Rapid CD4+ T-cell decline is associated with coreceptor switch among MSM primarily infected with HIV-1 CRF01_AE in Northeast China

Cui, Hu; Geng, Wenqing; Sun, Hong; Han, Xiaoxu; An, Minghui; Jiang, Yongjun; Zhang, Zining; Chen, Zhiwei; Xu, Junjie; Hu, Qinghai; Zhao, Bin; Zhou, Bennan

doi:10.1097/qad.0000000000001981

Cited by 21 publications

(21 citation statements)

References 47 publications

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“…CRF01_AE has been shown to be associated with a lower CD4 + T cell count and higher rates of CXCR4 coreceptor [7,8,36]. In our study, baseline CD4 + T cell count was lower in the CRF01_AE group than the non-CRF01_AE group.…”

Section: Discussionsupporting

confidence: 42%

“…After 96 weeks, approximately 20% of patients in both groups achieved HIV-1 DNA level ≤ 2 log 10 copies/10 6 PBMCs, and HIV-1 subtype was not found to be an independent risk factor for predicting low HIV-1 DNA levels at week 96. Previous studies mainly focused on the impact of viral subtype on the level of HIV-1 RNA and CD4 + T cell count, but rarely on HIV-1 DNA [7,8]. To our knowledge, this is the first national multicentre prospective cohort study in the world to assess the relationship of subtype and HIV-1 DNA reservoir after ART [25].…”

Section: Discussionmentioning

confidence: 98%

“…Untreated patients infected with HIV-1 CRF01_ AE subtype have a shorter median survival than patients of subtype B [4][5][6]. This finding may be explained by the predominant association of HIV-1 CRF01_AE subtype with CXCR4 rather than CCR5 tropism, or coreceptor switch of R5/X4 with prolonged infection time, ultimately leading to a more rapid disease progression [7,8].…”

Section: Introductionmentioning

confidence: 99%

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HIV-1 CRF01_AE subtype and HIV-1 DNA level among patients with chronic HIV-1 infection: a correlation study

et al. 2020

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Background: The impact of HIV-1 subtype (CRF01_AE and non-CRF01_AE) on HIV-1 DNA levels in HIV-1 chronically infected patients with suppressive antiretroviral therapy (ART) remains poorly understood. To evaluate the correlation of HIV-1 subtype with DNA level, and identify baseline predictors of HIV-1 DNA decay. Methods: ART-naïve HIV-1-infected patients from two large multi-center studies in China were classified into CRF01_AE and non-CRF01_AE subtype groups. Peripheral blood samples were collected at baseline and week 12, 24, 48 and 96 after ART initiation and total HIV-1 DNA levels were quantified by real-time PCR. HIV-1 DNA levels at week 96 were categorized into high, moderate, and low levels, reflecting HIV-1 DNA ≥ 3, 2-3, ≤ 2 log 10 copies/10 6 PBMCs, respectively, and the corresponding proportion of CRF01_AE and non-CRF01_AE subtype were compared. The baseline predictors of low HIV-1 total DNA levels (≤ 2 log 10 copies/10 6 PBMCs) at week 96 were evaluated using a logistic regression model. Results: Compared to the non-CRF01_AE subtypes (n = 185), patients with CRF01_AE subtype (n = 188) harboured a higher level of HIV-1 DNA (median: 3.19 vs. 2.95 log 10 copies/10 6 PBMCs, P < 0.001) prior to treatment. After 96 weeks of ART, HIV-1 DNA levels remained higher in the CRF01_AE subtype group (median: 2.63 vs. 2.39 log 10 copies/10 6 PBMCs, P = 0.002). There was no significant difference in the proportion of patients achieving high (22.3% vs. 14.6%, P = 0.054), moderate (59.6% vs. 60.5%, P = 0.849) and low levels (18.1% vs 24.9%, P = 0.111) between CRF01_AE and non-CRF01_AE groups. In the multivariable analysis, baseline HIV-1 DNA level and CD4 + T cell count but not the subtype were independent risk factors for achieving HIV-1 DNA level ≤ 2 log 10 copies/10 6 PBMCs. Conclusion: HIV-1 CRF01_AE subtype is neither correlated with HIV-1 DNA reservoir decline nor a prognostic factor for achieving lower HIV-1 DNA levels (≤ 2 log 10 copies/10 6 PBMCs) after ART. However, higher HIV-1 DNA level in HIV-1 CRF01_AE patients should be aroused much attention and strengthen surveillance during ART.

