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  Conference on Retroviruses
and Opportunistic Infections (CROI)
February 22-25, 2016, Boston MA
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Low ART Adherence Is Associated With Higher Inflammation Despite HIV
Suppression.......Wobbly ART Adherence Could Fuel Ongoing Inflammation
  Conference on Retroviruses and Opportunistic Infections (CROI), February 22-25, 2016, Boston
Mark Mascolini
Less than 100% adherence to antiretroviral therapy (ART) may not promote viral rebound but could stoke ongoing inflammation in people with HIV, according to a 924-man analysis of the Multicenter AIDS Cohort Study (MACS) [1].
Ongoing inflammation in people with an undetectable viral load can lead to cardiovascular disease, cognitive decline, and cancer, observed the MACS investigators who conducted this study. The potential role of poor ART adherence in this simmering inflammation remained largely unexplored until this study.
The MACS is an ongoing observational study of HIV-positive and at-risk men who have sex with men in five US cities; men make study visits every 6 months. This analysis focused on men who had inflammatory biomarkers measured, who took ART, and who had a viral load below 50 copies sometime during the 1998-2009 study period. Researchers assessed concentrations of two dozen biomarkers and modeled the data in relation to adherence with adjustment for variables that affect both adherence and biomarker concentrations (age, race, HCV infection, hypertension, and smoking). Men self-reported adherence as 6-month adherence (100% versus less) and 4-day adherence (100%, 85% to 99%, or less than 85%).
The 924 men studied had a median age of 48.4 at their MACS visit and had taken ART for a median of 5.4 years. About half took a protease inhibitor regimen, while 47% took a nonnucleoside. Most men (73%) were white, 28% smoked, 8% had HCV infection, 22% had hypertension, and 29% took statins. While 87% of men reported 100% 6-month adherence, 88% reported 100% 4-day adherence, 4% reported 85% to 99% 4-day adherence, and 8% reported less than 85% 4-day adherence.
In the analysis adjusted for adherence and biomarker variables, levels of six biomarkers were significantly higher in men reporting less than 100% 6-month adherence versus 100% adherence: TNF-alpha (estimate 10.9%, P < 0.001), IFN-gamma (15.2%, P = 0.005), C-reactive protein (20.1%, P = 0.009), IL-2 (14.2%, P = 0.024), IL-6 (10.9%, P = 0.019), and IL-10 (11.6%, P = 0.019). Levels of the same six markers were significantly higher in men who reported less than 85% versus 100% 4-day adherence. And levels of TNF-alpha were significantly higher in men who reported 85% to 99% 4-day adherence versus 100% 4-day adherence (estimate 9.8%, P = 0.016).
The MACS investigators concluded that suboptimal self-reported adherence can be linked to higher levels of inflammatory markers in men with an undetectable viral load, a finding "suggesting that ART adherence could have significant biological consequences that are independent of virologic suppression." They proposed that shaky adherence could allow "subclinical episodes of viral replication" [2] that promote inflammation and immune activation, even though they do not lead to viral rebounds.
1. Castillo-Mancilla JR, Brown TT, Erlandson KM, et al. Low ART Adherence is associated with higher inflammation despite HIV suppression. Conference on Retroviruses and Opportunistic Infections (CROI), February 22-25, 2016, Boston. Abstract 283.
2. Li JZ, Gallien S, Ribaudo H, et al. Incomplete adherence to antiretroviral therapy is associated with higher levels of residual HIV-1 viremia. AIDS. 2014;28:181-186. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4193963/
Reported by Jules Levin


Low ART Adherence Is Associated With Higher Inflammation Despite HIV Suppression
  Jose Castillo-Mancilla1, Todd Brown2, Kristine Erlandson1, Frank J. Palella Jr.3, Edward M. Gardner4, Bernard Macatangay5, Elizabeth C. Breen6, Lisa P. Jacobson2, Peter L. Anderson1, Nikolas Wada2
1Univ of Colorado, Denver, CO; 2Johns Hopkins Univ, Baltimore, MD; 3Northwestern Univ, Chicago, IL; 4Denver HlthMed Cntr, Denver, CO; 5Univ of Pittsburgh Schof Med, Pittsburgh, PA; 6Univ of California Los Angeles, Los Angeles, CA