Slow immunological progression in HIV-1 CRF07_BC-infected injecting drug users

Lin, Pei-Yu; Lai, Chung-Sheng; Yang, Jyh‐Chin; Huang, Hui-Lin; Huang, Ming‐Bao; Tsai, Mao‐Song; Yang, Chia‐Jui; Cheng, C. K.; Su, Yi‐Ching; Chang, Shu-Fang; Liu, Wen-Chun; Hung, Chien‐Ching; Chang, Sui‐Yuan; Chang, Shan‐Chwen

doi:10.1038/emi.2013.83

Cited by 26 publications

(33 citation statements)

References 49 publications

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“…A similar phenomenon has only been reported in one other case, that of CRF07_BC‐infected PWID in Taiwan . CRF07_BC viruses have a unique feature, a signature seven‐amino acid deletion in the p6 Gag protein , which results in defects in virus release, replication and infectivity . However, our preliminary data indicate that these defects are moderate and that the infection is only 20–30% less efficient than that of the wild‐type laboratory strain pNL4‐3 virus in a cell culture infectivity assay (Z. Cheng et al ., manuscript in preparation).…”

Section: Discussionsupporting

confidence: 83%

“…Here, we also report the novel and important finding that CRF07_BC is less virulent than CRF01_AE and HIV‐1 subtype B, indicating that patients infected with CRF07_BC may have longer survival times compared to individuals infected with the other two strains. A similar phenomenon has only been reported in one other case, that of CRF07_BC‐infected PWID in Taiwan . CRF07_BC viruses have a unique feature, a signature seven‐amino acid deletion in the p6 Gag protein , which results in defects in virus release, replication and infectivity .…”

Section: Discussionsupporting

confidence: 70%

“…Lin et al . found slower immunological progression, that is, the decrease of CD4 count from > 350 to < 350 cells/μL, for CRF07_BC‐infected PWIDs than for HIV‐1 subtype B‐infected MSM, but the two different populations may not be fully comparable, and, in addition, the endpoint of immunodeficiency or AIDS was not analysed . The detailed analysis performed in our study allowed us to conclude more definitively that infection with CRF01_AE leads to faster immunodeficiency progression than infection with CRF07_BC or CRF55_01B.…”

Section: Discussionmentioning

confidence: 67%

“…CRF07_BC was first identified in China, and some findings indicated that it was associated with significantly lower viral loads and slower disease progression in HIV‐1‐infected people who inject drugs (PWID) than in HIV‐1 B‐infected MSM . However, the lack of well‐designed longitudinal studies precluded confirmation of such associations .…”

Section: Introductionmentioning

confidence: 99%

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HIV‐1 genotype is independently associated with immunodeficiency progression among Chinese men who have sex with men: an observational cohort study

et al. 2019

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ObjectivesHIV-1 genetic diversity is increasing among men who have sex with men (MSM) in China, but the association of HIV-1 genotype with disease progression remains to be elucidated. MethodsWe collected data in an observational longitudinal cohort study of 860 HIV-1-infected MSM in Guangzhou, China between January 2008 and March 2017. Kaplan-Meier analysis and Cox proportional hazard model were used to predict the time from HIV-1 diagnosis to immunodeficiency progression (CD4 cell count < 200 cells/ll) as well as adjusted hazard ratio (aHR). ResultsCRF01_AE and HIV-1 subtype B infection were associated with higher percentage of patients progressed to immunodeficiency and higher incidence of immunodeficiency than infection with CRF07_BC or CRF55_01B. Compared with CRF07_BC, the time from HIV-1 diagnosis to immunodeficiency were different among the major HIV-1 genotypes, which ranked as follows, in descending order: CRF07_BC (7.03 years) > CRF55_01B (5.71 years, P = 0.014; aHR 3.752, P = 0.0923) > CRF01_AE (5.18 years, P < 0.001; aHR 4.733, P = 0.0152). HIV-1 genotype, viral load and baseline CD4 T-cell count were three independent variables associated with disease progression. ConclusionsOur results confirm differential rates of immunodeficiency progression as a function of HIV-1 genotype. The impact of HIV-1 genotype on HIV epidemics, patient management and prevention should be further investigated.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 67%

Section: Introductionmentioning

confidence: 99%

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HIV‐1 genotype is independently associated with immunodeficiency progression among Chinese men who have sex with men: an observational cohort study

et al. 2019

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“…Previous studies indicated that patients infected with the CRF07_BC Δ7 variant exhibited lower viral loads and slower disease progression compared with individuals infected with HIV-1 subtype B or CRF01_AE [6][7][8][9][10]. Previous in vitro studies showed that HIV-1 isolates and the infectious clone of CRF07_BC with the Δ7 mutation displayed relatively lower replication capacity and slower replication kinetics than HIV-1 subtype B or Thai B' [7,8]. Lin et al found that the Δ7 mutation resulted in a defect in virus particle release and Gag processing, which in turn caused the accumulation of immature virions on the plasma membrane [8].…”

mentioning

confidence: 99%

Elucidation of the Molecular Consequences of Two Unique p6Gag Mutations Derived from HIV-1 CRF07_BC-infected Patients