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Section: Discussionsupporting

confidence: 42%

Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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HIV-1 CRF01_AE subtype and HIV-1 DNA level among patients with chronic HIV-1 infection: a correlation study

et al. 2020

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“…CRF01_AE has been shown to be associated with a lower CD4 + T cell count and higher rates of CXCR4 co-receptor [7,8,36]. In our study, baseline CD4 + T cell count was lower in the CRF01_AE group than the non-CRF01_AE group.…”

Section: Discussionsupporting

confidence: 43%

HIV-1 CRF01_AE subtype and HIV-1 DNA level among patients with chronic HIV-1 infection: a correlation study

Lyu

Yue

Hsieh

et al. 2020

Preprint

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Background: The impact of HIV-1 subtype (CRF01_AE and non-CRF01_AE) on HIV-1 DNA levels in HIV-1 chronically infected patients with suppressive antiretroviral therapy (ART) remains poorly understood. To evaluate the correlation of HIV-1 subtype with DNA level, and identify baseline predictors of HIV-1 DNA decay. Methods : ART-naïve HIV-1-infected patients from two large multi-center studies in China were classified into CRF01_AE and non-CRF01_AE subtype groups. Peripheral blood samples were collected at baseline and week 12, 24, 48 and 96 after ART initiation and total HIV-1 DNA levels were quantified by real-time PCR. HIV-1 DNA levels at week 96 were categorized into high, moderate, and low levels, reflecting HIV-1 DNA ≥ 3, 2–3, ≤ 2 log 10 copies/10 6 PBMCs, respectively , and the corresponding proportion of CRF01_AE and non-CRF01_AE subtype were compared. The baseline predictors of low HIV-1 total DNA levels (≤ 2 log 10 copies/10 6 PBMCs) at week 96 were evaluated using a logistic regression model. Results: Compared to the non-CRF01_AE subtypes (n=185), patients with CRF01_AE subtype (n=188) harboured a higher level of HIV-1 DNA (median: 3.19 vs. 2.95 log 10 copies/10 6 PBMCs, P < 0.001) prior to treatment. After 96 weeks of ART, HIV-1 DNA levels remained higher in the CRF01_AE subtype group (median: 2.63 vs. 2.39 log 10 copies/10 6 PBMCs, P = 0.002). There was no significant difference in the proportion of patients achieving high (22.3% vs. 14.6%, P = 0.054), moderate (59.6% vs. 60.5%, P = 0.849) and low levels (18.1% vs 24.9%, P = 0.111) between CRF01_AE and non-CRF01_AE groups. In the multivariable analysis, baseline HIV-1 DNA level and CD4 + T cell count but not the subtype were independent risk factors for achieving HIV-1 DNA level ≤ 2 log 10 copies/10 6 PBMCs. Conclusion: HIV-1 CRF01_AE subtype is neither correlated with HIV-1 DNA reservoir decline nor a prognostic factor for achieving lower HIV-1 DNA levels (≤ 2 log 10 copies/10 6 PBMCs) after ART. However, higher HIV-1 DNA level in HIV-1 CRF01_AE patients should be aroused much attention and strengthen surveillance during ART.

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“…The primary isolate (R5 tropic, subtype CRF01_AE) had been isolated from the PBMCs of the MSM (men who have sex with men) at 63 days of HIV infection in our cohort. The primary isolate was generated in PHA and IL-2 stimulated PBMCs, which has been described previously ( 18 ). After 5 days, supernatant from infected cells was positive for p24 antigen by ELISA; after 22 days, p24 antigen level of supernatant reached to peak value (16 ng/mL).…”

Section: Methodsmentioning

confidence: 99%

The Early Antibody-Dependent Cell-Mediated Cytotoxicity Response Is Associated With Lower Viral Set Point in Individuals With Primary HIV Infection

et al. 2018

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Antibody-dependent cell-mediated cytotoxicity (ADCC) is an immune response largely mediated by natural killer (NK) cells that can lyse target cells and combat tumors and viral infections. However, the role of ADCC in response to primary HIV infection is poorly understood. In the present study, we explored the ADCC response and evaluated its characteristics in 85 HIV-infected individuals, including 42 with primary infections. Our results showed that ADCC occurs during acute infection, and the earliest ADCC response to a single peptide was detected at 52 days. Primary HIV-infected individuals exhibiting ADCC responses had lower viral set points than those with no ADCC response, and functional analyses demonstrated that the ADCC response could significantly inhibit viral infection during primary HIV infection. HIV epitopes that provoked the ADCC response were determined and three relatively conserved epitopes (HNVWATYACVPTDPNPQE, TSVIKQACPKISFDPIPI, and VVSTQLLLNGSLAEEEII) from the surface of the three-dimensional structure of the HIV Env protein were identified. Overall, our data indicate that ADCC responses may be significant for the control of HIV from an early stage during infection. These findings merit further investigation and will facilitate improvements in vaccines or therapeutic interventions against HIV infection.

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Rapid CD4+ T-cell decline is associated with coreceptor switch among MSM primarily infected with HIV-1 CRF01_AE in Northeast China

Abstract: Primary HIV-1 CRF01_AE infection among MSM in Northeast China is characterized by R5 viral infection and early R5 to X4/DM coreceptor switch, which is associated with rapid CD4 T-cell decline. The findings highlight the importance of immediate treatment among the CRF01_AE-infected MSM.

Cited by 21 publications

References 47 publications

HIV-1 CRF01_AE subtype and HIV-1 DNA level among patients with chronic HIV-1 infection: a correlation study

HIV-1 CRF01_AE subtype and HIV-1 DNA level among patients with chronic HIV-1 infection: a correlation study

HIV-1 CRF01_AE subtype and HIV-1 DNA level among patients with chronic HIV-1 infection: a correlation study

The Early Antibody-Dependent Cell-Mediated Cytotoxicity Response Is Associated With Lower Viral Set Point in Individuals With Primary HIV Infection

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