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Persistent Low Viremia Not Tied to Heart Disease,
AIDS, or Death in Large Cohort
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15th European AIDS Conference, October 21-24, 2015, Barcelona
Mark Mascolini
A viral load persistently between 50 and 400 copies did not raise the risk of cardiovascular disease (CVD), AIDS, or death in a 4400-person cohort in Italy [1]. In contrast, rebounding from a load below 50 copies to above 400 copies doubled the risk heart disease, AIDS, or death.
Over the past decade, research on the clinical impact of steady low-level viremia has yielded inconsistent results. A 7277-person Italian Icona Foundation Cohort study presented at this meeting found that a viral load between 51 and 500 copies boosted the risk of a new AIDS diagnosis but not of serious non-AIDS illness [2]. Analysis of 6440 people in the Dutch ATHENA cohort determined that a detectable load below 400 copies did not predict non-AIDS illness [3]. And a 17,902-person Antiretroviral Therapy Cohort Collaboration study saw no link between viremia between 51 to 499 copies and the risk of AIDS or death [4].
The Italian study focusing on CVD, AIDS, or death involved the Italian MASTER cohort [1], which includes about 24,500 HIV-positive adults in care at 8 centers in central Italy. Cohort members make study visits every 3 months. This analysis considered people who maintained a viral load below 50 copies for at least 24 weeks after starting antiretroviral therapy. The MASTER team evaluated two endpoints--(1) time to first cardiovascular event, AIDS, or death, and (2) time to first cardiovascular event or death--in three groups: people who kept their viral load under 50 copies, people with persistent low-level viremia (pLLV) between 50 and 400 copies on at least 2 consecutive measures, and people with virologic failure denoted by a viral load above 400 copies on 2 consecutive measures.
Of the 4393 people studied, 3576 (81%) maintained an undetectable viral load, 243 (6%) had pLLV, and 574 (13%) had virologic failure. When antiretroviral therapy began, age averaged 40.3 in the undetectable group, 41.1 in the pLLV group, and 37.1 in the failure group. Respective proportions of men were 74%, 72%, and 63%. Respective median pretreatment CD4 counts were 269, 215, and 265, and respective pretreatment viral loads 44,770, 75,000 and 48,180 copies.
For endpoint 1 (CVD, AIDS, or death) incidence per 1000 person-years measured 11.7 for the undetectable group, 9.3 for the pLLV group, and 21.6 for the failure group. For endpoint 2 (CVD or death), incidence per 1000 person-years was 8.6 in the undetectable group, 9.0 in the pLLV group, and 11.6 in the failure group.
Multivariate Cox regression analysis determined that people with virologic failure had a doubled risk of endpoint 1 compared with the undetectable group (hazard ratio [HR] estimate 2.155, 95% confidence interval [CI] 1.628 to 2.853). But the pLLV group did not have a higher risk of reaching endpoint 1 (HR estimate 0.704, 95% CI 0.391 to 1.270). For endpoint 2, regression analysis figured that virologic failure raised the risk about 50% compared with the undetectable group (HR estimate 1.498, 95% CI 1.040 to 2.157), whereas pLLV did not significantly affect risk (HR estimate 0.547, 95% CI 0.254 to 1.178).
Among other variables assessed, only older age when treatment began and pretreatment CD4 count affected the risk of reaching endpoint 1. Gender, Italian nationality, HIV transmission route, HBV or HCV coinfection, pretreatment viral load, and other variables did not. Besides older age, 2 other factors upped chances of reaching endpoint 2: HCV coinfection (HR estimate 1.723, 95% CI 1.116 to 2.660) and a cardiovascular event before antiretroviral therapy (HR estimate 2.597, 95% CI 1.248 to 5.404).
The MASTER team concluded that persistent low-level viremia does not affect risk of cardiovascular disease, AIDS, or death in their cohort.
References
1. Costarelli S, Bernasconi D, Lapadula G, et al. Persistent HIV low-level viremia and cardiovascular risk. 15th European AIDS Conference, October 21-24, 2015, Barcelona. Abstract PE13/41.
2. Antinori A, Cozzi Lepri A, Ammassari A, et al. Low-level viremia ranging from 50 to 500 copies/mL is associated to an increased risk of AIDS events in the Icona Foundation Cohort. 15th European AIDS Conference, October 21-24, 2015, Barcelona. Abstract PS4/2.
3. Zhang S, van Sighem A, Kesselring A, et al. Episodes of HIV viremia and the risk of non-AIDS diseases in patients on suppressive antiretroviral therapy. J Acquir Immune Defic Syndr. 2012;60:265-272. http://www.natap.org/2010/CROI/croi_128.htm
4. Antiretroviral Therapy Cohort Collaboration (ART-CC). Impact of low-level viremia on clinical and virological outcomes in treated HIV-1-infected patients. AIDS. 2015;29:373-383.
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