Positive Life NSW

I was fortunate to be able to attend the XVIII International AIDS Conference in Vienna in July thanks to sponsorship from Napwa. The conference is staged by the International AIDS Society every two years. It’s huge, attracting over 18,000 participants and 1,300 media delegates from nearly 200 countries. There were nearly 250 separate sessions and over 6,000 abstracts of HIV-associated work across all the political, social and biomedical sciences. The range and amount of creative thinking addressing every issue around HIV was amazing and the good work of tens of thousands of people was humbling. There was so much and so the following comments reflect some of my own interests and what might be interesting for PWH (people with HIV) in NSW. The big news was the relative success of the vaginal microbicides to prevent HIV transmission. This has been fully reported on elsewhere so I won’t cover that exciting development here.

Conference Highlights

Living longer-term with HIV: HIV treatments have improved to such an extent that PWH in resource-rich countries, like Australia, can now have life expectancy which is almost that of the general community. This is a doubleedged sword: with increasing years on treatment many PWH can expect to face the challenges of diseases of ageing, not to mention long term side effects from HIV meds. With that in mind the Monday afternoon session The Double-Edged Sword: Long-Term Complications of ART and HIV (MOSY03) reviewed recent information on some of the complications associated with HIV disease.

Bone of contention: Paddy Mallon provided a summary of recent research on HIV and bone disease. This indicates that PWH on treatment have reduced bone mineral density and that they continue to experience bone loss with time. The associated risk of fractures is increased. He reviewed the effect of differing antiretroviral treatments which suggest that combinations containing protease inhibitors (PIs) and nucleoside reverse transcriptase inhibitors (NRTIs) result in the greatest bone loss in the first two years after starting treatment.

HAART to Heart: Georg Behrens provided a similar survey of recent research on HIV and cardiovascular disease. He observed that HIV contributes to an increased risk of heart disease in a number of ways: HIV is associated with increased thickening of arteries (its contribution to thickening of arteries is more than that caused by smoking). HIV increases the release of proteins which can lead to blood clots, and while HAART reduces the stiffening of arteries associated with HIV, it does not restore blood flow to normal levels. Staying with a compromised immune system (low CD4 cell counts) is a major risk for heart attacks (myocardial infarction) and damage to major blood vessels, like the carotid artery.

There is a growing body of evidence that HIV disease is associated with increased risks of other heart and blood vessel conditions, including raised blood pressure and strokes. Behrens reviewed the evidence suggesting an association between abacavir and cardiovascular disease and indicated that it was still uncertain, although the association between abacavir and very slight increase in risk of heart attack is strongest at the initiation of treatment and probably decreases with time.

His discussion of abacavir referred to his article published in February in the journal Current Opinion in Infectious Diseases in which he suggested, that for people at significant risk of heart disease (e.g. family history of heart attack, existing heart disease, diabetes), it was imperative to reduce modifiable risk factors (e.g. smoking, high blood pressure, raised LDL cholesterol and triglycerides, and problematic drug use). For these people, “replacement of abacavir or change of the antiretroviral regimen might be considered”.

Kidney conundrums: Mohamed Atta reviewed kidney disease in PWH and in particular reviewed four major research studies published in 2010. These demonstrate that PWH have an increase in the markers of decreased kidney function. Having kidneys which are not adequately functioning increases the risk of heart disease. He discussed one study in which PWH with proteinuria (excess protein in their urine, a marker of kidney dysfunction) had double the risk of significant heart events. The same study showed that having decreased filtration through the kidneys had a similar risk of heart events. He then discussed risks to the kidneys from HIV treatments these included the risk of developing diabetes, high blood pressure, development of kidney stones and crystals of HIV drugs within the kidneys, and the role of tenofovir and atazanavir in kidney disease. Atta presented data from two European studies published in 2010 which indicated that the risk of kidney disease, while very small, nevertheless increased the longer people were on antiretrovirals, particularly tenofovir and atazanavir. This was especially true for people over 45.

Atta and the authors of two other papers published in 2010 suggest that the small decline in kidney function continues over time and that PWH using tenofovir should be regularly monitored for kidney function. None of them suggest that tenofovir use should be restricted at this stage, but that longer-term studies need to be undertaken to measure the effects of long-term exposure to tenofovir and other ARVs.

