Meeting report: 16th European AIDS Conference, 25-27 October 2017
Held every two years, the European AIDS Conference (EACS) brings together scientists from Europe to discuss and present the latest clinical research on HIV/AIDS. The 16th EACS took place from 25 to 27 October in Milan, Italy, and was attended by over 3,000 people. Data from SHM’s ATHENA cohort contributed to a number of oral and poster presentations at the conference. These presentations focused primarily on two topics, comorbidity in people living with HIV and the use of integrase inhibitors, and are described below.
Comorbidity and ageing
In a poster, Davide DeFrancesco from University College London presented longitudinal data on cognitive dysfunction in the COBRA project. COBRA stands for comorbidity in relation to age and is an EU-sponsored research collaboration in which the AMC and SHM participate. Cognitive function was assessed at study inclusion and after two years using a standardised battery covering six domains. The results showed that although people living with HIV on long-term successful combination antiretroviral therapy (cART) (n=134) had poorer cognitive performance at study inclusion, they underwent similar longitudinal changes over two years compared to appropriately chosen controls (n=79). The study also investigated associations between cognitive function at baseline and monocyte subsets and markers of neuronal damage and inflammation (NFL, Aβ1-42, Tau, p-Tau, neopterin, tryptophan, kynurenine). Baseline cognitive function (i.e., global T-score, processing speed and executive function) was found to be associated with higher concentrations of classical monocytes (p<0.01) and lower levels of non-classical/intermediate monocytes (p<0.01 for processing speed and executive function, p=0.06 for global T-score). Moreover, a weak positive association was found between global T-score and Tau concentration (rho=0.14, p=0.04), but not with other markers of neuronal damage in the cerebrospinal fluid, which may provide further insight into the pathogenesis of HIV-associated cognitive disorders.
The subject of comorbidities was also covered by Rosan van Zoest from the Amsterdam Institute of Global Health and Development (AIGHD) in a mini-lecture on the use of cohort data to study ageing-associated illnesses in people living with HIV. In particular, the talk focused on the use of such data to investigate both the role of possible premature or accelerated ageing in the high incidence of ageing-associated comorbidities in people living with HIV, as well as the contributing role of chronic systemic inflammation and antiretroviral therapy-related toxicities. In her lecture, Rosan stressed the importance of appropriately-selected control groups with similar demographic and lifestyle characteristics to help properly attribute the risk of comorbidity to either HIV and ART-associated factors or traditional risk factors. In addition, Rosan highlighted the multifactorial aspect of many ageing-associated comorbidities, providing several examples where, after adjustment for traditional risk factors, the apparent HIV effect was significantly attenuated or even lost significance.
The clinical worsening of an existing opportunistic infection or development a new infection soon after starting cART is known as immune reconstitution inflammatory syndrome (IRIS). At EACS, Ingeborg Wijting from Erasmus Medical Center, Rotterdam, gave an oral presentation on the risk of IRIS following the initiation of cART, with special attention to the class of integrase inhibitors. Integrase inhibitor-containing cART is associated with more rapid suppression of HIV replication and subsequent increases in CD4 counts, possibly putting people with advanced HIV infection (i.e., CD4 counts below 200 cells/mm3) and/or an active (or very recently treated) AIDS-defining opportunist infection at increased risk of IRIS. The study found that the use of integrase inhibitors was indeed associated with an increased risk of IRIS compared to other cART regimens. However, this increased risk was only demonstrated for raltegravir, and not for dolutegravir and elvitegravir. These differences could not be explained by the use of corticosteroid prophylaxis, timing of cART or of opportunistic infection treatment, type of opportunistic infections, or pre-cART CD4 count and HIV-1 viral load.
The second presentation on integrase inhibitors was given by Pauline Bollen from Radboud University Medical Center (Radboudumc) in Nijmegen. Pauline presented a poster on the rates of discontinuation of integrase inhibitor-containing cART in the Netherlands, as well as the associated reasons and risk factors for discontinuing. The study was initiated following a publication reporting unexpectedly high discontinuation rates of dolutegravir (DTG) because of neuropsychiatric adverse events (NPAE) in the OLVG hospital in Amsterdam. The results from Radboudumc showed that discontinuation of DTG-containing and elvitegravir/cobicistat-containing cART for either any reason or due to toxicity is infrequent, but that highly cART-experienced subjects starting either DTG or EVG/c had a higher risk of discontinuation both for any reason and for toxicity-related reasons than cART-naive subjects. Overall, 2.6% and 2.3% of cART-experienced individuals discontinued DTG-based or EVG/c-based cART due to toxicity and reported NPAEs, respectively. In conclusion, people living with HIV who had a higher number of previous discontinuations of cART due to toxicity, as well as those with prior and current use of psychoactive comedication, were at increased risk of discontinuation of both integrase inhibitors.