Understanding immune control of HIV infection in controllers should facilitate the development of therapeutic HIV vaccines. While CD8+ T cell responses to Gag proteins restricted by ‘protective’ HLA alleles exert a dominant effect, other immune responses also contribute to immune control. We have shown that IgG antibodies to HIV Gag proteins that have undergone isotype diversification, to include IgG2 as well as IgG1, may contribute to immune control and, furthermore, could be enhanced by vaccination (French MA et al. AIDS 2010 and 2013). We have investigated this further by optimising methods for demonstrating diversification of IgG antibodies to HIV p24.
Plasma samples from HIV controllers (n=14) and non-controllers (n=20) were examined for antibodies by ELISA using two forms of recombinant HIV p24 (cloned in E. coli or baculovirus) and native p24 protein as antigens. Assay conditions were optimised to minimise detection of low affinity antibodies detected in serum from non-HIV donors. Calibration was undertaken using sera containing high amounts of antibody and results expressed in arbitrary units. results: There were strong correlations between plasma levels of IgG1 and IgG2 antibodies to HIV p24 using E. coli-p24, baculovirus-p24 and native-p24 as antigens in HIV controllers (p<0.0001, 0.02, <0.0001, respectively) but not in non-controllers. Plasma levels of IgG1 antibodies to HIV p24 were higher in controllers than non-controllers using all 3 antigens (p=0.05, 0.04, 0.03, respectively) and the differences were even more pronounced for IgG2 antibodies to HIV p24 (p=0.005, 0.02, 0.003, respectively). Analyses in a single controller without ‘protective’ HLA-B alleles who progressed from an elite to a viraemic controller over 5 years demonstrated an inverse correlation between plasma HIV RNA levels and the ratio of IgG2/IgG1 antibody to HIV p24 (p=0.016).
Conclusion: Isotype diversification of IgG antibodies to HIV p24 is associated with natural control of HIV infection.
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.
REACH was a collaborative research and practice initiative to develop evidence building frameworks, capacity, tools and resources with the Victorian HIV community partnership.
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.
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.
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.
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.
Early first sexual intercourse has been proposed as an important marker of later sexual and reproductive health. Discussions of what constitutes early sexual debut in this context, however, have been limited.