HIV-1 Reservoir in Gut-Associated Lymphoid Tissue (GALT) in Primary HIV Infection

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HIV is a chronic disease that can be well controlled with daily medications, known as antiretroviral therapy (ART). Usually ART is not started straight away, but only after immune cells (CD4 T-cells) have fallen below a set level. Although ART has dramatically improved survival for people living with HIV, it cannot cure HIV and so once started, treatment is life-long. This is because current ART cannot remove HIV from cells containing virus in a resting state - known as the HIV reservoir. For this reason virus levels return and people can become unwell if ART is stopped. Lifelong ART is challenging due to drug side effects, treatment fatigue, viral drug-resistance and expense. Whilst curing HIV infection is not possible with ART alone, a period of time off treatment without detectable virus in the blood - "remission" maybe feasible and is highly attractive.Recent studies have shown that if ART is started immediately after an individual becomes infected with HIV a lower level of viral reservoir can be achieved than for those starting treatment in later stage disease. Unexpectedly, amongst some rare individuals treated from early infection, virus did not return to high levels even after therapy is stopped; this is called post-treatment control (PTC).Using current laboratory tests to measure HIV reservoir in blood cannot accurately predict who might achieve PCT. One reason blood tests measuring viral reservoir may not accurately predict PTC may be that the rebounding virus is not coming from blood cells. There are different HIV reservoirs in the body from which the virus can return; the largest is the gut which can be five times larger than the reservoir in the blood. It is hypothesized that virus that returns after ART is stopped maybe coming from reservoirs within the Gut-associated lymphoid tissue (GALT). To address this question, my key aim is to characterise and compare measures of viral reservoir in gut samples with those from blood from people who have started on early ART. This will be a sub-study of an ongoing study of treated early infection called HEATHER which is evaluating blood biomarkers of viral reservoir. Participants enrolled into the HEATHER study will be invited to additionally agree to an endoscopy where small samples of gut will be taken for research evaluation of viral reservoirs. These biopsy tests are routine procedures and will be performed by a doctor who specialises in such procedures at St Mary's Hospital in London. We will analyse the blood and gut samples using specialised laboratory tests at the University of Oxford in order to assess the types of cells which make up the reservoir and the amount of HIV in the gut reservoir compared with blood. We then aim to investigate if gut reservoir measures can predict which patients might safely interrupt ART and achieve PTC. Ultimately this will be tested by giving the option of interrupting treatment (as part of a study) but only amongst a very small number of patients deemed most likely to achieve PTC based on our study results. The results of this work will inform other studies which test new treatments aimed at curing HIV by helping the investigators to decide who can stop treatment without the virus returning.