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Viral Load of 51 to 500 Boosts Risk of AIDS But Not Serious Non-AIDS Illness
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15th European AIDS Conference, October 21-24, 2015, Barcelona
Mark Mascolini
A viral load between 51 and 500 copies raised the risk of a new AIDS diagnosis in a 7277-person analysis in the Icona Foundation Cohort [1]. But a viral load in this range did not predict a higher risk of serious non-AIDS illness.
Previous research has linked low-level viremia (defined various ways) to an eventual rebound above 1000 copies. But a 6440-person Dutch study found that a detectable load below 400 copies did not predict non-AIDS illness [2], and a 17,902-person Antiretroviral Therapy Cohort Collaboration study discerned no link between a viral load of 51 to 499 copies and the risk of AIDS or death [3].
To learn more about how a low but detectable viral load affects chances of AIDS, non-AIDS diseases, or death, Icona researchers analyzed people enrolled in the cohort who had at least 1 person-year of follow-up with a viral load of 1000 or lower more than 6 months after starting antiretroviral therapy. The endpoints were (1) 3-month incidence of a new AIDS diagnosis or death from any cause, and (2) 3-month incidence of a serious non-AIDS illness or death from any cause.
The researchers divided study participants into 4 groups by most recent viral load--3919 people with a load between 0 and 50 copies, 1811 with 51 to 200 copies, 1117 with 201 to 500 copies, and 430 with 501 to 1000 copies. Median ages across the 4 groups were 35 to 37, and women made up about one quarter of each group. Median viral load when antiretroviral therapy began was lowest in the 0-to-50-copy group (4.54 log10 versus 4.83, 4.78, and 4.92 in the next 3 higher groups, P < 0.001). Current CD4 count was significantly higher in the 0-to-50-copy group than in the next 3 higher groups (314 versus 284, 277, and 280, P < 0.001). Year when ART began was significantly later in the 0-to-50-copy group than in the next 3 higher groups (2010 versus 2003, 1998, and 1999, P < 0.001).
Incidence of AIDS or death in 3 months was significantly lower in people with a latest viral load between 0 and 50 copies (0.52 per 100 person-years, 95% confidence interval [CI] 0.43 to 0.62) than in the 51-to-200 group (1.25 per 100 person-years, 95% CI 0.94 to 1.66) or the 201-to-500 group (1.91 per 100 person-years, 95% CI 1.37 to 2.68) but not the 501-to-1000 group (1.06 per 1000 person-years, 95% CI 0.50 to 2.21). Incidence of a serious non-AIDS illness or death did not differ significantly between groups (1.46 per 100 person-years for 0-to-50 copies and, in ascending order, 1.77, 1.69, and 2.56).
Poisson regression analysis to figure the risk of AIDS/death or serious non-AIDS illness/death adjusted for age, gender, black ethnicity, HIV transmission mode, HCV status, AIDS diagnosis before combination antiretroviral therapy, current CD4 count, year starting combination antiretroviral therapy, and clinical center. This analysis determined that people with a most recent viral load of 51 to 200 copies had almost a 75% higher risk of a new AIDS diagnosis or death within 3 months than people with a load of 50 copies or lower (adjusted rate ratio [aRR] 1.74, 95% CI 1.23 to 2.47, P = 0.001). And people with a most recent load between 201 and 500 had more than a doubled risk of AIDS or death than the 0-to-50-copy group (aRR 2.30, 95% CI 1.53 to 3.44, P = 0.001).
The 501-to-1000-copy group did not differ significantly from the 0-to-50 group in risk of AIDS or death, possibly because people with steeply rising viral loads were changing antiretrovirals and thus not included in the analysis. As noted above, this group had by far the fewest participants. There was a trend toward a higher risk of a serious non-AIDS event in the next 3 months in the 501-to-1000 group than in the 0-to-50 group (aRR 1.54, 95% CI 0.94 to 2.52, P = 0.09). But risk of serious non-AIDS events was nearly identical in the 201-to-500 group, the 51-to-200 group, and the 0-to-50 group.
The Icona team noted that their analysis is limited by focusing on current viral load--not sustained viral loads--by the short-term (3-month) evaluation of clinical outcomes, and by the inability to adjust for adherence and other possible confounding variables. They suggested that their findings may prove useful in planning analyses that more tightly define virologic failure thresholds useful in clinical practice.
References
1. 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.
2. 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
3. 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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