Background:  PACTG 381 recruited 120 adolescents infected through risk behaviors, who began HAART, defined as 2 nucleoside reverse transcriptase inhibitors (NRTI) plus a protease inhibitor (PI) or efavirenz (EFV). Initial virologic outcome was poorer than expected based on adult and pediatric studies with only 69 of 118 (59%) subjects achieving undetectable viral loads at 24 weeks. Immunologic, virologic, and adherence data are now reported for the cohort followed for 3 years. 

Methods:  Virologic, immunologic, and treatment data were collected from subjects every 12 weeks beyond the first 24 weeks of therapy through 156 weeks. Adherence was measured by self report using an instrument developed to assess the number of ART doses missed during the previous 3 days. Cox proportional hazards models were used to assess the ieffect of self-reported adherence rates on ability to stay on study treatment and achieve and maintain control of viral load.

Results:  Of the 120 subjects starting HAART, 41 (34%) stayed on study treatment for the 3 years of observation, 20 remained on study but had discontinued HAART, and 59 were lost to follow-up. Of the 69 subjects with undetectable viral loads after 24 weeks, 29 (24%) remained undetectable after 3 years on study. Poorer short-term (to 16 weeks) adherence (p = 0.016), higher baseline viral load (p = 0.010), and higher CD8 naïve counts (p = 0.034) predicted virologic failure. By week 156, CD4 counts in these 29 subjects were lower but not statistically different than CD4 counts in HIV-uninfected youth participating in the REACH project. Perfect adherence during the first 16 weeks on study (i.e. no missed doses reported at any of the 4 study visits scheduled every 4 weeks after initiation of HAART) increased the likelihood of achieving control of viral load by 16 to 24 weeks (RR = 1.65; 95%CI 1.04 to 2.61, p = 0.032). Over the entire study, each 10% increase in percentage adherence decreased the risk of going off study treatment before the next study visit by 13% (RR = 0.87; 95%CI: 0.83 to 0.91, p <0.001). Similarly, each 10% increase in percentage adherence decreased the risk of virologic failure by 11% (RR = 0.89, 95%CI 0.84 to 0.93, p <0.001).

Conclusions:  Adolescents infected with HIV via high-risk behaviors have less than optimal responses to HAART therapy with only 24% achieving and maintaining undetectable viral loads over 3 years. Self-reported adherence strongly predicts virologic outcome and regimen success in adolescents initiating HAART.