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CROI 2015: Cardiovascular Risk Factors for HIV-Positive People

Consistent with past research, an analysis from New York City has shown that people with HIV are at higher risk for death due to cardiovascular disease, although this risk is declining, according to a report at the recent 2015 Conference on Retroviruses and Opportunistic Infections (CROI). Several other studies looked at cardiovascular risk factors in this population, including inflammatory biomarkers, chronic kidney disease, gut bacteria, and use of abacavir.

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CROI 2015: FRAX Fracture Prediction Tool Underestimates Fracture Risk in Men with HIV

The Fracture Risk Assessment Tool (FRAX), an online tool developed by the World Health Organization and used to help guide decisions about who to screen or treat in order to prevent bone fractures, underestimates overall risk of fracture in people living with HIV -- even with an adjustment experts have recommended to improve its accuracy for people with HIV -- according to an analysis of the Veterans Aging Cohort Study Virtual Cohort (VACS-VC) reported at the recent 2015 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle.

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CROI 2015: Cardiovascular Disease Among People with HIV

People living with HIV are at greater risk for cardiovascular disease (CVD) and events such as heart attacks. Several presentations at the recent 2015 Conference on Retroviruses and Opportunistic Infections (CROI) looked at CVD risk factors, how to better predict it, and approaches to risk reduction.

Predicting Cardiovascular Disease in People with HIV -- Can We Do Better?

Cardiovascular Risk Factors for HIV-Positive People

Statins May Reduce Risk of Heart Disease in People with HIV

4/10/15

CROI 2015: Does HIV Make You Fat? Study Connects Viral Load with Fat Gains

HIV infection or inflammatory changes associated with it may be responsible for fat accumulation and body fat redistribution, rather than antiretroviral drugs, according to a study presented at the recent 2015 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle.

[Produced in collaboration with Aidsmap]

Grace McComsey of Case Western University in Cleveland said that although the association of subcutaneous fat loss (lipoatrophy) with mitochondrial damage caused by certain HIV drugs is well-established -- and most of the world no longer uses the drugs like stavudine (d4T) that are most strongly associated with it -- 2 decades of research had failed to establish a cause for the distinctive fat gain(lipohypertrophy), especially in the trunk and within the abdomen, seen in some people with HIV on antiretroviral therapy (ART).

Initially these fat gains were associated with protease inhibitors (PIs) but switching from PIs to non-nucleoside reverse transcriptase inhibitors (NNRTIs) or to integrase inhibitors did not reverse fat gains. One study found greater fat gain in people taking boosted atazanavir (Reyataz) rather than efavirenz (Sustiva), but a general association with any drug or class of drugs had not been demonstrated. Given that untreated HIV infection usually results in weight loss, fat gains when people started ART, once it became available, may have understandably been associated with treatment rather than HIV.

The study McComsey presented, ACTG A5260s, compared changes in limb fat, trunk fat, visceral adipose tissue (central abdominal fat), and lean muscle mass in 1809 ART-naive patients starting either of the 2 boosted PIs atazanavir or darunavir (Prezista), or the integrase inhibitor raltegravir (Isentress), all combined with tenofovir/emtricitabine (Truvada).

DEXA and CAT scans measured fat and muscle distribution at baseline and nearly 2 years (96 weeks) later. They were then assessed for associations with drug regimen, baseline HIV viral load, Framingham risk score (a measure of the likelihood of cardiovascular disease), and a number of hormones, cytokines (cell messenger chemicals), and markers of inflammation: leptin (higher in obese people), adiponectin (lower in obese people), D-dimer (a coagulation marker), C-reactive protein (an inflammation indicator), and the cytokines or cytokine receptors interleukin 6 (IL-6), CD14, and CD163.

In terms of demographics, the study participants' average age was 36, 90% were men, and 44% were white (slightly more taking atazanavir). Their average pre-ART viral load was 34,150 copies/mL and their average CD4 count was 351 cells/mm³.  Those taking atazanavir had slightly, but not significantly, more limb and trunk fat, but not more visceral fat or muscle.

Limb, trunk, and visceral fat all increased during the 96 weeks on ART. Limb fat increased by 15% (20% on raltegravir), trunk fat by 22% (16% on atazanavir and 29% on raltegravir), and visceral fat by 31%; the differences between drugs were not statistically significant. Lean muscle mass increased slightly, by 2%, in people on atazanavir or raltegravir, and by 1.2% in patients taking darunavir; this was a significant difference but probably does not reflect any real difference between the drugs.

Increases in visceral fat were associated with lower leptin and higher adiponectin levels, but this probably is effect rather than cause, as adiponectin is secreted by fatty tissue. Subcutaneous limb fat gain was also associated with higher IL-6 and lean body mass gain with higher D-dimer and lower baseline CD4 -- the latter not unexpected, as lean body mass falls with AIDS.

However by far the strongest association with fat gain was with high viral load. There were mean increases of at least 25% and up to 35% in both subcutaneous and visceral fat in people who had a baseline viral load over 100,000 copies/mL, whichever drug they were taking. In patients with a baseline viral load below 100,000 copies/mL, the fat gains were below 10%, apart from a gain in visceral fat of about 14% in people taking raltegravir. She noted that even when adjusted for inflammatory markers, HIV viral load was still significantly associated with fat gain.

McComsey said that the fat gains observed were not necessarily those associated with health improvement due to control of HIV. "A 30% gain in visceral adipose tissue in just 2 years is pretty bad," she said. "Even limb fat increased by 1.5 kilos from a baseline of 7 kilos (21%). There was an average increase in 3.0 to 3.5 in people’s BMI [body mass index] score." Although people in general may be getting fatter, it does not happen as fast as this, she added.

3/17/15

Reference

GA McComsey, C Moser, JS Currier, et al. Body Composition Changes After Initiation of Raltegravir or Protease Inhibitors. 2015 Conference on Retroviruses and Opportunistic Infections. Seattle, February 23-24, 2015. Abstract 140.

CROI 2015: Predicting Cardiovascular Disease in People with HIV -- Can We Do Better?

Four existing models used to predict risk of cardiovascular disease (CVD) underestimated that risk in large cohorts of people living with HIV, according to research presented at the recent 2015 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle. Other studies suggested that even without that underestimation being taken into account, many HIV-positive people are currently undertreated with statins, which could protect them from cardiovascular events like myocardial infarction.

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CROI 2015: Tenofovir, Atazanavir & Lopinavir Associated with Raised Risk of Chronic Kidney Disease

Three antiretroviral drugs are associated with a slowly increasing rate of chronic kidney disease over time, researchers reported at the recent 2015 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle. Although the risk of developing chronic kidney disease was low for people with normal kidney function -- with fewer than 1% of patients in the large D:A:D cohort developing it -- the use of any of these drugs was associated with 2 to 3 times higher risk of kidney disease developing over the course of 5 years on the drug.

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CROI 2015: Stopping Co-trimoxazole During ART Raises Risk of Bacterial Illness and Malaria

Stopping trimethoprim/sulfamethoxazole (Co-trimoxazole) prophylaxis increases the risk of serious bacterial infections and malaria, even at high CD4 cell counts, among people with HIV taking antiretroviral therapy (ART) in Uganda, according to results of a randomized trial presented by Jonathan Levin of the UK Medical Research Council at the recent 2015 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle.

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CROI 2015: Statins May Reduce Risk of Heart Disease in People with HIV

Evidence is mounting that statin therapy can prevent the progression of coronary atherosclerosis (hardening and narrowing of the arteries supplying the heart) in people living with HIV, according to the results of 2 randomized clinical trials reported last week at the 2015 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle.

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