Different Distribution of HIV-1 Subtype and Drug Resistance Were Found among Treatment Naïve Individuals in Henan, Guangxi, and Yunnan Province of China

Li, Lin; Sun, Guixin; Liang, Shujia; Jianjian, Li; Li, Tianyi; Wang, Zhe; Liu, Wei; Yang, Sen; Liu, Yongjian; Wang, Xiaolin; Li, Jingyun

doi:10.1371/journal.pone.0075777

Cited by 32 publications

(43 citation statements)

References 28 publications

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“…Based upon these differences, we may have expected to see a higher rate of bone turnover in the TDF+LPVr group at baseline, however baseline BTM levels measured in our TDF+LPVr cohort fell within the range of baseline CTX and P1NP levels seen in the previously published switch studies, and were not significantly different from the baseline values of BTM in our treatment-naïve cohort. Finally, in this region HIV-1 Subtype B predominates [38], however to our knowledge there have been no studies suggesting that populations infected with different subtypes of HIV-1 demonstrate different bone turnover profiles in response to ART.…”

Section: Discussionmentioning

confidence: 99%

Increased bone resorption during tenofovir plus lopinavir/ritonavir therapy in Chinese individuals with HIV

et al. 2014

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Purpose Few studies have evaluated the effects of anti-retroviral therapy on skeletal metabolism in Asian populations infected with human immunodeficiency virus (HIV). Methods We performed a secondary analysis of bone turnover markers (BTM) at baseline and two years in stored plasma samples collected from 2/2009 – 1/2013 as part of a multi-center trial. Two groups were compared: 1) treatment-naïve patients initiated on zidovudine (AZT)/lamivudine (3TC) plus nevirapine (NVP), and 2) patients who failed first-line therapy and were switched to tenofovir (TDF)/3TC plus lopinavir/ritonavir (LPVr). Tests included the bone resorption marker, C-terminal cross-linking telopeptide of type-1 collagen (CTX) and the bone formation marker procollagen type 1 N-terminal propeptide (P1NP). Results In the TDF/3TC+LPVr group, samples were available from 59 patients at baseline and 56 patients at two years. Of these, 36 patients had samples available from both time points. In the AZT/3TC+NVP group, plasma samples were analyzed from 82 participants at baseline and of those, 61 had samples at two years. Median change over two years was greater in the TDF/3TC+LPVr group for both CTX (+0.24 ng/mL, IQR 0.10–0.43 vs. +0.09ng/mL, IQR −0.03 to 0.18, p=0.001) and P1NP (+25.5ng/mL, IQR 2.4–51.3 vs. +7.11 ng/mL, IQR −4.3 to 21.6, p=0.012). Differences remained after adjusting for age, sex, and body mass index. Conclusions Switching to TDF/3TC+LPVr after treatment failure resulted in greater increases in BTMs than initiation with AZT/3TC+NVP in Chinese patients with HIV. Following this change, bone resorption marker levels increased by nearly 60%, which is greater than the 25–35% increase from baseline described previously in non-Chinese populations. Further studies are warranted to elucidate these findings.

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Section: Discussionmentioning

confidence: 99%

Increased bone resorption during tenofovir plus lopinavir/ritonavir therapy in Chinese individuals with HIV

et al. 2014

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“…A molecular epidemiology study showed that CRF08_BC was the dominant subtype (59.8%) in Yunnan Province in the newly reported cases. 6 From 2007 to 2010, CRF08_BC accounted for over 40% of HIV-1 infections in Chinese blood donors. 7 In addition to IDUs, this CRF also spread through heterosexual contacts and predominated among heterosexuals in Yunnan Province.…”

Section: Introductionmentioning

confidence: 99%

“…7 In addition to IDUs, this CRF also spread through heterosexual contacts and predominated among heterosexuals in Yunnan Province. 6 Currently 26 antiretroviral agents using six different mechanisms of action have been licensed for the treatment of HIV infections in adults, half of which target the reverse transcriptase (RT). 8 RT inhibitors (RTIs) include nine nucleoside RTIs (NRTIs) and four nonnucleoside RTIs (NNRTIs).…”

Section: Introductionmentioning

confidence: 99%

In VitroSelection of HIV-1 CRF08_BC Variants Resistant to Reverse Transcriptase Inhibitors

