IQR) age was 36.9 (32.8–40.5) years, and 46 % had primary school education or lower. The median CD4 count was 196 (107–292) cells/mm³, and plasma HIV RNA was 4.1 (3.6–4.5) log₁₀ copies/ml. Almost all (97 %) had circulating recombinant CRF01_AE. At baseline, 20 (47 %) of the mLPV/r vs. 22 (44 %) of TDF/3TC/LPV/r arms met NCI criteria (p = 0.89). The frequency of NCI at week 48 was 30 vs. 32 % (p = 0.85) with 6 vs. 7 % (p = 0.85) developing NCI in the mLPV/r vs. TDF/3TC/LPV/r arms, respectively. Having NCI at baseline and lower education each predicted NCI at week 48. Depression scores at week 48 did not differ between arms (p = 0.47). Cerebrospinal fluid HIV RNA of <50 copies/ml at 48 weeks was observed in five out of seven in mLPV/r vs. three out of four in TDF/3TC/LPV/r arm. The rates of NCI and depression did not differ among cases failing NNRTI-based cART who received mLPV/r compared to LPV/r triple therapy.

Agsalda M, Kusao I, Troelstrup D, Velasco V-N, Shikuma C, Valcour V et al (2012) Monocytes with an inflammatory profile and high HIV DNA copy numbers characterize patients with neurocognitive deficits. Poster number 460. The 19th Conference on Retroviruses and Opportunistic Infections (CROI 2012), Seattle, WA, USA

Arribas JR, Delgado R, Arranz A, Munoz R, Portilla J, Pasquau J et al (2009) Lopinavir-ritonavir monotherapy versus lopinavir-ritonavir and 2 nucleosides for maintenance therapy of HIV: 96-week analysis. J Acquir Immune Defic Syndr 51(2):147–152PubMedCrossRef

Bierman WF, van Agtmael MA, Nijhuis M, Danner SA, Boucher CA (2009) HIV monotherapy with ritonavir-boosted protease inhibitors: a systematic review. AIDS 23(3):279–291PubMedCrossRef

Bunupuradah T, Chetchotisakd P, Ananworanich J, Munsakul W, Jirajariyavej S, Kantipong P et al (2012) A randomized comparison of second-line lopinavir/ritonavir monotherapy vs. tenofovir/lamivudine/lopinavir/ritonavir in patients failing NNRTI-regimens: the HIV STAR study. Antivir Ther. doi:10.3851/IMP2222

Ciccarelli N, Fabbiani M, Di Giambenedetto S, Fanti I, Baldonero E, Bracciale L et al (2011) Efavirenz associated with cognitive disorders in otherwise asymptomatic HIV-infected patients. Neurology 76(16):1403–1409PubMedCrossRef

Clotet B, Gomez JL (2011) Clinical study to evaluate the efficacy and safety of lopinavir/ritonavir monotherapy versus darunavir/ritonavir monotherapies as simplification switching strategies of PI/NNRTI-triple therapy based-regimens. NCT00994344. http://clinicaltrials.gov/ct2/show/NCT00994344?term=darunavir+monotherapy&rank=1. Accessed 5 Dec 2011.

Gonzalez-Scarano F, Martin-Garcia J (2005) The neuropathogenesis of AIDS. Nat Rev 5(1):69–81CrossRef

Gutmann C, Cusini A, Gunthard HF, Fux C, Hirschel B, Decosterd LA et al (2010) Randomized controlled study demonstrating failure of LPV/r monotherapy in HIV: the role of compartment and CD4-nadir. AIDS 24(15):2347–2354PubMed

Harezlak J, Buchthal S, Taylor M, Schifitto G, Zhong J, Daar E et al (2011) Persistence of HIV-associated cognitive impairment, inflammation, and neuronal injury in era of highly active antiretroviral treatment. AIDS 25(5):625–633PubMedCrossRef

Heaton RK, Franklin DR, Ellis RJ, McCutchan JA, Letendre SL, Leblanc S et al (2011) HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors. J Neurovirol 17(1):3–16PubMedCrossRef

Letendre SL, Ellis RJ, Ances BM, McCutchan JA (2010) Neurologic complications of HIV disease and their treatment. Top HIV Med 18(2):45–55PubMed

Liu Y, Tang XP, McArthur JC, Scott J, Gartner S (2000) Analysis of human immunodeficiency virus type 1 gp160 sequences from a patient with HIV dementia: evidence for monocyte trafficking into brain. J Neurovirol 6(Suppl 1):S70–S81PubMed

Lotrakul M, Sukanich P (1999) Development of the Thai Depression Inventory. J Med Assoc Thai 82(12):1200–1207PubMed

Marra CM, Zhao Y, Clifford DB, Letendre S, Evans S, Henry K et al (2009) Impact of combination antiretroviral therapy on cerebrospinal fluid HIV RNA and neurocognitive performance. AIDS 23(11):1359–1366PubMedCrossRef

