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  19th Conference on Retroviruses and
Opportunistic Infections
Seattle, WA March 5 - 8, 2012
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CROI 2012: "The Long & Winding Road of HIV Complications"
 
 
  http://app2.capitalreach.com/esp1204/servlet/tc?c=10164&cn=retro&s=20481&&dp=player.jsp&e=16653&mediaType=podiumVideo

In this final oral session on the last day at CROI there are 4 talks: Mike Yin gives a good talk on bone; Edwina Wright gives I think a great talk summarizing & reviewing cognitive, HIV dementia, the brain & HIV, where she says, reviews data from a meta-analysis where the CPE score (regimens with high CNS penetration) improve cognition, she says "current common practice is to use high CPE scoring regimens to treat patients with HAND, no evidence neuroHAART necessary if HAND is not present, we need a large randomised controlled study to answer this question"; keep in mind she is from Australia & this issue is controversial among neuro researchers here in the USA. She says about 30% of virologically suppressed HIV+ patients have HAND, she always mentions that a significant percent of patients in the USA have decteable HIV so dementia will occur and its treatable, so she encouraged our clinicians to look for it. She discusses there might be inflammation & activation going on in the brain despite virologic suppression in the plasma & even in the CNS. Jim Stein the cardiologist reasonably presents his cautionary thoughts on inflammation & CVD in HIV; Amy Justice gives I think a limited talk on comorbid conditions, aging & HIV.

Mike Yin does a nice job in reviewing bone & fracture risk in HIV+, where he presents data showing the higher prevalence of bone fracture in HIV+ vs HIV- in just about every age group starting at age 20 through 80 yrs old with a particular increase and separation in prevalence for HIV+ vs HIV- when patients when women reach 50 & men reach 40. He goes on to provide data from numerous studies showing higher incidence of fracture for HIV+ vs HIV- in WIHS (not significant but small numbers, in HOPS, in VACS (VA of note, significant but not a lot of difference between HIV+ vs HIV-, and in Danish cohort. Yin presents 4 additional studies reporting fractures rates in HIV+ at young ages where you can see studies reporting fracture incidence rates of 3-5/1000py in HIV+ patients 36-45 yrs old; and summarizes "rates of fragility and non-fragility fractures higher with HIV+". He discusses dexa bone screening recommendations where HIV+ indications are at 50 for men & women (CID 2010) and perhaps at 40 yrs old in Europe with high risks (see slide) due to HIV being considered now as a risk factor, but he went on to say these recommendations have not been studies and they contrast with recommendations in the general population for DXA at 65-70. Of note, in contrast by my view, Amy Justice (from the VA) gave a talk raising a cautionary note about aging & HIV and some of the fears regarding that. Her tone is one that makes some good points but also troubling to me: we should not fear-monger the potential risks that HIV may accelerate aging, premature onset of comorbid conditions: cancers, bone disease, renal, CVD, liver, brain/CNS; and apparently she said she heard clinicians at this CROI say "HIV+ individuals experience these conditions 20-30 yrs earlier than HIV-negs". While clearly such a general statement is not necessarily true, it appears some HIV+ patients are experiencing comorbid conditions at relatively younger ages, and in some cases much earlier. She appears to me to question quite strongly that HIV is accelerating this but I agree that we are not sure exactly how much HIV is causing this because ARTs & lifestyle history may play a role in HIV+ experiencing accelerated onset of these conditions. I would have preferred a more moderate tone in her overall talk because we don't want people to get overly scared but we do want screening when appropriate, as she expresses her concerns about over-screening & how it takes up too much clinician time so screening should be selective, and she also expresses concerns that polypharmacy has problems. I certainly agree we want judicious screening & pharmacy when it is important but I think the tone of this talk went too far & the more moderate position is I think better. The bone fracture data presented by Yin for some reason didn't have any presence in her talk where she focused more on cancers and how the cancer in HIV data appears to be skewed which it might be, each comorbid condition may be I think different.. A talk by Jim Stein, a cardiologist was I thought more judicious. While he cautioned that interpretation of biomarkers of inflammation & activation have limits the data does suggest HIV increases inflammation & activation. And as numerous studies show associations between HIV & these markers, we should wait for more data to show causation & outcomes, but of course in the area of CVD you need 10-20 years of followup for these types of studies and we don't have that yet. He says 'we don't really know that HIV increases risk for CVD', he emphasizes traditional risk factors quite a lot. The studies we have showing HIV increases CVD risk comes from studies with limited methodology including short followup, most of our patients are relatively young, and what are the confounding affects of ART, and the effects of lots of smoking among HIV+. In says "in 2012 there probably is an increased risk of heart attacks among HIV+ but its probably not as great as some of the people in this room say it is". He discusses that we have lots of data that inflammtion & activations markers are associated with conditions associated with increased risk for heart disease but mentions that the Grinspoon study discussed by David Wohl in his Complications CROI Report is the first study to show a "direct link" between vascular inflammation and HIV-infection and the inflammation in the HIV+ without known CVD was similar to HIV-negs with coronary disease. He says we need large, prospective studies to see if inflammation markers in fact predict CVD in HIV. Of course this will take many many years from now!!!! He concludes: HIV seropositivity probably is a marker of increased CVD risk, we don't know what the magnitude is of this increased risk and he said he thinks its on the small side, we need patients to get older to see what happens, in the meantime treat HIV & treat the risk factors.

