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.
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Acknowledgments
HIV STAR (The HIV Second-line Therapy AntiRetroviral study in patients who failed NNRTI-based regimens; clinical trial.gov number NCT00627055) was supported by grants from the Thai National Health Security Office (NHSO), Swiss cohort study, and the National Research Council of Thailand (NRCT). The antiretrovirals and laboratory monitoring were provided by NHSO. We are grateful to the patients for their participation in this study. We thank the Program for HIV Prevention and Treatment (PHPT) laboratory for facilitating laboratory testing and sample shipment of study sites in the North of Thailand. We thank HIV STAR study team for their dedication to this study. Lastly, we thank SEARCH for data of HIV-negative healthy controls.
Financial disclosure and conflict of interest
PC has received speaker honorarium or educational grant from Abbott, Bristol-Myers Squibb, Janssen-Cilag, GlaxoSmithKline, MSD, IDS, and Roche. JA has received speakers’ fees or honorarium from Gilead, ViiV Healthcare, and Abbott. BH has received travel grants and speaker fees from Janssen, Gilead, and MSD. KR has received speaker honoraria or educational grant support from Abbott, Gilead, Bristol-Myers Squibb, Merck, Roche, Jensen-Cilag, GlaxoSmithKline, Tibotec, and The Governmental pharmaceutical organization. Others declare no conflict of interest and that member of their immediate families do not have a financial interest in or arrangement with any commercial organization that may have a direct interest in the subject matter of this article.
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HIV STAR Study team
Faculty of Medicine, Khon Kaen University, Khon Kaen: Ploenchan Chetchotisakd, Piroon Mootsikapun, Siriluck Anunnatsiri, Prapatsorn Sriphanthabut, Ratchadaporn Wisai, Ratthanant Kaewmart, Viraphong Lulitanond, Parichat Seawsirikul, Manassinee Horsakulthai, Somjai Rattanamanee
Chonburi Hospital, Chonburi: Chureeratana Bowonwatanuwong, Prakit Yothipitak, Uangarun Ampunpong, Wanrada Pruksacholatarn,
Chiangrai Prachanukroh Hospital, Chiangrai: Pacharee Kantipong, Hutsaya Tantipong, Suwimon Saejung, Pottjavitt Ussawawuthipong, Ruengrit Jinasen, Phakamas Kumboua, Nussara Khampachua, Supawadee Sangjan, Jeerapat Chaiwangpha
Sanpatong Hospital, ChiangMai: Virat Klinbuayaem, Utoomporn Kumpeerapanya, Siraporn Muangchan, Pranee Leechanachai, Phennapha Klangsinsirikul, Yaowaluk Siriwarothai, Chokannikar Tunkham, Prathum Tachorn
Bamrasnaradura Infectious Disease Institute, Nonthaburi: Wisit Prasithsirikul, Patama Sutha, Unchana Thawornwan, Supeda Thongyen, Karuna Limjaroen, Sunanta Natprom
Faculty of Medicine, Ramathibodi Hospital, MahidolUniversity, Bangkok: Somnuek Sungkanuparph, Bucha Piyavong
Taksin Hospital, Bangkok: Supunnee Jirajariyavej, Ratchada Wattanasopon, Supawadee Asawasiriwilas, Jaratsri Itsariyathanakorn, Jittikarn Suthisiri
BMA Medical College and VajiraHospital, Bangkok: Warangkana Munsakul, Wisanee Phesajcha, Worramit Thapha, OrranuchTeansuwan, Nawaporn Sae-kao, Wipawan Karakate
Chulalongkorn University, Bangkok: Kiat Ruxrungtham, Sunee Sirivichayakul
HIV-NAT, the Thai Red Cross AIDS Research Centre, Bangkok: Kiat Ruxrungtham, Jintanat Ananworanich, Torsak Bunupuradah, Thanyawee Puthanakit, Somporn Chantbuddhiwet, Chatsuda Auchieng, Parinya Sutheerasak, Sasiwimol Ubolyam, Apicha Mahanontharit, Naphassanant Laopraynak, Nithima Panyanithisakul, Supalak Klungklang, Bulan Thongtha, Augchara Suwannawat, Sineenart Chautrakarn, Kobkaew Laohajinda, Peeraporn Kaew-on, Saengla Pradapmook, Sirikul Chanmano, Kanlaya Charoentonpuban, Stephen Kerr, JiratchayaWongsabut
Supported by: the Thai National Health Security Office, the Swiss cohort study, and the National Research Council of Thailand
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Bunupuradah, T., Chetchotisakd, P., Jirajariyavej, S. et al. Neurocognitive impairment in patients randomized to second-line lopinavir/ritonavir-based antiretroviral therapy vs. lopinavir/ritonavir monotherapy. J. Neurovirol. 18, 479–487 (2012). https://doi.org/10.1007/s13365-012-0127-9
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DOI: https://doi.org/10.1007/s13365-012-0127-9