People who naturally control HIV infection (slow progressors and viremic controllers) provide important insights into the immune correlates of protection against HIV. Understanding such immune correlates is vital to designing a vaccine against HIV. Both magnitude and breadth of protective immune responses are considered important in producing an effective, globally relevant HIV vaccine.
In trying to identify these immune responses, scientific endeavour has focused on antibody dependent cellular cytotoxicity (ADCC) as a novel HIV vaccine modality, after vaccine strategies based on neutralizing antibodies and T-cell immunity failed to demonstrate efficacy.
We studied ADCC immune responses to envelope glycoprotein subtypes A, B, BC, C, D, E and F using our previously described ADCC ICS assay in 15 people who naturally control their HIV infection (controllers) and compared this with 15 HIV subjects with progressive HIV infection (progressors). Controllers were subjects with CD4 >400 cells/ul, 7 or more years after diagnosis and/or with persistently low (<3000 copies/ml) or fully suppressed plasma viral loads. The magnitude was measured in terms of NK cell expression of CD107a+IFNg+ (<2%=low; 2-8%=medium and >8%=strong responses).
ADCC responses in controllers were higher than in progressors (medium to strong responses in 100% vs 53%; p <0.01). ADCC Ab responses were broader in HIV controllers (93% had cross reactivity to at least one subtype) than in HIV progressors (53%; p<0.01)). We also observed that the ADCC responses were higher to HIV-1 gp120 than gp140. Furthermore, we demonstrated that glycosylated envelope proteins elicit potent ADCC response and that responses to gp120 are higher than gp140.
The potency and breadth of ADCC responses that we have detected to envelope proteins in people who naturally control HIV infection may provide important insights into both prophylactic and therapeutic rational HIV vaccine design. Strong responses to gp120 may indicate hidden epitopes, not exposed in trimeric gp140. Strong responses to glycosylated envelope proteins suggest that glycolsylation is not dampening these responses.
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.
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.
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.