Association between detection of HIV-1 DNA resistance mutations by a sensitive assay at initiation of antiretroviral therapy and virologic failure
Gonzague Jourdain, Thor Andrew Wagner, Nicole Ngo-Giang-Huong, Wasna Sirirungsi, Virat Klinbuayaem, Federica Fregonese, Issaren Nantasen, Malee Techapornroong, Guttiga Halue, Ampaipith Nilmanat, Pakorn Wittayapraparat, Veeradet Chalermpolprapa, Panita Pathipvanich, Prapap Yuthavisuthi, Lisa M Frenkel, Marc Lallemant, Program for HIV Prevention and Treatment (PHPT) Study Group, Si Ariyadej, Su Ariyadej, P Pinyowittayakool, C Tantiyawarong, P Leenasirimakul, V Gomuthbutra, S Kahintapongs, C Sirinirundr, A Limtrakul, N Chuachamsai, M Techapornroong, P Yuthavisuthi, D Sinthuvanich, C Bowonwatanuwong, N Chotivanich, P Kittikoon, C Tantiyawarong, G Halue, W Leongjiranothai, J Hemvuttiphan, S Sangsawang, S Attawibool, O Kamsao, R Pittayanon, V Chalermpolprapa, P Hirunchote, A Nilmanat, S Lamlertkittikul, T Jarupanich, K Veerapradist, P Wittayapraparat, A Kanjanasing, C Jirawison, V Latdhivongsakorn, S Prommas, K Kengsakul, P Prateeprat, Y Vonglertvit, C Jongpipan, K Kongsing, S Kunkongkapan, A Chutanunta, T Sukhumanant, C Pinsuwan, P Kantipong, J Achalapong, R Srismith, S Yanpaisan, Y Buranawanitchakorn, C Putiyanun, C Kulkolakan, S Suwan, S Jungpichanvanich, T Changchit, W Panitsuk, P Sang-a-gad, T Chonladarat, N Pinyotrakoo, M Jittwatanakorn, P Bunjongjit, S Pipatnakulchai, S Hongyok, N Luekamlung, W Matanasaravoot, C Wannalit, S Yanpaisan, P Wongsarot, S Suphanich, P Kanchanakitsakul, P Sunalai, N Eiamsirikit, P Sabsanong, C M Hongsawinitkul, S Buranabanjasatean, S Piyaworawong, K Boonrod, J Ithisuknanth, P Jittiwattanapongs, P Thaingamsilp, B Suwannachat, S Nitpanich, S Tunsupasawasdikul, W Wannapira, P Thanomrat, W Boonyawatana, C Thundee, C Churaree, S Nakhapongse, S Tonmat, W Worngsatthanaphong, V Attakornwatana, B Aumpaporn, W Pornkitprasarn, W Rutirawat, W Susaengrat, J Ratanakosol, V Jarupoonphol, N Yuthakasaemsan, N P Ruttana-Aroongorn, T Wichatrong, N Winiyakul, W Sinchai, S Monchit, B Chetanachan, S Sungpapan, S Techapalokul, P Chirawatthanaphan, Y Srivarasat, T Buddhaboriwan, P Nakchun, D Langkafa, S Tunsupasawaskul, J Wongchinsri, S Surawongsin, T Chanpoo, N Thamanavat, P Hotrarapavanond, S Kamsrisuk, P Chetchotisakd, C Sakondhavat, W Laupattarakasem, S Kraitrakul, S Benchakhanta, R Thongdej, T Chaiyabut, P Kovit, A Rattanaparinya, B Jeerasuwannakul, W Atthakorn, W Supanchaimat, Gonzague Jourdain, Thor Andrew Wagner, Nicole Ngo-Giang-Huong, Wasna Sirirungsi, Virat Klinbuayaem, Federica Fregonese, Issaren Nantasen, Malee Techapornroong, Guttiga Halue, Ampaipith Nilmanat, Pakorn Wittayapraparat, Veeradet Chalermpolprapa, Panita Pathipvanich, Prapap Yuthavisuthi, Lisa M Frenkel, Marc Lallemant, Program for HIV Prevention and Treatment (PHPT) Study Group, Si Ariyadej, Su Ariyadej, P Pinyowittayakool, C Tantiyawarong, P Leenasirimakul, V Gomuthbutra, S Kahintapongs, C Sirinirundr, A Limtrakul, N Chuachamsai, M Techapornroong, P Yuthavisuthi, D Sinthuvanich, C Bowonwatanuwong, N Chotivanich, P Kittikoon, C Tantiyawarong, G Halue, W Leongjiranothai, J Hemvuttiphan, S Sangsawang, S Attawibool, O Kamsao, R Pittayanon, V Chalermpolprapa, P Hirunchote, A Nilmanat, S Lamlertkittikul, T Jarupanich, K Veerapradist, P Wittayapraparat, A Kanjanasing, C Jirawison, V Latdhivongsakorn, S Prommas, K Kengsakul, P Prateeprat, Y Vonglertvit, C Jongpipan, K Kongsing, S