574 Viral Dynamics and Their Relationship to Baseline Factors and Week 24 Virological Response in Non-perinatally HIV-1 Infected Adolescents Receiving HAART H. Wu*1, J. Lathey2, S. Spector2, P. Ruan3, J. Lindsey3, M. Hughes3, S. Douglas4, B.J. Rudy5, P.M. Flynn6 1Frontier Sci and Tech Res Fndn, Boston, MA; 2Univ of California at San Diego, La Jolla; 3Harvard Sch of Public Hlth, Boston, MA; 4Children's Hosp of Philadelphia, PA; 5Mt Sinai Med Ctr, New York, NY; and 6St Jude Children's Res Hosp, Memphis, TN
Background: HIV dynamics have been established for HIV-1 infected adults and infants. No data have been reported on non-perinatally HIV-1 infected adolescents. In a non-randomized observational study of non-perinatally HIV-1 infected adolescents receiving highly active antiretroviral therapy (HAART), we characterized viral dynamics and studied their relationship with baseline host factors and virological status after 24 wks on study.
Methods: Pediatric AIDS Clinical Trials Group (PACTG) study 381 enrolled 121 subjects, 120 of whom started therapy. Viral loads were measured approximately at entry, days 1, 2, 4, 7, 10, 14, 21, and weeks 4, 8, 12, 16, 24. Most subjects initiated the HAART regimens of 3TC/ZDV/EFV (48%) or 3TC/ZDV/NFV (37%) with the remaining subjects on various other HAART regimens. A biphasic nonlinear mixed-effects model for early viral dynamics was fit to the data and the viral decay rates for 115 evaluable subjects were estimated using empirical Bayes estimates.
Results: The average viral decay rates for the 2 phases were d1 = 0.588 ±0.110/day and d2 = 0.016 ±0.026/day, respectively. Individuals who received the 3TC/ZDV/EFV regimen had faster phase I viral decay rate (d1 = 0.610/day) than those who received 3TC/ZDV/NFV (d1 = 0.566/day, p = 0.006) or other HAART regimens (d1 = 0.539/day, p = 0.033). The phase I viral decay rates were positively correlated with baseline RNA levels (r = 0.443, p < 0.00001). A strong correlation between phase I viral decay rates and week 1 viral load reduction from baseline was observed (r = 0.89, p < 0.00001). Higher viral decay rates were significantly and positively related to the likelihood of having suppressed viral load at wk 24 (p = 0.047).
Conclusions: Our results suggest that viral dynamics in non-perinatally HIV-1 infected adolescents are similar to HIV-1 infected adults and infants. Our findings indicate that the 3TC/ZDV/EFV regimen may be more potent than 3TC/ZDV/NFV. Early viral dynamics were predictive of virological status after 24 wks on study. Wk 1 viral load reduction may be able to replace complicated phase I viral decay rates to evaluate the potency of antiretroviral regimens.
