Wide Variation in the Multiplicity of HIV-1 Infection among Injection Drug Users

ABSTRACT Recent studies indicate that sexual transmission of human immunodeficiency virus type 1 (HIV-1) generally results from productive infection by only one virus, a finding attributable to the mucosal barrier. Surprisingly, a recent study of injection drug users (IDUs) from St. Petersburg, Russia, also found most subjects to be acutely infected by a single virus. Here, we show by single-genome amplification and sequencing in a different IDU cohort that 60% of IDU subjects were infected by more than one virus, including one subject who was acutely infected by at least 16 viruses. Multivariant transmission was more common in IDUs than in heterosexuals (60% versus 19%; odds ratio, 6.14; 95% confidence interval [CI], 1.37 to 31.27; P = 0.008). These findings highlight the diversity in HIV-1 infection risks among different IDU cohorts and the challenges faced by vaccines in protecting against this mode of infection.

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Intersubtype Human Immunodeficiency Virus Type 1 Superinfection following Seroconversion to Primary Infection in Two Injection Drug Users

Journal of Virology ◽

10.1128/jvi.76.15.7444-7452.2002 ◽

2002 ◽

Vol 76 (15) ◽

pp. 7444-7452 ◽

Cited By ~ 123

Author(s):

Artur Ramos ◽

Dale J. Hu ◽

Lily Nguyen ◽

Kim-Oanh Phan ◽

Suphak Vanichseni ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Injection Drug Users ◽

Primary Infection ◽

Drug Users ◽

Injection Drug ◽

Immunodeficiency Virus ◽

Hiv 1

ABSTRACT In this study, we describe two cases of human immunodeficiency virus type 1 (HIV-1) intersubtype superinfection with CRF01_AE and subtype B strains, which occurred in two injection drug users participating in a prospective cohort study in Bangkok, Thailand. In both cases, the superinfecting strain was detected by molecular and serologic analyses several weeks after complete seroconversion to the primary infection with a strain belonging to a different subtype. Superinfection occurred despite specific T-cell and humoral antibody responses to the primary virus. In both cases, cross-subtype immune responses were limited or absent prior to the second infection. These data show that, in some individuals, the quality and quantity of the immune response elicited by primary HIV-1 infection may not protect against superinfection. This finding has important implications for vaccine design. HIV-1 vaccines, at a minimum, will need to include potent, broadly protective, conserved immunogens derived from several group M subtypes.

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Human Immunodeficiency Virus Type 1 Superinfection Was Not Detected following 215 Years of Injection Drug User Exposure

Journal of Virology ◽

10.1128/jvi.78.1.94-103.2004 ◽

2004 ◽

Vol 78 (1) ◽

pp. 94-103 ◽

Cited By ~ 50

Author(s):

Rose Tsui ◽

Belinda L. Herring ◽

Jason D. Barbour ◽

Robert M. Grant ◽

Peter Bacchetti ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

San Francisco ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Injection Drug Users ◽

Drug Users ◽

Injection Drug ◽

Immunodeficiency Virus ◽

Hiv 1

ABSTRACT Evidence for human immunodeficiency virus type 1 (HIV-1) superinfection was sought among 37 HIV-1-positive street-recruited active injection drug users (IDUs) from the San Francisco Bay area. HIV-1 sequences from pairs of samples collected 1 to 12 years apart, spanning a total of 215 years of exposure, were generated at p17 gag, the V3-V5 region of env, and/or the first exon of tat and phylogenetically analyzed. No evidence of HIV-1 superinfection was detected in which a highly divergent HIV-1 variant emerged at a frequency >20% of the serum viral quasispecies. Based on the reported risk behavior of the IDUs and the HIV-1 incidence in uninfected subjects in the same cohort, a total of 3.4 new infections would have been expected if existing infection conferred no protection from superinfection. Adjusted for risk behaviors, the estimated relative risk of superinfection compared with initial infection was therefore 0.0 (95% confidence interval, 0.00, 0.79; P = 0.02), indicating that existing infection conferred a statistically significant level of protection against superinfection with an HIV-1 strain of the same subtype, which was between 21 and 100%.

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Sexual transmission of HIV-1 among injection drug users in San Francisco, USA: risk-factor analysis

The Lancet ◽

10.1016/s0140-6736(00)04562-1 ◽

2001 ◽

Vol 357 (9266) ◽

pp. 1397-1401 ◽

Cited By ~ 266

Author(s):

Alex H Kral ◽

Ricky N Bluthenthal ◽

Jennifer Lorvick ◽

Lauren Gee ◽

Peter Bacchetti ◽

...

