On Thursday afternoon, under Theme B: Antiretroviral Therapy, things moved up a gear, with back to back presentations touching almost every aspect of the ART and the long term complications. Dr David Nolan from Royal Perth Hospital gave a thoroughly captivating revision around HIV treatment. He gave a brief account of the pre, early and late HAART treatment options, how things have evolved in terms of the choices, co morbidities, tolerability and toxicity.

He reflected on the contemporary challenges around decision making in clinical practice, how we can factor in the newer therapies and novel diagnostic approaches in our existing treatment and screening paradigms.

What do we know that we do not know?

David argued that despite of having potent ARTs with superior virological efficacy, we don’t have enough evidence to guide us on how to screen, monitor, and subsequently manage the emerging associated co morbidities including HIV neurocognitive impairment, chronic immune activation, and increased risk of malignancies.

What don’t we know that we do not know?

David threw up some very topical questions with both ethical and public health implications. Does it matter that there are things we don’t know? Should we change ART regimen just because we have newer drugs? What if HIV patients with sustained viral suppression do not want to change their old medications?

These are very complicated and yet practical questions, and we still do not  seem to have a simple answer. With discovery of newer, safer and simpler ART regimen, we are likely to find ourselves in a situation where we might simply not have enough evidence to guide clinical choices when it comes to changing or switching regimen. In that case he concluded that we might simply accept the fact that there will always be unknown unknowns.

He also discussed the rationale of ART treatment intensification (using Maraviroc for example) and what should be realistically expected. He pointed out that current evidence indicate that treatment intensification makes little difference in some of the important prognostic clinical parameters like viral load and immune activation markers. It does not appear to impact on viral reservoirs and residual viremia which tend to be established early following primary HIV infection. He posited that, in absence of robust evidence for treatment intensification, the seemingly logical approach will be to start treatment early following seroconversion.

This was arguably one the most thought provoking presentation I have attended in this conference. It raises some of the difficult issues clouding the field of HIV and ART treatment and long term treatment outcome. Obviously, there are things that we do know, and things we have been doing well in improving our knowledge and understanding of how ART works.

Perhaps, It is time to start thinking about how do we integrate the use of monocyte activations markers like sCD14, in the standard of care for our patients.  For the next few years it will be pretty much about the known unknowns and the unknown unknowns that will really determine if we are going to win another important dimension of this epidemic when every HIV patient has undetectable viral load.

Hi everyone,

Another interesting and interactive panel discussion featuring Professor Jennifer Hoy, Dr Julian Elliot, Dr Mark Boyd, Dr James McMahon, and Dr Mark Bloch. This discussion built on earlier plenary session presentations on Theme B: ARV Guidelines - When and What to Start.

Three interactive clinical scenario on starting ART were presented to the audience and the panellists. These cases reflected the daily practical challenges facing clinicians and patients in deciding the best regimen to start that will optimize treatment outcomes with minimal side effects. Dr Mark Bloch pointed out that  the decision on what to start should be tailored to the patient, taking into consideration their presenting general health, medical history, concurrent medical conditions, life style, emotional and psychological wellbeing and  socioeconomic status.

It was interesting to note from the panellists that while for patient simplicity of the treatment regimen and toxicity are most important issues to consider in starting and continuing with medications, for clinicians the decisions on what to start can be very challenging. Clinicians always find themselves in situations where the existing guidelines do not provide them evidence based recommendations on what to start or when and how to switch from one regimen to another, or from one drug to another.

The question of Abacavir and the risk of AMI for patients with or without background risk of cardiovascular disease was highlighted as the perfect example where the current evidence is still contentious. Mark Boyd also highlighted another challenge facing clinicians when they have to manage patients who are generally not represented in clinical trials. He gave example of patients with reduced kidney functions (measured by eGFR) and the lack of evidence from randomized trials for the use of petentially nephrotoxic drugs like Tenofovir (TDF) or drugs which have been shown to impact creatinine clearance(Dolutegravir and Cobicistat).

The take home message from this session is that clinicians need to carefully engage and comprehensively review their patients before starting or switching ART. They need to make sure that their patients understand existing guideline recommendations and options available, the potential adverse events and toxicity for each drug(s) they are going to take. It is also important for HIV clinicians to work collaboratively with  non HIV clinicians, and allied health professionals in managing non-AIDS conditions. This will eventually optimize treatment outcome and minimize any drug–drug interactions and risk of non AIDS events.

Hi everyone,

Another excellent plenary session presentation with some clinically relevant findings for primary care physicians and health promotion teams.

 

Associate professor Jo-Ann Passmore, from the University of Cape Town where she also heads the Genital mucosal and STI laboratory gave an insightful presentation on the association between genital tract immunity and susceptibility to HIV and STIs. Her group investigated the markers of inflammation on the vaginal mucosal in South African women prior to acquisition of HIV infection. They measured series of inflammatory cytokines and did screening for the STIs.

Interestingly, they found increased levels of pro inflammatory cytokines MIP-1β, MIP-1α which bind to the HIV CCR5 and facilitate entry of the HIV into the target cells. They also reported increased levels IP-10, and IL-8. The risk of HIV acquisition was significantly higher in women with evidence of genital inflammation, defined by at least 5 of the 9 inflammatory cytokines being raised [OR 3.2; 95% CI 1.3-7.9].

Amongst the STIs, Chlamydia was found to be the most inflammatory STI, while Bacterial Vaginosis was also associated with upregulation of the pro inflammatory cytokines.

Another interesting finding from this study was that there was no correlation between increased genital inflammatory cytokines and the plasma inflammatory cytokines. The clinical and immunological relevance of this finding in the context of long term immune activation for those who eventually got infected and the utility of genital inflammatory markers in clinical practice remains to be seen.

 

Although this study was done in South Africa, The findings further highlight the importance of screening for STIs particularly for all sexually active adolescents and women even in Australian setting. Also for health care providers and health promotion teams working with CALD communities  and Sex workers, this is work provide another compelling evidence for ramping up STI testing campaigns in order to reduce the new transmission of HIV  and other STIs.