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• Response to Kan et al.
  Yijia Li
  Published on: 26 October 2017

• Published on: 26 October 2017

  Response to Kan et al.

  • Yijia Li, Internal Medicine University of Pittsburgh School of Medicine

  Kan et al. nicely showed that in HIV-infected treatment-naïve first-line regimen initiators, four-year risk of virological failure (VF) and HIV drug resistance (HIVDR) were 11.8% and 5.0%, and they demonstrated that male and female participants had different risk factors for VF and HIVDR[1]. However, there are some limitations in this study that might be worth mentioning. First, in the inclusion phase, as the authors acknowledged, over half of the participants included in 2008 were lost to follow-up or excluded in 2012, which may generate selection bias. Hence, it would be important to compare the baseline characteristics in participants lost to follow-up/excluded and those who were included, in order to see whether there were any significant differences that may bias this study. Second, the authors did not account for baseline transmitted drug resistance mutation (DRM). Albeit rare, the prevalence of DRM was still 3% in treatment-naive participants in the year 2008, based on a meta-analysis[2]. As shown in a previous study in China with participants starting antiretroviral therapy (ART) between 2008-2010, baseline DRM is significantly associated with virological failure[3]. Coincidentally, this study found that HIVDR rate was 5.0%, comparable to the baseline DRM rate in the aforementioned meta-analysis. Thus, baseline DRM may actually affect HIVDR rate in this group of participants. Third, this study did not include men who have sex with men (MSM), which have become one o...

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  Kan et al. nicely showed that in HIV-infected treatment-naïve first-line regimen initiators, four-year risk of virological failure (VF) and HIV drug resistance (HIVDR) were 11.8% and 5.0%, and they demonstrated that male and female participants had different risk factors for VF and HIVDR[1]. However, there are some limitations in this study that might be worth mentioning. First, in the inclusion phase, as the authors acknowledged, over half of the participants included in 2008 were lost to follow-up or excluded in 2012, which may generate selection bias. Hence, it would be important to compare the baseline characteristics in participants lost to follow-up/excluded and those who were included, in order to see whether there were any significant differences that may bias this study. Second, the authors did not account for baseline transmitted drug resistance mutation (DRM). Albeit rare, the prevalence of DRM was still 3% in treatment-naive participants in the year 2008, based on a meta-analysis[2]. As shown in a previous study in China with participants starting antiretroviral therapy (ART) between 2008-2010, baseline DRM is significantly associated with virological failure[3]. Coincidentally, this study found that HIVDR rate was 5.0%, comparable to the baseline DRM rate in the aforementioned meta-analysis. Thus, baseline DRM may actually affect HIVDR rate in this group of participants. Third, this study did not include men who have sex with men (MSM), which have become one of the major routes of transmissions in China, especially in newly diagnosed HIV cases [4]. Fourth, subtype CRF01_AE, a predominant HIV subtype in Chinese[5] and southeast Asian[6] HIV population, especially in people infected via sexual transmission, was under-represented in this study. This subtype is related to fast HIV progression[5] but less VF[3] in Chinese population. Underrepresentation of this subtype may reduce the generalizability of this study to current Chinese and Asian HIV populations. Last, tenofovir-based regimens have become first-line in China after 2012 (instead of zidovudine- or stavudine- based regimens), and all newly diagnosed HIV individuals are eligible to free ART (instead of people with CD4 cell count ≤0.2x10^9/L or WHO stage III/IV), in line with WHO guideline published in late 2015 [7]. Therefore, this study result might not be generalizable to current first-line regimen initiators, and further studies focusing on HIV-infected participants starting ART after year 2015-2016 are warranted to evaluate factors associated with HIVDR or VF.

  References
  1. Kan W, Teng T, Liang S, et al. Predictors of HIV virological failure and drug resistance in Chinese patients after 48 months of antiretroviral treatment, 2008-2012: a prospective cohort study. BMJ Open 2017;7(9):e016012. doi: 10.1136/bmjopen-2017-016012
  2. Su Y, Zhang F, Liu H, et al. The prevalence of HIV-1 drug resistance among antiretroviral treatment naive individuals in mainland China: a meta-analysis. PLoS One 2014;9(10):e110652. doi: 10.1371/journal.pone.0110652
  3. Li Y, Gu L, Han Y, et al. HIV-1 subtype B/B' and baseline drug resistance mutation are associated with virologic failure: a multicenter cohort study in China. J Acquir Immune Defic Syndr 2015;68(3):289-97. doi: 10.1097/qai.0000000000000473
  4. UNAIDS. 2015 China AIDS Response Progress Report. 2015 [Available from: http://www.unaids.org/sites/default/files/country/documents/CHN_narrativ... accessed 10/25 2017.
  5. Li Y, Han Y, Xie J, et al. CRF01_AE subtype is associated with X4 tropism and fast HIV progression in Chinese patients infected through sexual transmission. AIDS 2014;28(4):521-30. doi: 10.1097/qad.0000000000000125
  6. Angelis K, Albert J, Mamais I, et al. Global Dispersal Pattern of HIV Type 1 Subtype CRF01_AE: A Genetic Trace of Human Mobility Related to Heterosexual Sexual Activities Centralized in Southeast Asia. J Infect Dis 2015;211(11):1735-44. doi: 10.1093/infdis/jiu666
  7. WHO Guidelines Approved by the Guidelines Review Committee. Guideline on When to Start Antiretroviral Therapy and on Pre-Exposure Prophylaxis for HIV. Geneva: World Health Organization 2015.

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  Conflict of Interest:
  None declared.

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