Zhang

et al. 2015

AIDS Research and Human Retroviruses

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Human immunodeficiency virus type 1 (HIV-1) circulating recombinant form 08_BC (CRF08_BC), carrying the recombinant reverse transcriptase (RT) gene from subtypes B and C, has recently become highly prevalent in Southern China. As the number of patients increases, it is important to characterize the drug resistance mutations of CRF08_BC, especially against widely used antiretrovirals. In this study, clinically isolated virus (2007CNGX-HK), confirmed to be CRF08_BC with its sequence deposited in GenBank (KF312642), was propagated in human peripheral blood mononuclear cells (PBMCs) with increasing concentrations of nevirapine (NVP), efavirenz (EFV), or lamivudine (3TC). Three different resistance patterns led by initial mutations of Y181C, E138G, and Y188C were detected after the selection with NVP. Initial mutations, in combination with other previously reported substitutions (K20R, D67N, V90I, K101R/E, V106I/A, V108I, F116L, E138R, A139V, V189I, G190A, D218E, E203K, H221Y, F227L, N348I, and T369I) or novel mutations (V8I, S134N, C162Y, L228I, Y232H, E396G, and D404N), developed during NVP selection. EFV-associated variations contained two initial mutations (L100I and Y188C) and three other mutations (V106L, F116Y, and A139V). Phenotypic analyses showed that E138R, Y181C, and G190A contributed high-level resistance to NVP, while L100I and V106L significantly reduced virus susceptibility to EFV. Y188C was 20-fold less sensitive to both NVP and EFV. As expected, M184I alone, or with V90I or D67N, decreased 3TC susceptibility by over 1,000-fold. Although the mutation profile obtained in culture may be different from the patients, these results may still provide useful information to monitor and optimize the antiretroviral regimens.

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“…The subtype distribution in Guangxi is approximately 75% CRF01AE and 25% B or BC recombinants. [8][9][10] Previous research in Thailand estimated that the FRR was 0% using a cutoff of 1.0 OD-n for 128 samples from CRF01_AE-infected subjects. 4 Additionally, individuals infected with subtype B and C historically have a low FRR.…”

mentioning

confidence: 99%

Short Communication: Low False Recent Rate of Limiting-Antigen Avidity Assay Among Long-Term Infected Subjects from Guangxi, China

Laeyendecker

Wendel

et al. 2015

AIDS Research and Human Retroviruses

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Assays used for HIV cross-sectional incidence testing can misclassify some individuals with nonrecent HIV infection as recently infected, overestimating HIV incidence. We analyzed the frequency and factors associated with false-recent misclassification on subjects from Quangxi, China known to have long-term infection using the limited antigen-avidity assay (LAg-Avidity). Stored samples from treatment-naive individuals from Guangxi, China were tested using the LAg-Avidity. A total of 362 samples from individuals known to be infected 2 to 13.5 years were tested and the false-recent rate (FRR), the frequency of samples with a positive result, was determined at different cutoff values of the assay. Additionally, factors associated with misclassification were determined. The FRR of the LAg-Avidity was 1.1% (4/362) using a cutoff of 1.5 normalized optical density units (OD-n). All four samples had viral loads >1,000 copies/ml. Using a cutoff of 3.0 OD-n the FRR was 5.5% (20/362), with four samples having viral loads <1,000 copies/ml. Factors associated with a higher odds of misclassification were female gender (OR 7.7, 95% CI 1.0-56.4) and being a female sex worker (OR 31.3,. At the higher cutoff, being of Zhuang decent, relative to Han, had higher odds of misclassification (OR 6.2, 95% CI 1.99-19.0). The LAg-Avidity assay had a low FRR in this Chinese population. Further investigations of the higher frequency of low LAg-Avidity results seen in female sex workers and individuals of Zhuang descent should be explored in a larger study.

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Different Distribution of HIV-1 Subtype and Drug Resistance Were Found among Treatment Naïve Individuals in Henan, Guangxi, and Yunnan Province of China

Cited by 32 publications

References 28 publications

Increased bone resorption during tenofovir plus lopinavir/ritonavir therapy in Chinese individuals with HIV

Increased bone resorption during tenofovir plus lopinavir/ritonavir therapy in Chinese individuals with HIV

In VitroSelection of HIV-1 CRF08_BC Variants Resistant to Reverse Transcriptase Inhibitors

Short Communication: Low False Recent Rate of Limiting-Antigen Avidity Assay Among Long-Term Infected Subjects from Guangxi, China

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