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Slips in Adherence Tied to Transient Viremia ("Blips")
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46th ICAAC, September 27-30, 2006, San Francisco
Mark Mascolini
September 28, 2006
Brief slips in adherence to therapy may explain "blips," the come-and-go viral load jumps above 50 copies in people whose regimen otherwise tightly controls HIV replication [1]. Although blips appear to be common in people taking potent antiretroviral regimens, no one has nailed down precisely why they happen. Possible explanations include poor adherence, drops in drug concentrations for other reasons, release of virus from activated latent reservoirs, or simply assay variations.
In this analysis Abbott researchers looked back at viral load readings and adherence gauged by electronic pill-bottle-cap openings in previously untreated people randomized to once- or twice-daily lopinavir/ritonavir plus nucleosides (studies M99-956 and M02-418). Trial participants had their viral loads measured every 4 weeks through week 24, every 8 weeks through week 28, and every 12 weeks through week 96.
The adherence analysis involved 223 people with bottle-cap data, 131 taking once-daily lopinavir and 92 twice-daily lopinavir. Defining blips as a viral load between 50 and 1000 copies followed on the next reading by a sub-50 load, the Abbott team recorded blips in 60 people (27%), 39 (30%) taking once-daily lopinavir and 21 (23%) taking the protease inhibitors (PIs) twice daily, a nonsignificant difference (P = 0.212).
The median blip was 82 copies, with a range from 51 to 858 copies. Neither pretreatment viral load nor pretreatment CD4 count foretold blips. Blip frequency did appear to rise slowly over time: 23.3% of blips happened before week 24, 36.7% between week 24 and week 48, and 40.0% after week 48.
Using the bottle-opening data, the researchers figured the average number of days a person took the prescribed doses in the week before a blip and compared that to the average number of days with correct adherence during a week with no blips in the same person. The average for the pre-blip period was significantly lower than the average for the no-blip period (5.55 versus 6.22 days, P = 0.007).
Bottle-cap data showed a jump in correct adherence in blippers just after their viral load spike. The trial design called for a follow-up viral load reading within 4 weeks of any blip. When people learned their viral load spike was a blip and not a full-fledged rebound, adherence subsided from this higher level back to the pre-blip baseline.
As in most previous studies, blips did not predict virologic failure in this study group. PI mutations arose in people with blips no more often than they did in those without blips. Nor did the 3TC-induced M184V mutation evolve more often in blippers than in nonblippers. Other work, however, has chronicled the emergence of resistant virus during blips [2,3]. One earlier study that did not see new resistance mutations during blips found a marginal correlation between blips and reported poor adherence (P = 0.08) [4]. The Abbott team cautions that their blip-related adherence and resistance results may not hold true for nonlopinavir regimens.
References
1. Podsadecki TJ, Vrijens B, Tousset E, et al. Lower adherence to HAART observed prior to transient HIV-1 viremia ("blips"). 46th ICAAC. September 27-30, 2006, San Francisco. Abstract H-1057.
2. Macias J, Palomares JC, Mira JA, et al. Transient rebounds of HIV plasma viremia are associated with the emergence of drug resistance mutations in patients on highly active antiretroviral therapy. J Infect 2005;51:195-200.
3. Cohen Stuart JW, Wensing AM, Kovacs C, et al. Transient relapses ("blips") of plasma HIV RNA levels during HAART are associated with drug resistance. JAIDS 2001;28:105-113.
4. Nettles RE, Kieffer TL, Kwon P, et al. Intermittent HIV-1 viremia (blips) and drug resistance in patients receiving HAART. JAMA 2005;293:817-829.
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