Kunkongkapan, A Chutanunta, T Sukhumanant, C Pinsuwan, P Kantipong, J Achalapong, R Srismith, S Yanpaisan, Y Buranawanitchakorn, C Putiyanun, C Kulkolakan, S Suwan, S Jungpichanvanich, T Changchit, W Panitsuk, P Sang-a-gad, T Chonladarat, N Pinyotrakoo, M Jittwatanakorn, P Bunjongjit, S Pipatnakulchai, S Hongyok, N Luekamlung, W Matanasaravoot, C Wannalit, S Yanpaisan, P Wongsarot, S Suphanich, P Kanchanakitsakul, P Sunalai, N Eiamsirikit, P Sabsanong, C M Hongsawinitkul, S Buranabanjasatean, S Piyaworawong, K Boonrod, J Ithisuknanth, P Jittiwattanapongs, P Thaingamsilp, B Suwannachat, S Nitpanich, S Tunsupasawasdikul, W Wannapira, P Thanomrat, W Boonyawatana, C Thundee, C Churaree, S Nakhapongse, S Tonmat, W Worngsatthanaphong, V Attakornwatana, B Aumpaporn, W Pornkitprasarn, W Rutirawat, W Susaengrat, J Ratanakosol, V Jarupoonphol, N Yuthakasaemsan, N P Ruttana-Aroongorn, T Wichatrong, N Winiyakul, W Sinchai, S Monchit, B Chetanachan, S Sungpapan, S Techapalokul, P Chirawatthanaphan, Y Srivarasat, T Buddhaboriwan, P Nakchun, D Langkafa, S Tunsupasawaskul, J Wongchinsri, S Surawongsin, T Chanpoo, N Thamanavat, P Hotrarapavanond, S Kamsrisuk, P Chetchotisakd, C Sakondhavat, W Laupattarakasem, S Kraitrakul, S Benchakhanta, R Thongdej, T Chaiyabut, P Kovit, A Rattanaparinya, B Jeerasuwannakul, W Atthakorn, W Supanchaimat
Abstract
Background: Antiretroviral therapy (ART) has become more available throughout the developing world during the past 5 years. The World Health Organization recommends nonnucleoside reverse-transcriptase inhibitor-based regimens as initial ART. However, their efficacy may be compromised by resistance mutations selected by single-dose nevirapine (sdNVP) used to prevent mother-to-child transmission of human immunodeficiency virus (HIV)-1. There is no simple and efficient method to detect such mutations at the initiation of ART.
Methods: One hundred eighty-one women who were participating in a clinical trial to prevent mother-to-child transmission and who started NVP-ART after they had received sdNVP or a placebo were included in the study. One hundred copies of each patient's HIV-1 DNA were tested for NVP-resistance point-mutations (K103N, Y181C, and G190A) with a sensitive oligonucleotide ligation assay that was able to detect mutants even at low concentrations (> or = 5% of the viral population). Virologic failure was defined as confirmed plasma HIV-1 RNA >50 copies/mL after 6 to 18 months of NVP-ART.
Results: At initiation of NVP-ART, resistance mutations were identified in 38 (26%) of 148 participants given sdNVP (K103N in 19 [13%], Y181C in 8 [5%], G190A in 28 [19%], and > or = 2 mutations in 15 [10%]), at a median 9.3 months after receipt of sdNVP. The risk of virologic failure was 0.62 (95% confidence interval [CI], 0.46-0.77) in women with > or = 1% resistance mutation, compared with a risk of 0.25 (95% CI, 0.17-0.35) in those without detectable resistance mutations (P < .001). Failure was independently associated with resistance, an interval of <6 months between sdNVP and NVP-ART initiation, and a viral load higher than the median at NVP-ART initiation.
Conclusions: Access to simple and inexpensive assays to detect low concentrations of NVP-resistant HIV-1 DNA before the initiation of ART could help improve the outcome of first-line ART.
Conflict of interest statement
The authors have no other potential conflicts of interest to disclose.
Figures
Source: PubMed