Munoz-Moreno JA, Fumaz CR, Ferrer MJ, Prats A, Negredo E, Garolera M et al (2008) Nadir CD4 cell count predicts neurocognitive impairment in HIV-infected patients. AIDS Res Hum Retroviruses 24(10):1301–1307PubMedCrossRef

Paton N et al. (2011) A randomized controlled trial of a strategy of switching to boosted protease inhibitor monotherapy versus continuing combination antiretroviral therapy for the long-term management of HIV-1 infected patients who have achieved sustained virological suppression on highly-active antiretroviral therapy. ISRCTN04857074. http://controlled-trials.com/ISRCTN04857074/pivot. Accessed 5 Dec 2011.

Perez-Valero I, Bayon C, Cambron I, Gonzalez A, Arribas JR (2011) Protease inhibitor monotherapy and the CNS: peace of mind? J Antimicrob Chemother 66(9):1954–1962PubMedCrossRef

Pulido F, Matarranz M, Rodriguez-Rivera V, Fiorante S, Hernando A (2010) Boosted protease inhibitor monotherapy. What have we learnt after seven years of research? AIDS Rev 12(3):127–134PubMed

Pumpradit W, Ananworanich J, Lolak S, Shikuma C, Paul R, Siangphoe U et al (2010) Neurocognitive impairment and psychiatric comorbidity in well-controlled human immunodeficiency virus-infected Thais from the 2NN Cohort Study. J Neurovirol 16(1):76–82PubMedCrossRef

Robertson KR, Smurzynski M, Parsons TD, Wu K, Bosch RJ, Wu J et al (2007) The prevalence and incidence of neurocognitive impairment in the HAART era. AIDS 21(14):1915–1921PubMedCrossRef

Smurzynski M, Wu K, Letendre S, Robertson K, Bosch RJ, Clifford DB et al (2011) Effects of central nervous system antiretroviral penetration on cognitive functioning in the ALLRT cohort. AIDS 25(3):357–365PubMedCrossRef

Valcour VG, Sithinamsuwan P, Nidhinandana S, Thitivichianlert S, Ratto-Kim S, Apateerapong W et al (2007) Neuropsychological abnormalities in patients with dementia in CRF 01_AE HIV-1 infection. Neurology 68(7):525–527PubMedCrossRef

Valcour VG, Shiramizu BT, Sithinamsuwan P, Nidhinandana S, Ratto-Kim S, Ananworanich J et al (2009) HIV DNA and cognition in a Thai longitudinal HAART initiation cohort: the SEARCH 001 Cohort Study. Neurology 72(11):992–998PubMedCrossRef

Valcour V, Sithinamsuwan P, Letendre S, Ances B (2010) Pathogenesis of HIV in the central nervous system. Curr HIV/AIDS Rep 8(1):54–61CrossRef

Valcour V, Paul R, Chiao S, Wendelken LA, Miller B (2011) Screening for cognitive impairment in human immunodeficiency virus. Clin Infect Dis 53(8):836–842PubMedCrossRef

Vernazza P, Daneel S, Schiffer V, Decosterd L, Fierz W, Klimkait T et al (2007) The role of compartment penetration in PI-monotherapy: the Atazanavir-Ritonavir Monomaintenance (ATARITMO) Trial. AIDS 21(10):1309–1315PubMedCrossRef

Vivithanaporn P, Nelles K, Deblock L, Newman SC, Gill MJ, Power C (2012) Hepatitis C virus co-infection increases neurocognitive impairment severity and risk of death in treated HIV/AIDS. J Neurol Sci 312(1–2):45–51PubMedCrossRef

Zogg JB, Woods SP, Weber E, Iudicello JE, Dawson MS, Grant I (2010) HIV-associated prospective memory impairment in the laboratory predicts failures on a semi-naturalistic measure of health care compliance. Clin Neuropsychol 24(6):945–962PubMedCrossRef

Titel: Neurocognitive impairment in patients randomized to second-line lopinavir/ritonavir-based antiretroviral therapy vs. lopinavir/ritonavir monotherapy
verfasst von: Torsak Bunupuradah
Ploenchan Chetchotisakd
Supunnee Jirajariyavej
Victor Valcour
Chureeratana Bowonwattanuwong
Warangkana Munsakul
Virat Klinbuayaem
Wisit Prasithsirikul
Jiratchaya Sophonphan
Apicha Mahanontharit
Bernard Hirschel
Sorakij Bhakeecheep
Kiat Ruxrungtham
Jintanat Ananworanich
On behalf of the HIV STAR Study Group
Publikationsdatum: 01.12.2012
Verlag: Springer US
Erschienen in: Journal of NeuroVirology / Ausgabe 6/2012
Print ISSN: 1355-0284
Elektronische ISSN: 1538-2443
DOI: https://doi.org/10.1007/s13365-012-0127-9

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