571 Possible Beneficial Effect of Sequential Use of HAART Regimens in Individuals with Undetectable Viral Load Changing Therapy Due to Drug Intolerance N.Khanna*1, G.Kaufmann1, R.Weber2, H.Furrer3, A.Telenti4, P.Vernazza5, E.Bernasconi6, B.Hirschel7, M.Battegay1 1Univ Hosp Basel, Switzerland; 2Univ Hosp Zurich, Switzerland; 3Univ Hosp Berne, Switzerland; 4CHUV Lausanne, Switzerland; 5Cantonal Hosp, St Gallen, Switzerland; 6Cantonal Hosp, Lugano, Switzerland; and 7Univ Hosp Geneva, Switzerland
Background: Adverse events are common in individuals receiving potent antiretroviral therapy (HAART) and frequently necessitate therapy changes. The sequential use of multiple drug regimens may increase the risk of drug resistance. We studied the characteristics of individuals with frequent changes of HAART due to drug intolerance and evaluated the effect on virologic and immunological responses.
Methods: Individuals of the Swiss HIV Cohort Study were included who commenced HAART in 1996-1998 and continued therapy without treatment interruption for at least 3 yrs. Excluded were subjects with missing baseline CD4 count or plasma HIV RNA. The virologic response was analyzed using a Cox proportional hazards model. The recovery of CD4 T-lymphocytes was analyzed in individuals permanently suppressing viral load to < 400 copies/mL stratified by the number of treatment changes.
Results: We followed 1,141 individuals (mean age: 39 yrs; 75% men) for a median of 57 months. Of these, 289 individuals (25.3%) had received 1, 426 (37.3%) 2, 242 (21.2%) 3, 111 (9.7%) 4, and 73 (6.4%) more than 4 therapies. The proportion of protease inhibitor (PI) containing therapies declined over time: 97% used a PI in the first, 69.4% in the second, 53.5% in the third, and 44% in the fourth regimen. The number of treatment changes did not depend on the risk group of HIV transmission, gender, duration of HIV-1 infection, baseline CD4/CD8 count ,or plasma HIV RNA. However, a trend towards a larger number of treatment changes in older age was observed (p = 0.09). A total 640 individuals (56.1%) were able to permanently suppress viral load to values < 400 copies/ml (virologic responders). Of virologic responders to the first drug regimen (70.3%), 80.1% succeeded on the second regimen. Of these, 86.5% succeeded on the 3rd, and of these 91.7% succeeded on the 4th regimen. After adjustment for baseline CD4 count, plasma HIV-1 RNA, and pretreatment virologic responders to the 1st, 2nd and 3rd drug regimen were significantly more likely to respond virologically to the second (HR: 2.5; 95%CI: 1.7-3.6), third (HR: 4.8; 95% CI: 2.4-9.5), and fourth drug regimen (HR: 9.1; 95% CI: 2.2-37.2). The increase in CD4 count did not depend on the number of treatment changes.
Conclusions: Treatment changes in virologic responders have no negative effect on the durability of the virologic and immunological response to HAART, but may even proof beneficial, probably preventing drug resistance.