Keyword(s):

Factor Analysis ◽

Risk Factor ◽

San Francisco ◽

Injection Drug Users ◽

Drug Users ◽

Sexual Transmission ◽

Injection Drug ◽

Risk Factor Analysis ◽

Sexual Transmission Of Hiv ◽

Hiv 1

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Prevalence of Different Genotypes of HIV-1 in Injection Drug Users in China: A Systematic Review and Meta-Analysis

Current HIV Research ◽

10.2174/1570162x17666190919115036 ◽

2019 ◽

Vol 17 (4) ◽

pp. 240-257

Author(s):

Yu Jiang ◽

Lincai Zhang ◽

Zongjie Hou ◽

Aixia Tu ◽

Ruijuan Qiao ◽

...

Keyword(s):

Systematic Review ◽

Injection Drug Users ◽

Drug Users ◽

Meta Analysis ◽

Sexual Transmission ◽

Injection Drug ◽

Subtype C ◽

Subtype B ◽

Prevalent Strain ◽

Hiv 1

Background: Since 1981, an increasing trend in HIV has been observed for transmission via injection drug users (IDUs), sexual transmission and mother-to-child transmission. The IDUs are blamed for early increases in HIV-positive cases in China. Objective: HIV genotypes of IDUs were comprehensively analysed to trace the source and relationships of the AIDS epidemic in China. Methods: Relevant databases written in English and Chinese were searched. Overall, 7,149 publications were identified in six databases. After screening 7,104 articles according to the inclusion and exclusion criteria, 45 studies consisting of 2,765 cases were finally identified. A meta-analysis was conducted using R MATLAB software, RevMan and SPSS. Subgroup analyses focused on time frame, region, and location of different genotypes of IDUs in China. Results: There were five dominant HIV-1 genotypes among the 2,765 IDU cases. The proportions of CRF07_BC, CRF01_AE, CRF08_BC, subtype B/B', and subtype C were 45.18% (95% CI: 33.55-57.08%), 16.00% (95% CI: 9.39-23.82%), 13.43% (95% CI: 7.32-20.84%), 3.58% (95% CI: 1.52-6.24%), and 0.90% (95% CI: 0.04-2.43%), respectively. HIV genotypes transmitted among IDUs in China are primarily CRF07-BC, followed by CRF01-AE and CRF08-BC. Across the different time frames and regions, CRF07_BC was the most prevalent HIV-1 genotype among IDUs, while CRF08_BC was the most prevalent genotype in the southwest region. Conclusion: Our study reveals that CRF07-BC was the dominant prevalent strain among IDUs from 1991 to 2015 in China, while CRF08-BC was the dominant prevalent strain among IDUs in southwestern China. This systematic review and meta-analysis shows evidence of the comprehensive prevalence of different genotypes, data and characteristics of HIV among IDUs in China.

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Molecular Characterization of Human Immunodeficiency Virus Type 1 and Hepatitis C Virus in Paid Blood Donors and Injection Drug Users in China

Journal of Virology ◽

10.1128/jvi.78.24.13591-13599.2004 ◽

2004 ◽

Vol 78 (24) ◽

pp. 13591-13599 ◽

Cited By ~ 105

Author(s):

Linqi Zhang ◽

Zhiwei Chen ◽

Yunzhen Cao ◽

Jian Yu ◽

Guanghan Li ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Injection Drug Users ◽

Drug Users ◽

Blood Donors ◽

Sexual Partners ◽

Hcv Genotypes ◽

Immunodeficiency Virus ◽

Hiv 1

ABSTRACT China is facing a rapid upsurge in cases of human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) infection due to large numbers of paid blood donors (PBD), injection drug users (IDU), and sexual partners of infected individuals. In this report, a total of 236 HIV-1-positive blood samples were collected from PBD, IDU, and their sexual partners in the most severely affected provinces, such as Henan, Yunnan, Guangxi, and Xinjiang. PCR was used to amplify the p17 region of gag and the C2-V3 region of env of HIV-1 and the 5′ noncoding region and a region of E1/E2 of HCV. Genetic characterization of viral sequences indicated that there are two major epidemics of HIV-1 and multiple HCV epidemics in China. The PBD and transfusion recipients in Henan harbored HIV-1 subtype B′, which is similar to the virus found in Thailand, and HCV genotypes 1b and 2a, whereas the IDU in Yunnan, Guangxi, and Xinjiang carried HIV-1 circulating recombinant forms 07 and 08, which resemble those in India, and HCV genotypes 1b, 3a, and 3b. Our findings show that the epidemics of HIV-1 and HCV infection in China are the consequences of multiple introductions. The distinct distribution patterns of both the HIV-1 and HCV genotypes in the different high-risk groups are tightly linked to the mode of transmission rather than geographic proximity. These findings provide information relevant to antiviral therapy and vaccine development in China and should assist public health workers in implementing measures to reduce the further dissemination of these viruses in the world's most populous nation.

