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CROI 2015: Does Emtricitabine Work Better than Lamivudine in Combination ART?

People with HIV who started an antiretroviral regimen containing emtricitabine (FTC; Emtriva) and NNRTIs were about half as likely to experience virological treatment failure as those who used the similar drug lamivudine (3TC; Epivir), according to an analysis of more than 6000 participants in the Dutch ATHENA cohort presented at the recent 2015 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle. No significant differences between emtricitabine and lamivudine were seen with boosted protease inhibitor regimens.

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CROI 2015: Researchers Discuss HIV Cure Strategies

Researchers at the recent 2015 Conference on Retroviruses and Opportunistic Infections in Seattle discussed a variety of approaches to achieve a functional cure, or prolonged remission of HIV. Most experts expect that a combination of multiple approaches will be needed.

Early Antiretroviral Treatment Reduces, but Does Not Eliminate HIV Reservoir

Experimental Agents Reverse HIV Latency, Help Immune System Fight Infected Cells

We May Need to Combine Many Approaches to Achieve a Cure for HIV

3/20/15

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CROI 2015: Cabotegravir and Rilpivirine Effective for HIV Maintenance Therapy at 96 Weeks

A combination of 2 once-daily oral antiretrovirals -- the next-generation integrase inhibitor cabotegravir (GSK1265744) and the approved NNRTI rilpivirine -- was as effective as an efavirenz-based regimen when used as maintenance therapy to keep viral load suppressed, according to a poster presented at the recent 2015 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle.

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CROI 2015: Early Antiretroviral Treatment Reduces, but Does Not Eliminate HIV Reservoir

Starting antiretroviral therapy (ART) very soon after infection may limit the size of the HIV reservoir and delay viral rebound after treatment interruption, according to several presentations at the recent 2015 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle. Other research showed that various biomarkers may predict who will experience HIV rebound after stopping ART.

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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.

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[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: 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: Circumcision is Reducing HIV Incidence in Uganda, Rakai Community Study Shows

The growing uptake of medical male circumcision by men in the Rakai district of Uganda is leading to a substantial reduction in HIV incidence among men in one of the districts worst affected by HIV, Xiangrong Kong of Johns Hopkins Bloomberg School of Public Health reported at the recent 2015 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle.

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