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Characterization of HIV-1 envelopes in acutely and chronically infected injection drug users.

ABSTRACT: Mucosally acquired human immunodeficiency virus type 1 (HIV-1) infection results from a limited number of variants, and these infecting strains potentially have unique properties, such as increased susceptibility to entry blockers, relative interferon-alpha (IFN-?) resistance, and replication differences in some primary cells. There is no data about the phenotypic properties of HIV-1 envelope variants found early after acquisition among subjects infected through injection drug use (IDU). For the first time, we compared the characteristics of virus envelopes among injection drug users sampled prior to seroconversion (HIV RNA+/Ab-), within 1 year (early), and more than 2 years (chronic) after estimated acquisition.Virus envelopes from 7 HIV RNA+/Ab- subjects possessed lower genetic diversity and divergence compared to 7 unrelated individuals sampled during the chronic phase of disease. Replication competent recombinant viruses incorporating the HIV RNA+/Ab- as compared to the chronic phase envelopes were significantly more sensitive to a CCR5 receptor inhibitor and IFN-? and showed a statistical trend toward greater sensitivity to a fusion blocker. The early as compared to chronic infection envelopes also demonstrated a statistical trend or significantly greater sensitivity to CCR5 and fusion inhibitor and IFN- ?. The HIV RNA+/Ab- as compared to chronic envelope viruses replicated to a lower extent in mature monocyte derived dendritic cells - CD4+ T cell co-cultures, but there were no significant replication differences in other primary cells among the viruses with envelopes from the 3 different stages of infection.Similar to mucosal acquisition, HIV-1 envelope quasispecies present in injection drug users prior to seroconversion have unique phenotypic properties compared to those circulating during the chronic phase of disease.

SUBMITTER: Etemad B

PROVIDER: S-EPMC4253609 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Characterization of HIV-1 envelopes in acutely and chronically infected injection drug users.

Etemad Behzad B Gonzalez Oscar A OA White Laura L Laeyendecker Oliver O Kirk Gregory D GD Mehta Shruti S Sagar Manish M

Retrovirology 20141128

<h4>Background</h4>Mucosally acquired human immunodeficiency virus type 1 (HIV-1) infection results from a limited number of variants, and these infecting strains potentially have unique properties, such as increased susceptibility to entry blockers, relative interferon-alpha (IFN-α) resistance, and replication differences in some primary cells. There is no data about the phenotypic properties of HIV-1 envelope variants found early after acquisition among subjects infected through injection drug ...[more]

PMID: 25430652

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Project description:Information about HBV sero-markers, infection stages and genotypes in HIV-1 infected and uninfected injection and non-injection drug users (IDUs) in Kenya remains elusive.A cross-sectional study examining HBV sero-marker, infection stages and genotypes was conducted among HIV-1 infected and uninfected, respectively, IDUs (n?=?157 and n?=?214) and non-IDUs (n?=?139 and n?=?48), and HIV-1 uninfected non-drug using controls (n?=?194) from coastal, Kenya. HBV sero-marker and infection stages were based on HBV 5-panel rapid test plasma sero-reactivity. DNA was extracted from acute and chronic plasma samples and genotypes established by nested-PCR and direct sequencing.HBsAg positivity was higher in HIV-1 infected IDUs (9.6%) relative to HIV-1 uninfected IDUs (2.3%), HIV-1 infected non-IDUs (3.6%), HIV-1 uninfected non-IDUs (0.0%) and non-drug users (2.6%; P?=?0.002). Contrastingly, HBsAb positivity was higher in HIV-1 uninfected IDUs (14.6%) and non-IDUs (16.8) in comparison to HIV-1 infected IDUs (8.3%), and non-IDUs (8.6%), and non-drug users (8.2%; P?=?0.023). HBcAb positivity was higher in HIV-1 infected IDUs (10.2%) compared to HIV-1 uninfected IDUs (3.3%), HIV-1 infected non-IDUs (6.5%), HIV-1 uninfected non-IDUs (2.1%) and non-drug users (4.6%; P?=?0.038). Acute (5.7%, 1.4%, 0.0%, 0.0% and 1.5%) and chronic (5.1%, 0.9%, 3.6%, 0.0% and 1.5%) stages were higher in HIV-1 infected IDUs, compared to HIV-1 uninfected IDUs, HIV-1 infected and uninfected non-IDUs and non-drug users, respectively. However, vaccine type response stage was higher in HIV-1 uninfected IDUs (15.4%) relative to HIV-1 infected IDUs (6.4%), and HIV-1 infected (6.5%), and uninfected (10.4%) non-IDUs, and non-drug users (5.7%; P?=?0.003). Higher resolved infection rates were also recorded in HIV-1 uninfected IDUs (11.2%) compared to HIV-1 infected IDUs (8.3%), and HIV-1 infected (7.2%), uninfected (6.3%) non-IDUs, and non-drug users (6.7%; P?=?0.479), respectively. Only A1 genotype showing minimal diversity was detected among the study participants.HBV sero-markers and infection staging are valuable in diagnosis and genotyping of HBV infections. Among IDUs, higher HBsAg and HBcAb positivity in HIV-1 infected and higher HBsAb positivity in HIV-1 negative IDUs suggests frequent exposure. Additionally, HBV genotype A is the dominant circulating genotype in both high and low risk populations of Kenya.

Dataset Information

Characterization of HIV-1 envelopes in acutely and chronically infected injection drug users.

Publications

Characterization of HIV-1 envelopes in acutely and chronically infected injection drug users.

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