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Low Multiplicity of HIV-1 Infection and No Vaccine Enhancement in VAX003 Injection Drug Users

Open Forum Infectious Diseases ◽

10.1093/ofid/ofu056 ◽

2014 ◽

Vol 1 (2) ◽

Cited By ~ 9

Author(s):

Sarah Sterrett ◽

Gerald H. Learn ◽

Paul T. Edlefsen ◽

Barton F. Haynes ◽

Beatrice H. Hahn ◽

...

Keyword(s):

Injection Drug Users ◽

Drug Users ◽

Virus Transmission ◽

Injection Drug ◽

Sieve Analysis ◽

Successful Vaccine ◽

Single Genome ◽

Multiple Virus ◽

Sieve Effect ◽

Hiv 1

Abstract Background. We performed human immunodeficiency virus type 1 (HIV-1) transmitted/founder (T/F) virus analysis of the VAX003 vaccine efficacy trial participants to characterize the transmission bottleneck and test for vaccine-associated reduction or enhancement of infection in this injection drug user (IDU) cohort. Methods. We performed single genome sequencing of plasma vRNA from 50 subjects sampled in early HIV infection. Sequences were analyzed phylogenetically, T/F viruses enumerated, and a sieve analysis performed. Results. Eight of 19 (42%) placebo recipients were productively infected by more than 1 virus (range 1–5, median 1, mean 1.7). This frequency of multiple virus transmission was greater than reported for heterosexual cohorts (19%, P = .03) but not statistically different from vaccine recipients (22.6%, P > .05), where the range was 1–3, median 1, and mean 1.3 (P > .05 for all comparisons). An atypical sieve effect was detected in Env V2 but was not associated with reduction or enhancement of virus acquisition. Conclusions. The number of T/F viruses in IDUs was surprising low, with 95% of individuals infected by only 1–3 viruses. This finding suggests that a successful vaccine or other prevention modality generally needs to protect against only one or a few viruses regardless of risk behavior. T/F analysis ide.jpegied an atypical genetic sieve in the V2 region of Envelope and found no evidence for vaccine-mediated enhancement in VAX003.

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Highly Productive Infection with Pseudotyped Human Immunodeficiency Virus Type 1 (HIV-1) Indicates No Intracellular Restrictions to HIV-1 Replication in Primary Human Astrocytes

Journal of Virology ◽

10.1128/jvi.75.17.7925-7933.2001 ◽

2001 ◽

Vol 75 (17) ◽

pp. 7925-7933 ◽

Cited By ~ 82

Author(s):

Mario Canki ◽

Janice Ngee Foong Thai ◽

Wei Chao ◽

Anuja Ghorpade ◽

Mary Jane Potash ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Human Immunodeficiency Virus Type ◽

Productive Infection ◽

Human Astrocytes ◽

Immunodeficiency Virus ◽

Infected Cells ◽

Virus Expression ◽

Hiv 1

ABSTRACT Human astrocytes can be infected with human immunodeficiency virus type 1 (HIV-1) in vitro and in vivo, but, in contrast to T lymphocytes and macrophages, virus expression is inefficient. To investigate the HIV-1 life cycle in human fetal astrocytes, we infected cells with HIV-1 pseudotyped with envelope glycoproteins of either amphotropic murine leukemia virus or vesicular stomatitis virus. Infection by both pseudotypes was productive and long lasting and reached a peak of 68% infected cells and 1.7 μg of viral p24 per ml of culture supernatant 7 days after virus inoculation and then continued with gradually declining levels of virus expression through 7 weeks of follow-up. This contrasted with less than 0.1% HIV-1 antigen-positive cells and 400 pg of extracellular p24 per ml at the peak of astrocyte infection with native HIV-1. Cell viability and growth kinetics were similar in infected and control cells. Northern blot analysis revealed the presence of major HIV-1 RNA species of 9, 4, and 2 kb in astrocytes exposed to pseudotyped (but not wild-type) HIV-1 at 2, 14, and 28 days after infection. Consistent with productive infection, the 9- and 4-kb viral transcripts in astrocytes infected by pseudotyped HIV-1 were as abundant as the 2-kb mRNA during 4 weeks of follow-up, and both structural and regulatory viral proteins were detected in infected cells by immunoblotting or cell staining. The progeny virus released by these cells was infectious. These results indicate that the major barrier to HIV-1 infection of primary astrocytes is at virus entry and that astrocytes have no intrinsic intracellular restriction to efficient HIV-1 replication.

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