Individual prognoses of long-term responses to antiretroviral treatment based on virological, immunological and pharmacological parameters measured during the first week under therapy

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Abstract
To predict long-term (12 weeks or longer) virological responses to antiretroviral treatment from measurements made during the first few days on therapy. Forty-one HIV-1 -infected children were treated with ritonavir for 12 weeks followed by triple drug combination treatment, and the kinetics of virus decay in plasma, ritonavir concentration and CD4 cell counts were measured. A robust multivariate pattern recognition method was used for prediction of the long-term virological responses. The virus decay rate constants calculated from measurements of plasma viral RNA concentrations on the first, second, third, fourth and seventh day on therapy, the drug concentrations in the plasma on day seven, and the pretreatment levels of viral RNA and CD4 cell counts, correlated with long-term levels of plasma HIV-1 RNA. The combination of these parameters contained sufficient information for correct and robust prediction of the long-term response in 88% of the treated children. The predictions of individual responses were stable as demonstrated by a cross-validation analysis, which was highly statistically significant (r = 0.87) and specific. These results demonstrate that multiple parameters determine the response to antiretroviral therapy and offer a very early measure of individual long-term responses, suggesting that treatment could be optimized after few days of therapy.

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