Australasian Society for HIV Medicine

CROI can sometimes feel like the Chicago Futures Exchange except the commodity is data: traders trying to corner the market, bullish statements when times are good, selling short when things don't look as rosy, insider trading and a bit of hedging along the way. As a consumer of data, it can be a challenge to sort out the wheat from the chaff. There are plenty of other sources of feedback and spin (http://www.clinicaloptions.com/ ; http://www.natap.org/ etc.) but here are some things that will change my practice.

People still die early with HIV/AIDS in high income countries. Why? Andrew Phillips (http://www.retroconference.org/2008/Abstracts/33423.htm abstract 8) examined data from a number of cohorts: An audit in the UK showed that 40% of deaths were attributed to a diagnosis too late for effective antiretroviral treatment (abstract 8). Older men, both MSM and heterosexual, are overrepresented in preventable mortality from late diagnosis, with the explanation that clinicians and patients may assume lower sexual risk behaviour or assign symptoms to ageing (http://www.retroconference.org/2008/Abstracts/33417.htm abstract 108).

AIDS deaths due to lymphomas and non-AIDS deaths associated with non-AIDS defining malignancies, cardiovascular disease, liver and renal disease also contribute to the increased mortality. As reported first at IAS by Sean Emery, these non-AIDS events are associated with lower CD4 cell counts. Further data at CROI (http://www.retroconference.org/2008/Abstracts/32757.htm abstract 139) gave some insights into possible mechanism: in the SMART study, those interrupting treatment experienced rises within one month in inflammatory markers such as Interleukin-6 (30%) and coagulation factors such as D-Dimer (16%). These rises were very strongly associated with mortality from all causes and more moderately associated with death from cardiovascular disease.

Concerns about the risk of cardiovascular disease in those on abacavir were headline news at CROI. By now, you would all have heard lots of spin from all sides about the interesting analysis of data from the DAD cohort showing a relative risk of MI of 1.08-1.21 per year of abacavir use (and 1.01-1.12 for DDI). Amongst all the talk of confounding and a lack of biological plausibility, I'll hedge and await more data from RCTs like Steal. Until there is a definitive answer, I will bet New York to George Bush's brain that in doctor/patient decision-making, it will sit with all the other blurry bits such as TDF/renal disease, efavirenz/lipoatrophy and nevirapine/efficacy.

On the subject of HIV testing, a US study on pre-test counselling for antenatal patients showed that women were equally satisfied with their decision to be tested for HIV after just being informed that they were being tested for HIV as well as other diseases, compared to the standard pre-test counselling (http://www.retroconference.org/2008/Abstracts/31203.htm abstract 535a, and poster in pdf). Earlier studies demonstrated a benefit of risk assessment and health education, particularly for those who test HIV positive. But is it time for Australian randomised controlled trials of different types of pre-test information provision, risk assessment and counselling?

Alarming data was presented on the continued high HIV incidence in the USA, (http://www.retroconference.org/2008/Abstracts/33434.htm abstract 53, and http://www.retroconference.org/2008/Abstracts/33402.htm abstract 54). Actual surveillance data supports models that suggest that the prevalence of HIV is up to 40% in 40 year old MSM. Other health problems in MSM such as mental health issues, discrimination, childhood sexual abuse and substance use (a syndemic) was blamed (abstract 53). The incidence in African American women is also very high, fuelled by a cycle of poverty, discrimination and incarceration which disturbs family formation and encourages concurrent sexual partnerships (abstract 54). Much hope was held for possible political change leading to broader Ottawa charter public health.

Many pundits picked over the bones of the recent adeno-virus prevention vaccine results. In the absence of a clear direction forward on vaccines and disappointing microbicide studies, prevention is a bear market. Desrosiers argued for a halt on human studies until non-human primate results are more consistent, although he happens to run a primate research centre (http://www.retroconference.org/2008/Abstracts/33477.htm abstract 91). Interesting data on high and sustained vaginal and cervical fluid levels of orally administered maraviroc suggested possible use in pre-exposure prophylaxis studies (http://www.retroconference.org/2008/Abstracts/33387.htm abstract 135LB). However, acyclovir 400mg bd continuously in HIV-negative HSV-2 + people (women in Africa and MSM in Peru/USA) did not appear to prevent HIV acquisition (http://www.retroconference.org/2008/Abstracts/31499.htm abstract 32). Circumcision of HIV-positive men in Rakai appeared to increase transmission in the first six months after the procedure, probably because men resumed sex before full healing and keratinisation of the penile head (http://www.retroconference.org/2008/Abstracts/33369.htm abstract 28LB). An injectable nanotechnology version of a NNRTI Etravirine, may provide adequate levels to allow monthly dosing, which may make it useful for treatment or pre-exposure prophylaxis (http://www.retroconference.org/2008/Abstracts/31749.htm abstract 134).

So how will I change my practice?

1. I will routinely offer HIV testing to all MSM who haven't been tested in the past year, especially the older ones-and other STI testing if I have time.
2. I will think cardiovascular disease and reducing risk factors as much as possible.
3. I will advise those patients who want to take a treatment interruption more strongly against the idea, particularly those with all the CVS risk factors, to try to stay on treatment.
4. I will try to identify HIV-negative syndemic patients although I have nothing new to offer them.
5. I will enrol patients onto the START study to help provide a true evidence based answer on early vs. late treatment commencement.
6. I will keep the abacavir information in the blurry data section of my brain and try to avoid the spin-cycle until more data emerges.

Relevant disclosure of support: Abbott funded my flight, rego and hotel. GSK took me to dinner at the conference. Gilead have paid me recently for my time providing advice on a website.