Cheng

Ablan²,

Freed³

et al. 2020

Preprint

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Background We previously observed that individuals infected with HIV-1 CRF07_BC showed slower disease progression than those infected with HIV-1 subtype B or CRF01_AE. CRF07_BC viruses carry two unique mutations in the p6 Gag protein: insertion of PTAPPE sequences downstream of the original Tsg101 binding domain, and deletion of a seven-amino-acid sequence ( 30 PIDKELY 36 ) that partially overlaps with the Alix binding domain. To further define the role of these mutations in virus release and replication, we introduced them into the HIV-1 proviral clone pNL4-3 for functional characterization. Results We found that the seven-amino-acid deletion, but not the PTAPPE insertion, significantly decreased virus release, Gag processing, and virus infectivity. The seven-amino-acid deletion also resulted in a virus replication defect in both T-cell lines and peripheral blood mononuclear cells. We found that these defects were caused by the seven-amino-acid deletion in p6 Gag , especially deletion of Tyr-36 of p6 Gag , not the deletion of the overlapping p6* sequence in the HIV-1 GagPol protein. The p6 Gag deletion mutant was resistant to a dominant-negative Alix fragment, suggesting a loss of binding between p6 Gag and Alix. Conclusions Our results indicate that the patient-derived seven-amino-acid deletion in p6 Gag of HIV-1 CRF07_BC virus affects virus release, infectivity and replication capacity by disrupting the interaction between HIV-1 p6 Gag and host protein Alix. These results may explain the slower disease progression observed in the subjects infected with HIV-1 CRF07_BC bearing this unique mutation.

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Association of demographics, HCV co‐infection, HIV‐1 subtypes and genetic clustering with late HIV diagnosis: a retrospective analysis from the Japanese Drug Resistance HIV‐1 Surveillance Network

et al. 2023

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Introduction Late diagnosis of the human immunodeficiency virus (HIV) is a major concern epidemiologically, socially and for national healthcare systems. Although the association of certain demographics with late HIV diagnosis has been reported in several studies, the association of other factors, including clinical and phylogenetic factors, remains unclear. In the present study, we conducted a nationwide analysis to explore the association of demographics, clinical factors, HIV‐1 subtypes/circulating recombinant form (CRFs) and genetic clustering with late HIV diagnosis in Japan, where new infections mainly occur among young men who have sex with men (MSM) in urban areas. Methods Anonymized data on demographics, clinical factors and HIV genetic sequences from 39.8% of people newly diagnosed with HIV in Japan were collected by the Japanese Drug Resistance HIV‐1 Surveillance Network from 2003 to 2019. Factors associated with late HIV diagnosis (defined as HIV diagnosis with a CD4 count <350 cells/μl) were identified using logistic regression. Clusters were identified by HIV‐TRACE with a genetic distance threshold of 1.5%. Results Of the 9422 people newly diagnosed with HIV enrolled in the surveillance network between 2003 and 2019, 7752 individuals with available CD4 count at diagnosis were included. Late HIV diagnosis was observed in 5522 (71.2%) participants. The overall median CD4 count at diagnosis was 221 (IQR: 62–373) cells/μl. Variables independently associated with late HIV diagnosis included age (adjusted odds ratio [aOR] 2.21, 95% CI 1.88–2.59, ≥45 vs. ≤29 years), heterosexual transmission (aOR 1.34, 95% CI 1.11–1.62, vs. MSM), living outside of Tokyo (aOR 1.18, 95% CI 1.05–1.32), hepatitis C virus (HCV) co‐infection (aOR 1.42, 95% CI 1.01–1.98) and not belonging to a cluster (aOR 1.30, 95% CI 1.12–1.51). CRF07_BC (aOR 0.34, 95% CI 0.18–0.65, vs. subtype B) was negatively associated with late HIV diagnosis. Conclusions In addition to demographic factors, HCV co‐infection, HIV‐1 subtypes/CRFs and not belonging to a cluster were independently associated with late HIV diagnosis in Japan. These results imply the need for public health programmes aimed at the general population, including but not limited to key populations, to encourage HIV testing.

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Slow immunological progression in HIV-1 CRF07_BC-infected injecting drug users

Cited by 26 publications

References 49 publications

HIV‐1 genotype is independently associated with immunodeficiency progression among Chinese men who have sex with men: an observational cohort study

HIV‐1 genotype is independently associated with immunodeficiency progression among Chinese men who have sex with men: an observational cohort study

Elucidation of the Molecular Consequences of Two Unique p6Gag Mutations Derived from HIV-1 CRF07_BC-infected Patients

Association of demographics, HCV co‐infection, HIV‐1 subtypes and genetic clustering with late HIV diagnosis: a retrospective analysis from the Japanese Drug Resistance HIV‐1 Surveillance Network

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