Please Sign In or Create an account
Longitudinal analysis of infection frequencies and genetic makeup of intracellular HIV-1 from tissue compartments during long-term suppressive therapy

Longitudinal analysis of infection frequencies and genetic makeup of intracellular HIV-1 from tissue compartments during long-term suppressive therapy

Efforts to eradicate HIV-1 require a comprehensive examination of the quantity and genetic makeup of HIV-1 populations within infected cells located in tissues throughout the body. Therefore, we conducted a longitudinal analysis of the infection frequencies and genetic makeup of HIV-1 in specific CD4+ T cell subsets in different tissue compartments from patients on long-term suppressive therapy.

Methods: Using single-genome and single-proviral sequencing techniques, we isolated intracellular HIV-1 genomes derived from defined subsets of T cells (naïve, central-, transitional-, and effector-memory) from peripheral blood, GALT, and lymph node tissue. Samples were collected at 2 time points (separated by 6 months) from 8 subjects on suppressive therapy (4-12 years): 5 who initiated therapy during acute infection and 3 who initiated therapy during chronic infection. Maximum likelihood phylogenetic trees were constructed using the general time reversible model.

Results: Comparison of the infection frequencies between the 2 time points showed similar (<6-fold difference) infection rates of memory T cell subsets from different tissue compartments for most subjects. In agreement with findings for time point 1, infection frequencies of all T cell subsets were higher in subjects treated during chronic infection than acute infection; time point 2 included transitional-memory T cells which were not examined at time point 1 (6-fold higher infection rate in chronic vs acute; p=0.036). Appoximately 30% of the intracellular HIV sequences appeared to encode replication-incompetent virus. Longitudinal phylogenetic analysis revealed the expansion of some HIV genetic populations and the contraction of others with little evidence of viral evolution. In one subject, a clonal species containing a 380bp deletion was dominant, and increased from 71% to 92% over 6 months in peripheral blood effector memory T cells.

Conclusions: Our findings suggest the pool of HIV-infected resting memory CD4+ T cells typically does not change dramatically over 6 months in different tissue compartments, reflecting a relatively stable HIV-infection frequency during suppressive therapy with the early initiation of effective therapy resulting in a lower reservoir size. The increase of clonal HIV-1 sequences, especially a large deletion mutant, indicates an expansion of cells with integrated proviral DNA rather than active viral replication.

Conference: ASHM 2013
Areas of Interest / Categories: AIDS 2013, HIV

AIDS 2013

Clinical factors associated with suboptimal adherence to antiretroviral therapy in Asia

Adherence to combination antiretroviral therapy (cART ) plays an important role on treatment outcomes. The TREAT Asia Studies to Evaluate Resistance – Monitoring Cohort Study (TASER-M) collects patients’ adherence based on a Visual Analogue Scale. The aim of this analysis was to assess the rates of, and factors associated with, suboptimal adherence in the first 24 months of initial cART in Asian patients.

Reinvigorating evidence for action and capacity in community HIV programs (REACH Project)

REACH was a collaborative research and practice initiative to develop evidence building frameworks, capacity, tools and resources with the Victorian HIV community partnership.

The impact of immune activation on natural killer cells in the setting of HIV infection

HIV disease is associated with chronic inflammation and activation of the innate immune system. This state, as measured using plasma markers of inflammation, persists following suppression of HIV viremia using antiretroviral therapy, and may increase risk of non-AIDS co-morbidities. The causes of innate immune activation in the setting of virological suppression are unclear. Natural killer (NK) cells are innate immune cells that kill virus-infected and transformed cells without prior sensitization. We have shown that NK cells are activated both phenotypically (elevated expression of HLA-DR) and functionally (increased spontaneous degranulation measured by CD107a surface expression) in virologically suppressed (VS) HIV+ individuals. NK cells also lose expression of CD16, the receptor which mediates antibody-dependent cellular cytotoxicity.

Men who take more risks avoid HIV testing due to structural barriers

Regular HIV testing is recommended in men who take sexual risks. We assessed the relationship between perceived barriers to HIV testing, and frequency of testing among men who engaged in unprotected anal intercourse with casual partners (UAIC), to inform HIV testing strategies.

Delayed HIV diagnoses among gay and bisexual men in Australia

The majority of HIV diagnoses including delayed diagnoses in Australia occur among men who report homosexual contact – hereafter called gay and bisexual men (GBM). Delayed diagnosis is strongly associated with increased HIV-related mortality and morbidity. People who are unaware of their HIV-positive status may also be unwittingly transmitting HIV. We assessed trends in delayed HIV diagnoses among GBM in Australia.

Complex case report that illustrates the paucity of data for long term management of Visceral Leishmania-HIV co-infection.

HIV-associated leishmaniasis, endemic in the Mediterranean basin is a growing problem in India, Brazil and East Africa. Despite surviving for than 20 years, the clinical course of our visceral-leishmania (VL)-HIV co-infected patient illustrates several management challenges including diagnosis, speciation and drug resistance; monitoring burden of disease; access to and use of VL-treatments; end-organ toxicity and the combined immunosuppressive effects of HIV-VL.

Chlamydia prevalence in adolescent Australians

Most Australian guidelines for clinical screening of chlamydia infection advise testing sexually active individuals aged 16-24 years. Recent research shows that age at first sex in Australia is decreasing; a recent Victorian survey showed 29% of respondents reported being sexually active before age 16 years. There is also evidence that younger age at first sex is associated with risk behavior such as unprotected sex and having multiple sex partners.