In March this year, in Atlanta, the Conference for Retroviruses and Opportunistic Infections (CROI) celebrated its 20th annual event http://retroconference.org/. The history of the American-led CROI is an eventful one. In 1991, after an uproar in congress about the wasteful use of resources, government officials from the USA were prohibited from attending the International AIDS Society (IAS) conference in Italy, and even sent back home upon arrival. Just a year later, the IAS conference was relocated from the USA to Netherlands, due to the barring of HIV-positive individuals from entering the USA. This led the USA to recognise the need for its own national forum, and so in 1993, the first holding of CROI took place in Boston. In 2009, President Barack Obama lifted the 22-year ban on the entry of HIV-positive individuals, repositioning CROI on the world stage. Over the years, CROI has continued to distance itself from political and commercial interests, with delegates restricted to researchers and scientists, with no industry and only limited media admitted.
Eliminating latent reservoirs through treatment
The headline-grabber at this year’s CROI was the ‘functional cure’ of an HIV-infected child, also known as the ‘Mississippi miracle’. The infant was aggressively treated from 31 hours post-partum until 18 months, after which treatment was interrupted when the child was lost to follow-up. Subsequent testing at 2 years found that the infant was HIV-negative on conventional HIV diagnostic tests, with the presence of only seemingly non-replicative virus pieces. This result has caused much excitement amongst scientists, and has led to the planning of randomised control trials and other studies to further understand this result.
A key success of the ‘Mississippi miracle’ is that no latent reservoir of replication-competent HIV developed in the infant. The study of latent reservoirs, and prospects for eliminating these through treatment, in adults and infants, was the topic of many CROI sessions.
Results from studies and modelling exercises
Apart from the laboratory science, a number of results from clinical trials and modelling exercises were presented, assessing a number of risk factors and interventions for various conditions. In the context of HIV, with Sub-Saharan Africa carrying the highest burden of the virus, many of the studies and lessons learned came from the African context. HIV interventions included condom usage, male circumcision, treatment as prevention (TasP), increased linkage to care, improved adherence and retention, pre-exposure prophylaxis (PreP) and microbicides, and prevention of mother to child transmission (PMTCT). Results from a number of prominent randomised control trials (such as VOICE, ARROW and HPTN046) were also presented and guidelines and standards for testing and treating patients were also discussed. Developments in the study of co-infections (such as tuberculosis) and non-AIDS complications (for example, malignancies and neurocognitive disorders) in HIV-positive patients were also presented, as well as scientific advances about conditions such as other sexually transmitted illnesses, diabetes, cardiovascular disease and hepatitis.
Evaluation of incidence assays
Of particular relevance to the work of SACEMA is the topic of HIV incidence estimation. Traditionally, HIV incidence is measured by counting the number of new infections observed while following HIV-negative subjects over time. However, such longitudinal studies present a number of short-comings, and therefore the notion of estimating incidence in cross-sectional surveys has attracted much interest, as highlighted in previous SACEMA quarterly articles (1,2,3). In a survey, an incidence assay is used to distinguish ‘recent’ from ‘non-recent’ HIV infection, and the prevalence of ‘recent’ infection is then used to estimate incidence (4,5,6). However, the widespread use of this approach has been hindered by the lack of both high-performance incidence assays and the rigorous evaluation of proposed incidence assays. Therefore, in 2010, the Bill and Melinda Gates Foundation awarded a grant to CEPHIA (the Consortium for the Performance and Evaluation of Incidence Assays) (7), whose goals are to overcome these obstacles, by developing a specimen repository and independently evaluating incidence assays, and therefore also provide the public with much needed guidance. CEPHIA is a collaboration between SACEMA; Public Health England (formerly called Health Protection Agency); University of California, San Francisco; and Blood Systems Research Institute.
At CROI, CEPHIA hosted a satellite session, where the much anticipated first independent assessments of incidence assays were presented. Various stakeholders attended the series of presentations, ranging from funders to test developers to those out in the field implementing cross-sectional incidence surveillance. Tests for recent infection are typically assessed against a ‘target product profile’, which has been developed and circulated within the scientific community (8,9). In particular, for precise incidence estimation, an incidence assay should produce a sufficiently enduring state of ‘recent’ infection (in the order of a year), while maintaining a low level of ‘false-recent’ results in long-infected subjects (typically less than 2%). An incidence assay should also exhibit properties such as good reproducibility, and feasible sample type, equipment and training requirements. It has been found that these criteria are difficult to meet collectively. With analysis and testing still on-going, preliminary assessments for four prominent incidence assays were presented. Results thus far suggest that currently available incidence assays continue to struggle to meet the target product profile, without further optimisation. The work of CEPHIA, as previewed at CROI and on-going, aims to greatly advance the area of cross-sectional incidence estimation by providing independent assessments and guidance, and fostering consensus in the scientific community.
CROI continues to push scientific frontiers, and it is with great interest that we wait to see what the 21st conference will offer; undoubtedly the most interesting and relevant research, study and modelling outcomes of the preceding year will be presented.