So what do I think. There have been a ton of studies finding associations between inflammation & activation markers & comorbid conditions: bone, CNS, CVD. Do we need more & better studies to link these to bad outcomes & how much affect HIV-related inflammation & activation directly causes comorbid & accelerated onset of comorbid conditions, YES? We need to sort out the affects of ARTs, HIV & lifestyle factors. But where there is smoke there is fire. We have studies finding HIV & ARTs disrupt bone metabolism, we have studies finding CVD associated with senescence & inflammation, we have studies linking activation & mortality. Do I encourage more & better studies, yes. Can we wait 10 years as Stein suggests to conduct long-term followup? We should do these long term followup studies but we can't wait and not take some actions, we must proceed now based on the presumption that we are seeing at the very least what appears to be patients experiencing accelerated onset of comorbid conditions, not all patients but a significant number of them. The question is what should we do? Well, Justice's recommendation not to screen too much because clinicians have limited time & not to prescribe too much because polypharmacy has issues is questionable to me. As an individual patient I want to be properly screened for conditions and if appropriate I want to consider appropriate medications. Prevention i the best medicine: diet & exercise, but also screening. We need to research interventions to address inflammation & activation, while we conduct better & more research. Being cautious in interpreting biomarkers does not mean being too or overly cautious and ignoring them. !!! Jules Levin

In Stein's talk he refers to this study:

CROI: HIV Infection Is Associated with Greater Amounts of Non-Calcified Coronary Artery Plaque: the Multicenter AIDS Cohort Study (MACS) - (04/04/11)

In this study the investigators found the the prevalence of non-calcified plaque in HIV+ was 72% and in HIV- 62% with a p-value of 0.02, which is statistically significant but after adjusting for CVD risk factors the p-value is 0.087, not significant. Stein used this data to mention in his talk to make the point that traditional risk factors trumped HIV. However, the authors also reported another key data point that Stein did not mention. The adjusted p-value for the HIV-effect on EXTENT of NCP was 0.03 (Figure 3 and Table 2). Why? I don't know but I think its important to consider both points of data in considering the affect of HIV itself, outside of traditional risk factors.

"The Long & Winding Road of HIV Complications"

http://app2.capitalreach.com/esp1204/servlet/tc?c=10164&cn=retro&s=20481&&dp=player.jsp&e=16653&mediaType=podiumVideo