Determinants of long-term highly active antiretroviral treatment efficacy

Abstract

Objectives. Predictors of the efficacy of highly active antiretroviral therapy (HAART) have been investigated in several studies. To increase current knowledge, the study aimed to acquire comprehensive data over an extended observation time, to obtain information on possible performance differences among individual drugs, and to identify factors with influence on the initial response to a HAART regimen and the sustainability of the response. Methods. The data were obtained from a prospective, single University Medical School HIV cohort. Clinical, laboratory, and treatment parameters for 475 patients were collected over 4.5 years. HAART efficacy was determined by analysis of variance and multivariate survival analysis. Results. The overall initial complete response (CR) (< 500 HIV-1 RNA copies/mL) was 76.3%. Use of indinavir [odds ratio (OR) = 2.747, P = 0.0009] and the number of new nucleoside reverse transcriptase inhibitors (NRTIs) (OR = 1.862, P = 0.0017) were positively associated with CR, while initial peripheral blood HIV RNA concentration (OR = 0.383, P<0.0001), use of saquinavir hard gel capsules (OR = 0.531, P= 0.0302), the number of successive HAART regimens (OR = 0.631, P<0.0001), and the number of previously used NRTIs (OR = 0.728, P = 0.0081) were negatively associated with CR. Sustainability of CR was positively correlated with use of indinavir [hazard ratio of relapse (HR) = 0.255, P<0.0001] and haemoglobin levels (HR = 0.873, P = 0.0124), but negatively correlated with initial HIV RNA concentration (HR = 1.273, P = 0.0003) and the number of previously used NRTIs (HR = 1.587, P<0.0001). A higher number of consecutive HAART regimens was associated with a markedly reduced CR, but with only a slightly higher risk of relapse. Conclusions. The initial response to HAART, as well as long-term efficacy, depends strongly on a few fundamental parameters that can easily be assessed in a clinical setting. There is a need for effective suppression of HIV replication over decades, and these factors should be considered early in treatment planning to identify patients with an unfavourable profile of risk factors for treatment failure.