The Distribution of Viral Blip Amplitudes During HAART

M. Di Mascio*1, J. Percus2, O. Percus2, A. S. Perelson3. 1National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, 2Courant Institute of Mathematical Sciences, New York, NY, 3Los Alamos National Laboratory, Los Alamos, NM (USA)

Background: We previously reported that in patients treated with HAART who achieve viral load (VL) suppression, viral blips more than 4 weeks apart occur at random, with a frequency that does not change with longer times of observation. The etiology of viral blips is currently unknown, but viral blip frequency inversely correlates with the decay of the latent reservoir, whose stability has been proposed as the major hurdle to HIV eradication. Material and Methods: 123 patients in 8 prospective studies [LPV/RIT/TDF/EFV/3TC; RIT/SAQ/AZT/3TC; ABC/APV/AZT/3TC; NLF/RIT/DDI/D4T; IND/AZT/3TC; NLF/AZT/3TC; RIT/AZT/3TC; ABC/APV/3TC] were analyzed. All patients were naïve to HAART. In 2-6 months, HAART reduced VL to < 50 copies/ml, and the patients showed a period of sustained viral load suppression. A viral blip is defined as any value of VL over 50 copies/ml and below 1000 copies/ml during the period of suppression. The distribution of viral blip amplitudes was obtained as the number of blips observed in the entire population of patients within fixed amplitude intervals. Blips are assumed to represent VL values over the threshold of detection of independent intermittent episodes of viremia characterized by common dynamic properties. Results: Viral blip amplitudes appear to be power-law distributed, with exponent 1.78 (95% C.I: 1.71-1.83). Such a distribution can be theoretically generated by randomly sampling the arrival of independent and overlapping elementary pulses of viremia, with kinetics showing faster decay at higher amplitudes and lower decay at lower amplitudes. Conclusions: We speculate that the dynamics of low fluctuations of viremia observed in patients during HAART is, in part, a discrete phenomenon involving elementary pulses of viremia. Potential physiological explanations of the origin of these elementary pulses are discussed.