Out of sight out of mind: Victor Valcour provided a review of brain impairment/dementia and HIV. He discussed the kinds of HIV-associated brain impairment which range from zero measurable impairment through mild loss of thinking and memory (called Mild Neurocognitive Disorder or MND) to HIV-associated dementia. He indicated, as several other studies at the Conference also suggested, that up to two out of five PWHmay have some impairment in thinking and memory. For most PWH this will be very slight and most people will be able to make changes in their lives to compensate (as we all do as we age). He suggested some possible causes for this which include: the persistence of HIV in tissues and cells (‘reservoirs’) out of the reach of current HIV drugs, drugs not fully controlling HIV in the central nervous system, and the effect of ageing. He discussed the connection between brain impairment and a range of other health issues, including: cardiovascular disease (included high blood pressure and thickening of the arteries), smoking, recreational drug use, coinfections (like hepatitis C), sleep apnoea and depression. He suggested that processes involved in Alzheimer’s disease were different to those seen in PWH but more research is needed.

Take home message

The PowerPoint presentations and excellent rapporteur summaries (well worth a read) are available at: http://www.aids2010.org

None of these issues were entirely unexpected: well managed HIV is still a major disease of inflammation which impact on many parts of the body. HIV treatment stops the destruction of the immune system but there are residual effects with which all PWH have to live. The take-home message for me was that PWH should keep control of HIV disease progression by sticking with their antiretroviral treatments. Ensure that all the necessary blood tests and monitoring of major organs is undertaken regularly by their HIV specialist and make the necessary lifestyle changes to stay healthy into the future.

This was only one session in a very busy week, there was much more, including encouraging news on the HIV drug front.

HIV drug developments: The new non-nucleoside reverse transcriptase inhibitor (nNRTI) rilpivirine, under new drug development, performed very well in trials. These compared it and efavirenz (both combined with two NRTIs, predominantly Truvada®) in treatment naïve patients. Participants in these studies were quite challenging with median viral loads of 100,000 copies/ ml before treatment commenced. Nearly 85% of participants had undetectable viral loads after 48 weeks of treatment with rilpivirine. Rilpivirine was better tolerated than efavirenz. Neurologic and psychiatric adverse events and rash were significantly less common with rilpivirine. Rilpivirine produced less increases in cholesterol and triglycerides than efavirenz. This is good news. A new drug application for rilpivirine was submitted to US authorities the week after IAS. It is expected that a similar application will soon be made to Australian authorities.

We learned a lot more about another promising new integrase inhibitor S/ GSK1349572 (572 for short). The data for phase II ‘SPRING’ trial in treatment naïve individuals were presented comparing 572 with efavirenz. Sixteen week data demonstrated very rapid suppression of HIV such that 80% of participants achieved undetectable viral load by week 8 and 90% were undetectable at week 16. The speed of suppression was significantly faster with 572 compared to efavirenz. 572 was very well tolerated and there were no serious adverse events related to 572 and very few discontinuation. The potential advantages of 572 in naïve patients over other integrase inhibitors include one pill, once daily dosing that does not require a boosting agent. If further trials produce good results and 572 is demonstrated to be safe and efficacious, it will probably be a few years before it becomes available in Australia.

Other good news was that the oncedaily dosing trial of nevirapine produced excellent results. Because both of the most commonly used NRTIs, abacavir and tenofovir, have side effects, there is an ongoing interest in testing combinations which do not use them (so-called NRTI-sparing regimes). Data from three small trials were presented: the PROGRESS study compared Kaletra + Truvada (a combination with 2 NRTIs) to Kaletra + raltegravir (NRTI-sparing) and showed similar efficacy. The SPARTAN study compared raltegravir to Truvada (both with atazanavir boosted with ritonavir). The raltegravir-based (NRTIsparing) combination performed well. The final NRTI-sparing combination on which data was presented was a small trial comparing maraviroc to Truvada (both with atazanavir boosted with ritonavir). Eighty percent of participants receiving maraviroc plus boosted atazanavir achieved an undetectable viral load by week 24. All these studies were small and of short duration. A large trial comparing raltegravir to Truvada (both with boosted darunavir) in PWH initiating their first treatment is about to start in Europe and it should provide some answers - though we will have to wait for some time to see these results.

Overall the Vienna conference provided lots of good news on the advances being made in HIV basic science, clinical care and treatments.

Neil McKellar Stewart is the HIV Health Maintenance Officer at ACON Northern Rivers in Lismore.